WorldWideScience

Sample records for action potential model

  1. Quadratic adaptive algorithm for solving cardiac action potential models.

    Science.gov (United States)

    Chen, Min-Hung; Chen, Po-Yuan; Luo, Ching-Hsing

    2016-10-01

    An adaptive integration method is proposed for computing cardiac action potential models accurately and efficiently. Time steps are adaptively chosen by solving a quadratic formula involving the first and second derivatives of the membrane action potential. To improve the numerical accuracy, we devise an extremum-locator (el) function to predict the local extremum when approaching the peak amplitude of the action potential. In addition, the time step restriction (tsr) technique is designed to limit the increase in time steps, and thus prevent the membrane potential from changing abruptly. The performance of the proposed method is tested using the Luo-Rudy phase 1 (LR1), dynamic (LR2), and human O'Hara-Rudy dynamic (ORd) ventricular action potential models, and the Courtemanche atrial model incorporating a Markov sodium channel model. Numerical experiments demonstrate that the action potential generated using the proposed method is more accurate than that using the traditional Hybrid method, especially near the peak region. The traditional Hybrid method may choose large time steps near to the peak region, and sometimes causes the action potential to become distorted. In contrast, the proposed new method chooses very fine time steps in the peak region, but large time steps in the smooth region, and the profiles are smoother and closer to the reference solution. In the test on the stiff Markov ionic channel model, the Hybrid blows up if the allowable time step is set to be greater than 0.1ms. In contrast, our method can adjust the time step size automatically, and is stable. Overall, the proposed method is more accurate than and as efficient as the traditional Hybrid method, especially for the human ORd model. The proposed method shows improvement for action potentials with a non-smooth morphology, and it needs further investigation to determine whether the method is helpful during propagation of the action potential. Copyright © 2016 Elsevier Ltd. All rights

  2. Re-modeling Chara action potential: II. The action potential form under salinity stress

    Directory of Open Access Journals (Sweden)

    Mary Jane Beilby

    2017-04-01

    Full Text Available In part I we established Thiel-Beilby model of the Chara action potential (AP. In part II the AP is investigated in detail at the time of saline stress. Even very short exposure of salt-sensitive Chara cells to artificial pond water with 50 mM NaCl (Saline APW modified the AP threshold and drastically altered the AP form. Detailed modeling of 14 saline APs from 3 cells established that both the Ca2+ pump and the Ca2+ channels on internal stores seem to be affected, with the changes sometimes cancelling and sometimes re-enforcing each other, leading to APs with long durations and very complex forms. The exposure to salinity offers further insights into AP mechanism and suggests future experiments. The prolonged APs lead to greater loss of chloride and potassium ions, compounding the effects of saline stress.

  3. Modelling in vivo action potential propagation along a giant axon.

    Science.gov (United States)

    George, Stuart; Foster, Jamie M; Richardson, Giles

    2015-01-01

    A partial differential equation model for the three-dimensional current flow in an excitable, unmyelinated axon is considered. Where the axon radius is significantly below a critical value R(crit) (that depends upon intra- and extra-cellular conductivity and ion channel conductance) the resistance of the intracellular space is significantly higher than that of the extracellular space, such that the potential outside the axon is uniformly small whilst the intracellular potential is approximated by the transmembrane potential. In turn, since the current flow is predominantly axial, it can be shown that the transmembrane potential is approximated by a solution to the one-dimensional cable equation. It is noted that the radius of the squid giant axon, investigated by (Hodgkin and Huxley 1952e), lies close to R(crit). This motivates us to apply the three-dimensional model to the squid giant axon and compare the results thus found to those obtained using the cable equation. In the context of the in vitro experiments conducted in (Hodgkin and Huxley 1952e) we find only a small difference between the wave profiles determined using these two different approaches and little difference between the speeds of action potential propagation predicted. This suggests that the cable equation approximation is accurate in this scenario. However when applied to the it in vivo setting, in which the conductivity of the surrounding tissue is considerably lower than that of the axoplasm, there are marked differences in both wave profile and speed of action potential propagation calculated using the two approaches. In particular, the cable equation significantly over predicts the increase in the velocity of propagation as axon radius increases. The consequences of these results are discussed in terms of the evolutionary costs associated with increasing the speed of action potential propagation by increasing axon radius.

  4. Map-based model of the cardiac action potential

    International Nuclear Information System (INIS)

    Pavlov, Evgeny A.; Osipov, Grigory V.; Chan, C.K.; Suykens, Johan A.K.

    2011-01-01

    A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

  5. Map-based model of the cardiac action potential

    Energy Technology Data Exchange (ETDEWEB)

    Pavlov, Evgeny A., E-mail: genie.pavlov@gmail.com [Department of Computational Mathematics and Cybernetics, Nizhny Novgorod State University, 23, Gagarin Avenue, 603950 Nizhny Novgorod (Russian Federation); Osipov, Grigory V. [Department of Computational Mathematics and Cybernetics, Nizhny Novgorod State University, 23, Gagarin Avenue, 603950 Nizhny Novgorod (Russian Federation); Chan, C.K. [Institute of Physics, Academia Sinica, 128 Sec. 2, Academia Road, Nankang, Taipei 115, Taiwan (China); Suykens, Johan A.K. [K.U. Leuven, ESAT-SCD/SISTA, Kasteelpark Arenberg 10, B-3001 Leuven (Heverlee) (Belgium)

    2011-07-25

    A simple computationally efficient model which is capable of replicating the basic features of cardiac cell action potential is proposed. The model is a four-dimensional map and demonstrates good correspondence with real cardiac cells. Various regimes of cardiac activity, which can be reproduced by the proposed model, are shown. Bifurcation mechanisms of these regimes transitions are explained using phase space analysis. The dynamics of 1D and 2D lattices of coupled maps which model the behavior of electrically connected cells is discussed in the context of synchronization theory. -- Highlights: → Recent experimental-data based models are complicated for analysis and simulation. → The simplified map-based model of the cardiac cell is constructed. → The model is capable for replication of different types of cardiac activity. → The spatio-temporal dynamics of ensembles of coupled maps are investigated. → Received data are analyzed in context of biophysical processes in the myocardium.

  6. A Parametric Computational Model of the Action Potential of Pacemaker Cells.

    Science.gov (United States)

    Ai, Weiwei; Patel, Nitish D; Roop, Partha S; Malik, Avinash; Andalam, Sidharta; Yip, Eugene; Allen, Nathan; Trew, Mark L

    2018-01-01

    A flexible, efficient, and verifiable pacemaker cell model is essential to the design of real-time virtual hearts that can be used for closed-loop validation of cardiac devices. A new parametric model of pacemaker action potential is developed to address this need. The action potential phases are modeled using hybrid automaton with one piecewise-linear continuous variable. The model can capture rate-dependent dynamics, such as action potential duration restitution, conduction velocity restitution, and overdrive suppression by incorporating nonlinear update functions. Simulated dynamics of the model compared well with previous models and clinical data. The results show that the parametric model can reproduce the electrophysiological dynamics of a variety of pacemaker cells, such as sinoatrial node, atrioventricular node, and the His-Purkinje system, under varying cardiac conditions. This is an important contribution toward closed-loop validation of cardiac devices using real-time heart models.

  7. Modeling of action potential generation in NG108-15 cells.

    Science.gov (United States)

    Molnar, Peter; Hickman, James J

    2014-01-01

    In order to explore the possibility of identifying toxins based on their effect on the shape of action potentials, we created a computer model of the action potential generation in NG108-15 cells (a neuroblastoma/glioma hybrid cell line). To generate the experimental data for model validation, voltage-dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated using the Hodgkin-Huxley formalism and were fitted to the recorded action potentials. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently, and their respective effects were identified based on the predicted changes in the fitted parameters.

  8. Action potential conduction between a ventricular cell model and an isolated ventricular cell

    NARCIS (Netherlands)

    Wilders, R.; Kumar, R.; Joyner, R. W.; Jongsma, H. J.; Verheijck, E. E.; Golod, D.; van Ginneken, A. C.; Goolsby, W. N.

    1996-01-01

    We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded

  9. Spatial and frequency domain ring source models for the single muscle fiber action potential

    DEFF Research Database (Denmark)

    Henneberg, Kaj-åge; R., Plonsey

    1994-01-01

    In the paper, single-fibre models for the extracellular action potential are developed that will allow the potential to the evaluated at an arbitrary field point in the extracellular space. Fourier-domain models are restricted in that they evaluate potentials at equidistant points along a line...... parallel to the fibre axis. Consequently, they cannot easily evaluate the potential at the boundary nodes of a boundary-element electrode model. The Fourier-domain models employ axial-symmetric ring source models, and thereby provide higher accuracy that the line source model, where the source is lumped...... including anisotropy show that the spatial models require extreme care in the integration procedure owing to the singularity in the weighting functions. With adequate sampling, the spatial models can evaluate extracellular potentials with high accuracy....

  10. A phantom axon setup for validating models of action potential recordings.

    Science.gov (United States)

    Rossel, Olivier; Soulier, Fabien; Bernard, Serge; Guiraud, David; Cathébras, Guy

    2016-08-01

    Electrode designs and strategies for electroneurogram recordings are often tested first by computer simulations and then by animal models, but they are rarely implanted for long-term evaluation in humans. The models show that the amplitude of the potential at the surface of an axon is higher in front of the nodes of Ranvier than at the internodes; however, this has not been investigated through in vivo measurements. An original experimental method is presented to emulate a single fiber action potential in an infinite conductive volume, allowing the potential of an axon to be recorded at both the nodes of Ranvier and the internodes, for a wide range of electrode-to-fiber radial distances. The paper particularly investigates the differences in the action potential amplitude along the longitudinal axis of an axon. At a short radial distance, the action potential amplitude measured in front of a node of Ranvier is two times larger than in the middle of two nodes. Moreover, farther from the phantom axon, the measured action potential amplitude is almost constant along the longitudinal axis. The results of this new method confirm the computer simulations, with a correlation of 97.6 %.

  11. Electrophysiological properties of computational human ventricular cell action potential models under acute ischemic conditions.

    Science.gov (United States)

    Dutta, Sara; Mincholé, Ana; Quinn, T Alexander; Rodriguez, Blanca

    2017-10-01

    Acute myocardial ischemia is one of the main causes of sudden cardiac death. The mechanisms have been investigated primarily in experimental and computational studies using different animal species, but human studies remain scarce. In this study, we assess the ability of four human ventricular action potential models (ten Tusscher and Panfilov, 2006; Grandi et al., 2010; Carro et al., 2011; O'Hara et al., 2011) to simulate key electrophysiological consequences of acute myocardial ischemia in single cell and tissue simulations. We specifically focus on evaluating the effect of extracellular potassium concentration and activation of the ATP-sensitive inward-rectifying potassium current on action potential duration, post-repolarization refractoriness, and conduction velocity, as the most critical factors in determining reentry vulnerability during ischemia. Our results show that the Grandi and O'Hara models required modifications to reproduce expected ischemic changes, specifically modifying the intracellular potassium concentration in the Grandi model and the sodium current in the O'Hara model. With these modifications, the four human ventricular cell AP models analyzed in this study reproduce the electrophysiological alterations in repolarization, refractoriness, and conduction velocity caused by acute myocardial ischemia. However, quantitative differences are observed between the models and overall, the ten Tusscher and modified O'Hara models show closest agreement to experimental data. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Control of clustered action potential firing in a mathematical model of entorhinal cortex stellate cells.

    Science.gov (United States)

    Tait, Luke; Wedgwood, Kyle; Tsaneva-Atanasova, Krasimira; Brown, Jon T; Goodfellow, Marc

    2018-07-14

    The entorhinal cortex is a crucial component of our memory and spatial navigation systems and is one of the first areas to be affected in dementias featuring tau pathology, such as Alzheimer's disease and frontotemporal dementia. Electrophysiological recordings from principle cells of medial entorhinal cortex (layer II stellate cells, mEC-SCs) demonstrate a number of key identifying properties including subthreshold oscillations in the theta (4-12 Hz) range and clustered action potential firing. These single cell properties are correlated with network activity such as grid firing and coupling between theta and gamma rhythms, suggesting they are important for spatial memory. As such, experimental models of dementia have revealed disruption of organised dorsoventral gradients in clustered action potential firing. To better understand the mechanisms underpinning these different dynamics, we study a conductance based model of mEC-SCs. We demonstrate that the model, driven by extrinsic noise, can capture quantitative differences in clustered action potential firing patterns recorded from experimental models of tau pathology and healthy animals. The differential equation formulation of our model allows us to perform numerical bifurcation analyses in order to uncover the dynamic mechanisms underlying these patterns. We show that clustered dynamics can be understood as subcritical Hopf/homoclinic bursting in a fast-slow system where the slow sub-system is governed by activation of the persistent sodium current and inactivation of the slow A-type potassium current. In the full system, we demonstrate that clustered firing arises via flip bifurcations as conductance parameters are varied. Our model analyses confirm the experimentally suggested hypothesis that the breakdown of clustered dynamics in disease occurs via increases in AHP conductance. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Directory of Open Access Journals (Sweden)

    Philip Gemmell

    Full Text Available Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+, inward rectifying K(+, L-type Ca(2+, and Na(+/K(+ pump currents in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al. at multiple cycle lengths (400, 600, 1,000 ms was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in

  14. Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

    Science.gov (United States)

    Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

    2014-01-01

    Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

  15. Coupled iterated map models of action potential dynamics in a one-dimensional cable of cardiac cells

    International Nuclear Information System (INIS)

    Wang Shihong; Xie Yuanfang; Qu Zhilin

    2008-01-01

    Low-dimensional iterated map models have been widely used to study action potential dynamics in isolated cardiac cells. Coupled iterated map models have also been widely used to investigate action potential propagation dynamics in one-dimensional (1D) coupled cardiac cells, however, these models are usually empirical and not carefully validated. In this study, we first developed two coupled iterated map models which are the standard forms of diffusively coupled maps and overcome the limitations of the previous models. We then determined the coupling strength and space constant by quantitatively comparing the 1D action potential duration profile from the coupled cardiac cell model described by differential equations with that of the coupled iterated map models. To further validate the coupled iterated map models, we compared the stability conditions of the spatially uniform state of the coupled iterated maps and those of the 1D ionic model and showed that the coupled iterated map model could well recapitulate the stability conditions, i.e. the spatially uniform state is stable unless the state is chaotic. Finally, we combined conduction into the developed coupled iterated map model to study the effects of coupling strength on wave stabilities and showed that the diffusive coupling between cardiac cells tends to suppress instabilities during reentry in a 1D ring and the onset of discordant alternans in a periodically paced 1D cable

  16. Simulation of action potential propagation in plants.

    Science.gov (United States)

    Sukhov, Vladimir; Nerush, Vladimir; Orlova, Lyubov; Vodeneev, Vladimir

    2011-12-21

    Action potential is considered to be one of the primary responses of a plant to action of various environmental factors. Understanding plant action potential propagation mechanisms requires experimental investigation and simulation; however, a detailed mathematical model of plant electrical signal transmission is absent. Here, the mathematical model of action potential propagation in plants has been worked out. The model is a two-dimensional system of excitable cells; each of them is electrically coupled with four neighboring ones. Ion diffusion between excitable cell apoplast areas is also taken into account. The action potential generation in a single cell has been described on the basis of our previous model. The model simulates active and passive signal transmission well enough. It has been used to analyze theoretically the influence of cell to cell electrical conductivity and H(+)-ATPase activity on the signal transmission in plants. An increase in cell to cell electrical conductivity has been shown to stimulate an increase in the length constant, the action potential propagation velocity and the temperature threshold, while the membrane potential threshold being weakly changed. The growth of H(+)-ATPase activity has been found to induce the increase of temperature and membrane potential thresholds and the reduction of the length constant and the action potential propagation velocity. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. A multiscale approach to modelling electrochemical processes occurring across the cell membrane with application to transmission of action potentials.

    Science.gov (United States)

    Richardson, G

    2009-09-01

    By application of matched asymptotic expansions, a simplified partial differential equation (PDE) model for the dynamic electrochemical processes occurring in the vicinity of a membrane, as ions selectively permeate across it, is formally derived from the Poisson-Nernst-Planck equations of electrochemistry. It is demonstrated that this simplified model reduces itself, in the limit of a long thin axon, to the cable equation used by Hodgkin and Huxley to describe the propagation of action potentials in the unmyelinated squid giant axon. The asymptotic reduction from the simplified PDE model to the cable equation leads to insights that are not otherwise apparent; these include an explanation of why the squid giant axon attains a diameter in the region of 1 mm. The simplified PDE model has more general application than the Hodgkin-Huxley cable equation and can, e.g. be used to describe action potential propagation in myelinated axons and neuronal cell bodies.

  18. [Hardware Implementation of Numerical Simulation Function of Hodgkin-Huxley Model Neurons Action Potential Based on Field Programmable Gate Array].

    Science.gov (United States)

    Wang, Jinlong; Lu, Mai; Hu, Yanwen; Chen, Xiaoqiang; Pan, Qiangqiang

    2015-12-01

    Neuron is the basic unit of the biological neural system. The Hodgkin-Huxley (HH) model is one of the most realistic neuron models on the electrophysiological characteristic description of neuron. Hardware implementation of neuron could provide new research ideas to clinical treatment of spinal cord injury, bionics and artificial intelligence. Based on the HH model neuron and the DSP Builder technology, in the present study, a single HH model neuron hardware implementation was completed in Field Programmable Gate Array (FPGA). The neuron implemented in FPGA was stimulated by different types of current, the action potential response characteristics were analyzed, and the correlation coefficient between numerical simulation result and hardware implementation result were calculated. The results showed that neuronal action potential response of FPGA was highly consistent with numerical simulation result. This work lays the foundation for hardware implementation of neural network.

  19. Modeling intentional inhibition of actions

    NARCIS (Netherlands)

    Thilakarathne, D.J.; Treur, J.

    2015-01-01

    Inspired by cognitive and neurological literature on action ownership and action awareness, in this paper a computational cognitive model for intentional inhibition (i.e.; the capacity to voluntarily suspend or inhibit an action) is introduced. The interplay between (positive) potential selection of

  20. A second-generation computational modeling of cardiac electrophysiology: response of action potential to ionic concentration changes and metabolic inhibition.

    Science.gov (United States)

    Alaa, Nour Eddine; Lefraich, Hamid; El Malki, Imane

    2014-10-21

    Cardiac arrhythmias are becoming one of the major health care problem in the world, causing numerous serious disease conditions including stroke and sudden cardiac death. Furthermore, cardiac arrhythmias are intimately related to the signaling ability of cardiac cells, and are caused by signaling defects. Consequently, modeling the electrical activity of the heart, and the complex signaling models that subtend dangerous arrhythmias such as tachycardia and fibrillation, necessitates a quantitative model of action potential (AP) propagation. Yet, many electrophysiological models, which accurately reproduce dynamical characteristic of the action potential in cells, have been introduced. However, these models are very complex and are very time consuming computationally. Consequently, a large amount of research is consecrated to design models with less computational complexity. This paper is presenting a new model for analyzing the propagation of ionic concentrations and electrical potential in space and time. In this model, the transport of ions is governed by Nernst-Planck flux equation (NP), and the electrical interaction of the species is described by a new cable equation. These set of equations form a system of coupled partial nonlinear differential equations that is solved numerically. In the first we describe the mathematical model. To realize the numerical simulation of our model, we proceed by a finite element discretization and then we choose an appropriate resolution algorithm. We give numerical simulations obtained for different input scenarios in the case of suicide substrate reaction which were compared to those obtained in literature. These input scenarios have been chosen so as to provide an intuitive understanding of dynamics of the model. By accessing time and space domains, it is shown that interpreting the electrical potential of cell membrane at steady state is incorrect. This model is general and applies to ions of any charge in space and time

  1. Period doubling cascades of limit cycles in cardiac action potential models as precursors to chaotic early Afterdepolarizations.

    Science.gov (United States)

    Kügler, Philipp; Bulelzai, M A K; Erhardt, André H

    2017-04-04

    Early afterdepolarizations (EADs) are pathological voltage oscillations during the repolarization phase of cardiac action potentials (APs). EADs are caused by drugs, oxidative stress or ion channel disease, and they are considered as potential precursors to cardiac arrhythmias in recent attempts to redefine the cardiac drug safety paradigm. The irregular behaviour of EADs observed in experiments has been previously attributed to chaotic EAD dynamics under periodic pacing, made possible by a homoclinic bifurcation in the fast subsystem of the deterministic AP system of differential equations. In this article we demonstrate that a homoclinic bifurcation in the fast subsystem of the action potential model is neither a necessary nor a sufficient condition for the genesis of chaotic EADs. We rather argue that a cascade of period doubling (PD) bifurcations of limit cycles in the full AP system paves the way to chaotic EAD dynamics across a variety of models including a) periodically paced and spontaneously active cardiomyocytes, b) periodically paced and non-active cardiomyocytes as well as c) unpaced and spontaneously active cardiomyocytes. Furthermore, our bifurcation analysis reveals that chaotic EAD dynamics may coexist in a stable manner with fully regular AP dynamics, where only the initial conditions decide which type of dynamics is displayed. EADs are a potential source of cardiac arrhythmias and hence are of relevance both from the viewpoint of drug cardiotoxicity testing and the treatment of cardiomyopathies. The model-independent association of chaotic EADs with period doubling cascades of limit cycles introduced in this article opens novel opportunities to study chaotic EADs by means of bifurcation control theory and inverse bifurcation analysis. Furthermore, our results may shed new light on the synchronization and propagation of chaotic EADs in homogeneous and heterogeneous multicellular and cardiac tissue preparations.

  2. A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup.

    Science.gov (United States)

    Gray, Richard A; Pathmanathan, Pras

    2016-10-01

    Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple "parsimonious" rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable mechanistic

  3. A collocation--Galerkin finite element model of cardiac action potential propagation.

    Science.gov (United States)

    Rogers, J M; McCulloch, A D

    1994-08-01

    A new computational method was developed for modeling the effects of the geometric complexity, nonuniform muscle fiber orientation, and material inhomogeneity of the ventricular wall on cardiac impulse propagation. The method was used to solve a modification to the FitzHugh-Nagumo system of equations. The geometry, local muscle fiber orientation, and material parameters of the domain were defined using linear Lagrange or cubic Hermite finite element interpolation. Spatial variations of time-dependent excitation and recovery variables were approximated using cubic Hermite finite element interpolation, and the governing finite element equations were assembled using the collocation method. To overcome the deficiencies of conventional collocation methods on irregular domains, Galerkin equations for the no-flux boundary conditions were used instead of collocation equations for the boundary degrees-of-freedom. The resulting system was evolved using an adaptive Runge-Kutta method. Converged two-dimensional simulations of normal propagation showed that this method requires less CPU time than a traditional finite difference discretization. The model also reproduced several other physiologic phenomena known to be important in arrhythmogenesis including: Wenckebach periodicity, slowed propagation and unidirectional block due to wavefront curvature, reentry around a fixed obstacle, and spiral wave reentry. In a new result, we observed wavespeed variations and block due to nonuniform muscle fiber orientation. The findings suggest that the finite element method is suitable for studying normal and pathological cardiac activation and has significant advantages over existing techniques.

  4. Screening action potentials: The power of light

    Directory of Open Access Journals (Sweden)

    Lars eKaestner

    2011-07-01

    Full Text Available Action potentials reflect the concerted activity of all electrogenic constituents in the plasma membrane during the excitation of a cell. Therefore, the action potential is an integrated readout and a promising parameter to detect electrophysiological failures or modifications thereof in diagnosis as well as in drug screens. Cellular action potentials can be recorded by optical approaches. To fulfill the pre-requirements to scale up for e.g. pharmacological screens the following preparatory work has to be provided: (i model cells under investigation need to represent target cells in the best possible manner; (ii optical sensors that can be either small molecule dyes or genetically encoded potential probes need to provide a reliable readout with minimal interaction with the naive behavior of the cells and (iii devices need to be capable to stimulate the cells, read out the signals with the appropriate speed as well as provide the capacity for a sufficient throughput. Here we discuss several scenarios for all three categories in the field of cardiac physiology and pharmacology and provide a perspective to use the power of light in screening cardiac action potentials.

  5. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    DEFF Research Database (Denmark)

    Olesen, Niels Erik; Westh, Peter; Holm, René

    2015-01-01

    of micelles with ITC were compared to a mass-action model (MAM) of reaction type: n⋅S⇌Mn. This analysis can provide guidelines for future ITC studies of systems behaving in accordance with this model such as micelles and proteins that undergo self-association to oligomers. Micelles with small aggregation...

  6. Microelectrode array measurement of potassium ion channel remodeling on the field action potential duration in rapid atrial pacing rabbits model.

    Science.gov (United States)

    Sun, Juan; Yan, Huang; Wugeti, Najina; Guo, Yujun; Zhang, Ling; Ma, Mei; Guo, Xingui; Jiao, Changan; Xu, Wenli; Li, Tianqi

    2015-01-01

    Atrial fibrillation (AF) arises from abnormalities in atrial structure and electrical activity. Microelectrode arrays (MEA) is a real-time, nondestructive measurement of the resting and action potential signal, from myocardial cells, to the peripheral circuit of electrophysiological activity. This study examined the field action potential duration (fAPD) of the right atrial appendage (RAA) by MEA in rapid atrial pacing (RAP) in the right atrium of rabbits. In addition, this study also investigated the effect of potassium ion channel blockers on fAPD. 40 New Zealand white rabbits of either sex were randomly divided into 3 groups: 1) the control, 2) potassium ion channel blocker (TEA, 4-Ap and BaCl2), and 3) amiodarone groups. The hearts were quickly removed and right atrial appendage sectioned (slice thickness 500 μm). Each slice was perfused with Tyrode's solution and continuously stimulated for 30 minutes. Sections from the control group were superfused with Tyrode's solution for 10 minutes, while the blocker groups and amiodarone were both treated with their respective compounds for 10 minutes each. The fAPD of RAA and action field action potential morphology were measured using MEA. In non-pace (control) groups, fAPD was 188.33 ± 18.29 ms after Tyrode's solution superfusion, and 173.91 ± 6.83 ms after RAP. In pace/potassium ion channel groups, TEA and BaCl2 superfusion prolonged atrial field action potential (fAPD) (control vs blocker: 176.67 ± 8.66 ms vs 196.11 ± 10.76 ms, 182.22 ± 12.87 ms vs 191.11 ± 13.09 ms with TEA and BaCl2 superfusion, respectively, P action potential in animal heart slices. After superfusing potassium ion channel blockers, fAPD was prolonged. These results suggest that Ito, IKur and IK1 remodel and mediate RAP-induced atrial electrical remodeling. Amiodarone alter potassium ion channel activity (Ito, IKur, IK1 and IKs), shortening fAPD.

  7. A computational model of the ionic currents, Ca2+ dynamics and action potentials underlying contraction of isolated uterine smooth muscle.

    Directory of Open Access Journals (Sweden)

    Wing-Chiu Tong

    2011-04-01

    Full Text Available Uterine contractions during labor are discretely regulated by rhythmic action potentials (AP of varying duration and form that serve to determine calcium-dependent force production. We have employed a computational biology approach to develop a fuller understanding of the complexity of excitation-contraction (E-C coupling of uterine smooth muscle cells (USMC. Our overall aim is to establish a mathematical platform of sufficient biophysical detail to quantitatively describe known uterine E-C coupling parameters and thereby inform future empirical investigations of physiological and pathophysiological mechanisms governing normal and dysfunctional labors. From published and unpublished data we construct mathematical models for fourteen ionic currents of USMCs: Ca2+ currents (L- and T-type, Na+ current, an hyperpolarization-activated current, three voltage-gated K+ currents, two Ca2+-activated K+ current, Ca2+-activated Cl current, non-specific cation current, Na+-Ca2+ exchanger, Na+-K+ pump and background current. The magnitudes and kinetics of each current system in a spindle shaped single cell with a specified surface area:volume ratio is described by differential equations, in terms of maximal conductances, electrochemical gradient, voltage-dependent activation/inactivation gating variables and temporal changes in intracellular Ca2+ computed from known Ca2+ fluxes. These quantifications are validated by the reconstruction of the individual experimental ionic currents obtained under voltage-clamp. Phasic contraction is modeled in relation to the time constant of changing [Ca2+]i. This integrated model is validated by its reconstruction of the different USMC AP configurations (spikes, plateau and bursts of spikes, the change from bursting to plateau type AP produced by estradiol and of simultaneous experimental recordings of spontaneous AP, [Ca2+]i and phasic force. In summary, our advanced mathematical model provides a powerful tool to

  8. Learning Actions Models: Qualitative Approach

    DEFF Research Database (Denmark)

    Bolander, Thomas; Gierasimczuk, Nina

    2015-01-01

    In dynamic epistemic logic, actions are described using action models. In this paper we introduce a framework for studying learnability of action models from observations. We present first results concerning propositional action models. First we check two basic learnability criteria: finite ident...

  9. Subtype-specific promoter-driven action potential imaging for precise disease modelling and drug testing in hiPSC-derived cardiomyocytes

    NARCIS (Netherlands)

    Chen, Zhifen; Xian, Wenying; Bellin, Milena; Dorn, Tatjana; Tian, Qinghai; Goedel, Alexander; Dreizehnter, Lisa; Schneider, Christine M.; Ward-van Oostwaard, Dorien; Ng, Judy King Man; Hinkel, Rabea; Pane, Luna Simona; Mummery, Christine L.; Lipp, Peter; Moretti, Alessandra; Laugwitz, Karl-Ludwig; Sinnecker, Daniel

    2016-01-01

    AIMS: Cardiomyocytes (CMs) generated from human induced pluripotent stem cells (hiPSCs) are increasingly used in disease modelling and drug evaluation. However, they are typically a heterogeneous mix of ventricular-, atrial-, and nodal-like cells based on action potentials (APs) and gene expression.

  10. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    International Nuclear Information System (INIS)

    Fischer, L.; Deppert, W.R.; Pfeifer, D.; Stanzel, S.; Weimer, M.; Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P.; Schaefer, W.R.

    2012-01-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  11. Potential hazards to embryo implantation: A human endometrial in vitro model to identify unwanted antigestagenic actions of chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, L.; Deppert, W.R. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Pfeifer, D. [Department of Hematology and Oncology, University Hospital Freiburg (Germany); Stanzel, S.; Weimer, M. [Department of Biostatistics, German Cancer Research Center, Heidelberg (Germany); Hanjalic-Beck, A.; Stein, A.; Straßer, M.; Zahradnik, H.P. [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany); Schaefer, W.R., E-mail: wolfgang.schaefer@uniklinik-freiburg.de [Department of Obstetrics and Gynecology, University Hospital Freiburg (Germany)

    2012-05-01

    Embryo implantation is a crucial step in human reproduction and depends on the timely development of a receptive endometrium. The human endometrium is unique among adult tissues due to its dynamic alterations during each menstrual cycle. It hosts the implantation process which is governed by progesterone, whereas 17β-estradiol regulates the preceding proliferation of the endometrium. The receptors for both steroids are targets for drugs and endocrine disrupting chemicals. Chemicals with unwanted antigestagenic actions are potentially hazardous to embryo implantation since many pharmaceutical antiprogestins adversely affect endometrial receptivity. This risk can be addressed by human tissue-specific in vitro assays. As working basis we compiled data on chemicals interacting with the PR. In our experimental work, we developed a flexible in vitro model based on human endometrial Ishikawa cells. Effects of antiprogestin compounds on pre-selected target genes were characterized by sigmoidal concentration–response curves obtained by RT-qPCR. The estrogen sulfotransferase (SULT1E1) was identified as the most responsive target gene by microarray analysis. The agonistic effect of progesterone on SULT1E1 mRNA was concentration-dependently antagonized by RU486 (mifepristone) and ZK137316 and, with lower potency, by 4-nonylphenol, bisphenol A and apigenin. The negative control methyl acetoacetate showed no effect. The effects of progesterone and RU486 were confirmed on the protein level by Western blotting. We demonstrated proof of principle that our Ishikawa model is suitable to study quantitatively effects of antiprogestin-like chemicals on endometrial target genes in comparison to pharmaceutical reference compounds. This test is useful for hazard identification and may contribute to reduce animal studies. -- Highlights: ► We compare progesterone receptor-mediated endometrial effects of chemicals and drugs. ► 4-Nonylphenol, bisphenol A and apigenin exert weak

  12. Impaired action potential initiation in GABAergic interneurons causes hyperexcitable networks in an epileptic mouse model carrying a human Na(V)1.1 mutation.

    Science.gov (United States)

    Hedrich, Ulrike B S; Liautard, Camille; Kirschenbaum, Daniel; Pofahl, Martin; Lavigne, Jennifer; Liu, Yuanyuan; Theiss, Stephan; Slotta, Johannes; Escayg, Andrew; Dihné, Marcel; Beck, Heinz; Mantegazza, Massimo; Lerche, Holger

    2014-11-05

    Mutations in SCN1A and other ion channel genes can cause different epileptic phenotypes, but the precise mechanisms underlying the development of hyperexcitable networks are largely unknown. Here, we present a multisystem analysis of an SCN1A mouse model carrying the NaV1.1-R1648H mutation, which causes febrile seizures and epilepsy in humans. We found a ubiquitous hypoexcitability of interneurons in thalamus, cortex, and hippocampus, without detectable changes in excitatory neurons. Interestingly, somatic Na(+) channels in interneurons and persistent Na(+) currents were not significantly changed. Instead, the key mechanism of interneuron dysfunction was a deficit of action potential initiation at the axon initial segment that was identified by analyzing action potential firing. This deficit increased with the duration of firing periods, suggesting that increased slow inactivation, as recorded for recombinant mutated channels, could play an important role. The deficit in interneuron firing caused reduced action potential-driven inhibition of excitatory neurons as revealed by less frequent spontaneous but not miniature IPSCs. Multiple approaches indicated increased spontaneous thalamocortical and hippocampal network activity in mutant mice, as follows: (1) more synchronous and higher-frequency firing was recorded in primary neuronal cultures plated on multielectrode arrays; (2) thalamocortical slices examined by field potential recordings revealed spontaneous activities and pathological high-frequency oscillations; and (3) multineuron Ca(2+) imaging in hippocampal slices showed increased spontaneous neuronal activity. Thus, an interneuron-specific generalized defect in action potential initiation causes multisystem disinhibition and network hyperexcitability, which can well explain the occurrence of seizures in the studied mouse model and in patients carrying this mutation. Copyright © 2014 the authors 0270-6474/14/3414874-16$15.00/0.

  13. Introducing the Action Potential to Psychology Students

    Science.gov (United States)

    Simon-Dack, Stephanie L.

    2014-01-01

    For this simple active learning technique for teaching, students are assigned "roles" and act out the process of the action potential (AP), including the firing threshold, ion-specific channels for ions to enter and leave the cell, diffusion, and the refractory period. Pre-post test results indicated that students demonstrated increased…

  14. Models in Action

    DEFF Research Database (Denmark)

    Juhl, Joakim

    This thesis is about mathematical modelling and technology development. While mathematical modelling has become widely deployed within a broad range of scientific practices, it has also gained a central position within technology development. The intersection of mathematical modelling and technol...

  15. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure

    DEFF Research Database (Denmark)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T

    2014-01-01

    AIMS: The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore...... the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. METHODS AND RESULTS: An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF...... ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease...

  16. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    International Nuclear Information System (INIS)

    Wang, Ruofan; Wang, Jiang; Deng, Bin; Liu, Chen; Wei, Xile; Tsang, K. M.; Chan, W. L.

    2014-01-01

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease

  17. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    Science.gov (United States)

    Wang, Ruofan; Wang, Jiang; Deng, Bin; Liu, Chen; Wei, Xile; Tsang, K. M.; Chan, W. L.

    2014-03-01

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

  18. A combined method to estimate parameters of the thalamocortical model from a heavily noise-corrupted time series of action potential

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ruofan; Wang, Jiang; Deng, Bin, E-mail: dengbin@tju.edu.cn; Liu, Chen; Wei, Xile [Department of Electrical and Automation Engineering, Tianjin University, Tianjin (China); Tsang, K. M.; Chan, W. L. [Department of Electrical Engineering, The Hong Kong Polytechnic University, Kowloon (Hong Kong)

    2014-03-15

    A combined method composing of the unscented Kalman filter (UKF) and the synchronization-based method is proposed for estimating electrophysiological variables and parameters of a thalamocortical (TC) neuron model, which is commonly used for studying Parkinson's disease for its relay role of connecting the basal ganglia and the cortex. In this work, we take into account the condition when only the time series of action potential with heavy noise are available. Numerical results demonstrate that not only this method can estimate model parameters from the extracted time series of action potential successfully but also the effect of its estimation is much better than the only use of the UKF or synchronization-based method, with a higher accuracy and a better robustness against noise, especially under the severe noise conditions. Considering the rather important role of TC neuron in the normal and pathological brain functions, the exploration of the method to estimate the critical parameters could have important implications for the study of its nonlinear dynamics and further treatment of Parkinson's disease.

  19. Membrane, action, and oscillatory potentials in simulated protocells

    Science.gov (United States)

    Syren, R. M.; Fox, S. W.; Przybylski, A. T.; Stratten, W. P.

    1982-01-01

    Electrical membrane potentials, oscillations, and action potentials are observed in proteinoid microspheres impaled with (3 M KCl) microelectrodes. Although effects are of greater magnitude when the vesicles contain glycerol and natural or synthetic lecithin, the results in the purely synthetic thermal protein structures are substantial, attaining 20 mV amplitude in some cases. The results add the property of electrical potential to the other known properties of proteinoid microspheres, in their role as models for protocells.

  20. Dual Optical Recordings for Action Potentials and Calcium Handling in Induced Pluripotent Stem Cell Models of Cardiac Arrhythmias Using Genetically Encoded Fluorescent Indicators

    Science.gov (United States)

    Song, LouJin; Awari, Daniel W.; Han, Elizabeth Y.; Uche-Anya, Eugenia; Park, Seon-Hye E.; Yabe, Yoko A.; Chung, Wendy K.

    2015-01-01

    Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics. PMID:25769651

  1. Numerical investigation of action potential transmission in plants

    Directory of Open Access Journals (Sweden)

    Mariusz Pietruszka

    2014-01-01

    Full Text Available In context of a fairly concise review of recent literature and well established experimental results we reconsider the problem of action potential propagating steadily down the plant cell(s. Having adopted slightly modified Hodgkin-Huxley set of differential equations for the action potential we carried out the numerical investigation of these equations in the course of time. We argue that the Hodgkin-Huxley-Katz model for the nerve impulse can be used to describe the phenomena which take place in plants - this point of view seems to be plausible since the mechanisms involving active ionic transport across membranes from the mathematical point of view are similar. Besides, we compare in a qualitative way our theoretical outcomes with typical experimental results for the action potentials which arise as the reaction of plants to electrical, mechanical and light stimuli. Moreover, we point out the relevance of the sequence of events during the pulse with the appropriate ionic fluxes.

  2. The Perception-Action Model

    DEFF Research Database (Denmark)

    Grünbaum, Thor

    2017-01-01

    Milner and Goodale’s Two Visual Systems Hypothesis (TVSH) is regarded as common ground in recent discussions of visual consciousness. A central part of TVSH is a functional model of vision and action (a functional perception-action model, PAM for short). In this paper, I provide a brief overview...... of these current discussions and argue that PAM is ambiguous between a strong and a weak version. I argue that, given a standard way of individuating computational mechanisms, the available evidence cannot be used to distinguish between these versions. This not only has consequences for philosophical theories...

  3. Quantitative Comparison of Effects of Dofetilide, Sotalol, Quinidine, and Verapamil between Human Ex vivo Trabeculae and In silico Ventricular Models Incorporating Inter-Individual Action Potential Variability

    Directory of Open Access Journals (Sweden)

    Oliver J. Britton

    2017-08-01

    Full Text Available Background:In silico modeling could soon become a mainstream method of pro-arrhythmic risk assessment in drug development. However, a lack of human-specific data and appropriate modeling techniques has previously prevented quantitative comparison of drug effects between in silico models and recordings from human cardiac preparations. Here, we directly compare changes in repolarization biomarkers caused by dofetilide, dl-sotalol, quinidine, and verapamil, between in silico populations of human ventricular cell models and ex vivo human ventricular trabeculae.Methods and Results:Ex vivo recordings from human ventricular trabeculae in control conditions were used to develop populations of in silico human ventricular cell models that integrated intra- and inter-individual variability in action potential (AP biomarker values. Models were based on the O'Hara-Rudy ventricular cardiomyocyte model, but integrated experimental AP variability through variation in underlying ionic conductances. Changes to AP duration, triangulation and early after-depolarization occurrence from application of the four drugs at multiple concentrations and pacing frequencies were compared between simulations and experiments. To assess the impact of variability in IC50 measurements, and the effects of including state-dependent drug binding dynamics, each drug simulation was repeated with two different IC50 datasets, and with both the original O'Hara-Rudy hERG model and a recently published state-dependent model of hERG and hERG block. For the selective hERG blockers dofetilide and sotalol, simulation predictions of AP prolongation and repolarization abnormality occurrence showed overall good agreement with experiments. However, for multichannel blockers quinidine and verapamil, simulations were not in agreement with experiments across all IC50 datasets and IKr block models tested. Quinidine simulations resulted in overprolonged APs and high incidence of repolarization

  4. Construction of 3D MR image-based computer models of pathologic hearts, augmented with histology and optical fluorescence imaging to characterize action potential propagation.

    Science.gov (United States)

    Pop, Mihaela; Sermesant, Maxime; Liu, Garry; Relan, Jatin; Mansi, Tommaso; Soong, Alan; Peyrat, Jean-Marc; Truong, Michael V; Fefer, Paul; McVeigh, Elliot R; Delingette, Herve; Dick, Alexander J; Ayache, Nicholas; Wright, Graham A

    2012-02-01

    Cardiac computer models can help us understand and predict the propagation of excitation waves (i.e., action potential, AP) in healthy and pathologic hearts. Our broad aim is to develop accurate 3D MR image-based computer models of electrophysiology in large hearts (translatable to clinical applications) and to validate them experimentally. The specific goals of this paper were to match models with maps of the propagation of optical AP on the epicardial surface using large porcine hearts with scars, estimating several parameters relevant to macroscopic reaction-diffusion electrophysiological models. We used voltage-sensitive dyes to image AP in large porcine hearts with scars (three specimens had chronic myocardial infarct, and three had radiofrequency RF acute scars). We first analyzed the main AP waves' characteristics: duration (APD) and propagation under controlled pacing locations and frequencies as recorded from 2D optical images. We further built 3D MR image-based computer models that have information derived from the optical measures, as well as morphologic MRI data (i.e., myocardial anatomy, fiber directions and scar definition). The scar morphology from MR images was validated against corresponding whole-mount histology. We also compared the measured 3D isochronal maps of depolarization to simulated isochrones (the latter replicating precisely the experimental conditions), performing model customization and 3D volumetric adjustments of the local conductivity. Our results demonstrated that mean APD in the border zone (BZ) of the infarct scars was reduced by ~13% (compared to ~318 ms measured in normal zone, NZ), but APD did not change significantly in the thin BZ of the ablation scars. A generic value for velocity ratio (1:2.7) in healthy myocardial tissue was derived from measured values of transverse and longitudinal conduction velocities relative to fibers direction (22 cm/s and 60 cm/s, respectively). The model customization and 3D volumetric

  5. Monophasic action potentials and activation recovery intervals as measures of ventricular action potential duration: experimental evidence to resolve some controversies

    NARCIS (Netherlands)

    Coronel, Ruben; de Bakker, Jacques M. T.; Wilms-Schopman, Francien J. G.; Opthof, Tobias; Linnenbank, André C.; Belterman, Charly N.; Janse, Michiel J.

    2006-01-01

    BACKGROUND: Activation recovery intervals (ARIs) and monophasic action potential (MAP) duration are used as measures of action potential duration in beating hearts. However, controversies exist concerning the correct way to record MAPs or calculate ARIs. We have addressed these issues

  6. NS5806 partially restores action potential duration but fails to ameliorate calcium transient dysfunction in a computational model of canine heart failure.

    Science.gov (United States)

    Maleckar, Mary M; Lines, Glenn T; Koivumäki, Jussi T; Cordeiro, Jonathan M; Calloe, Kirstine

    2014-11-01

    The study investigates how increased Ito, as mediated by the activator NS5806, affects excitation-contraction coupling in chronic heart failure (HF). We hypothesized that restoring spike-and-dome morphology of the action potential (AP) to a healthy phenotype would be insufficient to restore the intracellular Ca(2) (+) transient (CaT), due to HF-induced remodelling of Ca(2+) handling. An existing mathematical model of the canine ventricular myocyte was modified to incorporate recent experimental data from healthy and failing myocytes, resulting in models of both healthy and HF epicardial, midmyocardial, and endocardial cell variants. Affects of NS5806 were also included in HF models through its direct interaction with Kv4.3 and Kv1.4. Single-cell simulations performed in all models (control, HF, and HF + drug) and variants (epi, mid, and endo) assessed AP morphology and underlying ionic processes with a focus on calcium transients (CaT), how these were altered in HF across the ventricular wall, and the subsequent effects of varying compound concentration in HF. Heart failure model variants recapitulated a characteristic increase in AP duration (APD) in the disease. The qualitative effects of application of half-maximal effective concentration (EC50) of NS5806 on APs and CaT are heterogeneous and non-linear. Deepening in the AP notch with drug is a direct effect of the activation of Ito; both Ito and consequent alteration of IK1 kinetics cause decrease in AP plateau potential. Decreased APD50 and APD90 are both due to altered IK1. Analysis revealed that drug effects depend on transmurality. Ca(2+) transient morphology changes-increased amplitude and shorter time to peak-are due to direct increase in ICa,L and indirect larger SR Ca(2+) release subsequent to Ito activation. Downstream effects of a compound acting exclusively on sarcolemmal ion channels are difficult to predict. Remediation of APD to pre-failing state does not ameliorate dysfunction in CaT; however

  7. Decoupling Action Potential Bias from Cortical Local Field Potentials

    Directory of Open Access Journals (Sweden)

    Stephen V. David

    2010-01-01

    Full Text Available Neurophysiologists have recently become interested in studying neuronal population activity through local field potential (LFP recordings during experiments that also record the activity of single neurons. This experimental approach differs from early LFP studies because it uses high impendence electrodes that can also isolate single neuron activity. A possible complication for such studies is that the synaptic potentials and action potentials of the small subset of isolated neurons may contribute disproportionately to the LFP signal, biasing activity in the larger nearby neuronal population to appear synchronous and cotuned with these neurons. To address this problem, we used linear filtering techniques to remove features correlated with spike events from LFP recordings. This filtering procedure can be applied for well-isolated single units or multiunit activity. We illustrate the effects of this correction in simulation and on spike data recorded from primary auditory cortex. We find that local spiking activity can explain a significant portion of LFP power at most recording sites and demonstrate that removing the spike-correlated component can affect measurements of auditory tuning of the LFP.

  8. Teachers in Action Research: Assumptions and Potentials

    Science.gov (United States)

    Li, Yuen-Ling

    2008-01-01

    Research literature has long indicated that action research may stimulate practitioners themselves to actively evaluate the quality of their practice. This study is designed to report the use of action research for the development of early years professional practice by analyzing the pre-project and the post-project video-filmed teaching events.…

  9. Ionic channels underlying the ventricular action potential in zebrafish embryo.

    Science.gov (United States)

    Alday, Aintzane; Alonso, Hiart; Gallego, Monica; Urrutia, Janire; Letamendia, Ainhoa; Callol, Carles; Casis, Oscar

    2014-06-01

    Over the last years zebrafish has become a popular model in the study of cardiac physiology, pathology and pharmacology. Recently, the application of the 3Rs regulation and the characteristics of the embryo have reduced the use of adult zebrafish use in many studies. However, the zebrafish embryo cardiac physiology is poorly characterized since most works have used indirect techniques and direct recordings of cardiac action potential and ionic currents are scarce. In order to optimize the zebrafish embryo model, we used electrophysiological, pharmacological and immunofluorescence tools to identify the characteristics and the ionic channels involved in the ventricular action potentials of zebrafish embryos. The application of Na(+) or T-type Ca(+2) channel blockers eliminated the cardiac electrical activity, indicating that the action potential upstroke depends on Na(+) and T-type Ca(+2) currents. The plateau phase depends on L-type Ca(+2) channels since it is abolished by specific blockade. The direct channel blockade indicates that the action potential repolarization and diastolic potential depends on ERG K(+) channels. The presence in the embryonic heart of the Nav1.5, Cav1.2, Cav3.2 and ERG channels was also confirmed by immunofluorescence, while the absence of effect of specific blockers and immunostaining indicate that two K(+) repolarizing currents present in human heart, Ito and IKs, are absent in the embryonic zebrafish heart. Our results describe the ionic channels present and its role in the zebrafish embryo heart and support the use of zebrafish embryos to study human diseases and their use for drug testing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. AGAMA: Action-based galaxy modeling framework

    Science.gov (United States)

    Vasiliev, Eugene

    2018-05-01

    The AGAMA library models galaxies. It computes gravitational potential and forces, performs orbit integration and analysis, and can convert between position/velocity and action/angle coordinates. It offers a framework for finding best-fit parameters of a model from data and self-consistent multi-component galaxy models, and contains useful auxiliary utilities such as various mathematical routines. The core of the library is written in C++, and there are Python and Fortran interfaces. AGAMA may be used as a plugin for the stellar-dynamical software packages galpy (ascl:1411.008), AMUSE (ascl:1107.007), and NEMO (ascl:1010.051).

  11. Conduction velocity of antigravity muscle action potentials.

    Science.gov (United States)

    Christova, L; Kosarov, D; Christova, P

    1992-01-01

    The conduction velocity of the impulses along the muscle fibers is one of the parameters of the extraterritorial potentials of the motor units allowing for the evaluation of the functional state of the muscles. There are no data about the conduction velocities of antigravity muscleaction potentials. In this paper we offer a method for measuring conduction velocity of potentials of single MUs and the averaged potentials of the interference electromiogram (IEMG) lead-off by surface electrodes from mm. sternocleidomastoideus, trapezius, deltoideus (caput laterale) and vastus medialis. The measured mean values of the conduction velocity of antigravity muscles potentials can be used for testing the functional state of the muscles.

  12. Understanding the Electrical Behavior of the Action Potential in Terms of Elementary Electrical Sources

    Science.gov (United States)

    Rodriguez-Falces, Javier

    2015-01-01

    A concept of major importance in human electrophysiology studies is the process by which activation of an excitable cell results in a rapid rise and fall of the electrical membrane potential, the so-called action potential. Hodgkin and Huxley proposed a model to explain the ionic mechanisms underlying the formation of action potentials. However,…

  13. Enteral nutrients potentiate glucagon-like peptide-2 action and reduce dependence on parenteral nutrition in a rat model of human intestinal failure

    Science.gov (United States)

    Brinkman, Adam S.; Murali, Sangita G.; Hitt, Stacy; Solverson, Patrick M.; Holst, Jens J.

    2012-01-01

    Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that shows promise for the treatment of short bowel syndrome (SBS). Our objective was to investigate how combination GLP-2 + enteral nutrients (EN) affects intestinal adaption in a rat model that mimics severe human SBS and requires parenteral nutrition (PN). Male Sprague-Dawley rats were assigned to one of five groups and maintained with PN for 18 days: total parenteral nutrition (TPN) alone, TPN + GLP-2 (100 μg·kg−1·day−1), PN + EN + GLP-2(7 days), PN + EN + GLP-2(18 days), and a nonsurgical oral reference group. Animals underwent massive distal bowel resection followed by jejunocolic anastomosis and placement of jugular catheters. Starting on postoperative day 4, rats in the EN groups were allowed ad libitum access to EN. Groups provided PN + EN + GLP-2 had their rate of PN reduced by 0.25 ml/day starting on postoperative day 6. Groups provided PN + EN + GLP-2 demonstrated significantly greater body weight gain with similar energy intake and a safe 80% reduction in PN compared with TPN ± GLP-2. Groups provided PN + EN + GLP-2 for 7 or 18 days showed similar body weight gain, residual jejunal length, and digestive capacity. Groups provided PN + EN + GLP-2 showed increased jejunal GLP-2 receptor (GLP-2R), insulin-like growth factor-I (IGF-I), and IGF-binding protein-5 (IGFBP-5) expression. Treatment with TPN + GLP-2 demonstrated increased jejunal expression of epidermal growth factor. Cessation of GLP-2 after 7 days with continued EN sustained the majority of intestinal adaption and significantly increased expression of colonic proglucagon compared with PN + EN + GLP-2 for 18 days, and increased plasma GLP-2 concentrations compared with TPN alone. In summary, EN potentiate the intestinotrophic actions of GLP-2 by improving body weight gain allowing for a safe 80% reduction in PN with increased jejunal expression of GLP-2R, IGF-I, and IGFBP-5 following distal bowel

  14. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Stuart, Greg J.

    2008-01-01

    Action potential threshold is thought to be lowest in the axon, but when measured using conventional techniques, we found that action potential voltage threshold of rat cortical pyramidal neurons was higher in the axon than at other neuronal locations. In contrast, both current threshold and voltage

  15. Action potential propagation: ion current or intramembrane electric field?

    Science.gov (United States)

    Martí, Albert; Pérez, Juan J; Madrenas, Jordi

    2018-01-01

    The established action potential propagation mechanisms do not satisfactorily explain propagation on myelinated axons given the current knowledge of biological channels and membranes. The flow across ion channels presents two possible effects: the electric potential variations across the lipid bilayers (action potential) and the propagation of an electric field through the membrane inner part. The proposed mechanism is based on intra-membrane electric field propagation, this propagation can explain the action potential saltatory propagation and its constant delay independent of distance between Ranvier nodes in myelinated axons.

  16. Selective effects of an octopus toxin on action potentials

    Science.gov (United States)

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

    1. A lethal, water soluble toxin (Maculotoxin, MTX) with a molecular weight less than 540, can be extracted from the salivary glands of an octopus (Hapalochlaena maculosa). 2. MTX blocks action potentials in sartorius muscle fibres of toads without affecting the membrane potential. Delayed rectification is not inhibited by the toxin. 3. At low concentrations (10-6-10-5 g/ml.) MTX blocks action potentials only after a certain number have been elicited. The number of action potentials, which can be defined accurately, depends on the concentration of MTX and the concentration of sodium ions in the extracellular solution. 4. The toxin has no post-synaptic effect at the neuromuscular junction and it is concluded that it blocks neuromuscular transmission by inhibiting action potentials in motor nerve terminals. PMID:4330930

  17. Storage of energies - Translating potential into actions

    International Nuclear Information System (INIS)

    Signoret, Stephane; Mary, Olivier; Petitot, Pauline; Dejeu, Mathieu; De Santis, Audrey

    2015-01-01

    In this set of articles, a first one evokes issues discussed during a colloquium held in Paris by the European association for storage of energy, the possibilities mentioned about energy storage development in the French bill project for energy transition, and the importance of non-interconnected areas in the development of energy storage. A second article proposes an overview of developments and advances in energy storage in California which adopted suitable laws. The German situation is then briefly described: needs are still to be defined and a road map has been published in 2014, as technologies are expensive and the legal framework is still complex. The next article outlines the conditions of development of the power-to-gas sector (as a process of valorisation of excess electricity). An article gives an overview of technological developments in the field of electrochemical energy storage (batteries). The results of the PEPS study (a study on the potential of energy storage) in Europe are commented. An interview with a member of the French BRGM (Bureau of Mines) outlines the major role which underground storage could play in energy transition. The Seti project for an intelligent thermal energy storage and a better use of renewable energies is then presented. An article comments how to use foodstuff cold to make consumption cut-offs. A last article comments how superconductors could be used in the future for batteries. Few examples are briefly presented: a molten salt-based storage by Areva, a local production of green hydrogen in France, an innovating project of solar energy storage in Switzerland, and the Toucan solar plant in French Guyana

  18. Surface deformation during an action potential in pearled cells

    Science.gov (United States)

    Mussel, Matan; Fillafer, Christian; Ben-Porath, Gal; Schneider, Matthias F.

    2017-11-01

    Electric pulses in biological cells (action potentials) have been reported to be accompanied by a propagating cell-surface deformation with a nanoscale amplitude. Typically, this cell surface is covered by external layers of polymer material (extracellular matrix, cell wall material, etc.). It was recently demonstrated in excitable plant cells (Chara braunii) that the rigid external layer (cell wall) hinders the underlying deformation. When the cell membrane was separated from the cell wall by osmosis, a mechanical deformation, in the micrometer range, was observed upon excitation of the cell. The underlying mechanism of this mechanical pulse has, to date, remained elusive. Herein we report that Chara cells can undergo a pearling instability, and when the pearled fragments were excited even larger and more regular cell shape changes were observed (˜10 -100 μ m in amplitude). These transient cellular deformations were captured by a curvature model that is based on three parameters: surface tension, bending rigidity, and pressure difference across the surface. In this paper these parameters are extracted by curve-fitting to the experimental cellular shapes at rest and during excitation. This is a necessary step to identify the mechanical parameters that change during an action potential.

  19. Wireless cardiac action potential transmission with ultrasonically inserted silicon microprobes

    International Nuclear Information System (INIS)

    Shen, C J; Ramkumar, A; Lal, A; Gilmour, R F Jr

    2011-01-01

    This paper reports on the integration of ultrasonically inserted horn-shaped cardiac probes with wireless transmission of 3D cardiac action potential measurement for applications in ex vivo preparations such as monitoring the onset of ventricular fibrillation. Ultrasonically inserted silicon horn probes permit reduced penetration force during insertion, allowing silicon, a brittle material, to penetrate cardiac tissue. The probes also allow recording from multiple sites that are lithographically defined. An application-specific integrated circuit has been designed with a 40 dB amplifying stage and a frequency modulating oscillator at 95 MHz to wirelessly transmit the recorded action potentials. This ultrasonically inserted microprobe wireless system demonstrates the initial results in wireless monitoring of 3D action potential propagation, and the extraction of parameters of interest including the action potential duration and diastolic interval

  20. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth

    2006-01-01

    In prior exploratory research, we had designed a fiber optic sensor utilizing a long period Bragg grating for the purpose of detecting action potentials in axons optically, through a change in index...

  1. Studies on the Action Potential From a Thermodynamic Perspective

    DEFF Research Database (Denmark)

    Wang, Tian

    and nerves with ganglia. (2) Attempts have been made to measure the temperature change associated with an action potential as well as an oscillation reaction (Briggs-Rauscher reaction) that shares the adiabatic feature. It turns out that some practical issues need to be solved for the temperature measurement...... of the nerve impulses, while the measured temperature change during the oscillation reaction suggests that there are a reversible adiabatic process and a dissipative process. (3) Local anesthetic e↵ect on nerves is studied. Local anesthetic lidocaine causes a significant stimulus threshold shift of the action......Nerve impulse, also called action potential, has mostly been considered as a pure electrical phenomenon. However, changes in dimensions, e.g. thickness and length, and in temperature along with action potentials have been observed, which indicates that the nerve is a thermodynamic system. The work...

  2. A physical action potential generator: design, implementation and evaluation.

    Science.gov (United States)

    Latorre, Malcolm A; Chan, Adrian D C; Wårdell, Karin

    2015-01-01

    The objective was to develop a physical action potential generator (Paxon) with the ability to generate a stable, repeatable, programmable, and physiological-like action potential. The Paxon has an equivalent of 40 nodes of Ranvier that were mimicked using resin embedded gold wires (Ø = 20 μm). These nodes were software controlled and the action potentials were initiated by a start trigger. Clinically used Ag-AgCl electrodes were coupled to the Paxon for functional testing. The Paxon's action potential parameters were tunable using a second order mathematical equation to generate physiologically relevant output, which was accomplished by varying the number of nodes involved (1-40 in incremental steps of 1) and the node drive potential (0-2.8 V in 0.7 mV steps), while keeping a fixed inter-nodal timing and test electrode configuration. A system noise floor of 0.07 ± 0.01 μV was calculated over 50 runs. A differential test electrode recorded a peak positive amplitude of 1.5 ± 0.05 mV (gain of 40x) at time 196.4 ± 0.06 ms, including a post trigger delay. The Paxon's programmable action potential like signal has the possibility to be used as a validation test platform for medical surface electrodes and their attached systems.

  3. Components of action potential repolarization in cerebellar parallel fibres.

    Science.gov (United States)

    Pekala, Dobromila; Baginskas, Armantas; Szkudlarek, Hanna J; Raastad, Morten

    2014-11-15

    Repolarization of the presynaptic action potential is essential for transmitter release, excitability and energy expenditure. Little is known about repolarization in thin, unmyelinated axons forming en passant synapses, which represent the most common type of axons in the mammalian brain's grey matter.We used rat cerebellar parallel fibres, an example of typical grey matter axons, to investigate the effects of K(+) channel blockers on repolarization. We show that repolarization is composed of a fast tetraethylammonium (TEA)-sensitive component, determining the width and amplitude of the spike, and a slow margatoxin (MgTX)-sensitive depolarized after-potential (DAP). These two components could be recorded at the granule cell soma as antidromic action potentials and from the axons with a newly developed miniaturized grease-gap method. A considerable proportion of fast repolarization remained in the presence of TEA, MgTX, or both. This residual was abolished by the addition of quinine. The importance of proper control of fast repolarization was demonstrated by somatic recordings of antidromic action potentials. In these experiments, the relatively broad K(+) channel blocker 4-aminopyridine reduced the fast repolarization, resulting in bursts of action potentials forming on top of the DAP. We conclude that repolarization of the action potential in parallel fibres is supported by at least three groups of K(+) channels. Differences in their temporal profiles allow relatively independent control of the spike and the DAP, whereas overlap of their temporal profiles provides robust control of axonal bursting properties.

  4. Alteration of neural action potential patterns by axonal stimulation: the importance of stimulus location.

    Science.gov (United States)

    Crago, Patrick E; Makowski, Nathaniel S

    2014-10-01

    Stimulation of peripheral nerves is often superimposed on ongoing motor and sensory activity in the same axons, without a quantitative model of the net action potential train at the axon endpoint. We develop a model of action potential patterns elicited by superimposing constant frequency axonal stimulation on the action potentials arriving from a physiologically activated neural source. The model includes interactions due to collision block, resetting of the neural impulse generator, and the refractory period of the axon at the point of stimulation. Both the mean endpoint firing rate and the probability distribution of the action potential firing periods depend strongly on the relative firing rates of the two sources and the intersite conduction time between them. When the stimulus rate exceeds the neural rate, neural action potentials do not reach the endpoint and the rate of endpoint action potentials is the same as the stimulus rate, regardless of the intersite conduction time. However, when the stimulus rate is less than the neural rate, and the intersite conduction time is short, the two rates partially sum. Increases in stimulus rate produce non-monotonic increases in endpoint rate and continuously increasing block of neurally generated action potentials. Rate summation is reduced and more neural action potentials are blocked as the intersite conduction time increases. At long intersite conduction times, the endpoint rate simplifies to being the maximum of either the neural or the stimulus rate. This study highlights the potential of increasing the endpoint action potential rate and preserving neural information transmission by low rate stimulation with short intersite conduction times. Intersite conduction times can be decreased with proximal stimulation sites for muscles and distal stimulation sites for sensory endings. The model provides a basis for optimizing experiments and designing neuroprosthetic interventions involving motor or sensory stimulation.

  5. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocitie...... effort and attention to theory and practical detail that may be time consuming....

  6. Nambu sigma model and effective membrane actions

    Energy Technology Data Exchange (ETDEWEB)

    Jurco, Branislav, E-mail: jurco@karlin.mff.cuni.cz [Mathematical Institute, Charles University, Prague 186 75 (Czech Republic); Schupp, Peter, E-mail: p.schupp@jacobs-university.de [Jacobs University Bremen, 28759 Bremen (Germany); Maxwell Institute for Mathematical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, Scotland (United Kingdom)

    2012-07-09

    We propose an effective action for a p{sup Prime }-brane with open p-branes ending on it. The action has dual descriptions similar to the commutative and non-commutative ones of the DBI action for D-branes and open strings. The Poisson structure governing the non-commutativity of the D-brane is replaced by a Nambu structure and the open-closed string relations are generalized to the case of p-branes utilizing a novel Nambu sigma model description of p-branes. In the case of an M5-brane our action interpolates between M5-actions already proposed in the literature and matrix-model like actions involving Nambu structures.

  7. Nambu sigma model and effective membrane actions

    International Nuclear Information System (INIS)

    Jurčo, Branislav; Schupp, Peter

    2012-01-01

    We propose an effective action for a p ′ -brane with open p-branes ending on it. The action has dual descriptions similar to the commutative and non-commutative ones of the DBI action for D-branes and open strings. The Poisson structure governing the non-commutativity of the D-brane is replaced by a Nambu structure and the open-closed string relations are generalized to the case of p-branes utilizing a novel Nambu sigma model description of p-branes. In the case of an M5-brane our action interpolates between M5-actions already proposed in the literature and matrix-model like actions involving Nambu structures.

  8. A neural network model of causative actions

    Directory of Open Access Journals (Sweden)

    Jeremy eLee-Hand

    2015-06-01

    Full Text Available A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g. Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umilta et al., 2008; Hommel et al., 2013. In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John 'smashes' a cup, he brings about the event of 'the cup smashing'. Other actions do not bring about such effects. For instance, if John 'grabs' a cup, this action does not cause the cup to 'do' anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organised into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognises arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the 'causative actions' circuit in our model can be identified with a motor pathway reported in other work, specialising in 'functional' actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013.

  9. A neural network model of causative actions.

    Science.gov (United States)

    Lee-Hand, Jeremy; Knott, Alistair

    2015-01-01

    A common idea in models of action representation is that actions are represented in terms of their perceptual effects (see e.g., Prinz, 1997; Hommel et al., 2001; Sahin et al., 2007; Umiltà et al., 2008; Hommel, 2013). In this paper we extend existing models of effect-based action representations to account for a novel distinction. Some actions bring about effects that are independent events in their own right: for instance, if John smashes a cup, he brings about the event of the cup smashing. Other actions do not bring about such effects. For instance, if John grabs a cup, this action does not cause the cup to "do" anything: a grab action has well-defined perceptual effects, but these are not registered by the perceptual system that detects independent events involving external objects in the world. In our model, effect-based actions are implemented in several distinct neural circuits, which are organized into a hierarchy based on the complexity of their associated perceptual effects. The circuit at the top of this hierarchy is responsible for actions that bring about independently perceivable events. This circuit receives input from the perceptual module that recognizes arbitrary events taking place in the world, and learns movements that reliably cause such events. We assess our model against existing experimental observations about effect-based motor representations, and make some novel experimental predictions. We also consider the possibility that the "causative actions" circuit in our model can be identified with a motor pathway reported in other work, specializing in "functional" actions on manipulable tools (Bub et al., 2008; Binkofski and Buxbaum, 2013).

  10. On non-linear dynamics and an optimal control synthesis of the action potential of membranes (ideal and non-ideal cases) of the Hodgkin-Huxley (HH) mathematical model

    International Nuclear Information System (INIS)

    Chavarette, Fabio Roberto; Balthazar, Jose Manoel; Rafikov, Marat; Hermini, Helder Anibal

    2009-01-01

    In this paper, we have studied the plasmatic membrane behavior using an electric circuit developed by Hodgkin and Huxley in 1952 and have dealt with the variation of the amount of time related to the potassium and sodium conductances in the squid axon. They developed differential equations for the propagation of electric signals; the dynamics of the Hodgkin-Huxley model have been extensively studied both from the view point of its their biological implications and as a test bed for numerical methods, which can be applied to more complex models. Recently, an irregular chaotic movement of the action potential of the membrane was observed for a number of techniques of control with the objective to stabilize the variation of this potential. This paper analyzes the non-linear dynamics of the Hodgkin-Huxley mathematical model, and we present some modifications in the governing equations of the system in order to make it a non-ideal one (taking into account that the energy source has a limited power supply). We also developed an optimal linear control design for the action potential of membranes. Here, we discuss the conditions that allow the use of control linear feedback for this kind of non-linear system.

  11. Neuronal oscillations enhance stimulus discrimination by ensuring action potential precision

    DEFF Research Database (Denmark)

    Schaefer, Andreas T; Angelo, Kamilla; Spors, Hartwig

    2006-01-01

    generated membrane potential oscillations dramatically improve action potential (AP) precision by removing the membrane potential variance associated with jitter-accumulating trains of APs. This increased AP precision occurred irrespective of cell type and--at oscillation frequencies ranging from 3 to 65 Hz......Although oscillations in membrane potential are a prominent feature of sensory, motor, and cognitive function, their precise role in signal processing remains elusive. Here we show, using a combination of in vivo, in vitro, and theoretical approaches, that both synaptically and intrinsically......, membrane potential oscillations dramatically enhance the discriminatory capabilities of individual neurons and networks of cells and provide one attractive explanation for their abundance in neurophysiological systems....

  12. Awareness, Solidarity, and Action: An Educational Model

    Science.gov (United States)

    Reichenbach, Michael R.

    2016-01-01

    How Extension fosters social change and innovation can be improved through the use of theory-based educational models. Educational models can serve as foundations for the conceptual designs of educational interventions. I describe, using examples from my own work, one such model: the awareness, solidarity, and action model. This three-part model…

  13. Optical mapping of optogenetically shaped cardiac action potentials

    Science.gov (United States)

    Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

    2014-01-01

    Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

  14. TRH regulates action potential shape in cerebral cortex pyramidal neurons.

    Science.gov (United States)

    Rodríguez-Molina, Víctor; Patiño, Javier; Vargas, Yamili; Sánchez-Jaramillo, Edith; Joseph-Bravo, Patricia; Charli, Jean-Louis

    2014-07-07

    Thyrotropin releasing hormone (TRH) is a neuropeptide with a wide neural distribution and a variety of functions. It modulates neuronal electrophysiological properties, including resting membrane potential, as well as excitatory postsynaptic potential and spike frequencies. We explored, with whole-cell patch clamp, TRH effect on action potential shape in pyramidal neurons of the sensorimotor cortex. TRH reduced spike and after hyperpolarization amplitudes, and increased spike half-width. The effect varied with dose, time and cortical layer. In layer V, 0.5µM of TRH induced a small increase in spike half-width, while 1 and 5µM induced a strong but transient change in spike half-width, and amplitude; after hyperpolarization amplitude was modified at 5µM of TRH. Cortical layers III and VI neurons responded intensely to 0.5µM TRH; layer II neurons response was small. The effect of 1µM TRH on action potential shape in layer V neurons was blocked by G-protein inhibition. Inhibition of the activity of the TRH-degrading enzyme pyroglutamyl peptidase II (PPII) reproduced the effect of TRH, with enhanced spike half-width. Many cortical PPII mRNA+ cells were VGLUT1 mRNA+, and some GAD mRNA+. These data show that TRH regulates action potential shape in pyramidal cortical neurons, and are consistent with the hypothesis that PPII controls its action in this region. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Multiple modes of action potential initiation and propagation in mitral cell primary dendrite

    DEFF Research Database (Denmark)

    Chen, Wei R; Shen, Gongyu Y; Shepherd, Gordon M

    2002-01-01

    recordings with computational modeling to analyze action-potential initiation and propagation in the primary dendrite. In response to depolarizing current injection or distal olfactory nerve input, fast Na(+) action potentials were recorded along the entire length of the primary dendritic trunk. With weak......-to-moderate olfactory nerve input, an action potential was initiated near the soma and then back-propagated into the primary dendrite. As olfactory nerve input increased, the initiation site suddenly shifted to the distal primary dendrite. Multi-compartmental modeling indicated that this abrupt shift of the spike......-initiation site reflected an independent thresholding mechanism in the distal dendrite. When strong olfactory nerve excitation was paired with strong inhibition to the mitral cell basal secondary dendrites, a small fast prepotential was recorded at the soma, which indicated that an action potential was initiated...

  16. Scalar Potential Model progress

    Science.gov (United States)

    Hodge, John

    2007-04-01

    Because observations of galaxies and clusters have been found inconsistent with General Relativity (GR), the focus of effort in developing a Scalar Potential Model (SPM) has been on the examination of galaxies and clusters. The SPM has been found to be consistent with cluster cellular structure, the flow of IGM from spiral galaxies to elliptical galaxies, intergalactic redshift without an expanding universe, discrete redshift, rotation curve (RC) data without dark matter, asymmetric RCs, galaxy central mass, galaxy central velocity dispersion, and the Pioneer Anomaly. In addition, the SPM suggests a model of past expansion, past contraction, and current expansion of the universe. GR corresponds to the SPM in the limit in which a flat and static scalar potential field replaces the Sources and Sinks such as between clusters and on the solar system scale which is small relative to the distance to a Source. The papers may be viewed at http://web.infoave.net/˜scjh/ .

  17. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

    Conclusion: As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

  18. Consequences of Converting Graded to Action Potentials upon Neural Information Coding and Energy Efficiency

    Science.gov (United States)

    Sengupta, Biswa; Laughlin, Simon Barry; Niven, Jeremy Edward

    2014-01-01

    Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ∼50% in generator potentials, to ∼3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation. PMID:24465197

  19. Modeling Interdependent and Periodic Real-World Action Sequences

    Science.gov (United States)

    Kurashima, Takeshi; Althoff, Tim; Leskovec, Jure

    2018-01-01

    Mobile health applications, including those that track activities such as exercise, sleep, and diet, are becoming widely used. Accurately predicting human actions in the real world is essential for targeted recommendations that could improve our health and for personalization of these applications. However, making such predictions is extremely difficult due to the complexities of human behavior, which consists of a large number of potential actions that vary over time, depend on each other, and are periodic. Previous work has not jointly modeled these dynamics and has largely focused on item consumption patterns instead of broader types of behaviors such as eating, commuting or exercising. In this work, we develop a novel statistical model, called TIPAS, for Time-varying, Interdependent, and Periodic Action Sequences. Our approach is based on personalized, multivariate temporal point processes that model time-varying action propensities through a mixture of Gaussian intensities. Our model captures short-term and long-term periodic interdependencies between actions through Hawkes process-based self-excitations. We evaluate our approach on two activity logging datasets comprising 12 million real-world actions (e.g., eating, sleep, and exercise) taken by 20 thousand users over 17 months. We demonstrate that our approach allows us to make successful predictions of future user actions and their timing. Specifically, TIPAS improves predictions of actions, and their timing, over existing methods across multiple datasets by up to 156%, and up to 37%, respectively. Performance improvements are particularly large for relatively rare and periodic actions such as walking and biking, improving over baselines by up to 256%. This demonstrates that explicit modeling of dependencies and periodicities in real-world behavior enables successful predictions of future actions, with implications for modeling human behavior, app personalization, and targeting of health interventions. PMID

  20. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    Science.gov (United States)

    Yu, Yuguo; Hill, Adam P.; McCormick, David A.

    2012-01-01

    The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na+ channel inactivation, resulting in a marked reduction in overlap of the inward Na+, and outward K+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37–42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code. PMID:22511855

  1. Warm body temperature facilitates energy efficient cortical action potentials.

    Directory of Open Access Journals (Sweden)

    Yuguo Yu

    Full Text Available The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na(+ channel inactivation, resulting in a marked reduction in overlap of the inward Na(+, and outward K(+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na(+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37-42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code.

  2. Sensitivity of the amplitude of the single muscle fibre action potential to microscopic volume conduction parameters

    NARCIS (Netherlands)

    Alberts, B.A.; Rutten, Wim; Wallinga, W.; Boom, H.B.K.

    1988-01-01

    A microscopic model of volume conduction was applied to examine the sensitivity of the single muscle fibre action potential to variations in parameters of the source and of the volume conductor, such as conduction velocity, intracellular conductivity and intracellular volume fraction. The model

  3. Changes in action potentials and intracellular ionic homeostasis in a ventricular cell model related to a persistent sodium current in SCN5A mutations underlying LQT3

    Czech Academy of Sciences Publication Activity Database

    Christé, G.; Chahine, M.; Chevalier, P.; Pásek, Michal

    2008-01-01

    Roč. 96, - (2008), s. 281-293 ISSN 0079-6107 Institutional research plan: CEZ:AV0Z20760514 Keywords : cardiac cell * SCN5A mutation * Long QT syndrome * quantitative modelling Subject RIV: BO - Biophysics Impact factor: 6.388, year: 2008

  4. Modeling the Male Reproductive Endocrine Axis: Potential Role for a Delay Mechanism in the Inhibitory Action of Gonadal Steroids on GnRH Pulse Frequency.

    Science.gov (United States)

    Ferasyi, Teuku R; Barrett, P Hugh R; Blache, Dominique; Martin, Graeme B

    2016-05-01

    We developed a compartmental model so we could test mechanistic concepts in the control of the male reproductive endocrine axis. Using SAAM II computer software and a bank of experimental data from male sheep, we began by modeling GnRH-LH feed-forward and LH-T feedback. A key assumption was that the primary control signal comes from a hypothetical neural network (the PULSAR) that emits a digital (pulsatile) signal of variable frequency that drives GnRH secretion in square wave-like pulses. This model produced endocrine profiles that matched experimental observations for the testis-intact animal and for changes in GnRH pulse frequency after castration and T replacement. In the second stage of the model development, we introduced a delay in the negative feedback caused by the aromatization of T to estradiol at the brain level, a concept supported by empirical observations. The simulations showed how changes in the process of aromatization could affect the response of the pulsatile signal to inhibition by steroid feedback. The sensitivity of the PULSAR to estradiol was a critical factor, but the most striking observation was the effect of time delays. With longer delays, there was a reduction in the rate of aromatization and therefore a decrease in local estradiol concentrations, and the outcome was multiple-pulse events in the secretion of GnRH/LH, reflecting experimental observations. In conclusion, our model successfully emulates the GnRH-LH-T-GnRH loop, accommodates a pivotal role for central aromatization in negative feedback, and suggests that time delays in negative feedback are an important aspect of the control of GnRH pulse frequency.

  5. Delayed onset of changes in soma action potential genesis in nociceptive A-beta DRG neurons in vivo in a rat model of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Henry James L

    2009-09-01

    Full Text Available Abstract Background Clinical data on osteoarthritis (OA suggest widespread changes in sensory function that vary during the progression of OA. In previous studies on a surgically-induced animal model of OA we have observed that changes in structure and gene expression follow a variable trajectory over the initial days and weeks. To investigate mechanisms underlying changes in sensory function in this model, the present electrophysiological study compared properties of primary sensory nociceptive neurons at one and two months after model induction with properties in naïve control animals. Pilot data indicated no difference in C- or Aδ-fiber associated neurons and therefore the focus is on Aβ-fiber nociceptive neurons. Results At one month after unilateral derangement of the knee by cutting the anterior cruciate ligament and removing the medial meniscus, the only changes observed in Aβ-fiber dorsal root ganglion (DRG neurons were in nociceptor-like unresponsive neurons bearing a hump on the repolarization phase; these changes consisted of longer half width, reflecting slowed dynamics of AP genesis, a depolarized Vm and an increased AP amplitude. At two months, changes observed were in Aβ-fiber high threshold mechanoreceptors, which exhibited shorter AP duration at base and half width, shorter rise time and fall time, and faster maximum rising rate/maximum falling rate, reflecting accelerated dynamics of AP genesis. Conclusion These data indicate that Aβ nociceptive neurons undergo significant changes that vary in time and occur later than changes in structure and in nociceptive scores in this surgically induced OA model. Thus, if changes in Aβ-fiber nociceptive neurons in this model reflect a role in OA pain, they may relate to mechanisms underlying pain associated with advanced OA.

  6. A statistical model of future human actions

    International Nuclear Information System (INIS)

    Woo, G.

    1992-02-01

    A critical review has been carried out of models of future human actions during the long term post-closure period of a radioactive waste repository. Various Markov models have been considered as alternatives to the standard Poisson model, and the problems of parameterisation have been addressed. Where the simplistic Poisson model unduly exaggerates the intrusion risk, some form of Markov model may have to be introduced. This situation may well arise for shallow repositories, but it is less likely for deep repositories. Recommendations are made for a practical implementation of a computer based model and its associated database. (Author)

  7. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties.

    Science.gov (United States)

    Casale, Amanda E; Foust, Amanda J; Bal, Thierry; McCormick, David A

    2015-11-25

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two of the largest cortical interneuron subtypes in the mouse: fast-spiking interneurons, which are typically basket or chandelier neurons; and somatostatin containing interneurons, which are typically regular spiking Martinotti cells. We found that fast-spiking and somatostatin-expressing interneurons differed in their electrophysiological characteristics along their entire dendrosomatoaxonal extent. The action potentials generated in the somata and axons, including axon collaterals, of somatostatin-expressing interneurons are significantly broader than those generated in the same compartments of fast-spiking inhibitory interneurons. In addition, action potentials back-propagated into the dendrites of somatostatin-expressing interneurons much more readily than fast-spiking interneurons. Pharmacological investigations suggested that axonal action potential repolarization in both cell types depends critically upon Kv1 channels, whereas the axonal and somatic action potentials of somatostatin-expressing interneurons also depend on BK Ca(2+)-activated K(+) channels. These results indicate that the two broad classes of interneurons studied here have expressly different subcellular physiological properties, allowing them to perform unique computational roles in cortical circuit operations. Neurons in the cerebral cortex are of two major types: excitatory and inhibitory. The proper balance of excitation and inhibition in the brain is critical for its operation. Neurons contain three main

  8. Implementing participatory action research in Lithuania: potential and challenges

    Directory of Open Access Journals (Sweden)

    Gabija Jarašiūnaitė

    2015-12-01

    Full Text Available Participatory action research is a quite new approach to research in Lithuania. The aim of an article was to disscuss the potential and challenges of participatory action research while implementing it in Lithuanian organizations. The qualitative approach was chosen for the study using the method of Focus groups. 20 researchers from social and biomedicine sciences from six institutions of High education in Lithuania participated in the study. The results of the study showed that participatory action reasearch is seen as an approach with many possibilities because of a wide range of used methods, constant interactions with research participants and the lenght of the research process. Researchers value the possibility to access organization at the begining, during research process and evaluate the effectiveness of the changes after the process. The research challenges are associated with the competence of a researcher including his/her sensitivity during process, ability to involve active participation of organization members in the ongoing process by creating safe and trusting environment. Some specific challenges associated with Lithuanian organizations are organizations‘ tiredness of researches and lack of faith of the benefits of researches because of some previous experiences. Keywords: Participatory Action Research, Organization, Lithuania.

  9. [Effect of pulse magnetic field on distribution of neuronal action potential].

    Science.gov (United States)

    Zheng, Yu; Cai, Di; Wang, Jin-Hai; Li, Gang; Lin, Ling

    2014-08-25

    The biological effect on the organism generated by magnetic field is widely studied. The present study was aimed to observe the change of sodium channel under magnetic field in neurons. Cortical neurons of Kunming mice were isolated, subjected to 15 Hz, 1 mT pulse magnetic stimulation, and then the currents of neurons were recorded by whole-cell patch clamp. The results showed that, under magnetic stimulation, the activation process of Na(+) channel was delayed, and the inactivation process was accelerated. Given the classic three-layer model, the polarization diagram of cell membrane potential distribution under pulse magnetic field was simulated, and it was found that the membrane potential induced was associated with the frequency and intensity of magnetic field. Also the effect of magnetic field-induced current on action potential was simulated by Hodgkin-Huxley (H-H) model. The result showed that the generation of action potential was delayed, and frequency and the amplitudes were decreased when working current was between -1.32 μA and 0 μA. When the working current was higher than 0 μA, the generation frequency of action potential was increased, and the change of amplitudes was not obvious, and when the working current was lower than -1.32 μA, the time of rising edge and amplitudes of action potential were decreased drastically, and the action potential was unable to generate. These results suggest that the magnetic field simulation can affect the distribution frequency and amplitude of action potential of neuron via sodium channel mediation.

  10. Compound sensory action potential in normal and pathological human nerves

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

    The compound sensory nerve action potential (SNAP) is the result of phase summation and cancellation of single fiber potentials (SFAPs) with amplitudes that depend on fiber diameter, and the amplitude and shape of the SNAP is determined by the distribution of fiber diameters. Conduction velocities...... dispersion over increasing conduction distance is greater for the SNAP than CMAP, and demonstration of conduction block is therefore difficult. In addition, the effect of temporal dispersion on amplitude and shape is strongly dependent on the number of conducting fibers and their distribution, and......, with fiber loss or increased conduction velocity variability changes of the SNAP may be smaller than expected from normal nerve. The biophysical characteristics of sensory and motor fibers differ, and this may to some extent determine divergent pathophysiological changes in sensory and motor fibers...

  11. Cell-type-dependent action potentials and voltage-gated currents in mouse fungiform taste buds.

    Science.gov (United States)

    Kimura, Kenji; Ohtubo, Yoshitaka; Tateno, Katsumi; Takeuchi, Keita; Kumazawa, Takashi; Yoshii, Kiyonori

    2014-01-01

    Taste receptor cells fire action potentials in response to taste substances to trigger non-exocytotic neurotransmitter release in type II cells and exocytotic release in type III cells. We investigated possible differences between these action potentials fired by mouse taste receptor cells using in situ whole-cell recordings, and subsequently we identified their cell types immunologically with cell-type markers, an IP3 receptor (IP3 R3) for type II cells and a SNARE protein (SNAP-25) for type III cells. Cells not immunoreactive to these antibodies were examined as non-IRCs. Here, we show that type II cells and type III cells fire action potentials using different ionic mechanisms, and that non-IRCs also fire action potentials with either of the ionic mechanisms. The width of action potentials was significantly narrower and their afterhyperpolarization was deeper in type III cells than in type II cells. Na(+) current density was similar in type II cells and type III cells, but it was significantly smaller in non-IRCs than in the others. Although outwardly rectifying current density was similar between type II cells and type III cells, tetraethylammonium (TEA) preferentially suppressed the density in type III cells and the majority of non-IRCs. Our mathematical model revealed that the shape of action potentials depended on the ratio of TEA-sensitive current density and TEA-insensitive current one. The action potentials of type II cells and type III cells under physiological conditions are discussed. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Ontogeny of vestibular compound action potentials in the domestic chicken

    Science.gov (United States)

    Jones, S. M.; Jones, T. A.

    2000-01-01

    Compound action potentials of the vestibular nerve were measured from the surface of the scalp in 148 chickens (Gallus domesticus). Ages ranged from incubation day 18 (E18) to 22 days posthatch (P22). Responses were elicited using linear acceleration cranial pulses. Response thresholds decreased at an average rate of -0.45 dB/day. The decrease was best fit by an exponential model with half-maturity time constant of 5.1 days and asymptote of approximately -25.9 dB re:1.0 g/ms. Mean threshold approached within 3 dB of the asymptote by ages P6-P9. Similarly, response latencies decreased exponentially to within 3% of mature values at ages beyond P9. The half-maturity time constant for peripheral response peak latencies P1, N1, and P2 was comparable to thresholds and ranged from approximately 4.6 to 6.2 days, whereas central peaks (N2, P3, and N3) ranged from 2.9 to 3.4 days. Latency-intensity slopes for P1, N1, and P2 tended to decrease with age, reaching mature values within approximately 100 hours of hatching. Amplitudes increased as a function of age with average growth rates for response peaks ranging from 0.04 to 0.09 microV/day. There was no obvious asymptote to the growth of amplitudes over the ages studied. Amplitude-intensity slopes also increased modestly with age. The results show that gravity receptors are responsive to transient cranial stimuli as early as E19 in the chicken embryo. The functional response of gravity receptors continues to develop for many days after all major morphological structures are in place. Distinct maturational processes can be identified in central and peripheral neural relays. Functional improvements during maturation may result from refinements in the receptor epithelia, improvements in central and peripheral synaptic transmission, increased neural myelination, as well as changes in the mechanical coupling between the cranium and receptor organ.

  13. Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

    KAUST Repository

    Keener, James P.; Newby, Jay M.

    2011-01-01

    A stochastic interpretation of spontaneous action potential initiation is developed for the Morris-Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential

  14. Calcium-Induced calcium release during action potential firing in developing inner hair cells.

    Science.gov (United States)

    Iosub, Radu; Avitabile, Daniele; Grant, Lisa; Tsaneva-Atanasova, Krasimira; Kennedy, Helen J

    2015-03-10

    In the mature auditory system, inner hair cells (IHCs) convert sound-induced vibrations into electrical signals that are relayed to the central nervous system via auditory afferents. Before the cochlea can respond to normal sound levels, developing IHCs fire calcium-based action potentials that disappear close to the onset of hearing. Action potential firing triggers transmitter release from the immature IHC that in turn generates experience-independent firing in auditory neurons. These early signaling events are thought to be essential for the organization and development of the auditory system and hair cells. A critical component of the action potential is the rise in intracellular calcium that activates both small conductance potassium channels essential during membrane repolarization, and triggers transmitter release from the cell. Whether this calcium signal is generated by calcium influx or requires calcium-induced calcium release (CICR) is not yet known. IHCs can generate CICR, but to date its physiological role has remained unclear. Here, we used high and low concentrations of ryanodine to block or enhance CICR to determine whether calcium release from intracellular stores affected action potential waveform, interspike interval, or changes in membrane capacitance during development of mouse IHCs. Blocking CICR resulted in mixed action potential waveforms with both brief and prolonged oscillations in membrane potential and intracellular calcium. This mixed behavior is captured well by our mathematical model of IHC electrical activity. We perform two-parameter bifurcation analysis of the model that predicts the dependence of IHCs firing patterns on the level of activation of two parameters, the SK2 channels activation and CICR rate. Our data show that CICR forms an important component of the calcium signal that shapes action potentials and regulates firing patterns, but is not involved directly in triggering exocytosis. These data provide important insights

  15. The Potential of Deweyan-Inspired Action Research

    Science.gov (United States)

    Stark, Jody L.

    2014-01-01

    In its broadest sense, pragmatism could be said to be the philosophical orientation of all action research. Action research is characterized by research, action, and participation grounded in democratic principles and guided by the aim of social improvement. Furthermore, action research is an active process of inquiry that does not admit…

  16. Compound muscle action potential duration in critical illness neuromyopathy.

    Science.gov (United States)

    Kramer, Christopher L; Boon, Andrea J; Harper, C Michel; Goodman, Brent P

    2018-03-01

    We sought to determine the specificity of compound muscle action potential (CMAP) durations and amplitudes in a large critical illness neuromyopathy (CINM) cohort relative to controls with other neuromuscular conditions. Fifty-eight patients with CINM who had been seen over a 17-year period were retrospectively studied. Electrodiagnostic findings of the CINM cohort were compared with patients with axonal peripheral neuropathy and myopathy due to other causes. Mean CMAP durations were prolonged, and mean CMAP amplitudes were severely reduced both proximally and distally in all nerves studied in the CINM cohort relative to the control groups. The specificity of prolonged CMAP durations for CINM approached 100% if they were encountered in more than 1 nerve. Prolonged, low-amplitude CMAPs occur more frequently and with greater severity in CINM patients than in neuromuscular controls with myopathy and axonal neuropathy and are highly specific for the diagnosis of CINM. Muscle Nerve 57: 395-400, 2018. © 2017 Wiley Periodicals, Inc.

  17. Direct detection of a single evoked action potential with MRS in Lumbricus terrestris.

    Science.gov (United States)

    Poplawsky, Alexander J; Dingledine, Raymond; Hu, Xiaoping P

    2012-01-01

    Functional MRI (fMRI) measures neural activity indirectly by detecting the signal change associated with the hemodynamic response following brain activation. In order to alleviate the temporal and spatial specificity problems associated with fMRI, a number of attempts have been made to detect neural magnetic fields (NMFs) with MRI directly, but have thus far provided conflicting results. In this study, we used MR to detect axonal NMFs in the median giant fiber of the earthworm, Lumbricus terrestris, by examining the free induction decay (FID) with a sampling interval of 0.32 ms. The earthworm nerve cords were isolated from the vasculature and stimulated at the threshold of action potential generation. FIDs were acquired shortly after the stimulation, and simultaneous field potential recordings identified the presence or absence of single evoked action potentials. FIDs acquired when the stimulus did not evoke an action potential were summed as background. The phase of the background-subtracted FID exhibited a systematic change, with a peak phase difference of (-1.2 ± 0.3) × 10(-5) radians occurring at a time corresponding to the timing of the action potential. In addition, we calculated the possible changes in the FID magnitude and phase caused by a simulated action potential using a volume conductor model. The measured phase difference matched the theoretical prediction well in both amplitude and temporal characteristics. This study provides the first evidence for the direct detection of a magnetic field from an evoked action potential using MR. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Melatonin potentiates the anticonvulsant action of phenobarbital in neonatal rats.

    Science.gov (United States)

    Forcelli, Patrick A; Soper, Colin; Duckles, Anne; Gale, Karen; Kondratyev, Alexei

    2013-12-01

    Phenobarbital is the most commonly utilized drug for neonatal seizures. However, questions regarding safety and efficacy of this drug make it particularly compelling to identify adjunct therapies that could boost therapeutic benefit. One potential adjunct therapy is melatonin. Melatonin is used clinically in neonatal and pediatric populations, and moreover, it exerts anticonvulsant actions in adult rats. However, it has not been previously evaluated for anticonvulsant effects in neonatal rats. Here, we tested the hypothesis that melatonin would exert anticonvulsant effects, either alone, or in combination with phenobarbital. Postnatal day (P)7 rats were treated with phenobarbital (0-40mg/kg) and/or melatonin (0-80mg/kg) prior to chemoconvulsant challenge with pentylenetetrazole (100mg/kg). We found that melatonin significantly potentiated the anticonvulsant efficacy of phenobarbital, but did not exert anticonvulsant effects on its own. These data provide additional evidence for the further examination of melatonin as an adjunct therapy in neonatal/pediatric epilepsy. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. [Patterns of action potential firing in cortical neurons of neonatal mice and their electrophysiological property].

    Science.gov (United States)

    Furong, Liu; Shengtian, L I

    2016-05-25

    To investigate patterns of action potential firing in cortical heurons of neonatal mice and their electrophysiological properties. The passive and active membrane properties of cortical neurons from 3-d neonatal mice were observed by whole-cell patch clamp with different voltage and current mode. Three patterns of action potential firing were identified in response to depolarized current injection. The effects of action potential firing patterns on voltage-dependent inward and outward current were found. Neurons with three different firing patterns had different thresholds of depolarized current. In the morphology analysis of action potential, the three type neurons were different in rise time, duration, amplitude and threshold of the first action potential evoked by 80 pA current injection. The passive properties were similar in three patterns of action potential firing. These results indicate that newborn cortical neurons exhibit different patterns of action potential firing with different action potential parameters such as shape and threshold.

  20. Noise Enhances Action Potential Generation in Mouse Sensory Neurons via Stochastic Resonance.

    Science.gov (United States)

    Onorato, Irene; D'Alessandro, Giuseppina; Di Castro, Maria Amalia; Renzi, Massimiliano; Dobrowolny, Gabriella; Musarò, Antonio; Salvetti, Marco; Limatola, Cristina; Crisanti, Andrea; Grassi, Francesca

    2016-01-01

    Noise can enhance perception of tactile and proprioceptive stimuli by stochastic resonance processes. However, the mechanisms underlying this general phenomenon remain to be characterized. Here we studied how externally applied noise influences action potential firing in mouse primary sensory neurons of dorsal root ganglia, modelling a basic process in sensory perception. Since noisy mechanical stimuli may cause stochastic fluctuations in receptor potential, we examined the effects of sub-threshold depolarizing current steps with superimposed random fluctuations. We performed whole cell patch clamp recordings in cultured neurons of mouse dorsal root ganglia. Noise was added either before and during the step, or during the depolarizing step only, to focus onto the specific effects of external noise on action potential generation. In both cases, step + noise stimuli triggered significantly more action potentials than steps alone. The normalized power norm had a clear peak at intermediate noise levels, demonstrating that the phenomenon is driven by stochastic resonance. Spikes evoked in step + noise trials occur earlier and show faster rise time as compared to the occasional ones elicited by steps alone. These data suggest that external noise enhances, via stochastic resonance, the recruitment of transient voltage-gated Na channels, responsible for action potential firing in response to rapid step-wise depolarizing currents.

  1. Short latency compound action potentials from mammalian gravity receptor organs

    Science.gov (United States)

    Jones, T. A.; Jones, S. M.

    1999-01-01

    Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

  2. State and location dependence of action potential metabolic cost in cortical pyramidal neurons.

    Science.gov (United States)

    Hallermann, Stefan; de Kock, Christiaan P J; Stuart, Greg J; Kole, Maarten H P

    2012-06-03

    Action potential generation and conduction requires large quantities of energy to restore Na(+) and K(+) ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na(+)/K(+) charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.

  3. Learning to Act: Qualitative Learning of Deterministic Action Models

    DEFF Research Database (Denmark)

    Bolander, Thomas; Gierasimczuk, Nina

    2017-01-01

    In this article we study learnability of fully observable, universally applicable action models of dynamic epistemic logic. We introduce a framework for actions seen as sets of transitions between propositional states and we relate them to their dynamic epistemic logic representations as action...... in the limit (inconclusive convergence to the right action model). We show that deterministic actions are finitely identifiable, while arbitrary (non-deterministic) actions require more learning power—they are identifiable in the limit. We then move on to a particular learning method, i.e. learning via update......, which proceeds via restriction of a space of events within a learning-specific action model. We show how this method can be adapted to learn conditional and unconditional deterministic action models. We propose update learning mechanisms for the afore mentioned classes of actions and analyse...

  4. Additive action model for mixed irradiation

    International Nuclear Information System (INIS)

    Lam, G.K.Y.

    1984-01-01

    Recent experimental results indicate that a mixture of high and low LET radiation may have some beneficial features (such as lower OER but with skin sparing) for clinical use, and interest has been renewed in the study of mixtures of high and low LET radiation. Several standard radiation inactivation models can readily accommodate interaction between two mixed radiations, however, this is usually handled by postulating extra free parameters, which can only be determined by fitting to experimental data. A model without any free parameter is proposed to explain the biological effect of mixed radiations, based on the following two assumptions: (a) The combined biological action due to two radiations is additive, assuming no repair has taken place during the interval between the two irradiations; and (b) The initial physical damage induced by radiation develops into final biological effect (e.g. cell killing) over a relatively long period (hours) after irradiation. This model has been shown to provide satisfactory fit to the experiment results of previous studies

  5. Identification of motivations for unsafe driving actions and potential countermeasures

    Science.gov (United States)

    1982-03-01

    This report presents the findings of a preliminary investigation of drivers' motivations for selected unsafe driving actions (UDAs). The general objective of the study was to develop the test methods, procedures, and materials for collecting data for...

  6. The neutron optical model potential

    International Nuclear Information System (INIS)

    Hodgson, P.E.

    1989-01-01

    The present status of optical model calculations of neutron scattering and interactions is reviewed, with special emphasis on more recent developments and the more promising lines of research. The use of dispersion relations to provide an extra constraint on the potential is discussed, together with their application to studies of the Fermi surface anomaly. The application of potential inversion techniques to determine the form of the potential is also considered. (author). 39 refs, figs

  7. Deuteron microscopic optical model potential

    International Nuclear Information System (INIS)

    Guo Hairui; Han Yinlu; Shen Qingbiao; Xu Yongli

    2010-01-01

    A deuteron microscopic optical model potential is obtained by the Green function method through nuclear-matter approximation and local-density approximation based on the effective Skyrme interaction. The microscopic optical model potential is used to calculate the deuteron reaction cross sections and the elastic scattering angular distributions for some target nuclei in the mass range 6≤A≤208 with incident deuteron energies up to 200 MeV. The calculated results are compared with the experimental data.

  8. Dynamics of the inward rectifier K+ current during the action potential of guinea pig ventricular myocytes

    OpenAIRE

    Ibarra, J.; Morley, G.E.; Delmar, M.

    1991-01-01

    The potassium selective, inward rectifier current (IK1) is known to be responsible for maintaining the resting membrane potential of quiescent ventricular myocytes. However, the contribution of this current to the different phases of the cardiac action potential has not been adequately established. In the present study, we have used the action potential clamp (APC) technique to characterize the dynamic changes of a cesium-sensitive (i.e., Ik1) current which occur during the action potential. ...

  9. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Science.gov (United States)

    2011-04-19

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for the Devils Lake Regional Airport in Devils Lake, ND AGENCY: Federal Aviation Administration (FAA), Department of Transportation (DOT). ACTION...

  10. Scaling of the quark-antiquark potential and improved actions in SU(2) lattice gauge theory

    International Nuclear Information System (INIS)

    Montvay, I.; Gutbrod, F.

    1983-11-01

    The scaling behaviour of the quark-antiquark potential is investigated by a high statistics Monte Carlo calculation in SU(2) lattice gauge theory. Besides the standard one-plaquette action we also use Symanzik's tree-level improved action and Wilson's block-spin improved action. No significant differences between Symanzik's action and the standard action have been observed. For small β Wilson's action scales differently. The string tension value chi extracted from the data corresponds to Λsub(latt) = (0.018 +- 0.001) √chi for the one-plaquette action. (orig.)

  11. Cosmological models in the generalized Einstein action

    International Nuclear Information System (INIS)

    Arbab, A.I.

    2007-12-01

    We have studied the evolution of the Universe in the generalized Einstein action of the form R + β R 2 , where R is the scalar curvature and β = const. We have found exact cosmological solutions that predict the present cosmic acceleration. These models predict an inflationary de-Sitter era occurring in the early Universe. The cosmological constant (Λ) is found to decay with the Hubble constant (H) as, Λ ∝ H 4 . In this scenario the cosmological constant varies quadratically with the energy density (ρ), i.e., Λ ∝ ρ 2 . Such a variation is found to describe a two-component cosmic fluid in the Universe. One of the components accelerated the Universe in the early era, and the other in the present era. The scale factor of the Universe varies as a ∼ t n = 1/2 in the radiation era. The cosmological constant vanishes when n = 4/3 and n =1/2. We have found that the inclusion of the term R 2 mimics a cosmic matter that could substitute the ordinary matter. (author)

  12. [Effects of dauricine on action potentials and slow inward currents of guinea pig ventricular papillary muscles].

    Science.gov (United States)

    Li, S N; Zhang, K Y

    1992-11-01

    Effects of dauricine (Dau) on the action potentials (AP), the slow action potentials (SAP), and the slow inward currents (Isi) of guinea pig ventricular papillary muscles were observed by means of intracellular microelectrode and single sucrose gap voltage clamp technique. In the early stage, Dau shortened action potential duration 100 (APD100) and effective refractory period (ERP) (ERP/APD ERP, and APD20, significantly decreased action potential amplitude (APA), maximum velocity (Vmax), and overshot (OS) (ERP/APD > 1; P SAP induced by isoprenaline (P < 0.01), and remarkably inhibited Isi (P < 0.01). The results suggested that Dau exerted an inhibitory effect on Na+, Ca2+, and K+ channels.

  13. [Phenibut potentiation of the therapeutic action of antiparkinson agents].

    Science.gov (United States)

    Gol'dblat, Iu V; Lapin, I P

    1986-01-01

    It was observed in experiments on mice that the central action of phenibut (beta-phenyl-gamma-aminobutyric acid) diminished after destruction of brain dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the dopamine receptor blocker haloperidol which suggests the dopaminergic component in the action of phenibut. In 13 of 16 patients receiving long-term treatment with antiparkinsonic drugs, addition of phenibut (0.25 g thrice daily for 10 days) resulted in marked clinical improvement with a significant increase of motor activity, as well as diminution of both rigidity and tremor. Follow-up showed a significant lowering of muscle tone of rigid muscles, augmentation of their strength and amplitude of movements. In 8 patients receiving phenibut without antiparkinsonic drugs the results were negligible.

  14. Consumer-Related Food Waste: Causes and Potential for Action

    DEFF Research Database (Denmark)

    Aschemann-Witzel, Jessica; Hooge, Ilona de; Amani, Pegah

    2015-01-01

    behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions......In the past decade, food waste has received increased attention on both academic and societal levels. As a cause of negative economic, environmental and social effects, food waste is considered to be one of the sustainability issues that needs to be addressed. In developed countries, consumers...... are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert...

  15. Measurement Models for Reasoned Action Theory

    OpenAIRE

    Hennessy, Michael; Bleakley, Amy; Fishbein, Martin

    2012-01-01

    Quantitative researchers distinguish between causal and effect indicators. What are the analytic problems when both types of measures are present in a quantitative reasoned action analysis? To answer this question, we use data from a longitudinal study to estimate the association between two constructs central to reasoned action theory: behavioral beliefs and attitudes toward the behavior. The belief items are causal indicators that define a latent variable index while the attitude items are ...

  16. Oxidative shift in tissue redox potential increases beat-to-beat variability of action potential duration.

    Science.gov (United States)

    Kistamás, Kornél; Hegyi, Bence; Váczi, Krisztina; Horváth, Balázs; Bányász, Tamás; Magyar, János; Szentandrássy, Norbert; Nánási, Péter P

    2015-07-01

    Profound changes in tissue redox potential occur in the heart under conditions of oxidative stress frequently associated with cardiac arrhythmias. Since beat-to-beat variability (short term variability, SV) of action potential duration (APD) is a good indicator of arrhythmia incidence, the aim of this work was to study the influence of redox changes on SV in isolated canine ventricular cardiomyocytes using a conventional microelectrode technique. The redox potential was shifted toward a reduced state using a reductive cocktail (containing dithiothreitol, glutathione, and ascorbic acid) while oxidative changes were initiated by superfusion with H2O2. Redox effects were evaluated as changes in "relative SV" determined by comparing SV changes with the concomitant APD changes. Exposure of myocytes to the reductive cocktail decreased SV significantly without any detectable effect on APD. Application of H2O2 increased both SV and APD, but the enhancement of SV was the greater, so relative SV increased. Longer exposure to H2O2 resulted in the development of early afterdepolarizations accompanied by tremendously increased SV. Pretreatment with the reductive cocktail prevented both elevation in relative SV and the development of afterdepolarizations. The results suggest that the increased beat-to-beat variability during an oxidative stress contributes to the generation of cardiac arrhythmias.

  17. Acute effects of ethanol on action potential and intracellular Ca2+ transient in cardiac ventricular cells: a simulation study

    Czech Academy of Sciences Publication Activity Database

    Pásek, Michal; Bébarová, M.; Christé, G.; Šimurdová, M.; Šimurda, J.

    2016-01-01

    Roč. 54, č. 5 (2016), s. 753-762 ISSN 0140-0118 Institutional support: RVO:61388998 Keywords : ethanol * cardiomyocyte * action potential * rat ventricular cell model * human ventricular cell model Subject RIV: BO - Biophysics Impact factor: 1.916, year: 2016

  18. Model of dopant action in oxide cathodes

    International Nuclear Information System (INIS)

    Engelsen, Daniel den; Gaertner, Georg

    2005-01-01

    The paper describes an electrochemical model, which largely explains the formation of Ba in the oxide cathode at activation and normal operation. In a non-doped oxide cathode electrolysis of BaO is, besides the exchange reaction from the activators in the cathode nickel, an important source of Ba. By doping with rare earth oxides the conductivity of the oxide layer increases, which implies that the potential difference during current drawing over the oxide layer becomes lower and electrolysis of BaO is suppressed. This implies that the part of the electronic conductivity of the (Ba,Sr)O layer induced by the dopants also controls the sensitivity for poisoning: the higher the dopant level, the larger the sensitivity for poisoning. Furthermore, the suppression of electrolysis during normal operation largely explains why doped oxide cathodes have a better life performance than non-doped cathodes. Finally a hypothesis on the enhancement of sintering upon doping is presented

  19. Dynamics of action potential initiation in the GABAergic thalamic reticular nucleus in vivo.

    Science.gov (United States)

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

    Understanding the neural mechanisms of action potential generation is critical to establish the way neural circuits generate and coordinate activity. Accordingly, we investigated the dynamics of action potential initiation in the GABAergic thalamic reticular nucleus (TRN) using in vivo intracellular recordings in cats in order to preserve anatomically-intact axo-dendritic distributions and naturally-occurring spatiotemporal patterns of synaptic activity in this structure that regulates the thalamic relay to neocortex. We found a wide operational range of voltage thresholds for action potentials, mostly due to intrinsic voltage-gated conductances and not synaptic activity driven by network oscillations. Varying levels of synchronous synaptic inputs produced fast rates of membrane potential depolarization preceding the action potential onset that were associated with lower thresholds and increased excitability, consistent with TRN neurons performing as coincidence detectors. On the other hand the presence of action potentials preceding any given spike was associated with more depolarized thresholds. The phase-plane trajectory of the action potential showed somato-dendritic propagation, but no obvious axon initial segment component, prominent in other neuronal classes and allegedly responsible for the high onset speed. Overall, our results suggest that TRN neurons could flexibly integrate synaptic inputs to discharge action potentials over wide voltage ranges, and perform as coincidence detectors and temporal integrators, supported by a dynamic action potential threshold.

  20. Measurement Models for Reasoned Action Theory.

    Science.gov (United States)

    Hennessy, Michael; Bleakley, Amy; Fishbein, Martin

    2012-03-01

    Quantitative researchers distinguish between causal and effect indicators. What are the analytic problems when both types of measures are present in a quantitative reasoned action analysis? To answer this question, we use data from a longitudinal study to estimate the association between two constructs central to reasoned action theory: behavioral beliefs and attitudes toward the behavior. The belief items are causal indicators that define a latent variable index while the attitude items are effect indicators that reflect the operation of a latent variable scale. We identify the issues when effect and causal indicators are present in a single analysis and conclude that both types of indicators can be incorporated in the analysis of data based on the reasoned action approach.

  1. Consumer-Related Food Waste: Causes and Potential for Action

    Directory of Open Access Journals (Sweden)

    Jessica Aschemann-Witzel

    2015-05-01

    Full Text Available In the past decade, food waste has received increased attention on both academic and societal levels. As a cause of negative economic, environmental and social effects, food waste is considered to be one of the sustainability issues that needs to be addressed. In developed countries, consumers are one of the biggest sources of food waste. To successfully reduce consumer-related food waste, it is necessary to have a clear understanding of the factors influencing food waste-related consumer perceptions and behaviors. The present paper presents the results of a literature review and expert interviews on factors causing consumer-related food waste in households and supply chains. Results show that consumers’ motivation to avoid food waste, their management skills of food provisioning and food handling and their trade-offs between priorities have an extensive influence on their food waste behaviors. We identify actions that governments, societal stakeholders and retailers can undertake to reduce consumer-related food waste, highlighting that synergistic actions between all parties are most promising. Further research should focus on exploring specific food waste contexts and interactions more in-depth. Experiments and interventions in particular can contribute to a shift from analysis to solutions.

  2. Effective potential models for hadrons

    International Nuclear Information System (INIS)

    Lucha, W.

    1995-12-01

    The aim of these lectures is to give a self-contained introduction to nonrelativistic potential models, to their formulation as well as to their possible applications. At the price of some lack of (in a mathematical sense) rigorous derivations, we try to give a feeling and understanding for the simplest conceivable method to extract the explicit form of the forces acting between quarks from the interplay between experimental observations and theoretical considerations. According to this spirit, we demonstrate, in detail, how to obtain the underlying Hamiltonian and how to determine the Lorentz structure of the quark-(anti-)quark interaction potential from well-established experimental facts. (author)

  3. Fish oil curtails the human action potential dome in a heterogeneous manner: Implication for arrhythmogenesis

    NARCIS (Netherlands)

    Verkerk, Arie O.; den Ruijter, Hester M.; de Jonge, Nicolaas; Coronel, Ruben

    2009-01-01

    Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased

  4. Determination of cable parameters in skeletal muscle fibres during repetitive firing of action potentials

    Science.gov (United States)

    Riisager, Anders; Duehmke, Rudy; Nielsen, Ole Bækgaard; Huang, Christopher L; Pedersen, Thomas Holm

    2014-01-01

    Recent studies in rat muscle fibres show that repetitive firing of action potentials causes changes in fibre resting membrane conductance (Gm) that reflect regulation of ClC-1 Cl− and KATP K+ ion channels. Methodologically, these findings were obtained by inserting two microelectrodes at close proximity in the same fibres enabling measurements of fibre input resistance (Rin) in between action potential trains. Since the fibre length constant (λ) could not be determined, however, the calculation of Gm relied on the assumptions that the specific cytosolic resistivity (Ri) and muscle fibre volume remained constant during the repeated action potential firing. Here we present a three-microelectrode technique that enables determinations of multiple cable parameters in action potential-firing fibres including Rin and λ as well as waveform and conduction velocities of fully propagating action potentials. It is shown that in both rat and mouse extensor digitorum longus (EDL) fibres, action potential firing leads to substantial changes in both muscle fibre volume and Ri. The analysis also showed, however, that regardless of these changes, rat and mouse EDL fibres both exhibited initial decreases in Gm that were eventually followed by a ∼3-fold, fully reversible increase in Gm after the firing of 1450–1800 action potentials. Using this three-electrode method we further show that the latter rise in Gm was closely associated with excitation failures and loss of action potential signal above −20 mV. PMID:25128573

  5. Differential roles of two delayed rectifier potassium currents in regulation of ventricular action potential duration and arrhythmia susceptibility.

    Science.gov (United States)

    Devenyi, Ryan A; Ortega, Francis A; Groenendaal, Willemijn; Krogh-Madsen, Trine; Christini, David J; Sobie, Eric A

    2017-04-01

    Arrhythmias result from disruptions to cardiac electrical activity, although the factors that control cellular action potentials are incompletely understood. We combined mathematical modelling with experiments in heart cells from guinea pigs to determine how cellular electrical activity is regulated. A mismatch between modelling predictions and the experimental results allowed us to construct an improved, more predictive mathematical model. The balance between two particular potassium currents dictates how heart cells respond to perturbations and their susceptibility to arrhythmias. Imbalances of ionic currents can destabilize the cardiac action potential and potentially trigger lethal cardiac arrhythmias. In the present study, we combined mathematical modelling with information-rich dynamic clamp experiments to determine the regulation of action potential morphology in guinea pig ventricular myocytes. Parameter sensitivity analysis was used to predict how changes in ionic currents alter action potential duration, and these were tested experimentally using dynamic clamp, a technique that allows for multiple perturbations to be tested in each cell. Surprisingly, we found that a leading mathematical model, developed with traditional approaches, systematically underestimated experimental responses to dynamic clamp perturbations. We then re-parameterized the model using a genetic algorithm, which allowed us to estimate ionic current levels in each of the cells studied. This unbiased model adjustment consistently predicted an increase in the rapid delayed rectifier K + current and a drastic decrease in the slow delayed rectifier K + current, and this prediction was validated experimentally. Subsequent simulations with the adjusted model generated the clinically relevant prediction that the slow delayed rectifier is better able to stabilize the action potential and suppress pro-arrhythmic events than the rapid delayed rectifier. In summary, iterative coupling of

  6. Triangulation of the monophasic action potential causes flattening of the electrocardiographic T-wave

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Thomsen, Morten Bækgaard

    2012-01-01

    of the action potential under the effect of the IKr blocker sertindole and associated these changes to concurrent changes in the morphology of electrocardiographic T-waves in dogs. We show that, under the effect of sertindole, the peak changes in the morphology of action potentials occur at time points similar......It has been proposed that triangulation on the cardiac action potential manifests as a broadened, more flat and notched T-wave on the ECG but to what extent such morphology characteristics are indicative of triangulation is more unclear. In this paper, we have analyzed the morphological changes...... to those observed for the peak changes in T-wave morphology on the ECG. We further show that the association between action potential shape and ECG shape is dose-dependent and most prominent at the time corresponding to phase 3 of the action potential....

  7. Imaging Action Potential in Single Mammalian Neurons by Tracking the Accompanying Sub-Nanometer Mechanical Motion.

    Science.gov (United States)

    Yang, Yunze; Liu, Xian-Wei; Wang, Hui; Yu, Hui; Guan, Yan; Wang, Shaopeng; Tao, Nongjian

    2018-03-28

    Action potentials in neurons have been studied traditionally by intracellular electrophysiological recordings and more recently by the fluorescence detection methods. Here we describe a label-free optical imaging method that can measure mechanical motion in single cells with a sub-nanometer detection limit. Using the method, we have observed sub-nanometer mechanical motion accompanying the action potential in single mammalian neurons by averaging the repeated action potential spikes. The shape and width of the transient displacement are similar to those of the electrically recorded action potential, but the amplitude varies from neuron to neuron, and from one region of a neuron to another, ranging from 0.2-0.4 nm. The work indicates that action potentials may be studied noninvasively in single mammalian neurons by label-free imaging of the accompanying sub-nanometer mechanical motion.

  8. [Loudness optimized registration of compound action potential in cochlear implant recipients].

    Science.gov (United States)

    Berger, Klaus; Hocke, Thomas; Hessel, Horst

    2017-11-01

    Background Postoperative measurements of compound action potentials are not always possible due to the insufficient acceptance of the CI-recipients. This study investigated the impact of different parameters on the acceptance of the measurements. Methods Compound action potentials of 16 CI recipients were measured with different pulse-widths. Recipients performed a loudness rating at the potential thresholds with the different sequences. Results Compound action potentials obtained with higher pulse-widths were rated softer than those obtained with smaller pulse-widths. Conclusions Compound action potentials measured with higher pulse-widths generate a gap between loudest acceptable presentation level and potential threshold. This gap contributes to a higher acceptance of postoperative measurements. Georg Thieme Verlag KG Stuttgart · New York.

  9. Inducing repetitive action potential firing in neurons via synthesized photoresponsive nanoscale cellular prostheses.

    Science.gov (United States)

    Lu, Siyuan; Madhukar, Anupam

    2013-02-01

    Recently we reported an analysis that examined the potential of synthesized photovoltaic functional abiotic nanosystems (PVFANs) to modulate membrane potential and activate action potential firing in neurons. Here we extend the analysis to delineate the requirements on the electronic energy levels and the attendant photophysical properties of the PVFANs to induce repetitive action potential under continuous light, a capability essential for the proposed potential application of PVFANs as retinal cellular prostheses to compensate for loss of photoreceptors. We find that repetitive action potential firing demands two basic characteristics in the electronic response of the PVFANs: an exponential dependence of the PVFAN excited state decay rate on the membrane potential and a three-state system such that, following photon absorption, the electron decay from the excited state to the ground state is via intermediate state(s) whose lifetime is comparable to the refractory time following an action potential. In this study, the potential of synthetic photovoltaic functional abiotic nanosystems (PVFANs) is examined under continuous light to modulate membrane potential and activate action potential firing in neurons with the proposed potential application of PVFANs as retinal cellular prostheses. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Reconstruction of action potential of repolarization in patients with congenital long-QT syndrome

    International Nuclear Information System (INIS)

    Kandori, Akihiko; Shimizu, Wataru; Yokokawa, Miki; Kamakura, Shiro; Miyatake, Kunio; Murakami, Masahiro; Miyashita, Tsuyoshi; Ogata, Kuniomi; Tsukada, Keiji

    2004-01-01

    A method for reconstructing an action potential during the repolarization period was developed. This method uses a current distribution-plotted as a current-arrow map (CAM)-calculated using magnetocardiogram (MCG) signals. The current arrows are summarized during the QRS complex period and subtracted during the ST-T wave period in order to reconstruct the action-potential waveform. To ensure the similarity between a real action potential and the reconstructed action potential using CAM, a monophasic action potential (MAP) and an MCG of the same patient with type-I long-QT syndrome were measured. Although the MAP had one notch that was associated with early afterdepolarization (EAD), the reconstructed action potential had two large and small notches. The small notch timing agreed with the occurrence of the EAD in the MAP. On the other hand, the initiation time of an abnormal current distribution coincides with the appearance timing of the first large notch, and its end time coincides with that of the second small notch. These results suggest that a simple reconstruction method using a CAM based on MCG data can provide a similar action-potential waveform to a MAP waveform without having to introduce a catheter

  11. Distinct electrophysiological potentials for intention in action and prior intention for action

    DEFF Research Database (Denmark)

    Vinding, Mikkel C; Jensen, Mads; Overgaard, Morten

    2014-01-01

    The role of conscious intention in relation to motoric movements has become a major topic of investigation in neuroscience. Traditionally, reports of conscious intention have been compared to various features of the readiness-potential (RP) – an electrophysiological signal that appears before...... electrophysiological “intention potential” above the mid-frontal areas at the time participants formed a distal intention. This potential was only found when the distal intention was self-paced and not when the intention was formed in response to an external cue....

  12. Ionization from short-range potential under action of electromagnetic field of complex configuration

    CERN Document Server

    Rodionov, V N; Kravtsova, G A

    2002-01-01

    The transcendental equation for the complex energy is obtained on the basis of the exactly solvable 3D model of the short-acting potential and the Green time function in the intensive electromagnetic field, constituting the combination of the constant magnetic field and the circular-polarization wave field. The electron quasistationary states parameters in the delta-potential with an account of the action of the intensive external field of complex configuration are calculated. The problem on the possibility of stabilizing the bound states decay of the spinor and scalar particles through the intensive magnetic field is clarified. It is established that the obtained results regime the reexamination of the accepted notion on the stabilizing role of the strong magnetic field by the atoms ionization

  13. Predictive user modeling with actionable attributes

    NARCIS (Netherlands)

    Zliobaite, I.; Pechenizkiy, M.

    2013-01-01

    Different machine learning techniques have been proposed and used for modeling individual and group user needs, interests and preferences. In the traditional predictive modeling instances are described by observable variables, called attributes. The goal is to learn a model for predicting the target

  14. Action potentials in retinal ganglion cells are initiated at the site of maximal curvature of the extracellular potential.

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    The initiation of an action potential by extracellular stimulation occurs after local depolarization of the neuronal membrane above threshold. Although the technique shows remarkable clinical success, the site of action and the relevant stimulation parameters are not completely understood. Here we identify the site of action potential initiation in rabbit retinal ganglion cells (RGCs) interfaced to an array of extracellular capacitive stimulation electrodes. We determine which feature of the extracellular potential governs action potential initiation by simultaneous stimulation and recording RGCs interfaced in epiretinal configuration. Stimulation electrodes were combined to areas of different size and were presented at different positions with respect to the RGC. Based on stimulation by electrodes beneath the RGC soma and simultaneous sub-millisecond latency measurement we infer axonal initiation at the site of maximal curvature of the extracellular potential. Stimulation by electrodes at different positions along the axon reveals a nearly constant threshold current density except for a narrow region close to the cell soma. These findings are explained by the concept of the activating function modified to consider a region of lower excitability close to the cell soma. We present a framework how to estimate the site of action potential initiation and the stimulus required to cross threshold in neurons tightly interfaced to capacitive stimulation electrodes. Our results underscore the necessity of rigorous electrical characterization of the stimulation electrodes and of the interfaced neural tissue.

  15. Effects of tacrolimus on action potential configuration and transmembrane ion currents in canine ventricular cells.

    Science.gov (United States)

    Szabó, László; Szentandrássy, Norbert; Kistamás, Kornél; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Horváth, Balázs; Magyar, János; Bányász, Tamás; Pál, Balázs; Nánási, Péter P

    2013-03-01

    Tacrolimus is a commonly used immunosuppressive agent which causes cardiovascular complications, e.g., hypertension and hypertrophic cardiomyopathy. In spite of it, there is little information on the cellular cardiac effects of the immunosuppressive agent tacrolimus in larger mammals. In the present study, therefore, the concentration-dependent effects of tacrolimus on action potential morphology and the underlying ion currents were studied in canine ventricular cardiomyocytes. Standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques were applied in myocytes enzymatically dispersed from canine ventricular myocardium. Tacrolimus (3-30 μM) caused a concentration-dependent reduction of maximum velocity of depolarization and repolarization, action potential amplitude, phase-1 repolarization, action potential duration, and plateau potential, while no significant change in the resting membrane potential was observed. Conventional voltage clamp experiments revealed that tacrolimus concentrations ≥3 μM blocked a variety of ion currents, including I(Ca), I(to), I(K1), I(Kr), and I(Ks). Similar results were obtained under action potential voltage clamp conditions. These effects of tacrolimus developed rapidly and were fully reversible upon washout. The blockade of inward currents with the concomitant shortening of action potential duration in canine myocytes is the opposite of those observed previously with tacrolimus in small rodents. It is concluded that although tacrolimus blocks several ion channels at higher concentrations, there is no risk of direct interaction with cardiac ion channels when applying tacrolimus in therapeutic concentrations.

  16. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, Stefan; de Kock, Christiaan P. J.; Stuart, Greg J.; Kole, Maarten H. P.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action

  17. State and location dependence of action potential metabolic cost in cortical pyramidal neurons

    NARCIS (Netherlands)

    Hallermann, S.; de Kock, C.P.J.; Stuart, G.J.; Kole, M.H.

    2012-01-01

    Action potential generation and conduction requires large quantities of energy to restore Na + and K + ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na +K + charge overlap as a measure of action

  18. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Letzkus, Johannes J.; Stuart, Greg J.

    2007-01-01

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action

  19. A continuous-time neural model for sequential action.

    Science.gov (United States)

    Kachergis, George; Wyatte, Dean; O'Reilly, Randall C; de Kleijn, Roy; Hommel, Bernhard

    2014-11-05

    Action selection, planning and execution are continuous processes that evolve over time, responding to perceptual feedback as well as evolving top-down constraints. Existing models of routine sequential action (e.g. coffee- or pancake-making) generally fall into one of two classes: hierarchical models that include hand-built task representations, or heterarchical models that must learn to represent hierarchy via temporal context, but thus far lack goal-orientedness. We present a biologically motivated model of the latter class that, because it is situated in the Leabra neural architecture, affords an opportunity to include both unsupervised and goal-directed learning mechanisms. Moreover, we embed this neurocomputational model in the theoretical framework of the theory of event coding (TEC), which posits that actions and perceptions share a common representation with bidirectional associations between the two. Thus, in this view, not only does perception select actions (along with task context), but actions are also used to generate perceptions (i.e. intended effects). We propose a neural model that implements TEC to carry out sequential action control in hierarchically structured tasks such as coffee-making. Unlike traditional feedforward discrete-time neural network models, which use static percepts to generate static outputs, our biological model accepts continuous-time inputs and likewise generates non-stationary outputs, making short-timescale dynamic predictions. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

  20. On the scalar potential models from the isospectral potential class

    Energy Technology Data Exchange (ETDEWEB)

    Lima, V. Gomes [Universidade Federal Rural do Rio de Janeiro, Seropedica, RJ (Brazil). Dept. de Fisica; Santos, V. Silva [Paraiba Univ., Campina Grande, PB (Brazil). Dept. de Engenharia Civil; Rodrigues, R. de Lima [Centro Brasileiro de Pesquisas Fisicas (CBPF), Rio de Janeiro, RJ (Brazil)]. E-mail: rafaelr@cbpf.br

    2001-10-01

    The static field classical configuration in (1+1)-dimensions for new non-linear potential models is investigated from an isospectral potential class and the concept of bosonic zero mode solution. One of the models considered here has a static nontopological configuration with a single vacuum state, whose potential in the stability equation corresponds to broken a supersymmetry. (author)

  1. Selective activation of heteromeric SK channels contributes to action potential repolarization in mouse atrial myocytes.

    Science.gov (United States)

    Hancock, Jane M; Weatherall, Kate L; Choisy, Stéphanie C; James, Andrew F; Hancox, Jules C; Marrion, Neil V

    2015-05-01

    Activation of small conductance calcium-activated potassium (SK) channels is proposed to contribute to repolarization of the action potential in atrial myocytes. This role is controversial, as these cardiac SK channels appear to exhibit an uncharacteristic pharmacology. The objectives of this study were to resolve whether activation of SK channels contributes to atrial action potential repolarization and to determine the likely subunit composition of the channel. The effect of 2 SK channel inhibitors was assessed on outward current evoked in voltage clamp and on action potential duration in perforated patch and whole-cell current clamp recording from acutely isolated mouse atrial myocytes. The presence of SK channel subunits was assessed using immunocytochemistry. A significant component of outward current was reduced by the SK channel blockers apamin and UCL1684. Block by apamin displayed a sensitivity indicating that this current was carried by homomeric SK2 channels. Action potential duration was significantly prolonged by UCL1684, but not by apamin. This effect was accompanied by an increase in beat-to-beat variability and action potential triangulation. This pharmacology was matched by that of expressed heteromeric SK2-SK3 channels in HEK293 cells. Immunocytochemistry showed that atrial myocytes express both SK2 and SK3 channels with an overlapping expression pattern. Only proposed heteromeric SK2-SK3 channels are physiologically activated to contribute to action potential repolarization, which is indicated by the difference in pharmacology of evoked outward current and prolongation of atrial action potential duration. The effect of blocking this channel on the action potential suggests that SK channel inhibition during cardiac function has the potential to be proarrhythmic. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  2. Decision modeling for analyzing fire action outcomes

    Science.gov (United States)

    Donald MacGregor; Armando Gonzalez-Caban

    2008-01-01

    A methodology for incident decomposition and reconstruction is developed based on the concept of an "event-frame model." The event-frame model characterizes a fire incident in terms of (a) environmental events that pertain to the fire and the fire context (e.g., fire behavior, weather, fuels) and (b) management events that represent responses to the fire...

  3. Re-construction of action awareness depends on an internal model of action-outcome timing.

    Science.gov (United States)

    Stenner, Max-Philipp; Bauer, Markus; Machts, Judith; Heinze, Hans-Jochen; Haggard, Patrick; Dolan, Raymond J

    2014-04-01

    The subjective time of an instrumental action is shifted towards its outcome. This temporal binding effect is partially retrospective, i.e., occurs upon outcome perception. Retrospective binding is thought to reflect post-hoc inference on agency based on sensory evidence of the action - outcome association. However, many previous binding paradigms cannot exclude the possibility that retrospective binding results from bottom-up interference of sensory outcome processing with action awareness and is functionally unrelated to the processing of the action - outcome association. Here, we keep bottom-up interference constant and use a contextual manipulation instead. We demonstrate a shift of subjective action time by its outcome in a context of variable outcome timing. Crucially, this shift is absent when there is no such variability. Thus, retrospective action binding reflects a context-dependent, model-based phenomenon. Such top-down re-construction of action awareness seems to bias agency attribution when outcome predictability is low. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Pseudo potentials and model potentials in atomic collisions

    International Nuclear Information System (INIS)

    Reyes, O.; Jouin, H.; Fuentealba, P.

    1988-01-01

    In this work, it is discussed the main differences between the use of pseudo-potentials and model potentials in collision problems . It is shown the potential energy curves for distinct systems obtained with both kinds of potentials. (A.C.A.S.) [pt

  5. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Reporting potential natural disasters and initial... Assistance-General § 1945.19 Reporting potential natural disasters and initial actions. (a) Purpose. The purpose of reporting potential natural disasters is to provide a systematic procedure for rapid reporting...

  6. Recovery of Action Potentials and Twitches after K-contractures in Frog Skeletal Muscle(Physiology)

    OpenAIRE

    Atsuko, Suzuki; Ibuki, Shirakawa; Kazunari, Noguchi; Hirohiko, Kishi; Haruo, Sugi; Department of Physiology, School of Medicine, Teikyo University:(Present office)Department of Physical Therapy, Health Science University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University; Department of Physiology, School of Medicine, Teikyo University

    2004-01-01

    To give information about intracellular Ca^ translocation during and after K-contractures in vertebrate skeletal muscle fibers, we examined recovery of action potentials and twitches after interruption and spontaneous relaxation of K-contractures at low temperature (3℃) that greatly reduced the rate of Ca^ reuptake by the sarcoplasmic reticulum. On membrane repolarization interrupting K-contractures, the amplitude of both action potentials and twitches recovered quickly, while the falling pha...

  7. In-vitro characterization of a cochlear implant system for recording of evoked compound action potentials

    Science.gov (United States)

    2012-01-01

    Background Modern cochlear implants have integrated recording systems for measuring electrically evoked compound action potentials of the auditory nerve. The characterization of such recording systems is important for establishing a reliable basis for the interpretation of signals acquired in vivo. In this study we investigated the characteristics of the recording system integrated into the MED-EL PULSARCI100 cochlear implant, especially its linearity and resolution, in order to develop a mathematical model describing the recording system. Methods In-vitro setup: The cochlear implant, including all attached electrodes, was fixed in a tank of physiologic saline solution. Sinusoidal signals of the same frequency but with different amplitudes were delivered via a signal generator for measuring and recording on a single electrode. Computer simulations: A basic mathematical model including the main elements of the recording system, i.e. amplification and digitalization stage, was developed. For this, digital output for sinusoidal input signals of different amplitudes were calculated using in-vitro recordings as reference. Results Using an averaging of 100 measurements the recording system behaved linearly down to approximately -60 dB of the input signal range. Using the same method, a system resolution of 10 μV was determined for sinusoidal signals. The simulation results were in very good agreement with the results obtained from in-vitro experiments. Conclusions The recording system implemented in the MED-EL PULSARCI100 cochlear implant for measuring the evoked compound action potential of the auditory nerve operates reliably. The developed mathematical model provides a good approximation of the recording system. PMID:22531599

  8. Molecular motions that shape the cardiac action potential: Insights from voltage clamp fluorometry.

    Science.gov (United States)

    Zhu, Wandi; Varga, Zoltan; Silva, Jonathan R

    2016-01-01

    Very recently, voltage-clamp fluorometry (VCF) protocols have been developed to observe the membrane proteins responsible for carrying the ventricular ionic currents that form the action potential (AP), including those carried by the cardiac Na(+) channel, NaV1.5, the L-type Ca(2+) channel, CaV1.2, the Na(+)/K(+) ATPase, and the rapid and slow components of the delayed rectifier, KV11.1 and KV7.1. This development is significant, because VCF enables simultaneous observation of ionic current kinetics with conformational changes occurring within specific channel domains. The ability gained from VCF, to connect nanoscale molecular movement to ion channel function has revealed how the voltage-sensing domains (VSDs) control ion flux through channel pores, mechanisms of post-translational regulation and the molecular pathology of inherited mutations. In the future, we expect that this data will be of great use for the creation of multi-scale computational AP models that explicitly represent ion channel conformations, connecting molecular, cell and tissue electrophysiology. Here, we review the VCF protocol, recent results, and discuss potential future developments, including potential use of these experimental findings to create novel computational models. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Therapeutic action of ghrelin in a mouse model of colitis.

    Science.gov (United States)

    Gonzalez-Rey, Elena; Chorny, Alejo; Delgado, Mario

    2006-05-01

    Ghrelin is a novel growth hormone-releasing peptide with potential endogenous anti-inflammatory activities ameliorating some pathologic inflammatory conditions. Crohn's disease is a chronic debilitating disease characterized by severe T helper cell (Th)1-driven inflammation of the colon. The aim of this study was to investigate the therapeutic effect of ghrelin in a murine model of colitis. We examined the anti-inflammatory action of ghrelin in the colitis induced by intracolonic administration of trinitrobenzene sulfonic acid. Diverse clinical signs of the disease were evaluated, including weight loss, diarrhea, colitis, and histopathology. We also investigated the mechanisms involved in the potential therapeutic effect of ghrelin, such as inflammatory cytokines and chemokines, Th1-type response, and regulatory factors. Ghrelin ameliorated significantly the clinical and histopathologic severity of the trinitrobenzene sulfonic acid-induced colitis; abrogating body weight loss, diarrhea, and inflammation; and increasing survival. The therapeutic effect was associated with down-regulation of both inflammatory and Th1-driven autoimmune response through the regulation of a wide spectrum of inflammatory mediators. In addition, a partial involvement of interluekin-10/transforming growth factor-beta1-secreting regulatory T cells in this therapeutic effect was demonstrated. Importantly, the ghrelin treatment was therapeutically effective in established colitis and avoided the recurrence of the disease. Our data demonstrate novel anti-inflammatory actions for ghrelin in the gastrointestinal tract, ie, the capacity to deactivate the intestinal inflammatory response and to restore mucosal immune tolerance at multiple levels. Consequently, ghrelin administration represents a novel possible therapeutic approach for the treatment of Crohn's disease and other Th1-mediated inflammatory diseases, such as rheumatoid arthritis and multiple sclerosis.

  10. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    Science.gov (United States)

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  11. Mechanism of Action and Clinical Potential of Fingolimod for the Treatment of Stroke

    Directory of Open Access Journals (Sweden)

    Wentao Li

    2016-08-01

    Full Text Available Fingolimod (FTY720 is an orally bio-available immunomodulatory drug currently approved by the FDA for the treatment of multiple sclerosis. Currently, there is a significant interest in the potential benefits of FTY720 on stroke outcomes. FTY720 and the sphingolipid signaling pathway it modulates has a ubiquitous presence in the central nervous system and both rodent models and pilot clinical trials seem to indicate that the drug may improve overall functional recovery in different stroke subtypes. Although the precise mechanisms behind these beneficial effects are yet unclear, there is evidence that FTY720 has a role in regulating cerebrovascular responses, blood brain barrier permeability, and cell survival in the event of cerebrovascular insult. In this article, we critically review the data obtained from the latest laboratory findings and clinical trials involving both ischemic and hemorrhagic stroke, and attempt to form a cohesive picture of FTY720’s mechanisms of action in stroke

  12. Gauge invariant actions for string models

    International Nuclear Information System (INIS)

    Banks, T.

    1986-06-01

    String models of unified interactions are elegant sets of Feynman rules for the scattering of gravitons, gauge bosons, and a host of massive excitations. The purpose of these lectures is to describe the progress towards a nonperturbative formulation of the theory. Such a formulation should make the geometrical meaning of string theory manifest and explain the many ''miracles'' exhibited by the string Feynman rules. There are some new results on gauge invariant observables, on the cosmological constant, and on the symmetries of interacting string field theory. 49 refs

  13. Sensitivity to structure in action sequences: An infant event-related potential study.

    Science.gov (United States)

    Monroy, Claire D; Gerson, Sarah A; Domínguez-Martínez, Estefanía; Kaduk, Katharina; Hunnius, Sabine; Reid, Vincent

    2017-05-06

    Infants are sensitive to structure and patterns within continuous streams of sensory input. This sensitivity relies on statistical learning, the ability to detect predictable regularities in spatial and temporal sequences. Recent evidence has shown that infants can detect statistical regularities in action sequences they observe, but little is known about the neural process that give rise to this ability. In the current experiment, we combined electroencephalography (EEG) with eye-tracking to identify electrophysiological markers that indicate whether 8-11-month-old infants detect violations to learned regularities in action sequences, and to relate these markers to behavioral measures of anticipation during learning. In a learning phase, infants observed an actor performing a sequence featuring two deterministic pairs embedded within an otherwise random sequence. Thus, the first action of each pair was predictive of what would occur next. One of the pairs caused an action-effect, whereas the second did not. In a subsequent test phase, infants observed another sequence that included deviant pairs, violating the previously observed action pairs. Event-related potential (ERP) responses were analyzed and compared between the deviant and the original action pairs. Findings reveal that infants demonstrated a greater Negative central (Nc) ERP response to the deviant actions for the pair that caused the action-effect, which was consistent with their visual anticipations during the learning phase. Findings are discussed in terms of the neural and behavioral processes underlying perception and learning of structured action sequences. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Action potential bursts in central snail neurons elicited by paeonol: roles of ionic currents

    Science.gov (United States)

    Chen, Yi-hung; Lin, Pei-lin; Hsu, Hui-yu; Wu, Ya-ting; Yang, Han-yin; Lu, Dah-yuu; Huang, Shiang-suo; Hsieh, Ching-liang; Lin, Jaung-geng

    2010-01-01

    Aim: To investigate the effects of 2′-hydroxy-4′-methoxyacetophenone (paeonol) on the electrophysiological behavior of a central neuron (right parietal 4; RP4) of the giant African snail (Achatina fulica Ferussac). Methods: Intracellular recordings and the two-electrode voltage clamp method were used to study the effects of paeonol on the RP4 neuron. Results: The RP4 neuron generated spontaneous action potentials. Bath application of paeonol at a concentration of ≥500 μmol/L reversibly elicited action potential bursts in a concentration-dependent manner. Immersing the neurons in Co2+-substituted Ca2+-free solution did not block paeonol-elicited bursting. Pretreatment with the protein kinase A (PKA) inhibitor KT-5720 or the protein kinase C (PKC) inhibitor Ro 31-8220 did not affect the action potential bursts. Voltage-clamp studies revealed that paeonol at a concentration of 500 μmol/L had no remarkable effects on the total inward currents, whereas paeonol decreased the delayed rectifying K+ current (IKD) and the fast-inactivating K+ current (IA). Application of 4-aminopyridine (4-AP 5 mmol/L), an inhibitor of IA, or charybdotoxin 250 nmol/L, an inhibitor of the Ca2+-activated K+ current (IK(Ca)), failed to elicit action potential bursts, whereas tetraethylammonium chloride (TEA 50 mmol/L), an IKD blocker, successfully elicited action potential bursts. At a lower concentration of 5 mmol/L, TEA facilitated the induction of action potential bursts elicited by paeonol. Conclusion: Paeonol elicited a bursting firing pattern of action potentials in the RP4 neuron and this activity relates closely to the inhibitory effects of paeonol on the IKD. PMID:21042287

  15. Active action potential propagation but not initiation in thalamic interneuron dendrites

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

    Inhibitory interneurons of the dorsal lateral geniculate nucleus of the thalamus modulate the activity of thalamocortical cells in response to excitatory input through the release of inhibitory neurotransmitter from both axons and dendrites. The exact mechanisms by which release can occur from dendrites are, however, not well understood. Recent experiments using calcium imaging have suggested that Na/K based action potentials can evoke calcium transients in dendrites via local active conductances, making the back-propagating action potential a candidate for dendritic neurotransmitter release. In this study, we employed high temporal and spatial resolution voltage-sensitive dye imaging to assess the characteristics of dendritic voltage deflections in response to Na/K action potentials in interneurons of the mouse dorsal lateral geniculate nucleus. We found that trains or single action potentials elicited by somatic current injection or local synaptic stimulation led to action potentials that rapidly and actively back-propagated throughout the entire dendritic arbor and into the fine filiform dendritic appendages known to release GABAergic vesicles. Action potentials always appeared first in the soma or proximal dendrite in response to somatic current injection or local synaptic stimulation, and the rapid back-propagation into the dendritic arbor depended upon voltage-gated sodium and TEA-sensitive potassium channels. Our results indicate that thalamic interneuron dendrites integrate synaptic inputs that initiate action potentials, most likely in the axon initial segment, that then back-propagate with high-fidelity into the dendrites, resulting in a nearly synchronous release of GABA from both axonal and dendritic compartments. PMID:22171033

  16. Effect of an educational game on university students' learning about action potentials.

    Science.gov (United States)

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K

    2017-06-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na + -K + -ATPase pump. During the game activity, the students arranged the pieces to demonstrate how the ions move through the membrane in a resting state and during an action potential, linking the ion movement with a graph of the action potential. To test the effect of the game activity on student understanding, first-year dental students were given the game to play at different times in a series of classes teaching resting membrane potential and action potentials. In all experiments, students who played the game performed better in assessments. According to 98% of the students, the game supported the learning process. The data confirm the students' perception, indicating that the educational game improved their understanding about action potentials. Copyright © 2017 the American Physiological Society.

  17. Effects of Acetylcholine and Noradrenalin on Action Potentials of Isolated Rabbit Sinoatrial and Atrial Myocytes

    Science.gov (United States)

    Verkerk, Arie O.; Geuzebroek, Guillaume S. C.; Veldkamp, Marieke W.; Wilders, Ronald

    2012-01-01

    The autonomic nervous system controls heart rate and contractility through sympathetic and parasympathetic inputs to the cardiac tissue, with acetylcholine (ACh) and noradrenalin (NA) as the chemical transmitters. In recent years, it has become clear that specific Regulators of G protein Signaling proteins (RGS proteins) suppress muscarinic sensitivity and parasympathetic tone, identifying RGS proteins as intriguing potential therapeutic targets. In the present study, we have identified the effects of 1 μM ACh and 1 μM NA on the intrinsic action potentials of sinoatrial (SA) nodal and atrial myocytes. Single cells were enzymatically isolated from the SA node or from the left atrium of rabbit hearts. Action potentials were recorded using the amphotericin-perforated patch-clamp technique in the absence and presence of ACh, NA, or a combination of both. In SA nodal myocytes, ACh increased cycle length and decreased diastolic depolarization rate, whereas NA decreased cycle length and increased diastolic depolarization rate. Both ACh and NA increased maximum upstroke velocity. Furthermore, ACh hyperpolarized the maximum diastolic potential. In atrial myocytes stimulated at 2 Hz, both ACh and NA hyperpolarized the maximum diastolic potential, increased the action potential amplitude, and increased the maximum upstroke velocity. Action potential duration at 50 and 90% repolarization was decreased by ACh, but increased by NA. The effects of both ACh and NA on action potential duration showed a dose dependence in the range of 1–1000 nM, while a clear-cut frequency dependence in the range of 1–4 Hz was absent. Intermediate results were obtained in the combined presence of ACh and NA in both SA nodal and atrial myocytes. Our data uncover the extent to which SA nodal and atrial action potentials are intrinsically dependent on ACh, NA, or a combination of both and may thus guide further experiments with RGS proteins. PMID:22754533

  18. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells

    Science.gov (United States)

    Johnson, Stuart L.; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M.; Roberts, Terri P.; Masetto, Sergio; Knipper, Marlies; Kros, Corné J.; Marcotti, Walter

    2011-01-01

    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion cells and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials are intrinsically generated by immature IHCs of altricial rodents and that apical IHCs exhibit bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter ACh, by fine-tuning the IHC’s resting membrane potential (Vm), is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the Vm of apical and basal IHCs by activating SK2 channels. We hypothesize that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway. PMID:21572434

  19. Perturbation analysis of spontaneous action potential initiation by stochastic ion channels

    KAUST Repository

    Keener, James P.

    2011-07-01

    A stochastic interpretation of spontaneous action potential initiation is developed for the Morris-Lecar equations. Initiation of a spontaneous action potential can be interpreted as the escape from one of the wells of a double well potential, and we develop an asymptotic approximation of the mean exit time using a recently developed quasistationary perturbation method. Using the fact that the activating ionic channel\\'s random openings and closings are fast relative to other processes, we derive an accurate estimate for the mean time to fire an action potential (MFT), which is valid for a below-threshold applied current. Previous studies have found that for above-threshold applied current, where there is only a single stable fixed point, a diffusion approximation can be used. We also explore why different diffusion approximation techniques fail to estimate the MFT. © 2011 American Physical Society.

  20. Prediction of Thorough QT study results using action potential simulations based on ion channel screens.

    Science.gov (United States)

    Mirams, Gary R; Davies, Mark R; Brough, Stephen J; Bridgland-Taylor, Matthew H; Cui, Yi; Gavaghan, David J; Abi-Gerges, Najah

    2014-01-01

    Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms - IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration-effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1Hz and running to steady state, for a range of concentrations. We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥5ms was predicted with up to 79% sensitivity and 100% specificity. This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety

  1. The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

    Science.gov (United States)

    Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

    2015-08-01

    The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

  2. Prolonged action potential duration in cardiac ablation of PDK1 mice.

    Science.gov (United States)

    Han, Zhonglin; Jiang, Yu; Yang, Zhongzhou; Cao, Kejiang; Wang, Dao W

    2015-01-01

    The involvement of the AGC protein kinase family in regulating arrhythmia has drawn considerable attention, but the underlying mechanisms are still not clear. The aim of this study is to explore the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), one of upstream protein kinases of the AGC protein kinase family, in the pathogenesis of dysregulated electrophysiological basis. PDK1(F/F) αMHC-Cre mice and PDK1(F/F) mice were divided into experiment group and control group. Using patch clamping technology, we explored action potential duration in both groups, and investigated the functions of transient outward potassium channel and L-type Ca(2+) channel to explain the abnormal action potential duration. Significant prolongation action potential duration was found in mice with PDK1 deletion. Further, the peak current of transient outward potassium current and L-type Ca(2+) current were decreased by 84% and 49% respectively. In addition, dysregulation of channel kinetics lead to action potential duration prolongation further. In conclusion, we have demonstrated that PDK1 participates in action potential prolongation in cardiac ablation of PDK1 mice. This effect is likely to be mediated largely through downregulation of transient outward potassium current. These findings indicate the modulation of the PDK1 pathway could provide a new mechanism for abnormal electrophysiological basis.

  3. Action Potential Dynamics in Fine Axons Probed with an Axonally Targeted Optical Voltage Sensor.

    Science.gov (United States)

    Ma, Yihe; Bayguinov, Peter O; Jackson, Meyer B

    2017-01-01

    The complex and malleable conduction properties of axons determine how action potentials propagate through extensive axonal arbors to reach synaptic terminals. The excitability of axonal membranes plays a major role in neural circuit function, but because most axons are too thin for conventional electrical recording, their properties remain largely unexplored. To overcome this obstacle, we used a genetically encoded hybrid voltage sensor (hVOS) harboring an axonal targeting motif. Expressing this probe in transgenic mice enabled us to monitor voltage changes optically in two populations of axons in hippocampal slices, the large axons of dentate granule cells (mossy fibers) in the stratum lucidum of the CA3 region and the much finer axons of hilar mossy cells in the inner molecular layer of the dentate gyrus. Action potentials propagated with distinct velocities in each type of axon. Repetitive firing broadened action potentials in both populations, but at an intermediate frequency the degree of broadening differed. Repetitive firing also attenuated action potential amplitudes in both mossy cell and granule cell axons. These results indicate that the features of use-dependent action potential broadening, and possible failure, observed previously in large nerve terminals also appear in much finer unmyelinated axons. Subtle differences in the frequency dependences could influence the propagation of activity through different pathways to excite different populations of neurons. The axonally targeted hVOS probe used here opens up the diverse repertoire of neuronal processes to detailed biophysical study.

  4. Fokker-action principle for a system of particles interacting through a linear potential

    International Nuclear Information System (INIS)

    Rivacoba, A.

    1984-01-01

    A Fokker-action principle for a system of scalar particles interacting through their time-symmetric relativistic generalization of linear potential is obtained. From this action, motion equations and conservation laws for the total energy and angular momentum of the system, in which field contributions are included, are derived. These equations are exactly applied to the problem suggested by Schild of two particles moving in circular concentric orbits

  5. Theoretical study on optical model potential

    International Nuclear Information System (INIS)

    Lim Hung Gi.

    1984-08-01

    The optical model potential of non-local effect on the rounded edge of the potential is derived. On the basis of this potential the functional form of the optical model potential, the energy dependence and relationship of its parameters, and the dependency of the values of the parameters on energy change are shown in this paper. (author)

  6. Modulation of KCNQ1 alternative splicing regulates cardiac IKs and action potential repolarization.

    Science.gov (United States)

    Lee, Hsiang-Chun; Rudy, Yoram; Po-Yuan, Phd; Sheu, Sheng-Hsiung; Chang, Jan-Gowth; Cui, Jianmin

    2013-08-01

    Slow delayed-rectifier potassium current (IKs) channels, made of the pore-forming KCNQ1 and auxiliary KCNE1 subunits, play a key role in determining action potential duration (APD) in cardiac myocytes. The consequences of drug-induced KCNQ1 splice alteration remain unknown. To study the modulation of KCNQ1 alternative splicing by amiloride and the consequent changes in IKs and action potentials (APs) in ventricular myocytes. Canine endocardial, midmyocardial, and epicardial ventricular myocytes were isolated. Levels of KCNQ1a and KCNQ1b as well as a series of splicing factors were quantified by using the reverse transcriptase-polymerase chain reaction and Western blot. The effect of amiloride-induced changes in the KCNQ1b/total KCNQ1 ratio on AP was measured by using whole-cell patch clamp with and without isoproterenol. With 50 μmol/L of amiloride for 6 hours, KCNQ1a at transcriptional and translational levels increased in midmyocardial myocytes but decreased in endo- and epicardial myocytes. Likewise, changes in splicing factors in midmyocardial were opposite to that in endo- and epicardial myocytes. In midmyocardial myocytes amiloride shortened APD and decreased isoproterenol-induced early afterdepolarizations significantly. The same amiloride-induced effects were demonstrated by using human ventricular myocyte model for AP simulations under beta-adrenergic stimulation. Moreover, amiloride reduced the transmural dispersion of repolarization in pseudo-electrocardiogram. Amiloride regulates IKs and APs with transmural differences and reduces arrhythmogenicity through the modulation of KCNQ1 splicing. We suggested that the modulation of KCNQ1 splicing may help prevent arrhythmia. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  7. Motor Unit Action Potential Clustering—Theoretical Consideration for Muscle Activation during a Motor Task

    Directory of Open Access Journals (Sweden)

    Michael J. Asmussen

    2018-01-01

    Full Text Available During dynamic or sustained isometric contractions, bursts of muscle activity appear in the electromyography (EMG signal. Theoretically, these bursts of activity likely occur because motor units are constrained to fire temporally close to one another and thus the impulses are “clustered” with short delays to elicit bursts of muscle activity. The purpose of this study was to investigate whether a sequence comprised of “clustered” motor unit action potentials (MUAP can explain spectral and amplitude changes of the EMG during a simulated motor task. This question would be difficult to answer experimentally and thus, required a model to study this type of muscle activation pattern. To this end, we modeled two EMG signals, whereby a single MUAP was either convolved with a randomly distributed impulse train (EMG-rand or a “clustered” sequence of impulses (EMG-clust. The clustering occurred in windows lasting 5–100 ms. A final mixed signal of EMG-clust and EMG-rand, with ratios (1:1–1:10, was also modeled. A ratio of 1:1 would indicate that 50% of MUAP were randomly distributed, while 50% of “clustered” MUAP occurred in a given time window (5–100 ms. The results of the model showed that clustering MUAP caused a downshift in the mean power frequency (i.e., ~30 Hz with the largest shift occurring with a cluster window of 10 ms. The mean frequency shift was largest when the ratio of EMG-clust to EMG-rand was high. Further, the clustering of MUAP also caused a substantial increase in the amplitude of the EMG signal. This model potentially explains an activation pattern that changes the EMG spectra during a motor task and thus, a potential activation pattern of muscles observed experimentally. Changes in EMG measurements during fatiguing conditions are typically attributed to slowing of conduction velocity but could, per this model, also result from changes of the clustering of MUAP. From a clinical standpoint, this type of muscle

  8. Action potential energy efficiency varies among neuron types in vertebrates and invertebrates.

    Directory of Open Access Journals (Sweden)

    Biswa Sengupta

    2010-07-01

    Full Text Available The initiation and propagation of action potentials (APs places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na(+ and K(+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin-Huxley model of the squid axon, optimizing the kinetics or number of Na(+ and K(+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost.

  9. Action Potential Energy Efficiency Varies Among Neuron Types in Vertebrates and Invertebrates

    Science.gov (United States)

    Sengupta, Biswa; Stemmler, Martin; Laughlin, Simon B.; Niven, Jeremy E.

    2010-01-01

    The initiation and propagation of action potentials (APs) places high demands on the energetic resources of neural tissue. Each AP forces ATP-driven ion pumps to work harder to restore the ionic concentration gradients, thus consuming more energy. Here, we ask whether the ionic currents underlying the AP can be predicted theoretically from the principle of minimum energy consumption. A long-held supposition that APs are energetically wasteful, based on theoretical analysis of the squid giant axon AP, has recently been overturned by studies that measured the currents contributing to the AP in several mammalian neurons. In the single compartment models studied here, AP energy consumption varies greatly among vertebrate and invertebrate neurons, with several mammalian neuron models using close to the capacitive minimum of energy needed. Strikingly, energy consumption can increase by more than ten-fold simply by changing the overlap of the Na+ and K+ currents during the AP without changing the APs shape. As a consequence, the height and width of the AP are poor predictors of energy consumption. In the Hodgkin–Huxley model of the squid axon, optimizing the kinetics or number of Na+ and K+ channels can whittle down the number of ATP molecules needed for each AP by a factor of four. In contrast to the squid AP, the temporal profile of the currents underlying APs of some mammalian neurons are nearly perfectly matched to the optimized properties of ionic conductances so as to minimize the ATP cost. PMID:20617202

  10. RXP-E: a connexin43-binding peptide that prevents action potential propagation block

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi

    2008-01-01

    . Separately, RXP-E was concatenated to a cytoplasmic transduction peptide (CTP) for cytoplasmic translocation (CTP-RXP-E). The effect of RXP-E on action potential propagation was assessed by high-resolution optical mapping in monolayers of neonatal rat ventricular myocytes, containing approximately 20......% of randomly distributed myofibroblasts. In contrast to control experiments, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, action potential propagation was maintained, albeit at a slower velocity. Similarly, intracellular acidification (pH(i) 6.2) caused a loss...... of action potential propagation in control monolayers; however, propagation was maintained in CTP-RXP-E-treated cells, although at a slower rate. Patch-clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium currents, nor did it alter voltage dependence or amplitude of Kir2...

  11. Improving Cardiac Action Potential Measurements: 2D and 3D Cell Culture.

    Science.gov (United States)

    Daily, Neil J; Yin, Yue; Kemanli, Pinar; Ip, Brian; Wakatsuki, Tetsuro

    2015-11-01

    Progress in the development of assays for measuring cardiac action potential is crucial for the discovery of drugs for treating cardiac disease and assessing cardiotoxicity. Recently, high-throughput methods for assessing action potential using induced pluripotent stem cell (iPSC) derived cardiomyocytes in both two-dimensional monolayer cultures and three-dimensional tissues have been developed. We describe an improved method for assessing cardiac action potential using an ultra-fast cost-effective plate reader with commercially available dyes. Our methods improve dramatically the detection of the fluorescence signal from these dyes and make way for the development of more high-throughput methods for cardiac drug discovery and cardiotoxicity.

  12. Inter-subject variability in human atrial action potential in sinus rhythm versus chronic atrial fibrillation.

    Directory of Open Access Journals (Sweden)

    Carlos Sánchez

    Full Text Available Human atrial electrophysiology exhibits high inter-subject variability in both sinus rhythm (SR and chronic atrial fibrillation (cAF patients. Variability is however rarely investigated in experimental and theoretical electrophysiological studies, thus hampering the understanding of its underlying causes but also its implications in explaining differences in the response to disease and treatment. In our study, we aim at investigating the ability of populations of human atrial cell models to capture the inter-subject variability in action potential (AP recorded in 363 patients both under SR and cAF conditions.Human AP recordings in atrial trabeculae (n = 469 from SR and cAF patients were used to calibrate populations of computational SR and cAF atrial AP models. Three populations of over 2000 sampled models were generated, based on three different human atrial AP models. Experimental calibration selected populations of AP models yielding AP with morphology and duration in range with experimental recordings. Populations using the three original models can mimic variability in experimental AP in both SR and cAF, with median conductance values in SR for most ionic currents deviating less than 30% from their original peak values. All cAF populations show similar variations in G(K1, G(Kur and G(to, consistent with AF-related remodeling as reported in experiments. In all SR and cAF model populations, inter-subject variability in I(K1 and I(NaK underlies variability in APD90, variability in I(Kur, I(CaL and I(NaK modulates variability in APD50 and combined variability in Ito and I(Kur determines variability in APD20. The large variability in human atrial AP triangulation is mostly determined by I(K1 and either I(NaK or I(NaCa depending on the model.Experimentally-calibrated human atrial AP models populations mimic AP variability in SR and cAF patient recordings, and identify potential ionic determinants of inter-subject variability in human atrial AP

  13. Incorporated fish oil fatty acids prevent action potential shortening induced by circulating fish oil fatty acids

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

    Full Text Available Increased consumption of fatty fish, rich in omega-3 polyunsaturated fatty acids (3-PUFAs reduces the severity and number of arrhythmias. Long term 3-PUFA-intake modulates the activity of several cardiac ion channels leading to cardiac action potential shortening. Circulating 3-PUFAs in the bloodstream and incorporated 3-PUFAs in the cardiac membrane have a different mechanism to shorten the action potential. It is, however, unknown whether circulating 3-PUFAs in the bloodstream enhance or diminish the effects of incorporated 3-PUFAs. In the present study, we address this issue. Rabbits were fed a diet rich in fish oil (3 or sunflower oil (9, as control for 3 weeks. Ventricular myocytes were isolated by enzymatic dissociation and action potentials were measured using the perforated patch clamp technique in the absence and presence of acutely administered 3-PUFAs. Plasma of 3 fed rabbits contained more free eicosapentaenoic acid (EPA and isolated myocytes of 3 fed rabbits contained higher amounts of both EPA and docosahexaenoic acid (DHA in their sarcolemma compared to control. In the absence of acutely administered fatty acids, 3 myocytes had a shorter action potential with a more negative plateau than 9 myocytes. In the 9 myocytes, but not in the 3 myocytes, acute administration of a mixture of EPA+DHA shortened the action potential significantly. From these data we conclude that incorporated 3-PUFAs into the sarcolemma and acutely administered 3 fatty acids do not have a cumulative effect on action potential duration and morphology. As a consequence, patients with a high cardiac 3-PUFA status will probably not benefit from short term 3 supplementation as an antiarrhythmic therapy.

  14. Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus.

    Science.gov (United States)

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

    High-frequency synaptic transmission is depressed by moderate rises in the extracellular potassium concentration ([K+]o). Previous reports have indicated that depression of action potential signaling may underlie the synaptic depression. Here, we investigated the specific contribution of K+-induced action potential changes to synaptic depression. We found that glutamatergic transmission in the hippocampal area CA1 was significantly depressed by 8-10 mM [K+]o, but that GABAergic transmission remained intact. Riluzole, a drug that slows recovery from inactivation of voltage-gated sodium channels (NaChs), interacts with subthreshold [K+]o to depress afferent volleys and EPSCs strongly. Thus, elevated [K+]o likely depresses synapses by slowing NaCh recovery from inactivation. It is unclear from previous studies whether [K+]o-induced action potential depression is caused by changes in initiation, reliability, or waveform. We investigated these possibilities explicitly. [K+]o-induced afferent volley depression was independent of stimulus strength, suggesting that changes in action potential initiation do not explain [K+]o-induced depression. Measurements of action potentials from single axons revealed that 8 mM [K+]o increased conduction failures in a subpopulation of fibers and depressed action potential amplitude in all fibers. Together, these changes quantitatively account for the afferent volley depression. We estimate that conduction failure explains more than half of the synaptic depression observed at 8 mM [K+]o, with the remaining depression likely explained by waveform changes. These mechanisms of selective sensitivity of glutamate release to [K+]o accumulation represent a unique neuromodulatory mechanism and a brake on runaway excitation.

  15. A fast Na+/Ca2+-based action potential in a marine diatom.

    Directory of Open Access Journals (Sweden)

    Alison R Taylor

    Full Text Available BACKGROUND: Electrical impulses in animals play essential roles in co-ordinating an array of physiological functions including movement, secretion, environmental sensing and development. Underpinning many of these electrical signals is a fast Na+-based action potential that has been fully characterised only in cells associated with the neuromuscular systems of multicellular animals. Such rapid action potentials are thought to have evolved with the first metazoans, with cnidarians being the earliest representatives. The present study demonstrates that a unicellular protist, the marine diatom Odontella sinensis, can also generate a fast Na+/Ca2+ based action potential that has remarkably similar biophysical and pharmacological properties to invertebrates and vertebrate cardiac and skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: The kinetic, ionic and pharmacological properties of the rapid diatom action potential were examined using single electrode current and voltage clamp techniques. Overall, the characteristics of the fast diatom currents most closely resemble those of vertebrate and invertebrate muscle Na+/Ca2+ currents. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration of voltage-activated Na+ channels and the capacity to generate fast Na+-based action potentials in a unicellular photosynthetic organism. The biophysical and pharmacological characteristics together with the presence of a voltage activated Na+/Ca2+ channel homologue in the recently sequenced genome of the diatom Thalassiosira pseudonana, provides direct evidence supporting the hypothesis that this rapid signalling mechanism arose in ancestral unicellular eukaryotes and has been retained in at least two phylogenetically distant lineages of eukaryotes; opisthokonts and the stramenopiles. The functional role of the fast animal-like action potential in diatoms remains to be elucidated but is likely involved in rapid environmental sensing of these widespread and

  16. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.

    Science.gov (United States)

    Kistamás, Kornél; Szentandrássy, Norbert; Hegyi, Bence; Ruzsnavszky, Ferenc; Váczi, Krisztina; Bárándi, László; Horváth, Balázs; Szebeni, Andrea; Magyar, János; Bányász, Tamás; Kecskeméti, Valéria; Nánási, Péter P

    2013-06-15

    Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Channel sialic acids limit hERG channel activity during the ventricular action potential.

    Science.gov (United States)

    Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

    2013-02-01

    Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

  18. THE ACTION MODEL FOR MEASURING INFLUENCE IN ADVERTISING

    Directory of Open Access Journals (Sweden)

    Andrej Kovacic

    2014-09-01

    Full Text Available Despite the abundance of different theories there is little agreement on the suitable model that would explain how influence in advertising works. Historically, theoretical models have moved from including solely rational components towards including emotional components and from focusing on sequential processing towards hierarchy free processing models. Based on the existing literature, several most representative models are presented, described and evaluated. In a quest to explain a broader view on advertising influence we introduced the ACTION model (an acronym for Aim, Connection, Techniques, Identity, Opportunity and Numerous. Advantages, suggestions for future research and a critical discussion of using this model are further discussed.

  19. The different intracellular action potentials of fast and slow muscle fibres = Différences entre les potentiels d'action intracellulaires de fibres musculaires rapides et lentes

    NARCIS (Netherlands)

    Wallinga, W.; Gielen, Frans L.H.; Wirtz, Peter; de Jong, Paul; Broenink, Johannes F.

    1985-01-01

    The time course of the intracellular action potential was studied quantitatively, because it is an important factor in the generation of electromyographic signals. In in vivo preparations of the m. EDL and m. soleus of the rat single motor units were stimulated and intracellular action potentials

  20. Differential effects of thioridazine enantiomers on action potential duration in rabbit papillary muscle

    DEFF Research Database (Denmark)

    Jensen, Ask Schou; Pennisi, Cristian Pablo; Sevcencu, Cristian

    2015-01-01

    with (+)-thioridazine. In this study we for the first time investigate the cardiotoxicity of the isolated thioridazine enantiomers and show their effects on ventricular repolarization. The effects of (+)-thioridazine, (-)-thioridazine, and racemate on the rabbit ventricular action potential duration (APD) were...... investigated in a randomized controlled blinded experiment. Action potentials were measured in papillary muscles isolated from 21 female rabbits, and the drug effect on 90% APD in comparison with control (DeltaDelta-APD90) was evaluated. Increasing concentrations of (+)-thioridazine and the racemate caused...

  1. Animated pose templates for modeling and detecting human actions.

    Science.gov (United States)

    Yao, Benjamin Z; Nie, Bruce X; Liu, Zicheng; Zhu, Song-Chun

    2014-03-01

    This paper presents animated pose templates (APTs) for detecting short-term, long-term, and contextual actions from cluttered scenes in videos. Each pose template consists of two components: 1) a shape template with deformable parts represented in an And-node whose appearances are represented by the Histogram of Oriented Gradient (HOG) features, and 2) a motion template specifying the motion of the parts by the Histogram of Optical-Flows (HOF) features. A shape template may have more than one motion template represented by an Or-node. Therefore, each action is defined as a mixture (Or-node) of pose templates in an And-Or tree structure. While this pose template is suitable for detecting short-term action snippets in two to five frames, we extend it in two ways: 1) For long-term actions, we animate the pose templates by adding temporal constraints in a Hidden Markov Model (HMM), and 2) for contextual actions, we treat contextual objects as additional parts of the pose templates and add constraints that encode spatial correlations between parts. To train the model, we manually annotate part locations on several keyframes of each video and cluster them into pose templates using EM. This leaves the unknown parameters for our learning algorithm in two groups: 1) latent variables for the unannotated frames including pose-IDs and part locations, 2) model parameters shared by all training samples such as weights for HOG and HOF features, canonical part locations of each pose, coefficients penalizing pose-transition and part-deformation. To learn these parameters, we introduce a semi-supervised structural SVM algorithm that iterates between two steps: 1) learning (updating) model parameters using labeled data by solving a structural SVM optimization, and 2) imputing missing variables (i.e., detecting actions on unlabeled frames) with parameters learned from the previous step and progressively accepting high-score frames as newly labeled examples. This algorithm belongs to a

  2. Real time estimation of generation, extinction and flow of muscle fibre action potentials in high density surface EMG.

    Science.gov (United States)

    Mesin, Luca

    2015-02-01

    Developing a real time method to estimate generation, extinction and propagation of muscle fibre action potentials from bi-dimensional and high density surface electromyogram (EMG). A multi-frame generalization of an optical flow technique including a source term is considered. A model describing generation, extinction and propagation of action potentials is fit to epochs of surface EMG. The algorithm is tested on simulations of high density surface EMG (inter-electrode distance equal to 5mm) from finite length fibres generated using a multi-layer volume conductor model. The flow and source term estimated from interference EMG reflect the anatomy of the muscle, i.e. the direction of the fibres (2° of average estimation error) and the positions of innervation zone and tendons under the electrode grid (mean errors of about 1 and 2mm, respectively). The global conduction velocity of the action potentials from motor units under the detection system is also obtained from the estimated flow. The processing time is about 1 ms per channel for an epoch of EMG of duration 150 ms. A new real time image processing algorithm is proposed to investigate muscle anatomy and activity. Potential applications are proposed in prosthesis control, automatic detection of optimal channels for EMG index extraction and biofeedback. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Investigating a Potential Auxin-Related Mode of Hormetic/Inhibitory Action of the Phytotoxin Parthenin.

    Science.gov (United States)

    Belz, Regina G

    2016-01-01

    Parthenin is a metabolite of Parthenium hysterophorus and is believed to contribute to the weed's invasiveness via allelopathy. Despite the potential of parthenin to suppress competitors, low doses stimulate plant growth. This biphasic action was hypothesized to be auxin-like and, therefore, an auxin-related mode of parthenin action was investigated using two approaches: joint action experiments with Lactuca sativa, and dose-response experiments with auxin/antiauxin-resistant Arabidopsis thaliana genotypes. The joint action approach comprised binary mixtures of subinhibitory doses of the auxin 3-indoleacetic acid (IAA) mixed with parthenin or one of three reference compounds [indole-3-butyric acid (IBA), 2,3,5-triiodobenzoic acid (TIBA), 2-(p-chlorophenoxy)-2-methylpropionic acid (PCIB)]. The reference compounds significantly interacted with IAA at all doses, but parthenin interacted only at low doses indicating that parthenin hormesis may be auxin-related, in contrast to its inhibitory action. The genetic approach investigated the response of four auxin/antiauxin-resistant mutants and a wildtype to parthenin or two reference compounds (IAA, PCIB). The responses of mutant plants to the reference compounds confirmed previous reports, but differed from the responses observed for parthenin. Parthenin stimulated and inhibited all mutants independent of resistance. This provided no indication for an auxin-related action of parthenin. Therefore, the hypothesis of an auxin-related inhibitory action of parthenin was rejected in two independent experimental approaches, while the hypothesis of an auxin-related stimulatory effect could not be rejected.

  4. Rosewood oil induces sedation and inhibits compound action potential in rodents.

    Science.gov (United States)

    de Almeida, Reinaldo Nóbrega; Araújo, Demétrius Antonio Machado; Gonçalves, Juan Carlos Ramos; Montenegro, Fabrícia Costa; de Sousa, Damião Pergentino; Leite, José Roberto; Mattei, Rita; Benedito, Marco Antonio Campana; de Carvalho, José Gilberto Barbosa; Cruz, Jader Santos; Maia, José Guilherme Soares

    2009-07-30

    Aniba rosaeodora is an aromatic plant which has been used in Brazil folk medicine due to its sedative effect. Therefore, the purpose of the present study was to evaluate the sedative effect of linalool-rich rosewood oil in mice. In addition we sought to investigate the linalool-rich oil effects on the isolated nerve using the single sucrose-gap technique. Sedative effect was determined by measuring the potentiation of the pentobarbital-induced sleeping time. The compound action potential amplitude was evaluated as a way to detect changes in excitability of the isolated nerve. The results showed that administration of rosewood oil at the doses of 200 and 300 mg/kg significantly decreased latency and increased the duration of sleeping time. On the other hand, the dose of 100 mg/kg potentiated significantly the pentobarbital action decreasing pentobarbital latency time and increasing pentobarbital sleeping time. In addition, the effect of linalool-rich rosewood oil on the isolated nerve of the rat was also investigated through the single sucrose-gap technique. The amplitude of the action potential decreased almost 100% when it was incubated for 30 min at 100 microg/ml. From this study, it is suggested a sedative effect of linalool-rich rosewood oil that could, at least in part, be explained by the reduction in action potential amplitude that provokes a decrease in neuronal excitability.

  5. Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

    Science.gov (United States)

    Hardy, Matthew E L; Pervolaraki, Eleftheria; Bernus, Olivier; White, Ed

    2018-01-01

    We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na + -channel blocker (5 μM) ranolazine or the intracellular Ca 2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus

  6. Dark energy exponential potential models as curvature quintessence

    International Nuclear Information System (INIS)

    Capozziello, S; Cardone, V F; Piedipalumbo, E; Rubano, C

    2006-01-01

    It has been recently shown that, under some general conditions, it is always possible to find a fourth-order gravity theory capable of reproducing the same dynamics as a given dark energy model. Here, we discuss this approach for a dark energy model with a scalar field evolving under the action of an exponential potential. In the absence of matter, such a potential can be recovered from a fourth-order theory via a conformal transformation. Including the matter term, the function f(R) entering the generalized gravity Lagrangian can be reconstructed according to the dark energy model

  7. Inhibition by TRPA1 agonists of compound action potentials in the frog sciatic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Matsushita, Akitomo; Ohtsubo, Sena; Fujita, Tsugumi; Kumamoto, Eiichi, E-mail: kumamote@cc.saga-u.ac.jp

    2013-04-26

    Highlights: •TRPA1 agonists inhibited compound action potentials in frog sciatic nerves. •This inhibition was not mediated by TRPA1 channels. •This efficacy was comparable to those of lidocaine and cocaine. •We found for the first time an ability of TRPA1 agonists to inhibit nerve conduction. -- Abstract: Although TRPV1 and TRPM8 agonists (vanilloid capsaicin and menthol, respectively) at high concentrations inhibit action potential conduction, it remains to be unknown whether TRPA1 agonists have a similar action. The present study examined the actions of TRPA1 agonists, cinnamaldehyde (CA) and allyl isothiocyanate (AITC), which differ in chemical structure from each other, on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. CA and AITC concentration-dependently reduced the peak amplitude of the CAP with the IC{sub 50} values of 1.2 and 1.5 mM, respectively; these activities were resistant to a non-selective TRP antagonist ruthenium red or a selective TRPA1 antagonist HC-030031. The CA and AITC actions were distinct in property; the latter but not former action was delayed in onset and partially reversible, and CA but not AITC increased thresholds to elicit CAPs. A CAP inhibition was seen by hydroxy-α-sanshool (by 60% at 0.05 mM), which activates both TRPA1 and TRPV1 channels, a non-vanilloid TRPV1 agonist piperine (by 20% at 0.07 mM) and tetrahydrolavandulol (where the six-membered ring of menthol is opened; IC{sub 50} = 0.38 mM). It is suggested that TRPA1 agonists as well as TRPV1 and TRPM8 agonists have an ability to inhibit nerve conduction without TRP activation, although their agonists are quite different in chemical structure from each other.

  8. A relativistic quarkonium potential model

    International Nuclear Information System (INIS)

    Klima, B.; Maor, U.

    1984-04-01

    We review a recently developed relativistic quark-antiquark bound state equation using the expansion in intermediate states. Using a QCD motivated potential we succeeded very well to fit both the heavy systems (banti b, canti c) and the light systems (santi s, uanti u and danti d). Here we emphasize our results on heavy-light sustems and on the possible (tanti t) family. (orig.)

  9. Can Participatory Action Research Create Value for Business Model Innovation?

    DEFF Research Database (Denmark)

    Sparre, Mogens; Rasmussen, Ole Horn; Fast, Alf Michael

    Innovation (BMI)?” – has been investigated from five different perspectives based upon The Business Model Cube and The Where to Look Model. Using both established and newly developed tools the paper presents how. Theory and data from two cases are presented and it is demonstrated how industry increase......Abstract: Participatory Action Research (PAR) has a longer academic history compared with the idea of business models (BMs). This paper indicates how industries gain by using the combined methodology. The research question "Can participatory action research create value for Business Model...... their monetary and/or non-monetary value creation doing BMI based upon PAR. The process is essential and using the methodology of PAR creates meaning. Behind the process, the RAR methodology and its link to BM and BMI may contribute to theory construction and creation of a common language in academia around...

  10. Quantitative analysis of single muscle fibre action potentials recorded at known distances

    NARCIS (Netherlands)

    Albers, B.A.; Put, J.H.M.; Wallinga, W.; Wirtz, P.

    1989-01-01

    In vivo records of single fibre action potentials (SFAPs) have always been obtained at unknown distance from the active muscle fibre. A new experimental method has been developed enabling the derivation of the recording distance in animal experiments. A single fibre is stimulated with an

  11. Changes in time and frequency related aspects of motor unit action potentials during fatigue

    NARCIS (Netherlands)

    Wallinga, W.; Bouwens, Jeroen S.; Baten, Christian T.M.

    1996-01-01

    During fatigue the shape of motor unit action potentials (MUAPs) change. Characteristics of the MUAPs described before concern several time related aspects. No attention has been given to the frequency spectrum changes of MUAPS. The median frequency of MUAPS has now been determined for motor units

  12. Youth Participatory Action Research and Educational Transformation: The Potential of Intertextuality as a Methodological Tool

    Science.gov (United States)

    Bertrand, Melanie

    2016-01-01

    In this article, Melanie Bertrand explores the potential of using the concept of intertextuality--which captures the way snippets of written or spoken text from one source become incorporated into other sources--in the study and practice of youth participatory action research (YPAR). Though this collective and youth-centered form of research…

  13. Effect of an Educational Game on University Students' Learning about Action Potentials

    Science.gov (United States)

    Luchi, Kelly Cristina Gaviao; Montrezor, Luís Henrique; Marcondes, Fernanda K.

    2017-01-01

    The aim of this study was to evaluate the effect of an educational game that is used for teaching the mechanisms of the action potentials in cell membranes. The game was composed of pieces representing the intracellular and extracellular environments, ions, ion channels, and the Na+-K+-ATPase pump. During the game activity, the students arranged…

  14. The Transformative Potential of Action Research and ICT in the Second Language (L2) Classroom

    Science.gov (United States)

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

    This study shows the transformative potential of action research and information and communications technology (ICT) in the second language (L2) classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT…

  15. Action potential generation requires a high sodium channel density in the axon initial segment

    NARCIS (Netherlands)

    Kole, Maarten H. P.; Ilschner, Susanne U.; Kampa, Björn M.; Williams, Stephen R.; Ruben, Peter C.; Stuart, Greg J.

    2008-01-01

    The axon initial segment ( AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium ( Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel

  16. Anodal sensory nerve action potentials: From physiological understanding to potential clinical applicability.

    Science.gov (United States)

    Leote, Joao; Pereira, Pedro; Cabib, Christopher; Cipullo, Federica; Valls-Sole, Josep

    2016-06-01

    Low-intensity electrical stimuli of digital nerves may generate a double peak potential (DPp), composed of a cathodal (caAP) and an anodal (anAP) potential in orthodromic recordings. We studied the effects on caAP and anAP of stimuli of variable intensity, duration, and frequency. We also applied a conditioning stimulus to study potential differences in recovery time. The anAP was obtained in 33 of 40 healthy subjects (82.5%) and 4 of 20 patients with various types of sensory neuropathies (20%). Changes in stimulus duration and intensity had reciprocal effects on the amplitude of the anAP and the caAP. There were significant differences in recovery time between caAP and anAP after a conditioning stimulus. The caAP and anAP are 2 interdependent waveforms generated by different effects of the same stimulus over axons at the verge of depolarization. Muscle Nerve 53: 897-905, 2016. © 2015 Wiley Periodicals, Inc.

  17. A dual potassium channel activator improves repolarization reserve and normalizes ventricular action potentials

    DEFF Research Database (Denmark)

    Calloe, Kirstine; Di Diego, José M; Hansen, Rie Schultz

    2016-01-01

    in cultured canine cardiac myocytes and determined whether a dual K(+) current activator can normalize K(+) currents and restore action potential (AP) configuration. METHODS AND RESULTS: Ventricular myocytes were isolated and cultured for up to 48h. Current and voltage clamp recordings were made using patch...... of EADs. Our results suggest a potential benefit of K(+) current activators under conditions of reduced repolarization reserve including heart failure....

  18. Sigma models with purely Wess-Zumino-Witten actions

    International Nuclear Information System (INIS)

    Floreanini, R.; Percacci, R.; Sezgin, E.

    1988-11-01

    We study the dynamics of sigma models in arbitrary dimensions with purely Wess-Zumino-Witten actions (i.e. without kinetic terms), both from the Lagrangian and Hamiltonian point of view. These models have nontrivial gauge groups which contain the diffeomorphisms of space-time, as well as symmetry groups which in many cases turn out to be infinite dimensional. We give examples in 1,2,3 and 4 space-time dimensions.(author). 9 refs

  19. Action without Action Planning: The Potential of the Career Thinking Session in Enabling Transformational Career Learning and Development

    Science.gov (United States)

    Bassot, Barbara

    2017-01-01

    This paper examines the potential of the Career Thinking Session (CTS) model to career guidance and counselling practice with young people. A qualitative research study is presented, focusing on the case study of a client involved in the transition to higher education. The setting for the research is described and the origins of the CTS are…

  20. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

    Science.gov (United States)

    Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-03-05

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential.

  1. The DBI action, higher-derivative supergravity, and flattening inflaton potentials

    International Nuclear Information System (INIS)

    Bielleman, Sjoerd; Ibáñez, Luis E.; Pedro, Francisco G.; Valenzuela, Irene; Wieck, Clemens

    2016-01-01

    In string theory compactifications it is common to find an effective Lagrangian for the scalar fields with a non-canonical kinetic term. We study the effective action of the scalar position moduli of Type II Dp-branes. In many instances the kinetic terms are in fact modified by a term proportional to the scalar potential itself. This can be linked to the appearance of higher-dimensional supersymmetric operators correcting the Kähler potential. We identify the supersymmetric dimension-eight operators describing the α"′ corrections captured by the D-brane Dirac-Born-Infeld action. Our analysis then allows an embedding of the D-brane moduli effective action into an N=1 supergravity formulation. The effects of the potential-dependent kinetic terms may be very important if one of the scalars is the inflaton, since they lead to a flattening of the scalar potential. We analyze this flattening effect in detail and compute its impact on the CMB observables for single-field inflation with monomial potentials.

  2. A novel framework for feature extraction in multi-sensor action potential sorting.

    Science.gov (United States)

    Wu, Shun-Chi; Swindlehurst, A Lee; Nenadic, Zoran

    2015-09-30

    Extracellular recordings of multi-unit neural activity have become indispensable in neuroscience research. The analysis of the recordings begins with the detection of the action potentials (APs), followed by a classification step where each AP is associated with a given neural source. A feature extraction step is required prior to classification in order to reduce the dimensionality of the data and the impact of noise, allowing source clustering algorithms to work more efficiently. In this paper, we propose a novel framework for multi-sensor AP feature extraction based on the so-called Matched Subspace Detector (MSD), which is shown to be a natural generalization of standard single-sensor algorithms. Clustering using both simulated data and real AP recordings taken in the locust antennal lobe demonstrates that the proposed approach yields features that are discriminatory and lead to promising results. Unlike existing methods, the proposed algorithm finds joint spatio-temporal feature vectors that match the dominant subspace observed in the two-dimensional data without needs for a forward propagation model and AP templates. The proposed MSD approach provides more discriminatory features for unsupervised AP sorting applications. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Computer Simulations Support a Morphological Contribution to BDNF Enhancement of Action Potential Generation

    Directory of Open Access Journals (Sweden)

    Domenico F Galati

    2016-09-01

    Full Text Available Abstract Brain-derived neurotrophic factor (BDNF regulates both action potential (AP generation and neuron morphology. However, whether BDNF-induced changes in neuron morphology directly impact AP generation is unclear. We quantified BDNF’s effect on cultured cortical neuron morphological parameters and found that BDNF stimulates dendrite growth and addition of dendrites while increasing both excitatory and inhibitory presynaptic inputs in a spatially restricted manner. To gain insight into how these combined changes in neuron structure and synaptic input impact AP generation, we used the morphological parameters we gathered to generate computational models. Simulations suggest that BDNF-induced neuron morphologies generate more APs under a wide variety of conditions. Synapse and dendrite addition have the greatest impact on AP generation. However, subtle alterations in excitatory/inhibitory synapse ratio and strength have a significant impact on AP generation when synaptic activity is low. Consistent with these simulations, BDNF rapidly enhances spontaneous activity in cortical cultures. We propose that BDNF promotes neuron morphologies that are intrinsically more efficient at translating barrages of synaptic activity into APs, which is a previously unexplored aspect of BDNF’s function.

  4. Variations in interpulse interval of double action potentials during propagation in single neurons.

    Science.gov (United States)

    Villagran-Vargas, Edgar; Rodríguez-Sosa, Leonardo; Hustert, Reinhold; Blicher, Andreas; Laub, Katrine; Heimburg, Thomas

    2013-02-01

    In this work, we analyzed the interpulse interval (IPI) of doublets and triplets in single neurons of three biological models. Pulse trains with two or three spikes originate from the process of sensory mechanotransduction in neurons of the locust femoral nerve, as well as through spontaneous activity both in the abdominal motor neurons and the caudal photoreceptor of the crayfish. We show that the IPI for successive low-frequency single action potentials, as recorded with two electrodes at two different points along a nerve axon, remains constant. On the other hand, IPI in doublets either remains constant, increases or decreases by up to about 3 ms as the pair propagates. When IPI increases, the succeeding pulse travels at a slower speed than the preceding one. When IPI is reduced, the succeeding pulse travels faster than the preceding one and may exceed the normal value for the specific neuron. In both cases, IPI increase and reduction, the speed of the preceding pulse differs slightly from the normal value, therefore the two pulses travel at different speeds in the same nerve axon. On the basis of our results, we may state that the effect of attraction or repulsion in doublets suggests a tendency of the spikes to reach a stable configuration. We strongly suggest that the change in IPI during spike propagation of doublets opens up a whole new realm of possibilities for neural coding and may have major implications for understanding information processing in nervous systems. Copyright © 2012 Wiley Periodicals, Inc.

  5. Restitution slope is principally determined by steady-state action potential duration.

    Science.gov (United States)

    Shattock, Michael J; Park, Kyung Chan; Yang, Hsiang-Yu; Lee, Angela W C; Niederer, Steven; MacLeod, Kenneth T; Winter, James

    2017-06-01

    The steepness of the action potential duration (APD) restitution curve and local tissue refractoriness are both thought to play important roles in arrhythmogenesis. Despite this, there has been little recognition of the apparent association between steady-state APD and the slope of the restitution curve. The objective of this study was to test the hypothesis that restitution slope is determined by APD and to examine the relationship between restitution slope, refractoriness and susceptibility to VF. Experiments were conducted in isolated hearts and ventricular myocytes from adult guinea pigs and rabbits. Restitution curves were measured under control conditions and following intervention to prolong (clofilium, veratridine, bretylium, low [Ca]e, chronic transverse aortic constriction) or shorten (catecholamines, rapid pacing) ventricular APD. Despite markedly differing mechanisms of action, all interventions that prolonged the action potential led to a steepening of the restitution curve (and vice versa). Normalizing the restitution curve as a % of steady-state APD abolished the difference in restitution curves with all interventions. Effects on restitution were preserved when APD was modulated by current injection in myocytes pre-treated with the calcium chelator BAPTA-AM - to abolish the intracellular calcium transient. The non-linear relation between APD and the rate of repolarization of the action potential is shown to underpin the common influence of APD on the slope of the restitution curve. Susceptibility to VF was found to parallel changes in APD/refractoriness, rather than restitution slope. Steady-state APD is the principal determinant of the slope of the ventricular electrical restitution curve. In the absence of post-repolarization refractoriness, factors that prolong the action potential would be expected to steepen the restitution curve. However, concomitant changes in tissue refractoriness act to reduce susceptibility to sustained VF. Dependence on

  6. Using modeling to develop and evaluate a corrective action system

    International Nuclear Information System (INIS)

    Rodgers, L.

    1995-01-01

    At a former trucking facility in EPA Region 4, a corrective action system was installed to remediate groundwater and soil contaminated with gasoline and fuel oil products released from several underground storage tanks (USTs). Groundwater modeling was used to develop the corrective action plan and later used with soil vapor modeling to evaluate the systems effectiveness. Groundwater modeling was used to determine the effects of a groundwater recovery system on the water table at the site. Information gathered during the assessment phase was used to develop a three dimensional depiction of the subsurface at the site. Different groundwater recovery schemes were then modeled to determine the most effective method for recovering contaminated groundwater. Based on the modeling and calculations, a corrective action system combining soil vapor extraction (SVE) and groundwater recovery was designed. The system included seven recovery wells, to extract both soil vapor and groundwater, and a groundwater treatment system. Operation and maintenance of the system included monthly system sampling and inspections and quarterly groundwater sampling. After one year of operation the effectiveness of the system was evaluated. A subsurface soil gas model was used to evaluate the effects of the SVE system on the site contamination as well as its effects on the water table and groundwater recovery operations. Groundwater modeling was used in evaluating the effectiveness of the groundwater recovery system. Plume migration and capture were modeled to insure that the groundwater recovery system at the site was effectively capturing the contaminant plume. The two models were then combined to determine the effects of the two systems, acting together, on the remediation process

  7. MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf

    2013-04-01

    Full Text Available The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell, a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.

  8. Onset Dynamics of Action Potentials in Rat Neocortical Neurons and Identified Snail Neurons: Quantification of the Difference

    OpenAIRE

    Volgushev, Maxim; Malyshev, Aleksey; Balaban, Pavel; Chistiakova, Marina; Volgushev, Stanislav; Wolf, Fred

    2008-01-01

    The generation of action potentials (APs) is a key process in the operation of nerve cells and the communication between neurons. Action potentials in mammalian central neurons are characterized by an exceptionally fast onset dynamics, which differs from the typically slow and gradual onset dynamics seen in identified snail neurons. Here we describe a novel method of analysis which provides a quantitative measure of the onset dynamics of action potentials. This method captures the...

  9. Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells.

    Science.gov (United States)

    Johnson, Stuart L; Eckrich, Tobias; Kuhn, Stephanie; Zampini, Valeria; Franz, Christoph; Ranatunga, Kishani M; Roberts, Terri P; Masetto, Sergio; Knipper, Marlies; Kros, Corné J; Marcotti, Walter

    2011-06-01

    Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.

  10. Modelling of protective actions in the German Risk Study (FRG)

    International Nuclear Information System (INIS)

    Burkart, A.K.

    1981-01-01

    An emergency response model for nuclear accidents has to allow for a great number of widely different emergency conditions. In addition, it should be compatible with the pertinent laws, regulations, ordinances, guidelines, criteria and reference levels. The German (FRG) guidelines are basic and flexible rather than precise, many decisions being left to the emergency management. In the Risk Study these decisions had to be anticipated. After a brief discussion of the basis of the emergency response model employed in the German Risk Study (FRG), the essential requirements to be met are listed. The main part of the paper deals with the rationale and specification of protective actions. As a result of the calculations the numbers of persons and sizes of areas involved in protective actions are presented. The last section deals with the variation of input data. (author)

  11. Hadron spectrum in quenched lattice QCD and quark potential models

    International Nuclear Information System (INIS)

    Iwasaki, Y.; Yoshie, T.

    1989-01-01

    We show that the quenched lattice QCD gives a hadron spectrum which remarkably agrees with that of quark potential models for quark mass m q ≥ m strange , even when one uses the standard one-plaquette gauge action. This is contrary to what is stated in the literature. We clarify the reason of the discrepancy, paying close attention to systematic errors in numerical calculations. (orig.)

  12. Standard Model Effective Potential from Trace Anomalies

    Directory of Open Access Journals (Sweden)

    Renata Jora

    2018-01-01

    Full Text Available By analogy with the low energy QCD effective linear sigma model, we construct a standard model effective potential based entirely on the requirement that the tree level and quantum level trace anomalies must be satisfied. We discuss a particular realization of this potential in connection with the Higgs boson mass and Higgs boson effective couplings to two photons and two gluons. We find that this kind of potential may describe well the known phenomenology of the Higgs boson.

  13. One parameter model potential for noble metals

    International Nuclear Information System (INIS)

    Idrees, M.; Khwaja, F.A.; Razmi, M.S.K.

    1981-08-01

    A phenomenological one parameter model potential which includes s-d hybridization and core-core exchange contributions is proposed for noble metals. A number of interesting properties like liquid metal resistivities, band gaps, thermoelectric powers and ion-ion interaction potentials are calculated for Cu, Ag and Au. The results obtained are in better agreement with experiment than the ones predicted by the other model potentials in the literature. (author)

  14. Application of Emergency Action Levels from Potential Release at Research Reactor HANARO

    International Nuclear Information System (INIS)

    Kim, Jongsoo; Lee, Goan Yub; Lee, Hae Choi; Kim, Bong Suk

    2014-01-01

    Execution of the protective action promptly is possible that Emergency Action Levels (EALs) must be established for a radiological release from nuclear facility. The EALs for electric power reactor are already developed and applied to recognize an emergency situation rapidly. Recently the IAEA published the safety report including the EALs for research reactor. This paper describes the EALs to apply for a potential release pathway at the research reactor HANARO. The results of table 1 and 2 will be higher than actual because the weather condition in real situation is difference. However, the EALs applying the potential stack release, ground release and site can be useful for research reactor HANARO making the emergency declaration. The EALs at the site boundary of the table 3 can be applied to protect the off-site public

  15. The monophasic action potential upstroke: a means of characterizing local conduction.

    Science.gov (United States)

    Levine, J H; Moore, E N; Kadish, A H; Guarnieri, T; Spear, J F

    1986-11-01

    The upstrokes of monophasic action potentials (MAPs) recorded with an extracellular pressure electrode were characterized in isolated canine tissue preparations in vitro. The characteristics of the MAP upstroke were compared with those of the local action potential foot as well as with the characteristics of approaching electrical activation during uniform and asynchronous conduction. The upstroke of the MAP was exponential during uniform conduction. The time constant of rise of the MAP upstroke (TMAP) correlated with that of the action potential foot (Tfoot): TMAP + 1.01 Tfoot + 0.50; r2 = .80. Furthermore, changes in Tfoot with alterations in cycle length were associated with similar changes in TMAP: Tfoot = 1.06 TMAP - 0.11; r2 = .78. In addition, TMAP and Tfoot both deviated from exponential during asynchronous activation; the inflections that developed in the MAP upstroke correlated in time with intracellular action potential upstrokes that were asynchronous in onset in these tissues. Finally, the field of view of the MAP was determined and was found to be dependent in part on tissue architecture and the space constant. Specifically, the field of view of the MAP was found to be greater parallel compared with transverse to fiber orientation (6.02 +/- 1.74 vs 3.03 +/- 1.10 mm; p less than .01). These data suggest that the MAP upstroke may be used to define and characterize local electrical activation. The relatively large field of view of the MAP suggests that this technique may be a sensitive means to record focal membrane phenomena in vivo.

  16. Cardiac action potential repolarization revisited: early repolarization shows all-or-none behaviour.

    Science.gov (United States)

    Trenor, Beatriz; Cardona, Karen; Saiz, Javier; Noble, Denis; Giles, Wayne

    2017-11-01

    In healthy mammalian hearts the action potential (AP) waveform initiates and modulates each contraction, or heartbeat. As a result, AP height and duration are key physiological variables. In addition, rate-dependent changes in ventricular AP duration (APD), and variations in APD at a fixed heart rate are both reliable biomarkers of electrophysiological stability. Present guidelines for the likelihood that candidate drugs will increase arrhythmias rely on small changes in APD and Q-T intervals as criteria for safety pharmacology decisions. However, both of these measurements correspond to the final repolarization of the AP. Emerging clinical evidence draws attention to the early repolarization phase of the action potential (and the J-wave of the ECG) as an additional important biomarker for arrhythmogenesis. Here we provide a mechanistic background to this early repolarization syndrome by summarizing the evidence that both the initial depolarization and repolarization phases of the cardiac action potential can exhibit distinct time- and voltage-dependent thresholds, and also demonstrating that both can show regenerative all-or-none behaviour. An important consequence of this is that not all of the dynamics of action potential repolarization in human ventricle can be captured by data from single myocytes when these results are expressed as 'repolarization reserve'. For example, the complex pattern of cell-to-cell current flow that is responsible for AP conduction (propagation) within the mammalian myocardium can change APD and the Q-T interval of the electrocardiogram alter APD stability, and modulate responsiveness to pharmacological agents (such as Class III anti-arrhythmic drugs). © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  17. Facilitating cooperation in interprofessional education using a study activity model- An action research project’

    DEFF Research Database (Denmark)

    Hansen, Bodil Winther; Hatt, Camusa

    in interprofessional courses and if the model has a potential as mean of pedagogical development and collaboration. Methods The study is based on action research and is a mixed method study. In 2016 the project will gather data in cooperation with lecturers through qualitative methods and a followup on the baseline...... to further explore the potential of the study activity model as a mean of pedagogical development. The qualitative data will be processed by current hermeneutical and phenomenological methods. Outcomes and implications The outcome of the project should provide deeper insight into facilitating IPE and IPC......Title: Facilitating cooperation in interprofessional education using a study activity model- An action research project . Background Metropolitan University College has over the years developed interprofessional courses for students from 12 different professions, and since 2013 worked...

  18. Action potential-independent and pharmacologically unique vesicular serotonin release from dendrites

    Science.gov (United States)

    Colgan, Lesley A.; Cavolo, Samantha L.; Commons, Kathryn G.; Levitan, Edwin S.

    2012-01-01

    Serotonin released within the dorsal raphe nucleus (DR) induces feedback inhibition of serotonin neuron activity and consequently regulates mood-controlling serotonin release throughout the forebrain. Serotonin packaged in vesicles is released in response to action potentials by the serotonin neuron soma and terminals, but the potential for release by dendrites is unknown. Here three-photon (3P) microscopy imaging of endogenous serotonin in living rat brain slice, immunofluorescence and immuno-gold electron microscopy detection of VMAT2 (vesicular monoamine transporter 2) establish the presence of vesicular serotonin within DR dendrites. Furthermore, activation of glutamate receptors is shown to induce vesicular serotonin release from dendrites. However, unlike release from the soma and terminals, dendritic serotonin release is independent of action potentials, relies on L-type Ca2+ channels, is induced preferentially by NMDA, and displays distinct sensitivity to the selective serotonin reuptake inhibitor (SSRI) antidepressant fluoxetine. The unique control of dendritic serotonin release has important implications for DR physiology and the antidepressant action of SSRIs, dihydropyridines and NMDA receptor antagonists. PMID:23136413

  19. Automated grouping of action potentials of human embryonic stem cell-derived cardiomyocytes.

    Science.gov (United States)

    Gorospe, Giann; Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie; Vidal, Rene

    2014-09-01

    Methods for obtaining cardiomyocytes from human embryonic stem cells (hESCs) are improving at a significant rate. However, the characterization of these cardiomyocytes (CMs) is evolving at a relatively slower rate. In particular, there is still uncertainty in classifying the phenotype (ventricular-like, atrial-like, nodal-like, etc.) of an hESC-derived cardiomyocyte (hESC-CM). While previous studies identified the phenotype of a CM based on electrophysiological features of its action potential, the criteria for classification were typically subjective and differed across studies. In this paper, we use techniques from signal processing and machine learning to develop an automated approach to discriminate the electrophysiological differences between hESC-CMs. Specifically, we propose a spectral grouping-based algorithm to separate a population of CMs into distinct groups based on the similarity of their action potential shapes. We applied this method to a dataset of optical maps of cardiac cell clusters dissected from human embryoid bodies. While some of the nine cell clusters in the dataset are presented with just one phenotype, the majority of the cell clusters are presented with multiple phenotypes. The proposed algorithm is generally applicable to other action potential datasets and could prove useful in investigating the purification of specific types of CMs from an electrophysiological perspective.

  20. Determination of Nerve Fiber Diameter Distribution From Compound Action Potential: A Continuous Approach.

    Science.gov (United States)

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

    When a signal is initiated in the nerve, it is transmitted along each nerve fiber via an action potential (called single fiber action potential (SFAP)) which travels with a velocity that is related with the diameter of the fiber. The additive superposition of SFAPs constitutes the compound action potential (CAP) of the nerve. The fiber diameter distribution (FDD) in the nerve can be computed from the CAP data by solving an inverse problem. This is usually achieved by dividing the fibers into a finite number of diameter groups and solve a corresponding linear system to optimize FDD. However, number of fibers in a nerve can be measured sometimes in thousands and it is possible to assume a continuous distribution for the fiber diameters which leads to a gradient optimization problem. In this paper, we have evaluated this continuous approach to the solution of the inverse problem. We have utilized an analytical function for SFAP and an assumed a polynomial form for FDD. The inverse problem involves the optimization of polynomial coefficients to obtain the best estimate for the FDD. We have observed that an eighth order polynomial for FDD can capture both unimodal and bimodal fiber distributions present in vivo, even in case of noisy CAP data. The assumed FDD distribution regularizes the ill-conditioned inverse problem and produces good results.

  1. ER Stress-Mediated Signaling: Action Potential and Ca(2+) as Key Players.

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

    The proper functioning of the endoplasmic reticulum (ER) is crucial for multiple cellular activities and survival. Disturbances in the normal ER functions lead to the accumulation and aggregation of unfolded proteins, which initiates an adaptive response, the unfolded protein response (UPR), in order to regain normal ER functions. Failure to activate the adaptive response initiates the process of programmed cell death or apoptosis. Apoptosis plays an important role in cell elimination, which is essential for embryogenesis, development, and tissue homeostasis. Impaired apoptosis can lead to the development of various pathological conditions, such as neurodegenerative and autoimmune diseases, cancer, or acquired immune deficiency syndrome (AIDS). Calcium (Ca(2+)) is one of the key regulators of cell survival and it can induce ER stress-mediated apoptosis in response to various conditions. Ca(2+) regulates cell death both at the early and late stages of apoptosis. Severe Ca(2+) dysregulation can promote cell death through apoptosis. Action potential, an electrical signal transmitted along the neurons and muscle fibers, is important for conveying information to, from, and within the brain. Upon the initiation of the action potential, increased levels of cytosolic Ca(2+) (depolarization) lead to the activation of the ER stress response involved in the initiation of apoptosis. In this review, we discuss the involvement of Ca(2+) and action potential in ER stress-mediated apoptosis.

  2. A social identity model of pro-environmental action (SIMPEA).

    Science.gov (United States)

    Fritsche, Immo; Barth, Markus; Jugert, Philipp; Masson, Torsten; Reese, Gerhard

    2018-03-01

    Large-scale environmental crises are genuinely collective phenomena: they usually result from collective, rather than personal, behavior and how they are cognitively represented and appraised is determined by collectively shared interpretations (e.g., differing across ideological groups) and based on concern for collectives (e.g., humankind, future generations) rather than for individuals. Nevertheless, pro-environmental action has been primarily investigated as a personal decision-making process. We complement this research with a social identity perspective on pro-environmental action. Social identity is the human capacity to define the self in terms of "We" instead of "I," enabling people to think and act as collectives, which should be crucial given personal insufficiency to appraise and effectively respond to environmental crises. We propose a Social Identity Model of Pro-Environmental Action (SIMPEA) of how social identity processes affect both appraisal of and behavioral responses to large-scale environmental crises. We review related and pertinent research providing initial evidence for the role of 4 social identity processes hypothesized in SIMPEA. Specifically, we propose that ingroup identification, ingroup norms and goals, and collective efficacy determine environmental appraisals as well as both private and public sphere environmental action. These processes are driven by personal and collective emotions and motivations that arise from environmental appraisal and operate on both a deliberate and automatic processing level. Finally, we discuss SIMPEA's implications for the research agenda in environmental and social psychology and for interventions fostering pro-environmental action. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  3. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    Science.gov (United States)

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  4. ACTION-SPACE CLUSTERING OF TIDAL STREAMS TO INFER THE GALACTIC POTENTIAL

    Energy Technology Data Exchange (ETDEWEB)

    Sanderson, Robyn E.; Helmi, Amina [Kapteyn Astronomical Institute, P.O. Box 800, 9700 AV Groningen (Netherlands); Hogg, David W., E-mail: robyn@astro.columbia.edu [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States)

    2015-03-10

    We present a new method for constraining the Milky Way halo gravitational potential by simultaneously fitting multiple tidal streams. This method requires three-dimensional positions and velocities for all stars to be fit, but does not require identification of any specific stream or determination of stream membership for any star. We exploit the principle that the action distribution of stream stars is most clustered when the potential used to calculate the actions is closest to the true potential. Clustering is quantified with the Kullback-Leibler Divergence (KLD), which also provides conditional uncertainties for our parameter estimates. We show, for toy Gaia-like data in a spherical isochrone potential, that maximizing the KLD of the action distribution relative to a smoother distribution recovers the input potential. The precision depends on the observational errors and number of streams; using K III giants as tracers, we measure the enclosed mass at the average radius of the sample stars accurate to 3% and precise to 20%-40%. Recovery of the scale radius is precise to 25%, biased 50% high by the small galactocentric distance range of stars in our mock sample (1-25 kpc, or about three scale radii, with mean 6.5 kpc). 20-25 streams with at least 100 stars each are required for a stable confidence interval. With radial velocities (RVs) to 100 kpc, all parameters are determined with ∼10% accuracy and 20% precision (1.3% accuracy for the enclosed mass), underlining the need to complete the RV catalog for faint halo stars observed by Gaia.

  5. Action Research’s Potential to Foster Institutional Change for Urban Water Management

    Directory of Open Access Journals (Sweden)

    Dimitrios Zikos

    2013-04-01

    Full Text Available The paper discusses the potential of action research to meet the challenges entailed in institutional design for urban water management. Our overall aim is to briefly present action research and discuss its methodological merits with regard to the challenges posed by the different conceptual bases for extrapolating the effects of institutional design on institutional change. Thus, our aim is to explore how Action Research meets the challenge of scoping the field in an open fashion for determining the appropriate mechanisms of institutional change and supporting the emerging of new water institutions. To accomplish this aim, we select the Water Framework Directive (WFD as an illustrative driving force requiring changes in water management practices and implying the need for the emergence of new institutions. We employ a case of urban water management in the Volos Metropolitan Area, part of the Thessaly region in Greece, where a Pilot River Basin Plan was implemented. By applying action research and being involved in a long process of interaction between stakeholders, we examine the emergence of new institutions dealing with urban water management under the general principles of the major driving force for change: the WFD.

  6. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential.

    Science.gov (United States)

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

    Amongst the diverse and potent biological activities of free fatty acids (FFAs) is the ability to kill or inhibit the growth of bacteria. The antibacterial properties of FFAs are used by many organisms to defend against parasitic or pathogenic bacteria. Whilst their antibacterial mode of action is still poorly understood, the prime target of FFA action is the cell membrane, where FFAs disrupt the electron transport chain and oxidative phosphorylation. Besides interfering with cellular energy production, FFA action may also result from the inhibition of enzyme activity, impairment of nutrient uptake, generation of peroxidation and auto-oxidation degradation products or direct lysis of bacterial cells. Their broad spectrum of activity, non-specific mode of action and safety makes them attractive as antibacterial agents for various applications in medicine, agriculture and food preservation, especially where the use of conventional antibiotics is undesirable or prohibited. Moreover, the evolution of inducible FFA-resistant phenotypes is less problematic than with conventional antibiotics. The potential for commercial or biomedical exploitation of antibacterial FFAs, especially for those from natural sources, is discussed.

  7. Event-related potential effects of superior action anticipation in professional badminton players.

    Science.gov (United States)

    Jin, Hua; Xu, Guiping; Zhang, John X; Gao, Hongwei; Ye, Zuoer; Wang, Pin; Lin, Huiyan; Mo, Lei; Lin, Chong-De

    2011-04-04

    The ability to predict the trajectory of a ball based on the opponent's body kinematics has been shown to be critical to high-performing athletes in many sports. However, little is known about the neural correlates underlying such superior ability in action anticipation. The present event-related potential study compared brain responses from professional badminton players and non-player controls when they watched video clips of badminton games and predicted a ball's landing position. Replicating literature findings, the players made significantly more accurate judgments than the controls and showed better action anticipation. Correspondingly, they showed enlarged amplitudes of two ERP components, a P300 peaking around 350ms post-stimulus with a parietal scalp distribution and a P2 peaking around 250ms with a posterior-occipital distribution. The P300 effect was interpreted to reflect primed access and/or directing of attention to game-related memory representations in the players facilitating their online judgment of related actions. The P2 effect was suggested to reflect some generic learning effects. The results identify clear neural responses that differentiate between different levels of action anticipation associated with sports expertise. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Dynamics of action potential backpropagation in basal dendrites of prefrontal cortical pyramidal neurons.

    Science.gov (United States)

    Zhou, Wen-Liang; Yan, Ping; Wuskell, Joseph P; Loew, Leslie M; Antic, Srdjan D

    2008-02-01

    Basal dendrites of neocortical pyramidal neurons are relatively short and directly attached to the cell body. This allows electrical signals arising in basal dendrites to strongly influence the neuronal output. Likewise, somatic action potentials (APs) should readily propagate back into the basilar dendritic tree to influence synaptic plasticity. Two recent studies, however, determined that sodium APs are severely attenuated in basal dendrites of cortical pyramidal cells, so that they completely fail in distal dendritic segments. Here we used the latest improvements in the voltage-sensitive dye imaging technique (Zhou et al., 2007) to study AP backpropagation in basal dendrites of layer 5 pyramidal neurons of the rat prefrontal cortex. With a signal-to-noise ratio of > 15 and minimal temporal averaging (only four sweeps) we were able to sample AP waveforms from the very last segments of individual dendritic branches (dendritic tips). We found that in short- (< 150 microm) and medium (150-200 microm in length)-range basal dendrites APs backpropagated with modest changes in AP half-width or AP rise-time. The lack of substantial changes in AP shape and dynamics of rise is inconsistent with the AP-failure model. The lack of substantial amplitude boosting of the third AP in the high-frequency burst also suggests that in short- and medium-range basal dendrites backpropagating APs were not severely attenuated. Our results show that the AP-failure concept does not apply in all basal dendrites of the rat prefrontal cortex. The majority of synaptic contacts in the basilar dendritic tree actually received significant AP-associated electrical and calcium transients.

  9. Recording single neurons' action potentials from freely moving pigeons across three stages of learning.

    Science.gov (United States)

    Starosta, Sarah; Stüttgen, Maik C; Güntürkün, Onur

    2014-06-02

    While the subject of learning has attracted immense interest from both behavioral and neural scientists, only relatively few investigators have observed single-neuron activity while animals are acquiring an operantly conditioned response, or when that response is extinguished. But even in these cases, observation periods usually encompass only a single stage of learning, i.e. acquisition or extinction, but not both (exceptions include protocols employing reversal learning; see Bingman et al.(1) for an example). However, acquisition and extinction entail different learning mechanisms and are therefore expected to be accompanied by different types and/or loci of neural plasticity. Accordingly, we developed a behavioral paradigm which institutes three stages of learning in a single behavioral session and which is well suited for the simultaneous recording of single neurons' action potentials. Animals are trained on a single-interval forced choice task which requires mapping each of two possible choice responses to the presentation of different novel visual stimuli (acquisition). After having reached a predefined performance criterion, one of the two choice responses is no longer reinforced (extinction). Following a certain decrement in performance level, correct responses are reinforced again (reacquisition). By using a new set of stimuli in every session, animals can undergo the acquisition-extinction-reacquisition process repeatedly. Because all three stages of learning occur in a single behavioral session, the paradigm is ideal for the simultaneous observation of the spiking output of multiple single neurons. We use pigeons as model systems, but the task can easily be adapted to any other species capable of conditioned discrimination learning.

  10. Developmental impairment of compound action potential in the optic nerve of myelin mutant taiep rats.

    Science.gov (United States)

    Roncagliolo, Manuel; Schlageter, Carol; León, Claudia; Couve, Eduardo; Bonansco, Christian; Eguibar, José R

    2006-01-05

    The taiep rat is a myelin mutant with an initial hypomyelination, followed by a progressive demyelination of the CNS. The neurological correlates start with tremor, followed by ataxia, immobility episodes, epilepsy and paralysis. The optic nerve, an easily-isolable central tract fully myelinated by oligodendrocytes, is a suitable preparation to evaluate the developmental impairment of central myelin. We examined the ontogenic development of optic nerve compound action potentials (CAP) throughout the first 6 months of life of control and taiep rats. Control optic nerves (ON) develop CAPs characterized by three waves. Along the first month, the CAPs of taiep rats showed a delayed maturation, with lower amplitudes and longer latencies than controls; at P30, the conduction velocity has only a third of the normal value. Later, as demyelination proceeds, the conduction velocity of taiep ONs begins to decrease and CAPs undergo a gradual temporal dispersion. CAPs of control and taiep showed differences in their pharmacological sensitivity to TEA and 4-AP, two voltage dependent K+ channel-blockers. As compared with TEA, 4-AP induced a significant increase of the amplitudes and a remarkable broadening of CAPs. After P20, unlike controls, the greater sensitivity to 4-AP exhibited by taiep ONs correlates with the detachment and retraction of paranodal loops suggesting that potassium conductances could regulate the excitability as demyelination of CNS axons progresses. It is concluded that the taiep rat, a long-lived mutant, provides a useful model to study the consequences of partial demyelination and the mechanisms by which glial cells regulate the molecular organization and excitability of axonal membranes during development and disease.

  11. Anaesthetics stop diverse plant organ movements, affect endocytic vesicle recycling and ROS homeostasis, and block action potentials in Venus flytraps.

    Science.gov (United States)

    Yokawa, K; Kagenishi, T; Pavlovic, A; Gall, S; Weiland, M; Mancuso, S; Baluška, F

    2017-12-11

    Anaesthesia for medical purposes was introduced in the 19th century. However, the physiological mode of anaesthetic drug actions on the nervous system remains unclear. One of the remaining questions is how these different compounds, with no structural similarities and even chemically inert elements such as the noble gas xenon, act as anaesthetic agents inducing loss of consciousness. The main goal here was to determine if anaesthetics affect the same or similar processes in plants as in animals and humans. A single-lens reflex camera was used to follow organ movements in plants before, during and after recovery from exposure to diverse anaesthetics. Confocal microscopy was used to analyse endocytic vesicle trafficking. Electrical signals were recorded using a surface AgCl electrode. Mimosa leaves, pea tendrils, Venus flytraps and sundew traps all lost both their autonomous and touch-induced movements after exposure to anaesthetics. In Venus flytrap, this was shown to be due to the loss of action potentials under diethyl ether anaesthesia. The same concentration of diethyl ether immobilized pea tendrils. Anaesthetics also impeded seed germination and chlorophyll accumulation in cress seedlings. Endocytic vesicle recycling and reactive oxygen species (ROS) balance, as observed in intact Arabidopsis root apex cells, were also affected by all anaesthetics tested. Plants are sensitive to several anaesthetics that have no structural similarities. As in animals and humans, anaesthetics used at appropriate concentrations block action potentials and immobilize organs via effects on action potentials, endocytic vesicle recycling and ROS homeostasis. Plants emerge as ideal model objects to study general questions related to anaesthesia, as well as to serve as a suitable test system for human anaesthesia. © The Authors 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Simulations of the cardiac action potential based on the Hodgkin-Huxley kinetics with the use of Microsoft Excel spreadsheets.

    Science.gov (United States)

    Wu, Sheng-Nan

    2004-03-31

    The purpose of this study was to develop a method to simulate the cardiac action potential using a Microsoft Excel spreadsheet. The mathematical model contained voltage-gated ionic currents that were modeled using either Beeler-Reuter (B-R) or Luo-Rudy (L-R) phase 1 kinetics. The simulation protocol involves the use of in-cell formulas directly typed into a spreadsheet. The capability of spreadsheet iteration was used in these simulations. It does not require any prior knowledge of computer programming, although the use of the macro language can speed up the calculation. The normal configuration of the cardiac ventricular action potential can be well simulated in the B-R model that is defined by four individual ionic currents, each representing the diffusion of ions through channels in the membrane. The contribution of Na+ inward current to the rate of depolarization is reproduced in this model. After removal of Na+ current from the model, a constant current stimulus elicits an oscillatory change in membrane potential. In the L-R phase 1 model where six types of ionic currents were defined, the effect of extracellular K+ concentration on changes both in the time course of repolarization and in the time-independent K+ current can be demonstrated, when the solutions are implemented in Excel. Using the simulation protocols described here, the users can readily study and graphically display the underlying properties of ionic currents to see how changes in these properties determine the behavior of the heart cell. The method employed in these simulation protocols may also be extended or modified to other biological simulation programs.

  13. Baby Skyrme models without a potential term

    Science.gov (United States)

    Ashcroft, Jennifer; Haberichter, Mareike; Krusch, Steffen

    2015-05-01

    We develop a one-parameter family of static baby Skyrme models that do not require a potential term to admit topological solitons. This is a novel property as the standard baby Skyrme model must contain a potential term in order to have stable soliton solutions, though the Skyrme model does not require this. Our new models satisfy an energy bound that is linear in terms of the topological charge and can be saturated in an extreme limit. They also satisfy a virial theorem that is shared by the Skyrme model. We calculate the solitons of our new models numerically and observe that their form depends significantly on the choice of parameter. In one extreme, we find compactons while at the other there is a scale invariant model in which solitons can be obtained exactly as solutions to a Bogomolny equation. We provide an initial investigation into these solitons and compare them with the baby Skyrmions of other models.

  14. The real-time link between person perception and action: brain potential evidence for dynamic continuity.

    Science.gov (United States)

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J

    2011-01-01

    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

  15. Potentiation of E-4031-induced torsade de pointes by HMR1556 or ATX-II is not predicted by action potential short-term variability or triangulation.

    Science.gov (United States)

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

    2007-12-01

    Torsade de pointes (TdP) can be induced by a reduction in cardiac repolarizing capacity. The aim of this study was to assess whether IKs blockade or enhancement of INa could potentiate TdP induced by IKr blockade and to investigate whether short-term variability (STV) or triangulation of action potentials preceded TdP. Experiments were performed in open-chest, pentobarbital-anaesthetized, alpha 1-adrenoceptor-stimulated, male New Zealand White rabbits, which received three consecutive i.v. infusions of either the IKr blocker E-4031 (1, 3 and 10 nmol kg(-1) min(-1)), the IKs blocker HMR1556 (25, 75 and 250 nmol kg(-1) min(-1)) or E-4031 and HMR1556 combined. In a second study rabbits received either the same doses of E-4031, the INa enhancer, ATX-II (0.4, 1.2 and 4.0 nmol kg(-1)) or both of these drugs. ECGs and epicardial monophasic action potentials were recorded. HMR1556 alone did not cause TdP but increased E-4031-induced TdP from 25 to 80%. ATX-II alone caused TdP in 38% of rabbits, as did E-4031; 75% of rabbits receiving both drugs had TdP. QT intervals were prolonged by all drugs but the extent of QT prolongation was not related to the occurrence of TdP. No changes in STV were detected and triangulation was only increased after TdP occurred. Giving modulators of ion channels in combination substantially increased TdP but, in this model, neither STV nor triangulation of action potentials could predict TdP.

  16. A parabolic model for dimple potentials

    International Nuclear Information System (INIS)

    Aydin, Melike Cibik; Uncu, Haydar; Deniz, Coskun

    2013-01-01

    We study the truncated parabolic function and demonstrate that it is a representation of the Dirac δ function. We also show that the truncated parabolic function, used as a potential in the Schrödinger equation, has the same bound state spectrum, tunneling and reflection amplitudes as the Dirac δ potential, as the width of the parabola approximates to zero. Dirac δ potential is used to model dimple potentials which are utilized to increase the phase-space density of a Bose–Einstein condensate in a harmonic trap. We show that a harmonic trap with a δ function at the origin is a limiting case of the harmonic trap with a symmetric truncated parabolic potential around the origin. Hence, the truncated parabolic is a better candidate for modeling the dimple potentials. (paper)

  17. Baryons electromagnetic mass splittings in potential models

    International Nuclear Information System (INIS)

    Genovese, M.; Richard, J.-M.; Silvestre-Brac, B.; Varga, K.

    1998-01-01

    We study electromagnetic mass splittings of charmed baryons. We point out discrepancies among theoretical predictions in non-relativistic potential models; none of these predictions seems supported by experimental data. A new calculation is presented

  18. A potential model for quark confinement

    International Nuclear Information System (INIS)

    Thaler, J.; Iqbal, M.J.

    1985-02-01

    A static quark potential model obtained from a relativistic wave-equation is considered. The long-part of the quadratic terms is suppressed by a glueball exchange mechanism and compatibility with the meson spectra is shown

  19. Unjamming in models with analytic pairwise potentials

    NARCIS (Netherlands)

    Kooij, S.; Lerner, E.

    Canonical models for studying the unjamming scenario in systems of soft repulsive particles assume pairwise potentials with a sharp cutoff in the interaction range. The sharp cutoff renders the potential nonanalytic but makes it possible to describe many properties of the solid in terms of the

  20. Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

    Science.gov (United States)

    Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long

    2012-10-25

    The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

  1. Maxent modelling for predicting the potential distribution of Thai Palms

    DEFF Research Database (Denmark)

    Tovaranonte, Jantrararuk; Barfod, Anders S.; Overgaard, Anne Blach

    2011-01-01

    on presence data. The aim was to identify potential hot spot areas, assess the determinants of palm distribution ranges, and provide a firmer knowledge base for future conservation actions. We focused on a relatively small number of climatic, environmental and spatial variables in order to avoid...... overprediction of species distribution ranges. The models with the best predictive power were found by calculating the area under the curve (AUC) of receiver-operating characteristic (ROC). Here, we provide examples of contrasting predicted species distribution ranges as well as a map of modeled palm diversity...

  2. Model potential for electron scattering from rubidium

    Energy Technology Data Exchange (ETDEWEB)

    Gien, T.E. (Memorial Univ. of Newfoundland, St. John' s, NF (Canada). Dept. of Physics)

    1992-11-28

    An analytic model potential for the e[sup -]-Rb[sup +] system is generated from experimental data, using an iteration method. The potential obtained can reproduce rather accurately the energy levels of rubidium. We employed it in the calculation of elastic differential cross sections for electron (and positron) scatterings from rubidium in the conventional Glauber approximation. The differential cross sections calculated in the model potential approach are compared to those in the frozen-core approach, employing either the Clementi-Roetti or the Szasz-McGinn wavefunctions. The core correlation and polarization effects are found to significantly affect the cross section results. (author).

  3. Model potential for electron scattering from rubidium

    International Nuclear Information System (INIS)

    Gien, T.E.

    1992-01-01

    An analytic model potential for the e - -Rb + system is generated from experimental data, using an iteration method. The potential obtained can reproduce rather accurately the energy levels of rubidium. We employed it in the calculation of elastic differential cross sections for electron (and positron) scatterings from rubidium in the conventional Glauber approximation. The differential cross sections calculated in the model potential approach are compared to those in the frozen-core approach, employing either the Clementi-Roetti or the Szasz-McGinn wavefunctions. The core correlation and polarization effects are found to significantly affect the cross section results. (author)

  4. An Excel‐based implementation of the spectral method of action potential alternans analysis

    Science.gov (United States)

    Pearman, Charles M.

    2014-01-01

    Abstract Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro‐arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T‐wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. PMID:25501439

  5. An Excel-based implementation of the spectral method of action potential alternans analysis.

    Science.gov (United States)

    Pearman, Charles M

    2014-12-01

    Action potential (AP) alternans has been well established as a mechanism of arrhythmogenesis and sudden cardiac death. Proper interpretation of AP alternans requires a robust method of alternans quantification. Traditional methods of alternans analysis neglect higher order periodicities that may have greater pro-arrhythmic potential than classical 2:1 alternans. The spectral method of alternans analysis, already widely used in the related study of microvolt T-wave alternans, has also been used to study AP alternans. Software to meet the specific needs of AP alternans analysis is not currently available in the public domain. An AP analysis tool is implemented here, written in Visual Basic for Applications and using Microsoft Excel as a shell. This performs a sophisticated analysis of alternans behavior allowing reliable distinction of alternans from random fluctuations, quantification of alternans magnitude, and identification of which phases of the AP are most affected. In addition, the spectral method has been adapted to allow detection and quantification of higher order regular oscillations. Analysis of action potential morphology is also performed. A simple user interface enables easy import, analysis, and export of collated results. © 2014 The Author. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  6. Voltage Gated Calcium Channel Activation by Backpropagating Action Potentials Downregulates NMDAR Function

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Theis

    2018-04-01

    Full Text Available The majority of excitatory synapses are located on dendritic spines of cortical glutamatergic neurons. In spines, compartmentalized Ca2+ signals transduce electrical activity into specific long-term biochemical and structural changes. Action potentials (APs propagate back into the dendritic tree and activate voltage gated Ca2+ channels (VGCCs. For spines, this global mode of spine Ca2+ signaling is a direct biochemical feedback of suprathreshold neuronal activity. We previously demonstrated that backpropagating action potentials (bAPs result in long-term enhancement of spine VGCCs. This activity-dependent VGCC plasticity results in a large interspine variability of VGCC Ca2+ influx. Here, we investigate how spine VGCCs affect glutamatergic synaptic transmission. We combined electrophysiology, two-photon Ca2+ imaging and two-photon glutamate uncaging in acute brain slices from rats. T- and R-type VGCCs were the dominant depolarization-associated Ca2+conductances in dendritic spines of excitatory layer 2 neurons and do not affect synaptic excitatory postsynaptic potentials (EPSPs measured at the soma. Using two-photon glutamate uncaging, we compared the properties of glutamatergic synapses of single spines that express different levels of VGCCs. While VGCCs contributed to EPSP mediated Ca2+ influx, the amount of EPSP mediated Ca2+ influx is not determined by spine VGCC expression. On a longer timescale, the activation of VGCCs by bAP bursts results in downregulation of spine NMDAR function.

  7. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  8. Phenomenological aspects of nonrelativistic potential models

    International Nuclear Information System (INIS)

    Lucha, W.; Schoeberl, F.F.

    1989-01-01

    This review reports on the description of hardrons as bound states of quarks by nonrelativistic potential models. It contains a brief sketch of the way in which information on the form of the inter-quark potential may be gained from quantum chromodynamics, proofs of some general theorems related to the potential-model approach, a discussion of the significance of the treatment of bound states consisting of relativistically-moving constituents by the nonrelativistic Schroedinger formalism, as well as a brief survey of the motivations for the various proposed potential models. Finally, it illustrates the application of the developed theoretical framework at a few selected examples. 60 refs., 8 figs., 17 tabs. (Authors)

  9. Outcome producing potential influences twelve-month-olds' interpretation of a novel action as goal-directed.

    Science.gov (United States)

    Biro, Szilvia; Verschoor, Stephan; Coalter, Esther; Leslie, Alan M

    2014-11-01

    Learning about a novel, goal-directed action is a complex process. It requires identifying the outcome of the action and linking the action to its outcome for later use in new situations to predict the action or to anticipate its outcome. We investigated the hypothesis that linking a novel action to a salient change in the environment is critical for infants to assign a goal to the novel action. We report a study in which we show that 12-month-old infants, who were provided with prior experience with a novel action accompanied with a salient visible outcome in one context, can interpret the same action as goal-directed even in the absence of the outcome in another context. Our control condition shows that prior experience with the action, but without the salient effect, does not lead to goal-directed interpretation of the novel action. We also found that, for the case of 9-month-olds infants, prior experience with the outcome producing potential of the novel action does not facilitate a goal-directed interpretation of the action. However, this failure was possibly due to difficulties with generalizing the learnt association to another context rather than with linking the action to its outcome. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Single K ATP channel opening in response to action potential firing in mouse dentate granule neurons.

    Science.gov (United States)

    Tanner, Geoffrey R; Lutas, Andrew; Martínez-François, Juan Ramón; Yellen, Gary

    2011-06-08

    ATP-sensitive potassium channels (K(ATP) channels) are important sensors of cellular metabolic state that link metabolism and excitability in neuroendocrine cells, but their role in nonglucosensing central neurons is less well understood. To examine a possible role for K(ATP) channels in modulating excitability in hippocampal circuits, we recorded the activity of single K(ATP) channels in cell-attached patches of granule cells in the mouse dentate gyrus during bursts of action potentials generated by antidromic stimulation of the mossy fibers. Ensemble averages of the open probability (p(open)) of single K(ATP) channels over repeated trials of stimulated spike activity showed a transient increase in p(open) in response to action potential firing. Channel currents were identified as K(ATP) channels through blockade with glibenclamide and by comparison with recordings from Kir6.2 knock-out mice. The transient elevation in K(ATP) p(open) may arise from submembrane ATP depletion by the Na(+)-K(+) ATPase, as the pump blocker strophanthidin reduced the magnitude of the elevation. Both the steady-state and stimulus-elevated p(open) of the recorded channels were higher in the presence of the ketone body R-β-hydroxybutyrate, consistent with earlier findings that ketone bodies can affect K(ATP) activity. Using perforated-patch recording, we also found that K(ATP) channels contribute to the slow afterhyperpolarization following an evoked burst of action potentials. We propose that activity-dependent opening of K(ATP) channels may help granule cells act as a seizure gate in the hippocampus and that ketone-body-mediated augmentation of the activity-dependent opening could in part explain the effect of the ketogenic diet in reducing epileptic seizures.

  11. The Effects of Action Potential Stimulation on Pain, Swelling and Function of Patients with Knee Osteoarthritis

    Directory of Open Access Journals (Sweden)

    Razieh Sepehri

    2012-06-01

    Full Text Available Background: Knee osteoarthritis (OA is one of the most prevalent joint diseases. Electrical muscle stimulation is effective to improve its symptoms. Today, action potential stimulation (APS with various currents and periods is used to treat OA. This study aims at analyzing the effect of action potential stimulation in improving knee OA symptoms. Materials and Methods: In this clinical trial, patients with mild to moderate knee OA divided randomly in two groups each had 15 people. Along with the conventional exercises of physiotherapy, one group received 16 minutes action potential stimulation with the lowest intensity (sensible; but the other group besides receiving the conventional exercises of physiotherapy was connected into a plugged off machine for 16 minutes. Certain variables were measured and recorded four times. Results: Comparing the variables before and after intervention did not show any meaningful difference between the two groups. But within group, pain with p=0.0001 showed a meaningful decrease. Decreasing of swelling (inflammation in group 1 and 2 was meaningful with p<0.001 and p<0.001, respectively. For group 1, knee flexion range was improved meaningfully between first and fourth times as p<0.031, but it was not meaningful for group 2. Duration of 50 meters walking and step up and down from three steps significantly decreased in both groups. Conclusion: Although there was no significant difference in variables between two groups, but within both groups’ pain and swelling decreased and functional ability increased, thus, it can be concluded that type of APS does not play a key role in treating knee OA.

  12. Action potential propagation recorded from single axonal arbors using multi-electrode arrays.

    Science.gov (United States)

    Tovar, Kenneth R; Bridges, Daniel C; Wu, Bian; Randall, Connor; Audouard, Morgane; Jang, Jiwon; Hansma, Paul K; Kosik, Kenneth S

    2018-04-11

    We report the presence of co-occurring extracellular action potentials (eAPs) from cultured mouse hippocampal neurons among groups of planar electrodes on multi-electrode arrays (MEAs). The invariant sequences of eAPs among co-active electrode groups, repeated co-occurrences and short inter-electrode latencies are consistent with action potential propagation in unmyelinated axons. Repeated eAP co-detection by multiple electrodes was widespread in all our data records. Co-detection of eAPs confirms they result from the same neuron and allows these eAPs to be isolated from all other spikes independently of spike sorting algorithms. We averaged co-occurring events and revealed additional electrodes with eAPs that would otherwise be below detection threshold. We used these eAP cohorts to explore the temperature sensitivity of action potential propagation and the relationship between voltage-gated sodium channel density and propagation velocity. The sequence of eAPs among co-active electrodes 'fingerprints' neurons giving rise to these events and identifies them within neuronal ensembles. We used this property and the non-invasive nature of extracellular recording to monitor changes in excitability at multiple points in single axonal arbors simultaneously over several hours, demonstrating independence of axonal segments. Over several weeks, we recorded changes in inter-electrode propagation latencies and ongoing changes in excitability in different regions of single axonal arbors. Our work illustrates how repeated eAP co-occurrences can be used to extract physiological data from single axons with low electrode density MEAs. However, repeated eAP co-occurrences leads to over-sampling spikes from single neurons and thus can confound traditional spike-train analysis.

  13. National Water Model: Providing the Nation with Actionable Water Intelligence

    Science.gov (United States)

    Aggett, G. R.; Bates, B.

    2017-12-01

    The National Water Model (NWM) provides national, street-level detail of water movement through time and space. Operating hourly, this flood of information offers enormous benefits in the form of water resource management, natural disaster preparedness, and the protection of life and property. The Geo-Intelligence Division at the NOAA National Water Center supplies forecasters and decision-makers with timely, actionable water intelligence through the processing of billions of NWM data points every hour. These datasets include current streamflow estimates, short and medium range streamflow forecasts, and many other ancillary datasets. The sheer amount of NWM data produced yields a dataset too large to allow for direct human comprehension. As such, it is necessary to undergo model data post-processing, filtering, and data ingestion by visualization web apps that make use of cartographic techniques to bring attention to the areas of highest urgency. This poster illustrates NWM output post-processing and cartographic visualization techniques being developed and employed by the Geo-Intelligence Division at the NOAA National Water Center to provide national actionable water intelligence.

  14. Spectral action for Bianchi type-IX cosmological models

    International Nuclear Information System (INIS)

    Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde

    2015-01-01

    A rationality result previously proved for Robertson-Walker metrics is extended to a homogeneous anisotropic cosmological model, namely the Bianchi type-IX minisuperspace. It is shown that the Seeley-de Witt coefficients appearing in the expansion of the spectral action for the Bianchi type-IX geometry are expressed in terms of polynomials with rational coefficients in the cosmic evolution factors w_1(t),w_2(t),w_3(t), and their higher derivates with respect to time. We begin with the computation of the Dirac operator of this geometry and calculate the coefficients a_0,a_2,a_4 of the spectral action by using heat kernel methods and parametric pseudodifferential calculus. An efficient method is devised for computing the Seeley-de Witt coefficients of a geometry by making use of Wodzicki’s noncommutative residue, and it is confirmed that the method checks out for the cosmological model studied in this article. The advantages of the new method are discussed, which combined with symmetries of the Bianchi type-IX metric, yield an elegant proof of the rationality result.

  15. Spectral action for Bianchi type-IX cosmological models

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Wentao; Fathizadeh, Farzad; Marcolli, Matilde [Division of Physics, Mathematics and Astronomy, California Institute of Technology,1200 E. California Blvd., Pasadena, CA 91125 (United States)

    2015-10-13

    A rationality result previously proved for Robertson-Walker metrics is extended to a homogeneous anisotropic cosmological model, namely the Bianchi type-IX minisuperspace. It is shown that the Seeley-de Witt coefficients appearing in the expansion of the spectral action for the Bianchi type-IX geometry are expressed in terms of polynomials with rational coefficients in the cosmic evolution factors w{sub 1}(t),w{sub 2}(t),w{sub 3}(t), and their higher derivates with respect to time. We begin with the computation of the Dirac operator of this geometry and calculate the coefficients a{sub 0},a{sub 2},a{sub 4} of the spectral action by using heat kernel methods and parametric pseudodifferential calculus. An efficient method is devised for computing the Seeley-de Witt coefficients of a geometry by making use of Wodzicki’s noncommutative residue, and it is confirmed that the method checks out for the cosmological model studied in this article. The advantages of the new method are discussed, which combined with symmetries of the Bianchi type-IX metric, yield an elegant proof of the rationality result.

  16. Matrix models with non-even potentials

    International Nuclear Information System (INIS)

    Marzban, C.; Raju Viswanathan, R.

    1990-07-01

    We study examples of hermitian 1-matrix models with even and odd terms present in the potential. A definition of criticality is presented which in these cases leads to multicritical models falling into the same universality classes as those of the purely even potentials. We also show that, in our examples, for polynomial potentials ending in odd powers (unbounded) the coupling constants, in addition to their expected real critical values, also admit critical values which alternate between imaginary/real values in the odd/even terms. We find that, remarkably, the ensuing statistical models are insensitive to the real/imaginary nature of these critical values. This feature may be of relevance in the recently-studied connection between matrix models and the moduli space of Riemann surfaces. (author). 9 refs

  17. Maximizing effectiveness of adaptation action in Pacific Island communities using coastal wave attenuation models

    Science.gov (United States)

    Jung, H.; Carruthers, T.; Allison, M. A.; Weathers, D.; Moss, L.; Timmermans, H.

    2017-12-01

    Pacific Island communities are highly vulnerable to the effects of climate change, specifically accelerating rates of sea level rise, changes to storm intensity and associated rainfall patterns resulting in flooding and shoreline erosion. Nature-based adaptation is being planned not only to reduce the risk from shoreline erosion, but also to support benefits of a healthy ecosystem (e.g., supporting fisheries or coral reefs). In order to assess potential effectiveness of the nature-based actions to dissipate wave energy, two-dimensional X-Beach models were developed to predict the wave attenuation effect of coastal adaptation actions at the pilot sites—the villages of Naselesele and Somosomo on Taveuni island, Fiji. Both sites are experiencing serious shoreline erosion due to sea level rise and storm wave. The water depth (single-beam bathymetry), land elevation (truck-based LiDAR), and vegetation data including stem density and height were collected in both locations in a June 2017 field experiment. Wave height and water velocity were also measured for the model setup and calibration using a series of bottom-mounted instruments deployed in the 0-15 m water depth portions of the study grid. The calibrated model will be used to evaluate a range of possible adaptation actions identified by the community members of Naselesele and Somosomo. Particularly, multiple storm scenario runs with management-relevant shoreline restoration/adaptation options will be implemented to evaluate efficiencies of each adaptation action (e.g., no action, with additional planted trees, with sand mining, with seawalls constructed with natural materials, etc.). These model results will help to better understand how proposed adaption actions may influence future shoreline change and maximize benefits to communities in island nations across the SW Pacific.

  18. Sensitivity of Rabbit Ventricular Action Potential and Ca2+ Dynamics to Small Variations in Membrane Currents and Ion Diffusion Coefficients

    Directory of Open Access Journals (Sweden)

    Yuan Hung Lo

    2013-01-01

    Full Text Available Little is known about how small variations in ionic currents and Ca2+ and Na+ diffusion coefficients impact action potential and Ca2+ dynamics in rabbit ventricular myocytes. We applied sensitivity analysis to quantify the sensitivity of Shannon et al. model (Biophys. J., 2004 to 5%–10% changes in currents conductance, channels distribution, and ion diffusion in rabbit ventricular cells. We found that action potential duration and Ca2+ peaks are highly sensitive to 10% increase in L-type Ca2+ current; moderately influenced by 10% increase in Na+-Ca2+ exchanger, Na+-K+ pump, rapid delayed and slow transient outward K+ currents, and Cl− background current; insensitive to 10% increases in all other ionic currents and sarcoplasmic reticulum Ca2+ fluxes. Cell electrical activity is strongly affected by 5% shift of L-type Ca2+ channels and Na+-Ca2+ exchanger in between junctional and submembrane spaces while Ca2+-activated Cl−-channel redistribution has the modest effect. Small changes in submembrane and cytosolic diffusion coefficients for Ca2+, but not in Na+ transfer, may alter notably myocyte contraction. Our studies highlight the need for more precise measurements and further extending and testing of the Shannon et al. model. Our results demonstrate usefulness of sensitivity analysis to identify specific knowledge gaps and controversies related to ventricular cell electrophysiology and Ca2+ signaling.

  19. Conduction velocity of action potentials measured from unidimensional latency-topography in human and frog skeletal muscle fibers.

    Science.gov (United States)

    Homma, S; Nakajima, Y; Hayashi, K; Toma, S

    1986-01-01

    Conduction of an action potential along skeletal muscle fibers was graphically displayed by unidimensional latency-topography, UDLT. Since the slopes of the equipotential line were linear and the width of the line was constant, it was possible to calculate conduction velocity from the slope. To determine conduction direction of the muscle action potential elicited by electric stimulation applied directly to the muscle, surface recording electrodes were placed on a two-dimensional plane over a human muscle. Thus a bi-dimensional topography was obtained. Then, twelve or sixteen surface electrodes were placed linearly along the longitudinal direction of the action potential conduction which was disclosed by the bi-dimensional topography. Thus conduction velocity of muscle action potential in man, calculated from the slope, was for m. brachioradialis, 3.9 +/- 0.4 m/s; for m. biceps brachii, 3.6 +/- 0.2 m/s; for m. sternocleidomastoideus, 3.6 +/- 0.4 m/s. By using a tungsten microelectrode to stimulate the motor axons, a convex-like equipotential line of an action potential in UDLT was obtained from human muscle fibers. Since a similar pattern of UDLT was obtained from experiments on isolated frog muscles, in which the muscle action potential was elicited by stimulating the motor axon, it was assumed that the maximum of the curve corresponds to the end-plate region, and that the slopes on both sides indicate bi-directional conduction of the action potential.

  20. Exact effective action for (1+1)-dimensional fermions in an Abelian background at finite temperature and chemical potential

    International Nuclear Information System (INIS)

    Maciel, Soraya G.; Perez, Silvana

    2008-01-01

    In this paper we study the effects of a nonzero chemical potential in (1+1)-dimensional quantum field models at finite temperature. We particularly consider massless fermions in an Abelian gauge field background and calculate the effective action by evaluating the n-point functions. We find that the structure of the amplitudes corresponds to a generalization of the structure noted earlier in a calculation without a chemical potential (the associated integrals carry the dependence on the chemical potential). Our calculation shows that the chiral anomaly is unaffected by the presence of a chemical potential at finite temperature. However, unlike in the absence of a chemical potential, odd point functions do not vanish. We trace this to the fact that in the presence of a chemical potential the generalized charge conjugation symmetry of the theory allows for such amplitudes. In fact, we find that all the even point functions are even functions of μ, while the odd point functions are odd functions of μ which is consistent with this generalized charge conjugation symmetry. We show that the origin of the structure of the amplitudes is best seen from a formulation of the theory in terms of left- and right-handed spinors. The calculations are also much simpler in this formulation and it clarifies many other aspects of the theory.

  1. Comparative investigations of manual action representations: evidence that chimpanzees represent the costs of potential future actions involving tools.

    Science.gov (United States)

    Frey, Scott H; Povinelli, Daniel J

    2012-01-12

    The ability to adjust one's ongoing actions in the anticipation of forthcoming task demands is considered as strong evidence for the existence of internal action representations. Studies of action selection in tool use reveal that the behaviours that we choose in the present moment differ depending on what we intend to do next. Further, they point to a specialized role for mechanisms within the human cerebellum and dominant left cerebral hemisphere in representing the likely sensory costs of intended future actions. Recently, the question of whether similar mechanisms exist in other primates has received growing, but still limited, attention. Here, we present data that bear on this issue from a species that is a natural user of tools, our nearest living relative, the chimpanzee. In experiment 1, a subset of chimpanzees showed a non-significant tendency for their grip preferences to be affected by anticipation of the demands associated with bringing a tool's baited end to their mouths. In experiment 2, chimpanzees' initial grip preferences were consistently affected by anticipation of the forthcoming movements in a task that involves using a tool to extract a food reward. The partial discrepancy between the results of these two studies is attributed to the ability to accurately represent differences between the motor costs associated with executing the two response alternatives available within each task. These findings suggest that chimpanzees are capable of accurately representing the costs of intended future actions, and using those predictions to select movements in the present even in the context of externally directed tool use.

  2. Potentiating action of propofol at GABAA receptors of retinal bipolar cells

    DEFF Research Database (Denmark)

    Yue, Lan; Xie, An; Bruzik, Karol S

    2011-01-01

    Purpose. Propofol (2,6-diisopropyl phenol), a widely used systemic anesthetic, is known to potentiate GABA(A) receptor activity in a number of CNS neurons and to produce changes in electroretinographically recorded responses of the retina. However, little is known about propofol's effects...... on specific retinal neurons. The authors investigated the action of propofol on GABA-elicited membrane current responses of retinal bipolar cells, which have both GABA(A) and GABA(C) receptors. Methods. Single, enzymatically dissociated bipolar cells obtained from rat retina were treated with propofol...... + propofol) led to a progressive increase in peak response amplitude and, at higher propofol concentrations, additional changes that included a prolonged time course of response recovery. Pre-exposure of the cell to perfusing propofol typically enhanced the rate of development of potentiation produced...

  3. Traditional Japanese medicines inhibit compound action potentials in the frog sciatic nerve.

    Science.gov (United States)

    Matsushita, Akitomo; Fujita, Tsugumi; Ohtsubo, Sena; Kumamoto, Eiichi

    2016-02-03

    Traditional Japanese (Kampo) medicines have a variety of clinical effects including pain alleviation, but evidence for a mechanism for their pain relief has not yet been elucidated fully. Considering that Kampo medicine contains many plant-derived chemicals having an ability to inhibit nerve action potential conduction, it is possible that this medicine inhibits nerve conduction. The purpose of the present study was to know how various Kampo medicines affect nerve conduction. We examined the effects of Kampo and crude medicines on compound action potentials (CAPs) recorded from the frog sciatic nerve by using the air-gap method. Daikenchuto, rikkosan, kikyoto, rikkunshito, shakuyakukanzoto and kakkonto concentration-dependently reduced the peak amplitude of the CAP. Among the Kampo medicines, daikenchuto was the most effective in inhibiting CAPs. Daikenchuto is composed of three kinds of crude medicine, Japanese pepper, processed ginger and ginseng radix. When the crude medicines were tested, Japanese pepper and processed ginger reduced CAP peak amplitudes, while ginseng radix hardly affected CAPs. Moreover, there was an interaction between the Japanese pepper and processed ginger activities in such that one medicine at low but not high concentrations increased the extent of the inhibition by the other one that was co-applied. Kampo medicines have an ability to inhibit nerve conduction. This action of daikenchuto is due to Japanese pepper and processed ginger but not ginseng radix, probably through an interaction between Japanese pepper and processed ginger in a manner dependent on their concentrations. Nerve conduction inhibition could contribute to at least a part of Kampo medicine's clinical effects such as pain alleviation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts

    Science.gov (United States)

    Markes, Alexander R.; Okundaye, Amenawon O.; Qu, Zhilin; Mende, Ulrike; Choi, Bum-Rak

    2018-01-01

    Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs) and/or cardiac fibroblasts (CFs) and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair. PMID:29715271

  5. Directed fusion of cardiac spheroids into larger heterocellular microtissues enables investigation of cardiac action potential propagation via cardiac fibroblasts.

    Directory of Open Access Journals (Sweden)

    Tae Yun Kim

    Full Text Available Multicellular spheroids generated through cellular self-assembly provide cytoarchitectural complexities of native tissue including three-dimensionality, extensive cell-cell contacts, and appropriate cell-extracellular matrix interactions. They are increasingly suggested as building blocks for larger engineered tissues to achieve shapes, organization, heterogeneity, and other biomimetic complexities. Application of these tissue culture platforms is of particular importance in cardiac research as the myocardium is comprised of distinct but intermingled cell types. Here, we generated scaffold-free 3D cardiac microtissue spheroids comprised of cardiac myocytes (CMs and/or cardiac fibroblasts (CFs and used them as building blocks to form larger microtissues with different spatial distributions of CMs and CFs. Characterization of fusing homotypic and heterotypic spheroid pairs revealed an important influence of CFs on fusion kinetics, but most strikingly showed rapid fusion kinetics between heterotypic pairs consisting of one CF and one CM spheroid, indicating that CMs and CFs self-sort in vitro into the intermixed morphology found in the healthy myocardium. We then examined electrophysiological integration of fused homotypic and heterotypic microtissues by mapping action potential propagation. Heterocellular elongated microtissues which recapitulate the disproportionate CF spatial distribution seen in the infarcted myocardium showed that action potentials propagate through CF volumes albeit with significant delay. Complementary computational modeling revealed an important role of CF sodium currents and the spatial distribution of the CM-CF boundary in action potential conduction through CF volumes. Taken together, this study provides useful insights for the development of complex, heterocellular engineered 3D tissue constructs and their engraftment via tissue fusion and has implications for arrhythmogenesis in cardiac disease and repair.

  6. Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains.

    Science.gov (United States)

    Nourski, Kirill V; Abbas, Paul J; Miller, Charles A; Robinson, Barbara K; Jeng, Fuh-Cherng

    2005-04-01

    This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

  7. Biophysical foundations for the study of the electrical excitability and action potential propagation in myocardium

    International Nuclear Information System (INIS)

    Suarez Antola, R.

    1991-01-01

    The electric current flow in the heterogeneous and anysotropic volume conductor of the myocardium is studied. The equations of bidomain theory are derived using an approach framed in the theory of averaged fields, introducing microscopic, mesoscopic and macroscopic spatial scales. However, the procedure, compatible with the histological and the anatomical details of the organ, is different from the multiple scale asymptotic expansions usually applied in homogeneization problems. A probabilistic approach framed in large numbers theorems is used to derive the equation for membrane ionic current from the stochastic activity of the channels at the microscopic level. An operational procedure suitable to define a sharp bidomain boundary from the fuzzy distribution of structural details and physical properties at the histological level is given. The problem of threshold is studied. The sizes and shapes of critical masses of cardiac cells that must be depolarized above threshold in order to produce a propagated action potential are determined by an approximate analytical procedure. The concept of family of threshold patterns for the emergence of action potentials in the heart is introduced. This concept is applied to discuss the conditions of emergence of ectopic focus. Analytical formulae are derived, for the time constant and the rheobase for electrical stimulation of the myocardium. These formulae are in good agreement with known experimental results. New experiments that could be done to confirm or reject them are suggested

  8. The effect of recording site on extracted features of motor unit action potential.

    Science.gov (United States)

    Artuğ, N Tuğrul; Goker, Imran; Bolat, Bülent; Osman, Onur; Kocasoy Orhan, Elif; Baslo, M Baris

    2016-06-01

    Motor unit action potential (MUAP), which consists of individual muscle fiber action potentials (MFAPs), represents the electrical activity of the motor unit. The values of the MUAP features are changed by denervation and reinnervation in neurogenic involvement as well as muscle fiber loss with increased diameter variability in myopathic diseases. The present study is designed to investigate how increased muscle fiber diameter variability affects MUAP parameters in simulated motor units. In order to detect this variation, simulated MUAPs were calculated both at the innervation zone where the MFAPs are more synchronized, and near the tendon, where they show increased temporal dispersion. Reinnervation in neurogenic state increases MUAP amplitude for the recordings at both the innervation zone and near the tendon. However, MUAP duration and the number of peaks significantly increased in a case of myopathy for recordings near the tendon. Furthermore, of the new features, "number of peaks×spike duration" was found as the strongest indicator of MFAP dispersion in myopathy. MUAPs were also recorded from healthy participants in order to investigate the biological counterpart of the simulation data. MUAPs which were recorded near to tendon revealed significantly prolonged duration and decreased amplitude. Although the number of peaks was increased by moving the needle near to tendon, this was not significant. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The Influence of Glutamate on Axonal Compound Action Potential In Vitro.

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

    Background  Our previous experiments demonstrated modulation of the amplitude of the axonal compound action potential (CAP) by electrical stimulation. To verify assumption that glutamate released from axons could be involved in this phenomenon, the modification of the axonal CAP induced by glutamate was investigated. Objectives  The major objective of this research is to verify the hypothesis that axonal activity would trigger the release of glutamate, which in turn would interact with specific axonal receptors modifying the amplitude of the action potential. Methods  Segments of the sciatic nerve were exposed to exogenous glutamate in vitro, and CAP was recorded before and after glutamate application. In some experiments, the release of radioactive glutamate analog from the sciatic nerve exposed to exogenous glutamate was also evaluated. Results  The glutamate-induced increase in CAP was blocked by different glutamate receptor antagonists. The effect of glutamate was not observed in Ca-free medium, and was blocked by antagonists of calcium channels. Exogenous glutamate, applied to the segments of sciatic nerve, induced the release of radioactive glutamate analog, demonstrating glutamate-induced glutamate release. Immunohistochemical examination revealed that axolemma contains components necessary for glutamatergic neurotransmission. Conclusion  The proteins of the axonal membrane can under the influence of electrical stimulation or exogenous glutamate change membrane permeability and ionic conductance, leading to a change in the amplitude of CAP. We suggest that increased axonal activity leads to the release of glutamate that results in changes in the amplitude of CAPs.

  10. The potential model of coloured quarks

    International Nuclear Information System (INIS)

    Greenberg, O.W.

    1981-01-01

    The success of the additive potential model of colored quarks for the masses, decay rates, and other properties of single mesons and baryons does not imply that this model can yield the observed meson-nucleon and nucleon-nucleon interactions. We give a comprehensive discussion of this issue. In agreement with previous authors, we conclude that, on the contrary, this model predicts inverse-power color-analog van der Waals potentials between separated hadrons which are in substantial contradiction with experimental data. We also discuss pathologies of non-abelian confining potentials, and show that the hamiltonian is unbounded below for an arbitrary number of quarks and antiquarks in a definite color state for all color states, except the singlet, triplet, and antitriplet. (orig.)

  11. A single quark effective potential model

    International Nuclear Information System (INIS)

    Bodmann, B.E.J.; Vasconcellos, C.A.Z.

    1994-01-01

    In the present work we construct a radial spherical symmetric single quark potential model for the nucleon, consistent with asymptotic freedom and confinement. The quark mass enters as potential parameter and that way induces indirectly an isospin dependence in the interaction. As a consequence, a contribution to the negative charge square radius of the neutron arises an an effect of the quark core, which simulates an isospin symmetry breaking effect in the nucleon due to strong interaction. (author)

  12. Promoting HIV Vaccine Research in African American Communities: Does the Theory of Reasoned Action Explain Potential Outcomes of Involvement?

    Science.gov (United States)

    Frew, Paula M; Archibald, Matthew; Martinez, Nina; del Rio, Carlos; Mulligan, Mark J

    2007-01-01

    The HIV/AIDS pandemic continues to challenge the African American community with disproportionate rates of infection, particularly among young women ages 25 to 34 years. Development of a preventive HIV vaccine may bring a substantial turning point in this health crisis. Engagement of the African American community is necessary to improve awareness of the effort and favorably influence attitudes and referent norms. The Theory of Reasoned Action (TRA) may be a useful framework for exploration of community engagement outcomes including future attendance, community mobilization, and study participation. Within the context of HIV vaccine outreach, we conducted a cross-sectional survey in early 2007 with 175 African-American adults (>/= 18 years). Confirmatory factor analysis and structural equation modeling were performed and the findings support the potential of the model in understanding behavioral intentions toward HIV vaccine research.

  13. Brain Functors: A Mathematical Model of Intentional Perception and Action

    Directory of Open Access Journals (Sweden)

    David Ellerman

    2016-03-01

    Full Text Available Category theory has foundational importance because it provides conceptual lenses to characterize what is important and universal in mathematics - with adjunctions being the primary lens. If adjunctions are so important in mathematics, then perhaps they will isolate concepts of some importance in the empirical sciences. But the applications of adjunctions have been hampered by an overly restrictive formulation that avoids heteromorphisms or hets. By reformulating an adjunction using hets, it is split into two parts, a left and a right semiadjunction. Semiadjunctions (essentially a formulation of universal mapping properties using hets can then be combined in a new way to define the notion of a brain functor that provides an abstract model of the intentionality of perception and action (as opposed to the passive reception of sense-data or the reflex generation of behavior.

  14. Effect of acute stretch injury on action potential and network activity of rat neocortical neurons in culture.

    Science.gov (United States)

    Magou, George C; Pfister, Bryan J; Berlin, Joshua R

    2015-10-22

    The basis for acute seizures following traumatic brain injury (TBI) remains unclear. Animal models of TBI have revealed acute hyperexcitablility in cortical neurons that could underlie seizure activity, but studying initiating events causing hyperexcitability is difficult in these models. In vitro models of stretch injury with cultured cortical neurons, a surrogate for TBI, allow facile investigation of cellular changes after injury but they have only demonstrated post-injury hypoexcitability. The goal of this study was to determine if neuronal hyperexcitability could be triggered by in vitro stretch injury. Controlled uniaxial stretch injury was delivered to a spatially delimited region of a spontaneously active network of cultured rat cortical neurons, yielding a region of stretch-injured neurons and adjacent regions of non-stretched neurons that did not directly experience stretch injury. Spontaneous electrical activity was measured in non-stretched and stretch-injured neurons, and in control neuronal networks not subjected to stretch injury. Non-stretched neurons in stretch-injured cultures displayed a three-fold increase in action potential firing rate and bursting activity 30-60 min post-injury. Stretch-injured neurons, however, displayed dramatically lower rates of action potential firing and bursting. These results demonstrate that acute hyperexcitability can be observed in non-stretched neurons located in regions adjacent to the site of stretch injury, consistent with reports that seizure activity can arise from regions surrounding the site of localized brain injury. Thus, this in vitro procedure for localized neuronal stretch injury may provide a model to study the earliest cellular changes in neuronal function associated with acute post-traumatic seizures. Copyright © 2015. Published by Elsevier B.V.

  15. Defining the action spectrum of potential PGC-1α activators on a mitochondrial and cellular level in vivo.

    Science.gov (United States)

    Hofer, Annette; Noe, Natalie; Tischner, Christin; Kladt, Nikolay; Lellek, Veronika; Schauß, Astrid; Wenz, Tina

    2014-05-01

    Previous studies have demonstrated a therapeutic benefit of pharmaceutical PGC-1α activation in cellular and murine model of disorders linked to mitochondrial dysfunction. While in some cases, this effect seems to be clearly associated with boosting of mitochondrial function, additional alterations as well as tissue- and cell-type-specific effects might play an important role. We initiated a comprehensive analysis of the effects of potential PGC-1α-activating drugs and pharmaceutically targeted the PPAR (bezafibrate, rosiglitazone), AMPK (AICAR, metformin) and Sirt1 (resveratrol) pathways in HeLa cells, neuronal cells and PGC-1α-deficient MEFs to get insight into cell type specificity and PGC-1α dependence of their working action. We used bezafibrate as a model drug to assess the effect on a tissue-specific level in a murine model. Not all analyzed drugs activate the PGC pathway or alter mitochondrial protein levels. However, they all affect supramolecular assembly of OXPHOS complexes and OXPHOS protein stability. In addition, a clear drug- and cell-type-specific influence on several cellular stress pathways as well as on post-translational modifications could be demonstrated, which might be relevant to fully understand the action of the analyzed drugs in the disease state. Importantly, the effect on the activation of mitochondrial biogenesis and stress response program upon drug treatment is PGC-1α dependent in MEFs demonstrating not only the pleiotropic effects of this molecule but points also to the working mechanism of the analyzed drugs. The definition of the action spectrum of the different drugs forms the basis for a defect-specific compensation strategy and a future personalized therapeutic approach.

  16. Urocortin2 prolongs action potential duration and modulates potassium currents in guinea pig myocytes and HEK293 cells.

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

    We previously reported that activation of corticotropin releasing factor receptor type 2 by urocortin2 up-regulates both L-type Ca(2+) channels and intracellular Ca(2+) concentration in ventricular myocytes and plays an important role in cardiac contractility and arrhythmogenesis. This study goal was to further test the hypothesis that urocortin2 may modulate action potentials as well as rapidly and slowly activating delayed rectifier potassium currents. With whole cell patch-clamp techniques, action potentials and slowly activating delayed rectifier potassium currents were recorded in isolated guinea pig ventricular myocytes, respectively. And rapidly activating delayed rectifier potassium currents were tested in hERG-HEK293 cells. Urocortin2 produced a time- and concentration-dependent prolongation of action potential duration. The EC50 values of action potential duration and action potential duration at 90% of repolarization were 14.73 and 24.3nM respectively. The prolongation of action potential duration of urocortin2 was almost completely or partly abolished by H-89 (protein kinase A inhibitor) or KB-R7943 (Na(+)/Ca(2+) exchange inhibitor) pretreatment respectively. And urocortin2 caused reduction of rapidly activating delayed rectifier potassium currents in hERG-HEK293 cells. In addition, urocortin2 slowed the rate of slowly activating delayed rectifier potassium channel activation, and rightward shifted the threshold of slowly activating delayed rectifier potassium currents to more positive potentials. Urocortin2 prolonged action potential duration via activation of protein kinase A and Na(+)/ Ca(2+) exchange in isolated guinea pig ventricular myocytes in a time- and concentration- dependent manner. In hERG-HEK293 cells, urocortin2 reduced rapidly activating delayed rectifier potassium current density which may contribute to action potential duration prolongation. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Decay rates of quarkonia and potential models

    International Nuclear Information System (INIS)

    Rai, Ajay Kumar; Pandya, J N; Vinodkumar, P C

    2005-01-01

    The decay rates of cc-bar and b-barb mesons have been studied with contributions from different correction terms. The corrections based on hard processes involved in the decays are quantitatively studied in the framework of different phenomenological potential models

  18. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    Science.gov (United States)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  19. The Belem Framework for Action: Harnessing the Power and Potential of Adult Learning and Education for a Viable Future

    Science.gov (United States)

    Adult Learning, 2012

    2012-01-01

    This article presents the Belem Framework for Action. This framework focuses on harnessing the power and potential of adult learning and education for a viable future. This framework begins with a preamble on adult education and towards lifelong learning.

  20. Analytic models of plausible gravitational lens potentials

    International Nuclear Information System (INIS)

    Baltz, Edward A.; Marshall, Phil; Oguri, Masamune

    2009-01-01

    Gravitational lenses on galaxy scales are plausibly modelled as having ellipsoidal symmetry and a universal dark matter density profile, with a Sérsic profile to describe the distribution of baryonic matter. Predicting all lensing effects requires knowledge of the total lens potential: in this work we give analytic forms for that of the above hybrid model. Emphasising that complex lens potentials can be constructed from simpler components in linear combination, we provide a recipe for attaining elliptical symmetry in either projected mass or lens potential. We also provide analytic formulae for the lens potentials of Sérsic profiles for integer and half-integer index. We then present formulae describing the gravitational lensing effects due to smoothly-truncated universal density profiles in cold dark matter model. For our isolated haloes the density profile falls off as radius to the minus fifth or seventh power beyond the tidal radius, functional forms that allow all orders of lens potential derivatives to be calculated analytically, while ensuring a non-divergent total mass. We show how the observables predicted by this profile differ from that of the original infinite-mass NFW profile. Expressions for the gravitational flexion are highlighted. We show how decreasing the tidal radius allows stripped haloes to be modelled, providing a framework for a fuller investigation of dark matter substructure in galaxies and clusters. Finally we remark on the need for finite mass halo profiles when doing cosmological ray-tracing simulations, and the need for readily-calculable higher order derivatives of the lens potential when studying catastrophes in strong lenses

  1. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology.

    Science.gov (United States)

    De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella

    2016-11-23

    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT 2A receptor as a partial agonist and 5-HT 1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT 2A . More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

  2. d-Lysergic Acid Diethylamide (LSD as a Model of Psychosis: Mechanism of Action and Pharmacology

    Directory of Open Access Journals (Sweden)

    Danilo De Gregorio

    2016-11-01

    Full Text Available d-Lysergic Acid Diethylamide (LSD is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1 and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA mechanism or acting on TAAR1 receptors.

  3. Latent Class Models in action: bridging social capital & Internet usage.

    Science.gov (United States)

    Neves, Barbara Barbosa; Fonseca, Jaime R S

    2015-03-01

    This paper explores how Latent Class Models (LCM) can be applied in social research, when the basic assumptions of regression models cannot be validated. We examine the usefulness of this method with data collected from a study on the relationship between bridging social capital and the Internet. Social capital is defined here as the resources that are potentially available in one's social ties. Bridging is a dimension of social capital, usually related to weak ties (acquaintances), and a source of instrumental resources such as information. The study surveyed a stratified random sample of 417 inhabitants of Lisbon, Portugal. We used LCM to create the variable bridging social capital, but also to estimate the relationship between bridging social capital and Internet usage when we encountered convergence problems with the logistic regression analysis. We conclude by showing a positive relationship between bridging and Internet usage, and by discussing the potential of LCM for social science research. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Transient accelerating scalar models with exponential potentials

    International Nuclear Information System (INIS)

    Cui Wen-Ping; Zhang Yang; Fu Zheng-Wen

    2013-01-01

    We study a known class of scalar dark energy models in which the potential has an exponential term and the current accelerating era is transient. We find that, although a decelerating era will return in the future, when extrapolating the model back to earlier stages (z ≳ 4), scalar dark energy becomes dominant over matter. So these models do not have the desired tracking behavior, and the predicted transient period of acceleration cannot be adopted into the standard scenario of the Big Bang cosmology. When couplings between the scalar field and matter are introduced, the models still have the same problem; only the time when deceleration returns will be varied. To achieve re-deceleration, one has to turn to alternative models that are consistent with the standard Big Bang scenario.

  5. Electrophysiologic evaluation of lumbosacral single nerve roots using compound muscle action potentials.

    Science.gov (United States)

    Ogura, Taku; Shikata, Hideto; Hase, Hitoshi; Mori, Masaki; Hayashida, Taturo; Osawa, Toru; Mikami, Yasuo; Kubo, Toshikazu

    2003-10-01

    Transcutaneous electrical stimulation applied to the vertebral column produces compound muscle action potentials (CMAPs) from the leg muscles. Using this method, we evaluated the efferent pathways of the lumbosacral nerve roots. The subjects were 26 healthy volunteers and 31 patients with lumbar disc herniation (LDH). CMAP recordings were obtained from the bilateral vastus medialis, tibialis anterior, extensor digitorum brevis, and abductor hallucis muscles using low-output-impedance stimulation. In normal subjects, the CMAP latency increased linearly with the distance between the stimulating electrode and the recording electrode, with little difference in latency between the left and the right sides in each subject. The CMAP amplitude was significantly lower in the patients with LDH, and the latency was also prolonged when the stimulating electrode was placed above the lesion. This technique may thus be a useful noninvasive method for assessing lumbosacral nerve root function in patients with LDH.

  6. Sensory nerve action potentials and sensory perception in women with arthritis of the hand.

    Science.gov (United States)

    Calder, Kristina M; Martin, Alison; Lydiate, Jessica; MacDermid, Joy C; Galea, Victoria; MacIntyre, Norma J

    2012-05-10

    Arthritis of the hand can limit a person's ability to perform daily activities. Whether or not sensory deficits contribute to the disability in this population remains unknown. The primary purpose of this study was to determine if women with osteoarthritis (OA) or rheumatoid arthritis (RA) of the hand have sensory impairments. Sensory function in the dominant hand of women with hand OA or RA and healthy women was evaluated by measuring sensory nerve action potentials (SNAPs) from the median, ulnar and radial nerves, sensory mapping (SM), and vibratory and current perception thresholds (VPT and CPT, respectively) of the second and fifth digits. All SNAP amplitudes were significantly lower for the hand OA and hand RA groups compared with the healthy group (p sensory fibers in the median, ulnar and radial nerves. Less apparent were losses in conduction speed or sensory perception.

  7. Action Potential Modulation of Neural Spin Networks Suggests Possible Role of Spin

    CERN Document Server

    Hu, H P

    2004-01-01

    In this paper we show that nuclear spin networks in neural membranes are modulated by action potentials through J-coupling, dipolar coupling and chemical shielding tensors and perturbed by microscopically strong and fluctuating internal magnetic fields produced largely by paramagnetic oxygen. We suggest that these spin networks could be involved in brain functions since said modulation inputs information carried by the neural spike trains into them, said perturbation activates various dynamics within them and the combination of the two likely produce stochastic resonance thus synchronizing said dynamics to the neural firings. Although quantum coherence is desirable and may indeed exist, it is not required for these spin networks to serve as the subatomic components for the conventional neural networks.

  8. Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications

    DEFF Research Database (Denmark)

    Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter

    2009-01-01

    PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...

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

    Directory of Open Access Journals (Sweden)

    Jack Kent

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

  10. β1-Adrenoceptor autoantibodies affect action potential duration and delayed rectifier potassium currents in guinea pigs.

    Science.gov (United States)

    Zhao, Yuhui; Huang, Haixia; Du, Yunhui; Li, Xiao; Lv, Tingting; Zhang, Suli; Wei, Hua; Shang, Jianyu; Liu, Ping; Liu, Huirong

    2015-01-01

    β1-Adrenoceptor autoantibodies (β1-AAs) affect the action potential duration (APD) in cardiomyocytes and are related to ventricular arrhythmias. The delayed rectifier potassium current (I K) plays a crucial role in APD, but the effects of β1-AAs on I K have not been completely illuminated. This work aimed to observe the effects of β1-AAs on I K and APD and further explore the mechanisms of β1-AA-mediated ventricular arrhythmias. β1-AAs were obtained from sera of patients with coronary heart disease (CHD) and nonsustained ventricular tachycardia. With whole-cell patch clamp technique, action potentials and I K were recorded. The results illustrated 0.1 μmol/L β1-AAs shortened APD at 50 % (APD50) and 90 % (APD90) of the repolarization. However, at 0.01 μmol/L, β1-AAs had no effects on either APD90 or APD50 (P > 0.05). At 0.001 μmol/L, β1-AAs significantly prolonged APD90 and APD50. Moreover, β1-AAs (0.001, 0.01, 0.1 μmol/L) dose-dependently increased the rapidly activating delayed rectifier potassium current (I Kr), but similarly decreased the slowly activating delayed rectifier potassium current (I Ks) and increased L-type calcium currents at the different concentrations. Taken together, the IKr increase induced by high β1-AA concentrations is responsible for a significant APD reduction which would contribute to repolarization changes and trigger the malignant ventricular arrhythmias in CHD patients.

  11. Sodium Channel β2 Subunits Prevent Action Potential Propagation Failures at Axonal Branch Points.

    Science.gov (United States)

    Cho, In Ha; Panzera, Lauren C; Chin, Morven; Hoppa, Michael B

    2017-09-27

    Neurotransmitter release depends on voltage-gated Na + channels (Na v s) to propagate an action potential (AP) successfully from the axon hillock to a synaptic terminal. Unmyelinated sections of axon are very diverse structures encompassing branch points and numerous presynaptic terminals with undefined molecular partners of Na + channels. Using optical recordings of Ca 2+ and membrane voltage, we demonstrate here that Na + channel β2 subunits (Na v β2s) are required to prevent AP propagation failures across the axonal arborization of cultured rat hippocampal neurons (mixed male and female). When Na v β2 expression was reduced, we identified two specific phenotypes: (1) membrane excitability and AP-evoked Ca 2+ entry were impaired at synapses and (2) AP propagation was severely compromised with >40% of axonal branches no longer responding to AP-stimulation. We went on to show that a great deal of electrical signaling heterogeneity exists in AP waveforms across the axonal arborization independent of axon morphology. Therefore, Na v β2 is a critical regulator of axonal excitability and synaptic function in unmyelinated axons. SIGNIFICANCE STATEMENT Voltage-gated Ca 2+ channels are fulcrums of neurotransmission that convert electrical inputs into chemical outputs in the form of vesicle fusion at synaptic terminals. However, the role of the electrical signal, the presynaptic action potential (AP), in modulating synaptic transmission is less clear. What is the fidelity of a propagating AP waveform in the axon and what molecules shape it throughout the axonal arborization? Our work identifies several new features of AP propagation in unmyelinated axons: (1) branches of a single axonal arborization have variable AP waveforms independent of morphology, (2) Na + channel β2 subunits modulate AP-evoked Ca 2+ -influx, and (3) β2 subunits maintain successful AP propagation across the axonal arbor. These findings are relevant to understanding the flow of excitation in the

  12. Sympathetic Nervous Regulation of Calcium and Action Potential Alternans in the Intact Heart.

    Science.gov (United States)

    Winter, James; Bishop, Martin J; Wilder, Catherine D E; O'Shea, Christopher; Pavlovic, Davor; Shattock, Michael J

    2018-01-01

    Rationale: Arrhythmogenic cardiac alternans are thought to be an important determinant for the initiation of ventricular fibrillation. There is limited information on the effects of sympathetic nerve stimulation (SNS) on alternans in the intact heart and the conclusions of existing studies, focused on investigating electrical alternans, are conflicted. Meanwhile, several lines of evidence implicate instabilities in Ca handling, not electrical restitution, as the primary mechanism underpinning alternans. Despite this, there have been no studies on Ca alternans and SNS in the intact heart. The present study sought to address this, by application of voltage and Ca optical mapping for the simultaneous study of APD and Ca alternans in the intact guinea pig heart during direct SNS. Objective : To determine the effects of SNS on APD and Ca alternans in the intact guinea pig heart and to examine the mechanism(s) by which the effects of SNS are mediated. Methods and Results : Studies utilized simultaneous voltage and Ca optical mapping in isolated guinea pig hearts with intact innervation. Alternans were induced using a rapid dynamic pacing protocol. SNS was associated with rate-independent shortening of action potential duration (APD) and the suppression of APD and Ca alternans, as indicated by a shift in the alternans threshold to faster pacing rates. Qualitatively similar results were observed with exogenous noradrenaline perfusion. In contrast with previous reports, both SNS and noradrenaline acted to flatten the slope of the electrical restitution curve. Pharmacological block of the slow delayed rectifying potassium current (I Ks ), sufficient to abolish I Ks -mediated APD-adaptation, partially reversed the effects of SNS on pacing-induced alternans. Treatment with cyclopiazonic acid, an inhibitor of the sarco(endo)plasmic reticulum ATPase, had opposite effects to that of SNS, acting to increase susceptibility to alternans, and suggesting that accelerated Ca reuptake

  13. Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods.

    Science.gov (United States)

    Aruoma, Okezie I

    2003-01-01

    The study of free radicals and antioxidants in biology is producing medical revolution that promises a new age of health and disease management. From prevention of the oxidative reactions in foods, pharmaceuticals and cosmetics to the role of reactive oxygen species (ROS) in chronic degenerative diseases including cancer, autoimmune, inflammatory, cardiovascular and neurodegenerative (e.g. Alzheimer's disease, Parkinson's disease, multiple sclerosis, Downs syndrome) and aging challenges continue to emerge from difficulties associated with methods used in evaluating antioxidant actions in vivo. Our interest presently is focused on development of neurodegeneration models based on the integrity of neuronal cells in the central nervous system and how they are protected by antioxidants when challenged by neurotoxins as well as Fenton chemistry models based on the profile of polyunsaturated fatty acids (PUFAs) for the assessment of antioxidant actions in vivo. Use continues to be made of several in vitro analytical tools to characterise the antioxidant propensity of bioactive compounds in plant foods and supplements. For example, the oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), total oxidant scavenging capacity (TOSC), the deoxyribose assay, assays involving oxidative DNA damage, assays involving reactive nitrogen intermediates (e.g. ONOO(-)), Trolox equivalent antioxidant capacity (TEAC) and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. There is need to agree governance on in vitro antioxidant methods based on an understanding of the mechanisms involved. Because some of the assays are done in non-physiological pH values, it is impossible to extrapolate the results to physiological environment. The consensus of opinion is that a mix of these tools should be used in assessing the antioxidant activities in vitro. The proof of bio-efficacy must emanate from application of reliable in vivo models where markers of baseline oxidative

  14. Variational methods and effective actions in string models

    International Nuclear Information System (INIS)

    Dereli, T.; Tucker, R.W.

    1987-01-01

    Effective actions motivated by zero-order and first-order actions are examined. Particular attention is devoted to a variational procedure that is consistent with the structure equations involving the Lorentz connection. Attention is drawn to subtleties that can arise in varying higher-order actions and an efficient procedure developed to handle these cases using the calculus of forms. The effect of constrained variations on the field equations is discussed. (author)

  15. Potential Beneficiaries of the Obama Administration’s Executive Action Programs Deeply Embedded in US Society

    Directory of Open Access Journals (Sweden)

    Donald Kerwin

    2016-03-01

    Full Text Available The Obama administration has developed two broad programs to defer immigration enforcement actions against undocumented persons living in the United States: (1 Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA; and (2 Deferred Action for Childhood Arrivals (DACA. The DACA program, which began in August 2012, was expanded on November 20, 2014. DAPA and the DACA expansion (hereinafter referred to as “DACA-plus” are currently under review by the US Supreme Court and subject to an active injunction.This paper offers a statistical portrait of the intended direct beneficiaries of DAPA, DACA, and DACA-plus. It finds that potential DAPA, DACA, and DACA-plus recipients are deeply embedded in US society, with high employment rates, extensive US family ties, long tenure, and substantial rates of English-language proficiency. The paper also notes various groups that would benefit indirectly from the full implementation of DAPA and DACA or, conversely, would suffer from the removal of potential beneficiaries of these programs. For example, all those who would rely on the retirement programs of the US government will benefit from the high employment rates and relative youth of the DACA population, while many US citizens who rely on the income of a DAPA-eligible parent would fall into poverty or extreme poverty should that parent be removed from the United States.This paper offers an analysis of potential DAPA and DACA beneficiaries. In an earlier study, the authors made the case for immigration reform based on long-term trends related to the US undocumented population, including potential DAPA and DACA beneficiaries (Warren and Kerwin 2015. By contrast, this paper details the degree to which these populations have become embedded in US society. It also compares persons eligible for the original DACA program with those eligible for DACA-plus.As stated, the great majority of potential DAPA and DACA recipients enjoy strong family

  16. Action potentials and ion conductances in wild-type and CALHM1-knockout type II taste cells

    Science.gov (United States)

    Saung, Wint Thu; Foskett, J. Kevin

    2017-01-01

    Taste bud type II cells fire action potentials in response to tastants, triggering nonvesicular ATP release to gustatory neurons via voltage-gated CALHM1-associated ion channels. Whereas CALHM1 regulates mouse cortical neuron excitability, its roles in regulating type II cell excitability are unknown. In this study, we compared membrane conductances and action potentials in single identified TRPM5-GFP-expressing circumvallate papillae type II cells acutely isolated from wild-type (WT) and Calhm1 knockout (KO) mice. The activation kinetics of large voltage-gated outward currents were accelerated in cells from Calhm1 KO mice, and their associated nonselective tail currents, previously shown to be highly correlated with ATP release, were completely absent in Calhm1 KO cells, suggesting that CALHM1 contributes to all of these currents. Calhm1 deletion did not significantly alter resting membrane potential or input resistance, the amplitudes and kinetics of Na+ currents either estimated from action potentials or recorded from steady-state voltage pulses, or action potential threshold, overshoot peak, afterhyperpolarization, and firing frequency. However, Calhm1 deletion reduced the half-widths of action potentials and accelerated the deactivation kinetics of transient outward currents, suggesting that the CALHM1-associated conductance becomes activated during the repolarization phase of action potentials. NEW & NOTEWORTHY CALHM1 is an essential ion channel component of the ATP neurotransmitter release mechanism in type II taste bud cells. Its contribution to type II cell resting membrane properties and excitability is unknown. Nonselective voltage-gated currents, previously associated with ATP release, were absent in cells lacking CALHM1. Calhm1 deletion was without effects on resting membrane properties or voltage-gated Na+ and K+ channels but contributed modestly to the kinetics of action potentials. PMID:28202574

  17. A model for production, perception, and acquisition of actions in face-to-face communication.

    Science.gov (United States)

    Kröger, Bernd J; Kopp, Stefan; Lowit, Anja

    2010-08-01

    The concept of action as basic motor control unit for goal-directed movement behavior has been used primarily for private or non-communicative actions like walking, reaching, or grasping. In this paper, literature is reviewed indicating that this concept can also be used in all domains of face-to-face communication like speech, co-verbal facial expression, and co-verbal gesturing. Three domain-specific types of actions, i.e. speech actions, facial actions, and hand-arm actions, are defined in this paper and a model is proposed that elucidates the underlying biological mechanisms of action production, action perception, and action acquisition in all domains of face-to-face communication. This model can be used as theoretical framework for empirical analysis or simulation with embodied conversational agents, and thus for advanced human-computer interaction technologies.

  18. Four-quark states in potential model

    International Nuclear Information System (INIS)

    Badalyan, A.M.; Kitoroage, D.I.

    1987-01-01

    The mass spectrum of S-wave q 2 q -2 mesons of u, d, s quarks is calculated in the framework of the nonrelativistic potential model and compared with the bag model predictions. The spin-spin splittings of almost all four-quark mesons with J PC = 0 ++ , 2 ++ , 1 +- are shown to coincide with an accuracy of ∼ 50 MeV in both approaches. Two exceptions are O S (9), C π S (9) mesons for which the discrepancy is ∼ 300 MeV. Calculated centers of gravity of the multiplets are systematically ∼ 120 MeV higher than the MIT bag predictions

  19. Parity doublers in chiral potential quark models

    International Nuclear Information System (INIS)

    Kalashnikova, Yu. S.; Nefediev, A. V.; Ribeiro, J. E. F. T.

    2007-01-01

    The effect of spontaneous breaking of chiral symmetry over the spectrum of highly excited hadrons is addressed in the framework of a microscopic chiral potential quark model (Generalised Nambu-Jona-Lasinio model) with a vectorial instantaneous quark kernel of a generic form. A heavy-light quark-antiquark bound system is considered, as an example, and the Lorentz nature of the effective light-quark potential is identified to be a pure Lorentz-scalar, for low-lying states in the spectrum, and to become a pure spatial Lorentz vector, for highly excited states. Consequently, the splitting between the partners in chiral doublets is demonstrated to decrease fast in the upper part of the spectrum so that neighboring states of an opposite parity become almost degenerate. A detailed microscopic picture of such a 'chiral symmetry restoration' in the spectrum of highly excited hadrons is drawn and the corresponding scale of restoration is estimated

  20. Regulation and regulatory role of WNT signaling in potentiating FSH action during bovine dominant follicle selection.

    Directory of Open Access Journals (Sweden)

    P S P Gupta

    Full Text Available Follicular development occurs in wave like patterns in monotocous species such as cattle and humans and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. To further elucidate potential mechanisms controlling dominant follicle selection, granulosa cell RNA harvested from F1 (largest and F2 (second largest follicles isolated at predeviation (PD and onset of diameter deviation (OD stages of the first follicular wave was subjected to preliminary RNA transcriptome analysis. Expression of numerous WNT system components was observed. Hence experiments were performed to test the hypothesis that WNT signaling modulates FSH action on granulosa cells during follicular waves. Abundance of mRNA for WNT pathway members was evaluated in granulosa cells harvested from follicles at emergence (EM, PD, OD and early dominance (ED stages of the first follicular wave. In F1 follicles, abundance of CTNNB1 and DVL1 mRNAs was higher and AXIN2 mRNA was lower at ED versus EM stages and DVL1 and FZD6 mRNAs were higher and AXIN2 mRNA was lower in F1 versus F2 follicle at the ED stage. Bovine granulosa cells were treated in vitro with increasing doses of the WNT inhibitor IWR-1+/- maximal stimulatory dose of FSH. IWR-1 treatment blocked the FSH-induced increase in granulosa cell numbers and reduced the FSH-induced increase in estradiol. Granulosa cells were also cultured in the presence or absence of FSH +/- IWR-1 and hormonal regulation of mRNA for WNT pathway members and known FSH targets determined. FSH treatment increased CYP19A1, CCND2, CTNNB1, AXIN2 and FZD6 mRNAs and the stimulatory effect on CYP19A1 mRNA was reduced by IWR-1. In contrast, FSH reduced CARTPT mRNA and IWR-1 partially reversed the inhibitory effect of FSH. Results support temporal and hormonal regulation and a potential role for WNT signaling in potentiating FSH action during dominant follicle selection.

  1. Backpropagating Action Potentials Enable Detection of Extrasynaptic Glutamate by NMDA Receptors

    Directory of Open Access Journals (Sweden)

    Yu-Wei Wu

    2012-05-01

    Full Text Available Synaptic NMDA receptors (NMDARs are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, backpropagating action potentials (bAPs recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are “protected,” under baseline conditions, from such glutamate influences by perisynaptic transporters: we detect bAP-evoked Ca2+ entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca2+ entry either downregulates or upregulates an h-channel conductance (Gh of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of Gh plasticity. Gh plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.

  2. Human neural tuning estimated from compound action potentials in normal hearing human volunteers

    Science.gov (United States)

    Verschooten, Eric; Desloovere, Christian; Joris, Philip X.

    2015-12-01

    The sharpness of cochlear frequency tuning in humans is debated. Evoked otoacoustic emissions and psychophysical measurements suggest sharper tuning in humans than in laboratory animals [15], but this is disputed based on comparisons of behavioral and electrophysiological measurements across species [14]. Here we used evoked mass potentials to electrophysiologically quantify tuning (Q10) in humans. We combined a notched noise forward masking paradigm [9] with the recording of trans tympanic compound action potentials (CAP) from masked probe tones in awake human and anesthetized monkey (Macaca mulatta). We compare our results to data obtained with the same paradigm in cat and chinchilla [16], and find that CAP-Q10values in human are ˜1.6x higher than in cat and chinchilla and ˜1.3x higher than in monkey. To estimate frequency tuning of single auditory nerve fibers (ANFs) in humans, we derive conversion functions from ANFs in cat, chinchilla, and monkey and apply these to the human CAP measurements. The data suggest that sharp cochlear tuning is a feature of old-world primates.

  3. Incorporating institutions and collective action into a sociohydrological model of flood resilience

    Science.gov (United States)

    Yu, David J.; Sangwan, Nikhil; Sung, Kyungmin; Chen, Xi; Merwade, Venkatesh

    2017-02-01

    Stylized sociohydrological models have mainly used social memory aspects such as community awareness or sensitivity to connect hydrologic change and social response. However, social memory alone does not satisfactorily capture the details of how human behavior is translated into collective action for water resources governance. Nor is it the only social mechanism by which the two-way feedbacks of sociohydrology can be operationalized. This study contributes toward bridging of this gap by developing a sociohydrological model of a flood resilience that includes two additional components: (1) institutions for collective action, and (2) connections to an external economic system. Motivated by the case of community-managed flood protection systems (polders) in coastal Bangladesh, we use the model to understand critical general features that affect long-term resilience of human-flood systems. Our findings suggest that occasional adversity can enhance long-term resilience. Allowing some hydrological variability to enter into the polder can increase its adaptive capacity for resilience through the preservation of social norm for collective action. Further, there are potential trade-offs associated with optimization of flood resistance through structural measures. By reducing sensitivity to floods, the system may become more fragile under the double impact of floods and economic change.

  4. Understanding the cellular mode of action of vernakalant using a computational model: answers and new questions

    Directory of Open Access Journals (Sweden)

    Loewe Axel

    2015-09-01

    Full Text Available Vernakalant is a new antiarrhythmic agent for the treatment of atrial fibrillation. While it has proven to be effective in a large share of patients in clinical studies, its underlying mode of action is not fully understood. In this work, we aim to link experimental data from the subcellular, tissue, and system level using an in-silico approach. A Hill’s equation-based drug model was extended to cover the frequency dependence of sodium channel block. Two model variants were investigated: M1 based on subcellular data and M2 based on tissue level data. 6 action potential (AP markers were evaluated regarding their dose, frequency and substrate dependence. M1 comprising potassium, sodium, and calcium channel block reproduced the reported prolongation of the refractory period. M2 not including the effects on potassium channels reproduced reported AP morphology changes on the other hand. The experimentally observed increase of ERP accompanied by a shortening of APD90 was not reproduced. Thus, explanations for the drug-induced changes are provided while none of the models can explain the effects in their entirety. These results foster the understanding of vernakalant’s cellular mode of action and point out relevant gaps in our current knowledge to be addressed in future in-silico and experimental research on this aspiring antiarrhythmic agent.

  5. Melatonin: Action as antioxidant and potential applications in human disease and aging

    International Nuclear Information System (INIS)

    Bonnefont-Rousselot, Dominique; Collin, Fabrice

    2010-01-01

    This review aims at describing the beneficial properties of melatonin related to its antioxidant effects. Oxidative stress, i.e., an imbalance between the production of reactive oxygen species and antioxidant defences, is involved in several pathological conditions such as cardiovascular or neurological disease, and in aging. Therefore, research for antioxidants has developed. However, classical antioxidants often failed to exhibit beneficial effects, especially in metabolic diseases. Melatonin has been shown as a specific antioxidant due to its amphiphilic feature that allows it to cross physiological barriers, thereby reducing oxidative damage in both lipid and aqueous cell environments. Studies on the antioxidant action of melatonin are reported, with a special mention to water gamma radiolysis as a method to produce oxygen-derived free radicals, and on structure-activity relationships of melatonin derivatives. Mass spectrometry-based techniques have been developed to identify melatonin oxidation products. Besides its ability to scavenge several radical species, melatonin regulates the activity of antioxidant enzymes (indirect antioxidant properties). Efficient detection methods confirmed the presence of melatonin in several plant products. Therapeutic potential of melatonin relies either on increasing melatonin dietary intake or on supplementation with supraphysiological dosages. Clinical trials showed that melatonin could be efficient in preventing cell damage, as well under acute (sepsis, asphyxia in newborns) as under chronic (metabolic and neurodegenerative diseases, cancer, inflammation, aging). Its global action on oxidative stress, together with its rhythmicity that plays a role in several metabolic functions, lead melatonin to be of great interest for future clinical research in order to improve public health.

  6. Effective action and cluster properties of the abelian Higgs model

    Energy Technology Data Exchange (ETDEWEB)

    Balaban, T; Imbrie, J Z; Jaffe, A

    1988-02-01

    We continue our program to establish the Higgs mechanism and mass gap for the abelian Higgs model in two and three dimensions. We develop a multiscale cluster expansion for the high frequency modes of the theory, within a framework of iterated renormalization group transformations. The expansions yield decoupling properties needed for a proof of exponential decay of correlations. The result of this analysis is a gauge invariant unit lattice theory with a deep Higgs potential of the shape required to exhibit the Higgs mechanism.

  7. Unjamming in models with analytic pairwise potentials

    Science.gov (United States)

    Kooij, Stefan; Lerner, Edan

    2017-06-01

    Canonical models for studying the unjamming scenario in systems of soft repulsive particles assume pairwise potentials with a sharp cutoff in the interaction range. The sharp cutoff renders the potential nonanalytic but makes it possible to describe many properties of the solid in terms of the coordination number z , which has an unambiguous definition in these cases. Pairwise potentials without a sharp cutoff in the interaction range have not been studied in this context, but should in fact be considered to understand the relevance of the unjamming phenomenology in systems where such a cutoff is not present. In this work we explore two systems with such interactions: an inverse power law and an exponentially decaying pairwise potential, with the control parameters being the exponent (of the inverse power law) for the former and the number density for the latter. Both systems are shown to exhibit the characteristic features of the unjamming transition, among which are the vanishing of the shear-to-bulk modulus ratio and the emergence of an excess of low-frequency vibrational modes. We establish a relation between the pressure-to-bulk modulus ratio and the distance to unjamming in each of our model systems. This allows us to predict the dependence of other key observables on the distance to unjamming. Our results provide the means for a quantitative estimation of the proximity of generic glass-forming models to the unjamming transition in the absence of a clear-cut definition of the coordination number and highlight the general irrelevance of nonaffine contributions to the bulk modulus.

  8. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates"

    DEFF Research Database (Denmark)

    Berg, Rune W.; Stauning, Marius Tving; Sorensen, Jakob Balslev

    2017-01-01

    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around − 70 mV). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite...

  9. A conceptual model for translating omic data into clinical action

    Directory of Open Access Journals (Sweden)

    Timothy M Herr

    2015-01-01

    Full Text Available Genomic, proteomic, epigenomic, and other "omic" data have the potential to enable precision medicine, also commonly referred to as personalized medicine. The volume and complexity of omic data are rapidly overwhelming human cognitive capacity, requiring innovative approaches to translate such data into patient care. Here, we outline a conceptual model for the application of omic data in the clinical context, called "the omic funnel." This model parallels the classic "Data, Information, Knowledge, Wisdom pyramid" and adds context for how to move between each successive layer. Its goal is to allow informaticians, researchers, and clinicians to approach the problem of translating omic data from bench to bedside, by using discrete steps with clearly defined needs. Such an approach can facilitate the development of modular and interoperable software that can bring precision medicine into widespread practice.

  10. Uncertainty Driven Action (UDA) model: A foundation for unifying perspectives on design activity

    DEFF Research Database (Denmark)

    Cash, Philip; Kreye, Melanie

    2017-01-01

    are linked via uncertainty perception. The foundations of the UDA model in the design literature are elaborated in terms of the three core actions and their links to designer cognition and behaviour, utilising definitions and concepts from Activity Theory. The practical relevance and theoretical......This paper proposes the Uncertainty Driven Action (UDA) model, which unifies the fragmented literature on design activity. The UDA model conceptualises design activity as a process consisting of three core actions: information action, knowledge-sharing action, and representation action, which...... contributions of the UDA model are discussed. This paper contributes to the design literature by offering a comprehensive formalisation of design activity of individual designers, which connects cognition and action, to provide a foundation for understanding previously disparate descriptions of design activity....

  11. Potential-well model in acoustic tweezers.

    Science.gov (United States)

    Kang, Shih-Tsung; Yeh, Chih-Kuang

    2010-06-01

    Standing-wave acoustic tweezers are popularly used for non-invasive and non-contact particle manipulation. Because of their good penetration in biological tissue, they also show promising prospects for in vivo applications. According to the concept of an optical vortex, we propose an acoustics-vortex- based trapping model of acoustic tweezers. A four-element 1-MHz planar transducer was used to generate 1-MHz sine waves at 1 MPa, with adjacent elements being driven with a pi/2-rad phase difference. Each element was a square with a side length of 5.08 mm, with kerfs initially set at 0.51 mm. An acoustic vortex constituting the spiral motion of an acoustic wave around the beam axis was created, with an axial null. Applying Gor'kov's theory in the Rayleigh regime yielded the potential energy and radiation force for use in subsequent analysis. In the transverse direction, the vortex structure behaved as a series of potential wells that tended to drive a suspended particle toward the beam axis. They were highly fragmented in the near field that is very close to the transducer where there was spiral interference, and well-constructed in the far field. We found that the significant trapping effect was only present between these two regions in the transverse direction--particles were free to move along the beam axis, and a repulsive force was observed in the outer acoustic vortex. Because the steepness of the potential gradient near an axial null dominates the trapping effect, the far field of the acoustic vortex is inappropriate for trapping. Particles too close to the transducer are not sufficiently trapped because of the fragmented potential pattern. We suggest that the ideal distance from the transducer for trapping particles is in front of one-fourth of the Rayleigh distance, based on the superposition of the wavefronts. The maximum trapping force acting on a 13-mum polystyrene sphere in the produced acoustic vortex was 50.0 pN, and it was possible to trap

  12. Ventricular action potential adaptation to regular exercise: role of β-adrenergic and KATP channel function.

    Science.gov (United States)

    Wang, Xinrui; Fitts, Robert H

    2017-08-01

    Regular exercise training is known to affect the action potential duration (APD) and improve heart function, but involvement of β-adrenergic receptor (β-AR) subtypes and/or the ATP-sensitive K + (K ATP ) channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel-running or control groups; they were anesthetized after 6-8 wk of training, and myocytes were isolated. Exercise training significantly increased APD of apex and base myocytes at 1 Hz and decreased APD at 10 Hz. Ca 2+ transient durations reflected the changes in APD, while Ca 2+ transient amplitudes were unaffected by wheel running. The nonselective β-AR agonist isoproterenol shortened the myocyte APD, an effect reduced by wheel running. The isoproterenol-induced shortening of APD was largely reversed by the selective β 1 -AR blocker atenolol, but not the β 2 -AR blocker ICI 118,551, providing evidence that wheel running reduced the sensitivity of the β 1 -AR. At 10 Hz, the K ATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained than control rats, implicating a role for this channel in the exercise-induced APD shortening at 10 Hz. A novel finding of this work was the dual importance of altered β 1 -AR responsiveness and K ATP channel function in the training-induced regulation of APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates, where sympathetic drive is low, by prolonging APD and Ca 2+ influx; during exercise, an increase in K ATP channel activity would shorten APD and, thus, protect the heart against Ca 2+ overload or inadequate filling. NEW & NOTEWORTHY Our data demonstrated that regular exercise prolonged the action potential and Ca 2+ transient durations in myocytes isolated from apex and base regions at 1-Hz and shortened both at 10-Hz stimulation. Novel findings were that wheel running shifted the

  13. Impact of sarcoplasmic reticulum calcium release on calcium dynamics and action potential morphology in human atrial myocytes: a computational study.

    Directory of Open Access Journals (Sweden)

    Jussi T Koivumäki

    Full Text Available Electrophysiological studies of the human heart face the fundamental challenge that experimental data can be acquired only from patients with underlying heart disease. Regarding human atria, there exist sizable gaps in the understanding of the functional role of cellular Ca²+ dynamics, which differ crucially from that of ventricular cells, in the modulation of excitation-contraction coupling. Accordingly, the objective of this study was to develop a mathematical model of the human atrial myocyte that, in addition to the sarcolemmal (SL ion currents, accounts for the heterogeneity of intracellular Ca²+ dynamics emerging from a structurally detailed sarcoplasmic reticulum (SR. Based on the simulation results, our model convincingly reproduces the principal characteristics of Ca²+ dynamics: 1 the biphasic increment during the upstroke of the Ca²+ transient resulting from the delay between the peripheral and central SR Ca²+ release, and 2 the relative contribution of SL Ca²+ current and SR Ca²+ release to the Ca²+ transient. In line with experimental findings, the model also replicates the strong impact of intracellular Ca²+ dynamics on the shape of the action potential. The simulation results suggest that the peripheral SR Ca²+ release sites define the interface between Ca²+ and AP, whereas the central release sites are important for the fire-diffuse-fire propagation of Ca²+ diffusion. Furthermore, our analysis predicts that the modulation of the action potential duration due to increasing heart rate is largely mediated by changes in the intracellular Na+ concentration. Finally, the results indicate that the SR Ca²+ release is a strong modulator of AP duration and, consequently, myocyte refractoriness/excitability. We conclude that the developed model is robust and reproduces many fundamental aspects of the tight coupling between SL ion currents and intracellular Ca²+ signaling. Thus, the model provides a useful framework for future

  14. Acting in solidarity : Testing an extended dual pathway model of collective action by bystander group members

    NARCIS (Netherlands)

    Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

    We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach,

  15. Quark model and equivalent local potential

    International Nuclear Information System (INIS)

    Takeuchi, Sachiko; Shimizu, Kiyotaka

    2002-01-01

    In this paper, we investigate the short-range repulsion given by the quark cluster model employing an inverse scattering problem. We find that the local potential which reproduces the same phase shifts as those given by the quark cluster model has a strong repulsion at short distances in the NN 1 S 0 channel. There, however, appears an attractive pocket at very short distances due to a rather weak repulsive behavior at very high energy. This repulsion-attractive-pocket structure becomes more manifest in the channel which has an almost forbidden state, ΣN(T=3/2) 3 S 1 . In order to see what kinds of effects are important to reproduce the short-range repulsion in the quark cluster model, we investigate the contribution coming from the one-gluon-exchange potential and the normalization separately. It is clarified that the gluon exchange constructs the short-range repulsion in the NN 1 S 0 while the quark Pauli-blocking effect governs the feature of the repulsive behavior in the ΣN(T=3/2) 3 S 1 channel

  16. Computerised analysis of sulphate action on model concrete piles

    Digital Repository Service at National Institute of Oceanography (India)

    Deshmukh, A.M.; Balasubramanian, S.; Venugopal, C.

    Sulphate action severely affects the durability of marine structures. It is imperative to study precisely the effects of magnesium sulphate on pile foundations in the marine environment. In the present paper an attempt is made to assess and analyse...

  17. Action Algebras and Model Algebras in Denotational Semantics

    Science.gov (United States)

    Guedes, Luiz Carlos Castro; Haeusler, Edward Hermann

    the same way as that for functional denotational types. For example, PASCAL arrays belong to the “language inherent” aspect, while the Store domain seems to belong to the “model dependent” aspect. This distinction was important because it focussed attention on optimizing the model dependent semantic domains to obtain a more efficient implementation.) The research led to a nice conclusion: The guidelines of Action Semantics induce a clear separation of the model and language inherent aspects of a language’s semantics. A good implementation of facets, particularly the model dependent ones, leads to generation of an efficient compiler. In this article we discuss the separation of the language inherent and model-inherent domains at the theoretical and conceptual level. In doing so, the authors hope to show how Professor Mosses’s influence extended beyond his technical advice to his professional and personal examples on the supervision of PhD research.

  18. Frequency decoding of periodically timed action potentials through distinct activity patterns in a random neural network

    International Nuclear Information System (INIS)

    Reichenbach, Tobias; Hudspeth, A J

    2012-01-01

    Frequency discrimination is a fundamental task of the auditory system. The mammalian inner ear, or cochlea, provides a place code in which different frequencies are detected at different spatial locations. However, a temporal code based on spike timing is also available: action potentials evoked in an auditory-nerve fiber by a low-frequency tone occur at a preferred phase of the stimulus—they exhibit phase locking—and thus provide temporal information about the tone's frequency. Humans employ this temporal information for discrimination of low frequencies. How might such temporal information be read out in the brain? Here we employ statistical and numerical methods to demonstrate that recurrent random neural networks in which connections between neurons introduce characteristic time delays, and in which neurons require temporally coinciding inputs for spike initiation, can perform sharp frequency discrimination when stimulated with phase-locked inputs. Although the frequency resolution achieved by such networks is limited by the noise in phase locking, the resolution for realistic values reaches the tiny frequency difference of 0.2% that has been measured in humans. (paper)

  19. Correlates of a single cortical action potential in the epidural EEG

    Science.gov (United States)

    Teleńczuk, Bartosz; Baker, Stuart N; Kempter, Richard; Curio, Gabriel

    2015-01-01

    To identify the correlates of a single cortical action potential in surface EEG, we recorded simultaneously epidural EEG and single-unit activity in the primary somatosensory cortex of awake macaque monkeys. By averaging over EEG segments coincident with more than hundred thousand single spikes, we found short-lived (≈ 0.5 ms) triphasic EEG deflections dominated by high-frequency components > 800 Hz. The peak-to-peak amplitude of the grand-averaged spike correlate was 80 nV, which matched theoretical predictions, while single-neuron amplitudes ranged from 12 to 966 nV. Combining these estimates with post-stimulus-time histograms of single-unit responses to median-nerve stimulation allowed us to predict the shape of the evoked epidural EEG response and to estimate the number of contributing neurons. These findings establish spiking activity of cortical neurons as a primary building block of high-frequency epidural EEG, which thus can serve as a quantitative macroscopic marker of neuronal spikes. PMID:25554430

  20. Benefits of Nut Consumption on Insulin Resistance and Cardiovascular Risk Factors: Multiple Potential Mechanisms of Actions

    Directory of Open Access Journals (Sweden)

    Yoona Kim

    2017-11-01

    Full Text Available Epidemiological and clinical studies have indicated that nut consumption could be a healthy dietary strategy to prevent and treat type 2 diabetes (T2DM and related cardiovascular disease (CVD. The objective of this review is to examine the potential mechanisms of action of nuts addressing effects on glycemic control, weight management, energy balance, appetite, gut microbiota modification, lipid metabolism, oxidative stress, inflammation, endothelial function and blood pressure with a focus on data from both animal and human studies. The favourable effects of nuts could be explained by the unique nutrient composition and bioactive compounds in nuts. Unsaturated fatty acids (monounsaturated fatty acids and polyunsaturated fatty acids present in nuts may play a role in glucose control and appetite suppression. Fiber and polyphenols in nuts may also have an anti-diabetic effect by altering gut microbiota. Nuts lower serum cholesterol by reduced cholesterol absorption, inhibition of HMG-CoA reductase and increased bile acid production by stimulation of 7-α hydroxylase. Arginine and magnesium improve inflammation, oxidative stress, endothelial function and blood pressure. In conclusion, nuts contain compounds that favourably influence glucose homeostasis, weight control and vascular health. Further investigations are required to identify the most important mechanisms by which nuts decrease the risk of T2DM and CVD.

  1. Boron-doped nanocrystalline diamond microelectrode arrays monitor cardiac action potentials.

    Science.gov (United States)

    Maybeck, Vanessa; Edgington, Robert; Bongrain, Alexandre; Welch, Joseph O; Scorsone, Emanuel; Bergonzo, Philippe; Jackman, Richard B; Offenhäusser, Andreas

    2014-02-01

    The expansion of diamond-based electronics in the area of biological interfacing has not been as thoroughly explored as applications in electrochemical sensing. However, the biocompatibility of diamond, large safe electrochemical window, stability, and tunable electronic properties provide opportunities to develop new devices for interfacing with electrogenic cells. Here, the fabrication of microelectrode arrays (MEAs) with boron-doped nanocrystalline diamond (BNCD) electrodes and their interfacing with cardiomyocyte-like HL-1 cells to detect cardiac action potentials are presented. A nonreductive means of structuring doped and undoped diamond on the same substrate is shown. The resulting BNCD electrodes show high stability under mechanical stress generated by the cells. It is shown that by fabricating the entire surface of the MEA with NCD, in patterns of conductive doped, and isolating undoped regions, signal detection may be improved up to four-fold over BNCD electrodes passivated with traditional isolators. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Multifocal fluorescence microscope for fast optical recordings of neuronal action potentials.

    Science.gov (United States)

    Shtrahman, Matthew; Aharoni, Daniel B; Hardy, Nicholas F; Buonomano, Dean V; Arisaka, Katsushi; Otis, Thomas S

    2015-02-03

    In recent years, optical sensors for tracking neural activity have been developed and offer great utility. However, developing microscopy techniques that have several kHz bandwidth necessary to reliably capture optically reported action potentials (APs) at multiple locations in parallel remains a significant challenge. To our knowledge, we describe a novel microscope optimized to measure spatially distributed optical signals with submillisecond and near diffraction-limit resolution. Our design uses a spatial light modulator to generate patterned illumination to simultaneously excite multiple user-defined targets. A galvanometer driven mirror in the emission path streaks the fluorescence emanating from each excitation point during the camera exposure, using unused camera pixels to capture time varying fluorescence at rates that are ∼1000 times faster than the camera's native frame rate. We demonstrate that this approach is capable of recording Ca(2+) transients resulting from APs in neurons labeled with the Ca(2+) sensor Oregon Green Bapta-1 (OGB-1), and can localize the timing of these events with millisecond resolution. Furthermore, optically reported APs can be detected with the voltage sensitive dye DiO-DPA in multiple locations within a neuron with a signal/noise ratio up to ∼40, resolving delays in arrival time along dendrites. Thus, the microscope provides a powerful tool for photometric measurements of dynamics requiring submillisecond sampling at multiple locations. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

    Directory of Open Access Journals (Sweden)

    Le Sun

    Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

  4. The transformative potential of action research and ICT in the Second Language (L2 classroom

    Directory of Open Access Journals (Sweden)

    Farren Margaret

    2015-12-01

    Full Text Available This study shows the transformative potential of action research and information and communications technology (ICT in the second language (L2 classroom. Two enquiries from teacher-researchers are detailed in the article. Their engagement in a collaborative professional development Masters programme was pivotal in designing and implementing ICT creatively in their classroom. Gee (2008 advocates the use of the preferred media of our classroom students in order to address their learning. Prensky (2001 urges us to feel the fear and do it anyway with our digital native classes. A post-primary teacher and a primary teacher show us how they felt the fear, did it and transformed aspects of their own teaching in the process. The Masters programme required the teachers to engage with innovative practices, informed by their own values, and integrate technologies that were new to them into their repertoire of classroom strategies. Peer validation meetings with colleagues enabled meaningful insights to emerge from the research. The teachers improve and transform their second language (L2 practice in collaboration and validation with others.

  5. Effects of terpineol on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    M.R. Moreira

    2001-10-01

    Full Text Available Terpineol, a volatile terpenoid alcohol of low toxicity, is widely used in the perfumery industry. It is an important chemical constituent of the essential oil of many plants with widespread applications in folk medicine and in aromatherapy. The effects of terpineol on the compound action potential (CAP of rat sciatic nerve were studied. Terpineol induced a dose-dependent blockade of the CAP. At 100 µM, terpineol had no demonstrable effect. At 300 µM terpineol, peak-to-peak amplitude and conduction velocity of CAP were significantly reduced at the end of 180-min exposure of the nerve to the drug, from 3.28 ± 0.22 mV and 33.5 ± 7.05 m/s, respectively, to 1.91 ± 0.51 mV and 26.2 ± 4.55 m/s. At 600 µM, terpineol significantly reduced peak-to-peak amplitude and conduction velocity from 2.97 ± 0.55 mV and 32.8 ± 3.91 m/s to 0.24 ± 0.23 mV and 2.72 ± 2.72 m/s, respectively (N = 5. All these effects developed slowly and were reversible upon 180-min washout.

  6. Spine Calcium Transients Induced by Synaptically-Evoked Action Potentials Can Predict Synapse Location and Establish Synaptic Democracy

    Science.gov (United States)

    Meredith, Rhiannon M.; van Ooyen, Arjen

    2012-01-01

    CA1 pyramidal neurons receive hundreds of synaptic inputs at different distances from the soma. Distance-dependent synaptic scaling enables distal and proximal synapses to influence the somatic membrane equally, a phenomenon called “synaptic democracy”. How this is established is unclear. The backpropagating action potential (BAP) is hypothesised to provide distance-dependent information to synapses, allowing synaptic strengths to scale accordingly. Experimental measurements show that a BAP evoked by current injection at the soma causes calcium currents in the apical shaft whose amplitudes decay with distance from the soma. However, in vivo action potentials are not induced by somatic current injection but by synaptic inputs along the dendrites, which creates a different excitable state of the dendrites. Due to technical limitations, it is not possible to study experimentally whether distance information can also be provided by synaptically-evoked BAPs. Therefore we adapted a realistic morphological and electrophysiological model to measure BAP-induced voltage and calcium signals in spines after Schaffer collateral synapse stimulation. We show that peak calcium concentration is highly correlated with soma-synapse distance under a number of physiologically-realistic suprathreshold stimulation regimes and for a range of dendritic morphologies. Peak calcium levels also predicted the attenuation of the EPSP across the dendritic tree. Furthermore, we show that peak calcium can be used to set up a synaptic democracy in a homeostatic manner, whereby synapses regulate their synaptic strength on the basis of the difference between peak calcium and a uniform target value. We conclude that information derived from synaptically-generated BAPs can indicate synapse location and can subsequently be utilised to implement a synaptic democracy. PMID:22719238

  7. Burst analysis tool for developing neuronal networks exhibiting highly varying action potential dynamics

    Directory of Open Access Journals (Sweden)

    Fikret Emre eKapucu

    2012-06-01

    Full Text Available In this paper we propose a firing statistics based neuronal network burst detection algorithm for neuronal networks exhibiting highly variable action potential dynamics. Electrical activity of neuronal networks is generally analyzed by the occurrences of spikes and bursts both in time and space. Commonly accepted analysis tools employ burst detection algorithms based on predefined criteria. However, maturing neuronal networks, such as those originating from human embryonic stem cells (hESC, exhibit highly variable network structure and time-varying dynamics. To explore the developing burst/spike activities of such networks, we propose a burst detection algorithm which utilizes the firing statistics based on interspike interval (ISI histograms. Moreover, the algorithm calculates interspike interval thresholds for burst spikes as well as for pre-burst spikes and burst tails by evaluating the cumulative moving average and skewness of the ISI histogram. Because of the adaptive nature of the proposed algorithm, its analysis power is not limited by the type of neuronal cell network at hand. We demonstrate the functionality of our algorithm with two different types of microelectrode array (MEA data recorded from spontaneously active hESC-derived neuronal cell networks. The same data was also analyzed by two commonly employed burst detection algorithms and the differences in burst detection results are illustrated. The results demonstrate that our method is both adaptive to the firing statistics of the network and yields successful burst detection from the data. In conclusion, the proposed method is a potential tool for analyzing of hESC-derived neuronal cell networks and thus can be utilized in studies aiming to understand the development and functioning of human neuronal networks and as an analysis tool for in vitro drug screening and neurotoxicity assays.

  8. The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake.

    Science.gov (United States)

    Böhm, Jennifer; Scherzer, Sönke; Krol, Elzbieta; Kreuzer, Ines; von Meyer, Katharina; Lorey, Christian; Mueller, Thomas D; Shabala, Lana; Monte, Isabel; Solano, Roberto; Al-Rasheid, Khaled A S; Rennenberg, Heinz; Shabala, Sergey; Neher, Erwin; Hedrich, Rainer

    2016-02-08

    Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na(+)-rich animal and nutrition for the plant. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Action Potential Shortening and Impairment of Cardiac Function by Ablation of Slc26a6.

    Science.gov (United States)

    Sirish, Padmini; Ledford, Hannah A; Timofeyev, Valeriy; Thai, Phung N; Ren, Lu; Kim, Hyo Jeong; Park, Seojin; Lee, Jeong Han; Dai, Gu; Moshref, Maryam; Sihn, Choong-Ryoul; Chen, Wei Chun; Timofeyeva, Maria Valeryevna; Jian, Zhong; Shimkunas, Rafael; Izu, Leighton T; Chiamvimonvat, Nipavan; Chen-Izu, Ye; Yamoah, Ebenezer N; Zhang, Xiao-Dong

    2017-10-01

    Intracellular pH (pH i ) is critical to cardiac excitation and contraction; uncompensated changes in pH i impair cardiac function and trigger arrhythmia. Several ion transporters participate in cardiac pH i regulation. Our previous studies identified several isoforms of a solute carrier Slc26a6 to be highly expressed in cardiomyocytes. We show that Slc26a6 mediates electrogenic Cl - /HCO 3 - exchange activities in cardiomyocytes, suggesting the potential role of Slc26a6 in regulation of not only pH i , but also cardiac excitability. To test the mechanistic role of Slc26a6 in the heart, we took advantage of Slc26a6 knockout ( Slc26a6 -/ - ) mice using both in vivo and in vitro analyses. Consistent with our prediction of its electrogenic activities, ablation of Slc26a6 results in action potential shortening. There are reduced Ca 2+ transient and sarcoplasmic reticulum Ca 2+ load, together with decreased sarcomere shortening in Slc26a6 -/ - cardiomyocytes. These abnormalities translate into reduced fractional shortening and cardiac contractility at the in vivo level. Additionally, pH i is elevated in Slc26a6 -/ - cardiomyocytes with slower recovery kinetics from intracellular alkalization, consistent with the Cl - /HCO 3 - exchange activities of Slc26a6. Moreover, Slc26a6 -/ - mice show evidence of sinus bradycardia and fragmented QRS complex, supporting the critical role of Slc26a6 in cardiac conduction system. Our study provides mechanistic insights into Slc26a6, a unique cardiac electrogenic Cl - /HCO 3 - transporter in ventricular myocytes, linking the critical roles of Slc26a6 in regulation of pH i , excitability, and contractility. pH i is a critical regulator of other membrane and contractile proteins. Future studies are needed to investigate possible changes in these proteins in Slc26a6 -/ - mice. © 2017 American Heart Association, Inc.

  10. Potential Beneficiaries of the Obama Administration’s Executive Action Programs Deeply Embedded in US Society

    OpenAIRE

    Donald Kerwin; Robert Warren

    2016-01-01

    The Obama administration has developed two broad programs to defer immigration enforcement actions against undocumented persons living in the United States: (1) Deferred Action for Parents of Americans and Lawful Permanent Residents (DAPA); and (2) Deferred Action for Childhood Arrivals (DACA). The DACA program, which began in August 2012, was expanded on November 20, 2014. DAPA and the DACA expansion (hereinafter referred to as “DACA-plus”) are currently under review by the US Supreme Court ...

  11. Electrostatic potential map modelling with COSY Infinity

    International Nuclear Information System (INIS)

    Maloney, J.A.; Baartman, R.; Planche, T.; Saminathan, S.

    2016-01-01

    COSY Infinity (Makino and Berz, 2005) is a differential-algebra based simulation code which allows accurate calculation of transfer maps to arbitrary order. COSY’s existing internal procedures were modified to allow electrostatic elements to be specified using an array of field potential data from the midplane. Additionally, a new procedure was created allowing electrostatic elements and their fringe fields to be specified by an analytic function. This allows greater flexibility in accurately modelling electrostatic elements and their fringe fields. Applied examples of these new procedures are presented including the modelling of a shunted electrostatic multipole designed with OPERA, a spherical electrostatic bender, and the effects of different shaped apertures in an electrostatic beam line.

  12. Modelling Dowel Action of Discrete Reinforcing Bars in Cracked Concrete Structures

    International Nuclear Information System (INIS)

    Kwan, A. K. H.; Ng, P. L.; Lam, J. Y. K.

    2010-01-01

    Dowel action is one of the component actions for shear force transfer in cracked reinforced concrete. In finite element analysis of concrete structures, the use of discrete representation of reinforcing bars is considered advantageous over the smeared representation due to the relative ease of modelling the bond-slip behaviour. However, there is very limited research on how to simulate the dowel action of discrete reinforcing bars. Herein, a numerical model for dowel action of discrete reinforcing bars crossing cracks in concrete is developed. The model features the derivation of dowel stiffness matrix based on beam-on-elastic-foundation theory and the direct assemblage of dowel stiffness into the concrete element stiffness matrices. The dowel action model is incorporated in a nonlinear finite element programme with secant stiffness formulation. Deep beams tested in the literature are analysed and it is found that the incorporation of dowel action model improves the accuracy of analysis.

  13. Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

    Science.gov (United States)

    Rubi, Lena; Eckert, Daniel; Boehm, Stefan; Hilber, Karlheinz; Koenig, Xaver

    2017-04-01

    Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias.

  14. Toxicity, sublethal effects, and potential modes of action of select fungicides on freshwater fish and invertebrates

    Science.gov (United States)

    Elskus, Adria A.

    2012-01-01

    Despite decades of agricultural and urban use of fungicides and widespread detection of these pesticides in surface waters, relatively few data are available on the effects of fungicides on fish and invertebrates in the aquatic environment. Nine fungicides are reviewed in this report: azoxystrobin, boscalid, chlorothalonil, fludioxonil, myclobutanil, fenarimol, pyraclostrobin, pyrimethanil, and zoxamide. These fungicides were identified as emerging chemicals of concern because of their high or increasing global use rates, detection frequency in surface waters, or likely persistence in the environment. A review of the literature revealed significant sublethal effects of fungicides on fish, aquatic invertebrates, and ecosystems, including zooplankton and fish reproduction, fish immune function, zooplankton community composition, metabolic enzymes, and ecosystem processes, such as leaf decomposition in streams, among other biological effects. Some of these effects can occur at fungicide concentrations well below single-species acute lethality values (48- or 96-hour concentration that effects a response in 50 percent of the organisms, that is, effective concentration killing 50 percent of the organisms in 48 or 96 hours) and chronic sublethal values (for example, 21-day no observed adverse effects concentration), indicating that single-species toxicity values may dramatically underestimate the toxic potency of some fungicides. Fungicide modes of toxic action in fungi can sometimes reflect the biochemical and (or) physiological effects of fungicides observed in vertebrates and invertebrates; however, far more studies are needed to explore the potential to predict effects in nontarget organisms based on specific fungicide modes of toxic action. Fungicides can also have additive and (or) synergistic effects when used with other fungicides and insecticides, highlighting the need to study pesticide mixtures that occur in surface waters. For fungicides that partition to

  15. Associations between motor unit action potential parameters and surface EMG features.

    Science.gov (United States)

    Del Vecchio, Alessandro; Negro, Francesco; Felici, Francesco; Farina, Dario

    2017-10-01

    The surface interference EMG signal provides some information on the neural drive to muscles. However, the association between neural drive to muscle and muscle activation has long been debated with controversial indications due to the unavailability of motor unit population data. In this study, we clarify the potential and limitations of interference EMG analysis to infer motor unit recruitment strategies with an experimental investigation of several concurrently active motor units and of the associated features of the surface EMG. For this purpose, we recorded high-density surface EMG signals during linearly increasing force contractions of the tibialis anterior muscle, up to 70% of maximal force. The recruitment threshold (RT), conduction velocity (MUCV), median frequency (MDF MU ), and amplitude (RMS MU ) of action potentials of 587 motor units from 13 individuals were assessed and associated with features of the interference EMG. MUCV was positively associated with RT ( R 2 = 0.64 ± 0.14), whereas MDF MU and RMS MU showed a weaker relation with RT ( R 2 = 0.11 ± 0.11 and 0.39 ± 0.24, respectively). Moreover, the changes in average conduction velocity estimated from the interference EMG predicted well the changes in MUCV ( R 2 = 0.71), with a strong association to ankle dorsiflexion force ( R 2 = 0.81 ± 0.12). Conversely, both the average EMG MDF and RMS were poorly associated with motor unit recruitment. These results clarify the limitations of EMG spectral and amplitude analysis in inferring the neural strategies of muscle control and indicate that, conversely, the average conduction velocity could provide relevant information on these strategies. NEW & NOTEWORTHY The surface EMG provides information on the neural drive to muscles. However, the associations between EMG features and neural drive have been long debated due to unavailability of motor unit population data. Here, by using novel highly accurate decomposition of the EMG, we related motor unit

  16. Facilitating Youth to Take Sustainability Actions: The Potential of Peer Education

    Science.gov (United States)

    de Vreede, Catherine; Warner, Alan; Pitter, Robert

    2014-01-01

    Peer education is an understudied yet valuable strategy for sustainability educators in shifting youth to take action for sustainability. This case study conceptualizes the change process in facilitating youth to take sustainability actions, and explores the benefits, dynamics, and challenges of peer education as a strategy in facilitating change.…

  17. Mathematical Model for the Sequential Action of Radiation and Heat on Yeast Cells

    International Nuclear Information System (INIS)

    Kim, Jin Kyu; Lee, Yun Jong; Kim, Su Hyoun; Nili, Mohammad; Zhurakovskaya, Galina P.; Petin, Vladislav G.

    2009-01-01

    It is well known that the synergistic interaction of hyperthermia with ionizing radiation and other agents is widely used in hyperthermic oncology. Interaction between two agents may be considered as synergistic or antagonistic when the effect produced is greater or smaller than the sum of the two single responses. It has long be considered that the mechanism of synergistic interaction of hyperthermia and ionizing radiation may be brought about by an inhibition of the repair from sublethal and potentially lethal damage at the cellular level. The inhibition of the recovery process after combined treatments cannot be considered as a reason for the synergy, but rather would be the expected and predicted consequence of the production of irreversible damage. On the basis of it, a simple mathematical model of the synergistic interaction of two agents acting simultaneously has been proposed. However, the model has not been applied to predict the degree of interaction of heat and ionizing radiation after their sequential action. Extension of the model to the sequential treatment of heat and ionizing radiation seems to be of interest for theoretical and practical reasons. Thus, the purposes of the present work is to suggest the simplest mathematical model which would be able to account for the results obtained and currently available experimental information on the sequential action of radiation and heat.

  18. Action potential influences spatial perception: Evidence for genuine top-down effects on perception.

    Science.gov (United States)

    Witt, Jessica K

    2017-08-01

    The action-specific account of spatial perception asserts that a perceiver's ability to perform an action, such as hitting a softball or walking up a hill, impacts the visual perception of the target object. Although much evidence is consistent with this claim, the evidence has been challenged as to whether perception is truly impacted, as opposed to the responses themselves. These challenges have recently been organized as six pitfalls that provide a framework with which to evaluate the empirical evidence. Four case studies of action-specific effects are offered as evidence that meets the framework's high bar, and thus that demonstrates genuine perceptual effects. That action influences spatial perception is evidence that perceptual and action-related processes are intricately and bidirectionally linked.

  19. Activation of Mechanosensitive Transient Receptor Potential/Piezo Channels in Odontoblasts Generates Action Potentials in Cocultured Isolectin B4-negative Medium-sized Trigeminal Ganglion Neurons.

    Science.gov (United States)

    Sato, Masaki; Ogura, Kazuhiro; Kimura, Maki; Nishi, Koichi; Ando, Masayuki; Tazaki, Masakazu; Shibukawa, Yoshiyuki

    2018-04-27

    Various stimuli to the dentin surface elicit dentinal pain by inducing dentinal fluid movement causing cellular deformation in odontoblasts. Although odontoblasts detect deformation by the activation of mechanosensitive ionic channels, it is still unclear whether odontoblasts are capable of establishing neurotransmission with myelinated A delta (Aδ) neurons. Additionally, it is still unclear whether these neurons evoke action potentials by neurotransmitters from odontoblasts to mediate sensory transduction in dentin. Thus, we investigated evoked inward currents and evoked action potentials form trigeminal ganglion (TG) neurons after odontoblast mechanical stimulation. We used patch clamp recordings to identify electrophysiological properties and record evoked responses in TG neurons. We classified TG cells into small-sized and medium-sized neurons. In both types of neurons, we observed voltage-dependent inward currents. The currents from medium-sized neurons showed fast inactivation kinetics. When mechanical stimuli were applied to odontoblasts, evoked inward currents were recorded from medium-sized neurons. Antagonists for the ionotropic adenosine triphosphate receptor (P2X 3 ), transient receptor potential channel subfamilies, and Piezo1 channel significantly inhibited these inward currents. Mechanical stimulation to odontoblasts also generated action potentials in the isolectin B 4 -negative medium-sized neurons. Action potentials in these isolectin B 4 -negative medium-sized neurons showed a short duration. Overall, electrophysiological properties of neurons indicate that the TG neurons with recorded evoked responses after odontoblast mechanical stimulation were myelinated Aδ neurons. Odontoblasts established neurotransmission with myelinated Aδ neurons via P2X 3 receptor activation. The results also indicated that mechanosensitive TRP/Piezo1 channels were functionally expressed in odontoblasts. The activation of P2X 3 receptors induced an action potential

  20. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

    Science.gov (United States)

    Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

    2018-01-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  1. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    Science.gov (United States)

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  2. Common Marmosets: A Potential Translational Animal Model of Juvenile Depression

    Directory of Open Access Journals (Sweden)

    Nicole Leite Galvão-Coelho

    2017-09-01

    Full Text Available Major depression is a psychiatric disorder with high prevalence in the general population, with increasing expression in adolescence, about 14% in young people. Frequently, it presents as a chronic condition, showing no remission even after several pharmacological treatments and persisting in adult life. Therefore, distinct protocols and animal models have been developed to increase the understanding of this disease or search for new therapies. To this end, this study investigated the effects of chronic social isolation and the potential antidepressant action of nortriptyline in juvenile Callithrix jacchus males and females by monitoring fecal cortisol, body weight, and behavioral parameters and searching for biomarkers and a protocol for inducing depression. The purpose was to validate this species and protocol as a translational model of juvenile depression, addressing all domain criteria of validation: etiologic, face, functional, predictive, inter-relational, evolutionary, and population. In both sexes and both protocols (IDS and DPT, we observed a significant reduction in cortisol levels in the last phase of social isolation, concomitant with increases in autogrooming, stereotyped and anxiety behaviors, and the presence of anhedonia. The alterations induced by chronic social isolation are characteristic of the depressive state in non-human primates and/or in humans, and were reversed in large part by treatment with an antidepressant drug (nortriptyline. Therefore, these results indicate C. jacchus as a potential translational model of juvenile depression by addressing all criteria of validation.

  3. Electrically evoked compound action potentials artefact rejection by independent component analysis: procedure automation.

    Science.gov (United States)

    Akhoun, Idrick; McKay, Colette; El-Deredy, Wael

    2015-01-15

    Independent-components-analysis (ICA) successfully separated electrically-evoked compound action potentials (ECAPs) from the stimulation artefact and noise (ECAP-ICA, Akhoun et al., 2013). This paper shows how to automate the ECAP-ICA artefact cancellation process. Raw-ECAPs without artefact rejection were consecutively recorded for each stimulation condition from at least 8 intra-cochlear electrodes. Firstly, amplifier-saturated recordings were discarded, and the data from different stimulus conditions (different current-levels) were concatenated temporally. The key aspect of the automation procedure was the sequential deductive source categorisation after ICA was applied with a restriction to 4 sources. The stereotypical aspect of the 4 sources enables their automatic classification as two artefact components, a noise and the sought ECAP based on theoretical and empirical considerations. The automatic procedure was tested using 8 cochlear implant (CI) users and one to four stimulus electrodes. The artefact and noise sources were successively identified and discarded, leaving the ECAP as the remaining source. The automated ECAP-ICA procedure successfully extracted the correct ECAPs compared to standard clinical forward masking paradigm in 22 out of 26 cases. ECAP-ICA does not require extracting the ECAP from a combination of distinct buffers as it is the case with regular methods. It is an alternative that does not have the possible bias of traditional artefact rejections such as alternate-polarity or forward-masking paradigms. The ECAP-ICA procedure bears clinical relevance, for example as the artefact rejection sub-module of automated ECAP-threshold detection techniques, which are common features of CI clinical fitting software. Copyright © 2014. Published by Elsevier B.V.

  4. Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

    Directory of Open Access Journals (Sweden)

    Joshua Kuang-Chao Chen

    Full Text Available Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001. There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes

  5. Effects of estragole on the compound action potential of the rat sciatic nerve

    Directory of Open Access Journals (Sweden)

    J.H. Leal-Cardoso

    2004-08-01

    Full Text Available Estragole, a relatively nontoxic terpenoid ether, is an important constituent of many essential oils with widespread applications in folk medicine and aromatherapy and known to have potent local anesthetic activity. We investigated the effects of estragole on the compound action potential (CAP of the rat sciatic nerve. The experiments were carried out on sciatic nerves dissected from Wistar rats. Nerves, mounted in a moist chamber, were stimulated at a frequency of 0.2 Hz, with electric pulses of 50-100-µs duration at 10-20 V, and evoked CAP were monitored on an oscilloscope and recorded on a computer. CAP control parameters were: peak-to-peak amplitude (PPA, 9.9 ± 0.55 mV (N = 15, conduction velocity, 92.2 ± 4.36 m/s (N = 15, chronaxy, 45.6 ± 3.74 µs (N = 5, and rheobase, 3.9 ± 0.78 V (N = 5. Estragole induced a dose-dependent blockade of the CAP. At 0.6 mM, estragole had no demonstrable effect. At 2.0 and 6.0 mM estragole, PPA was significantly reduced at the end of 180-min exposure of the nerve to the drug to 85.6 ± 3.96 and 13.04 ± 1.80% of control, respectively. At 4.0 mM, estragole significantly altered PPA, conduction velocity, chronaxy, and rheobase (P <= 0.05, ANOVA; N = 5 to 49.3 ± 6.21 and 77.7 ± 3.84, 125.9 ± 10.43 and 116.7 ± 4.59%, of control, respectively. All of these effects developed slowly and were reversible upon a 300-min wash-out. The data show that estragole dose-dependently blocks nerve excitability.

  6. Action Relations. Basic Design Concepts for Behaviour Modelling and Refinement.

    NARCIS (Netherlands)

    Quartel, Dick

    This thesis presents basic design concepts, design methods and a basic design language for distributed system behaviours. This language is based on two basic concepts: the action concept and the causality relation concept. Our methods focus on behaviour refinement, which consists of replacing an

  7. The energy cost of action potential propagation in dopamine neurons: clues to susceptibility in Parkinson's disease.

    Science.gov (United States)

    Pissadaki, Eleftheria K; Bolam, J Paul

    2013-01-01

    Dopamine neurons of the substantia nigra pars compacta (SNc) are uniquely sensitive to degeneration in Parkinson's disease (PD) and its models. Although a variety of molecular characteristics have been proposed to underlie this sensitivity, one possible contributory factor is their massive, unmyelinated axonal arbor that is orders of magnitude larger than other neuronal types. We suggest that this puts them under such a high energy demand that any stressor that perturbs energy production leads to energy demand exceeding supply and subsequent cell death. One prediction of this hypothesis is that those dopamine neurons that are selectively vulnerable in PD will have a higher energy cost than those that are less vulnerable. We show here, through the use of a biology-based computational model of the axons of individual dopamine neurons, that the energy cost of axon potential propagation and recovery of the membrane potential increases with the size and complexity of the axonal arbor according to a power law. Thus SNc dopamine neurons, particularly in humans, whose axons we estimate to give rise to more than 1 million synapses and have a total length exceeding 4 m, are at a distinct disadvantage with respect to energy balance which may be a factor in their selective vulnerability in PD.

  8. Synthesis of sulfenamides, derivatives of morpholine, 4-aminomorpholine and thiomorpholine as compounds of potential radioprotective action

    Energy Technology Data Exchange (ETDEWEB)

    Strzelczyk, M.; Kucharski, A. (Wojskowa Akademia Medyczna, Lodz (Poland))

    1979-01-01

    Sulfenamides belong to the group of compounds displaying radioprotective action. Their mechanism of action is based mainly on the protection against oxygenation. Six compounds were synthetized four of which i.e. 3-nitrophenylothiomorpholine, 2,4-dinitrophenylothiomorpholine, 2,4-dinitrophenylothio-4-aminomorpholine and 2,4-dinitrophenylothiothiomorpholine were to date not described in the literature. The structure of the synthetized compounds was confirmed by elementary and infrared spectral analysis.

  9. Flattening of the electrocardiographic T-wave is a sign of proarrhythmic risk and a reflection of action potential triangulation

    DEFF Research Database (Denmark)

    Bhuiyan, Tanveer Ahmed; Graff, Claus; Kanters, J.K.

    2013-01-01

    Drug-induced triangulation of the cardiac action potential is associated with increased risk of arrhythmic events. It has been suggested that triangulation causes a flattening of the electrocardiographic T-wave but the relationship between triangulation, T-wave flattening and onset of arrhythmia ...

  10. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  11. Nanoelectronics-biology frontier: From nanoscopic probes for action potential recording in live cells to three-dimensional cyborg tissues

    OpenAIRE

    Duan, Xiaojie; Fu, Tian-Ming; Liu, Jia; Lieber, Charles M.

    2013-01-01

    Semiconductor nanowires configured as the active channels of field-effect transistors (FETs) have been used as detectors for high-resolution electrical recording from single live cells, cell networks, tissues and organs. Extracellular measurements with substrate supported silicon nanowire (SiNW) FETs, which have projected active areas orders of magnitude smaller than conventional microfabricated multielectrode arrays (MEAs) and planar FETs, recorded action potential and field potential signa...

  12. Concentration addition and independent action model: Which is better in predicting the toxicity for metal mixtures on zebrafish larvae.

    Science.gov (United States)

    Gao, Yongfei; Feng, Jianfeng; Kang, Lili; Xu, Xin; Zhu, Lin

    2018-01-01

    The joint toxicity of chemical mixtures has emerged as a popular topic, particularly on the additive and potential synergistic actions of environmental mixtures. We investigated the 24h toxicity of Cu-Zn, Cu-Cd, and Cu-Pb and 96h toxicity of Cd-Pb binary mixtures on the survival of zebrafish larvae. Joint toxicity was predicted and compared using the concentration addition (CA) and independent action (IA) models with different assumptions in the toxic action mode in toxicodynamic processes through single and binary metal mixture tests. Results showed that the CA and IA models presented varying predictive abilities for different metal combinations. For the Cu-Cd and Cd-Pb mixtures, the CA model simulated the observed survival rates better than the IA model. By contrast, the IA model simulated the observed survival rates better than the CA model for the Cu-Zn and Cu-Pb mixtures. These findings revealed that the toxic action mode may depend on the combinations and concentrations of tested metal mixtures. Statistical analysis of the antagonistic or synergistic interactions indicated that synergistic interactions were observed for the Cu-Cd and Cu-Pb mixtures, non-interactions were observed for the Cd-Pb mixtures, and slight antagonistic interactions for the Cu-Zn mixtures. These results illustrated that the CA and IA models are consistent in specifying the interaction patterns of binary metal mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Action Relations. Basic Design Concepts for Behaviour Modelling and Refinement.

    OpenAIRE

    Quartel, Dick

    1998-01-01

    This thesis presents basic design concepts, design methods and a basic design language for distributed system behaviours. This language is based on two basic concepts: the action concept and the causality relation concept. Our methods focus on behaviour refinement, which consists of replacing an abstract behaviour by a more concrete behaviour, such that the concrete behaviour conforms to the abstract behaviour. An important idea underlying this thesis is that an effective design methodology s...

  14. Governance issues, potentials and failures of participative collective action in the Kafue Flats, Zambia

    Directory of Open Access Journals (Sweden)

    Harry Nixon Chabwela

    2010-09-01

    2004 for creating by-laws based on initiatives of local staff of the Department of Fisheries, local interest groups and researchers. A broad local debate on how to manage the fisheries in a sustainable way and develop locally based by-laws for joint management of fisheries gives good potential for success and appears promising for the future of fisheries in Kafue Flats. Despite many difficulties it is an example of local collective action in order to scale up governance of common-pool resources.

  15. Acute Elevated Glucose Promotes Abnormal Action Potential-Induced Ca2+ Transients in Cultured Skeletal Muscle Fibers

    Directory of Open Access Journals (Sweden)

    Erick O. Hernández-Ochoa

    2017-01-01

    Full Text Available A common comorbidity of diabetes is skeletal muscle dysfunction, which leads to compromised physical function. Previous studies of diabetes in skeletal muscle have shown alterations in excitation-contraction coupling (ECC—the sequential link between action potentials (AP, intracellular Ca2+ release, and the contractile machinery. Yet, little is known about the impact of acute elevated glucose on the temporal properties of AP-induced Ca2+ transients and ionic underlying mechanisms that lead to muscle dysfunction. Here, we used high-speed confocal Ca2+ imaging to investigate the temporal properties of AP-induced Ca2+ transients, an intermediate step of ECC, using an acute in cellulo model of uncontrolled hyperglycemia (25 mM, 48 h.. Control and elevated glucose-exposed muscle fibers cultured for five days displayed four distinct patterns of AP-induced Ca2+ transients (phasic, biphasic, phasic-delayed, and phasic-slow decay; most control muscle fibers show phasic AP-induced Ca2+ transients, while most fibers exposed to elevated D-glucose displayed biphasic Ca2+ transients upon single field stimulation. We hypothesize that these changes in the temporal profile of the AP-induced Ca2+ transients are due to changes in the intrinsic excitable properties of the muscle fibers. We propose that these changes accompany early stages of diabetic myopathy.

  16. Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

    Science.gov (United States)

    Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

    2017-01-01

    Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

  17. ANTICONVULSANT AND ANTIEPILEPTIC ACTIONS OF 2-DEOXY-DGLUCOSE IN EPILEPSY MODELS

    Science.gov (United States)

    Stafstrom, Carl E.; Ockuly, Jeffrey C.; Murphree, Lauren; Valley, Matthew T.; Roopra, Avtar; Sutula, Thomas P.

    2009-01-01

    Objective Conventional anticonvulsants reduce neuronal excitability through effects on ion channels and synaptic function. Anticonvulsant mechanisms of the ketogenic diet remain incompletely understood. Since carbohydrates are restricted in patients on the ketogenic diet, we evaluated the effects of limiting carbohydrate availability by reducing glycolysis using the glycolytic inhibitor 2-deoxy-D-glucose (2DG) in experimental models of seizures and epilepsy. Methods Acute anticonvulsant actions of 2DG were assessed in vitro in rat hippocampal slices perfused with 7.5mM [K+]o, 4-aminopyridine (4-AP), or bicuculline and in vivo against seizures evoked by 6 Hz stimulation in mice, audiogenic stimulation in Fring’s mice, and maximal electroshock and subcutaneous Metrazol in rats. Chronic antiepileptic effects of 2DG were evaluated in rats kindled from olfactory bulb or perforant path. Results 2DG (10mM) reduced interictal epileptiform bursts induced by high [K+]o, 4-AP and bicuculline, and electrographic seizures induced by high [K+]o in CA3 of hippocampus. 2DG reduced seizures evoked by 6 Hz stimulation in mice (ED50 = 79.7 mg/kg) and audiogenic stimulation in Fring’s mice (ED50 = 206.4 mg/kg). 2DG exerted chronic antiepileptic action by increasing afterdischarge thresholds in perforant path (but not olfactory bulb) kindling and caused a 2-fold slowing in progression of kindled seizures at both stimulation sites. 2DG did not protect against maximal electroshock or Metrazol seizures. Interpretation The glycolytic inhibitor 2DG exerts acute anticonvulsant and chronic antiepileptic actions and has a novel pattern of effectiveness in preclinical screening models. These results identify metabolic regulation as a potential therapeutic target for seizure suppression and modification of epileptogenesis. PMID:19399874

  18. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    Science.gov (United States)

    Merç, Ali

    2015-01-01

    The purpose of this study was to determine Turkish EFL teachers' attitudes towards classroom observation. 204 teachers from different school settings responded to an online questionnaire. Data were analyzed according to three types of attitudes towards classroom observation: perceptions, sentiments, and readiness for action. The findings revealed…

  19. Acupuncture therapy: mechanism of action, efficacy, and safety: a potential intervention for psychogenic disorders?

    Science.gov (United States)

    2014-01-01

    Scientific bases for the mechanism of action of acupuncture in the treatment of pain and the pathogenic mechanism of acupuncture points are briefly summarized. The efficacy and safety of acupuncture therapy is discussed based on the results of German clinical trials. A conclusion on the role for acupuncture in the treatment of psychogenic disorders could not be reached. PMID:24444292

  20. Consolidated Quarterly Report: Number of potential release sites subject to corrective action

    Energy Technology Data Exchange (ETDEWEB)

    Cochran, John R.; Cochran, John R.

    2017-04-01

    This Sandia National Laboratories, New Mexico Environmental Restoration Operations (ER) Consolidated Quarterly Report (ER Quarterly Report) fulfills all quarterly reporting requirements set forth in the Resource Conservation and Recovery Act Facility Operating Permit and the Compliance Order on Consent. The 12 sites in the corrective action process are listed in Table I-1.

  1. Motivations and possible actions of potential criminal adversaries of US nuclear programs

    International Nuclear Information System (INIS)

    Bass, G.; Jenkins, B.; Kellen, K.; Krofcheek, J.; Petty, G.; Reinstedt, R.; Ronfeldt, D.

    1981-01-01

    The motivations that might impel individuals or groups to undertake criminal actions against US nuclear facilities or programs are explored in the report (R and R-2554-SL) from which this note is taken. The analysis involves examination of the motivations behind nuclear-related crimes that have already occurred and of those behind analogous nonnuclear crimes

  2. On the Potentials for Synergy Between COST Action TU1406 and the JCSS

    DEFF Research Database (Denmark)

    Nielsen, Michael Havbro Faber

    On of the main challenges of COST Action TU1406 is to identify, categorize and to the extent possible represent performance indicators of roadway bridges in a manner supporting decision making for their service life integrity management. This calls for an information consistent approach accounting...

  3. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS

    Science.gov (United States)

    Dodman, Stephanie L.; Lai, Kerri; Campet, Melissa; Cavallero-Lotocki, Renee; Hopkins, Aaron; Onidi, Christine

    2014-01-01

    Deliberate investigation into practice is an essential of the National Association for Professional Development Schools' defining elements of a Professional Development School (PDS). This article reports on the pilot efforts of one PDS as it initiated deliberate investigation through action research with a small group of teacher candidates. The…

  4. From Fiction to Fact to Potential Action: Generating Prosocial Attitudes and Behaviors Using Young Adult Literature

    Science.gov (United States)

    Hays, Alice

    2017-01-01

    This dissertation investigates the impact reading Young Adult Literature (YAL) has on students' empathetic responses as well as their capacity to take action regarding a social justice issue chosen by the student. Drawing on data from a 10th grade honors classroom at a Title 1 school in the Southwest, this ethnographic case study investigates how…

  5. Two-loop calculation of the effective potential for the Wess-Zumino model

    International Nuclear Information System (INIS)

    Fogleman, G.; Starkmann, G.D.; Viswanathan, K.S.; Simon Fraser Univ., Burnaby, British Columbia

    1983-01-01

    The effective potential for the supersymmetric Wess-Zumino model is computed off-shell to two loops. A renormalization procedure which preserves positivity of the kinetic terms in the effective action is implemented. Supersymmetry is not broken to this order. (orig.)

  6. Proposed actions are no actions: re-modeling an ontology design pattern with a realist top-level ontology.

    Science.gov (United States)

    Seddig-Raufie, Djamila; Jansen, Ludger; Schober, Daniel; Boeker, Martin; Grewe, Niels; Schulz, Stefan

    2012-09-21

    Ontology Design Patterns (ODPs) are representational artifacts devised to offer solutions for recurring ontology design problems. They promise to enhance the ontology building process in terms of flexibility, re-usability and expansion, and to make the result of ontology engineering more predictable. In this paper, we analyze ODP repositories and investigate their relation with upper-level ontologies. In particular, we compare the BioTop upper ontology to the Action ODP from the NeOn an ODP repository. In view of the differences in the respective approaches, we investigate whether the Action ODP can be embedded into BioTop. We demonstrate that this requires re-interpreting the meaning of classes of the NeOn Action ODP in the light of the precepts of realist ontologies. As a result, the re-design required clarifying the ontological commitment of the ODP classes by assigning them to top-level categories. Thus, ambiguous definitions are avoided. Classes of real entities are clearly distinguished from classes of information artifacts. The proposed approach avoids the commitment to the existence of unclear future entities which underlies the NeOn Action ODP. Our re-design is parsimonious in the sense that existing BioTop content proved to be largely sufficient to define the different types of actions and plans. The proposed model demonstrates that an expressive upper-level ontology provides enough resources and expressivity to represent even complex ODPs, here shown with the different flavors of Action as proposed in the NeOn ODP. The advantage of ODP inclusion into a top-level ontology is the given predetermined dependency of each class, an existing backbone structure and well-defined relations. Our comparison shows that the use of some ODPs is more likely to cause problems for ontology developers, rather than to guide them. Besides the structural properties, the explanation of classification results were particularly hard to grasp for 'self-sufficient' ODPs as

  7. New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

    Science.gov (United States)

    Kolodziejczyk, Patrycjusz; Gromotowicz-Poplawska, Anna; Aleksiejczuk, Michal; Chabielska, Ewa; Tutka, Piotr; Miltyk, Wojciech

    2018-03-26

    Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although, this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disordes, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MR). Now we know that the mechanism of aldosterone action in cardiovascular system is much more complex, since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-incuced harmful effects in the cardiovascular system. Therefore, the involvement of some other than MR, receptors and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of a cardiovascular system. The confirmation of multiple mechanisms of aldosterone action opens a new perspective for more effective therapeutic intervention in aldosterone-related CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

    Science.gov (United States)

    Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

    2017-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

  9. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  10. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  11. Feature-Specific Event-Related Potential Effects to Action- and Sound-Related Verbs during Visual Word Recognition.

    Science.gov (United States)

    Popp, Margot; Trumpp, Natalie M; Kiefer, Markus

    2016-01-01

    Grounded cognition theories suggest that conceptual representations essentially depend on modality-specific sensory and motor systems. Feature-specific brain activation across different feature types such as action or audition has been intensively investigated in nouns, while feature-specific conceptual category differences in verbs mainly focused on body part specific effects. The present work aimed at assessing whether feature-specific event-related potential (ERP) differences between action and sound concepts, as previously observed in nouns, can also be found within the word class of verbs. In Experiment 1, participants were visually presented with carefully matched sound and action verbs within a lexical decision task, which provides implicit access to word meaning and minimizes strategic access to semantic word features. Experiment 2 tested whether pre-activating the verb concept in a context phase, in which the verb is presented with a related context noun, modulates subsequent feature-specific action vs. sound verb processing within the lexical decision task. In Experiment 1, ERP analyses revealed a differential ERP polarity pattern for action and sound verbs at parietal and central electrodes similar to previous results in nouns. Pre-activation of the meaning of verbs in the preceding context phase in Experiment 2 resulted in a polarity-reversal of feature-specific ERP effects in the lexical decision task compared with Experiment 1. This parallels analogous earlier findings for primed action and sound related nouns. In line with grounded cognitions theories, our ERP study provides evidence for a differential processing of action and sound verbs similar to earlier observation for concrete nouns. Although the localizational value of ERPs must be viewed with caution, our results indicate that the meaning of verbs is linked to different neural circuits depending on conceptual feature relevance.

  12. 2PI effective action for the SYK model and tensor field theories

    Science.gov (United States)

    Benedetti, Dario; Gurau, Razvan

    2018-05-01

    We discuss the two-particle irreducible (2PI) effective action for the SYK model and for tensor field theories. For the SYK model the 2PI effective action reproduces the bilocal reformulation of the model without using replicas. In general tensor field theories the 2PI formalism is the only way to obtain a bilocal reformulation of the theory, and as such is a precious instrument for the identification of soft modes and for possible holographic interpretations. We compute the 2PI action for several models, and push it up to fourth order in the 1 /N expansion for the model proposed by Witten in [1], uncovering a one-loop structure in terms of an auxiliary bilocal action.

  13. The potential for multi-disciplinary primary health care services to take action on the social determinants of health: actions and constraints.

    Science.gov (United States)

    Baum, Frances E; Legge, David G; Freeman, Toby; Lawless, Angela; Labonté, Ronald; Jolley, Gwyneth M

    2013-05-10

    The Commission on the Social Determinants of Health and the World Health Organization have called for action to address the social determinants of health. This paper considers the extent to which primary health care services in Australia are able to respond to this call. We report on interview data from an empirical study of primary health care centres in Adelaide and Alice Springs, Australia. Sixty-eight interviews were held with staff and managers at six case study primary health care services, regional health executives, and departmental funders to explore how their work responded to the social determinants of health and the dilemmas in doing so. The six case study sites included an Aboriginal Community Controlled Organisation, a sexual health non-government organisation, and four services funded and managed by the South Australian government. While respondents varied in the extent to which they exhibited an understanding of social determinants most were reflexive about the constraints on their ability to take action. Services' responses to social determinants included delivering services in a way that takes account of the limitations individuals face from their life circumstances, and physical spaces in the primary health care services being designed to do more than simply deliver services to individuals. The services also undertake advocacy for policies that create healthier communities but note barriers to them doing this work. Our findings suggest that primary health care workers are required to transverse "dilemmatic space" in their work. The absence of systematic supportive policy, frameworks and structure means that it is hard for PHC services to act on the Commission on the Social Determinants of Health's recommendations. Our study does, however, provide evidence of the potential for PHC services to be more responsive to social determinants given more support and by building alliances with communities and social movements. Further research on the value

  14. Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells

    Science.gov (United States)

    Yaniv, Yael; Ganesan, Ambhighainath; Yang, Dongmei; Ziman, Bruce D.; Lyashkov, Alexey E.; Levchenko, Andre; Zhang, Jin; Lakatta, Edward G.

    2015-01-01

    cAMP-PKA protein kinase is a key nodal signaling pathway that regulates a wide range of heart pacemaker cell functions. These functions are predicted to be involved in regulation of spontaneous action potential (AP) generation of these cells. Here we investigate if the kinetics and stoichiometry of increase in PKA activity match the increase in AP firing rate in response to β-adrenergic receptor (β-AR) stimulation or phosphodiesterase (PDE) inhibition, that alter the AP firing rate of heart sinoatrial pacemaker cells. In cultured adult rabbit pacemaker cells infected with an adenovirous expressing the FRET sensor AKAR3, the EC50 in response to graded increases in the intensity of β-AR stimulation (by Isoproterenol) the magnitude of the increases in PKA activity and the spontaneous AP firing rate were similar (0.4±0.1nM vs. 0.6±0.15nM, respectively). Moreover, the kinetics (t1/2) of the increases in PKA activity and spontaneous AP firing rate in response to β-AR stimulation or PDE inhibition were tightly linked. We characterized the system rate-limiting biochemical reactions by integrating these experimentally derived data into mechanistic-computational model. Model simulations predicted that phospholamban phosphorylation is a potent target of the increase in PKA activity that links to increase in spontaneous AP firing rate. In summary, the kinetics and stoichiometry of increases in PKA activity in response to a physiological (β-AR stimulation) or pharmacological (PDE inhibitor) stimuli match those of changes in the AP firing rate. Thus Ca2+-cAMP/PKA-dependent phosphorylation limits the rate and magnitude of increase in spontaneous AP firing rate. PMID:26241846

  15. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Directory of Open Access Journals (Sweden)

    Marino DiFranco

    Full Text Available Exercise intolerance in chronic heart failure (HF has been attributed to abnormalities of the skeletal muscles. Muscle function depends on intact excitation-contraction coupling (ECC, but ECC studies in HF models have been inconclusive, due to deficiencies in the animal models and tools used to measure calcium (Ca2+ release, mandating investigations in skeletal muscle from HF patients. The purpose of this study was to test the hypothesis that Ca2+ release is significantly impaired in the skeletal muscle of HF patients in whom exercise capacity is severely diminished compared to age-matched healthy volunteers.Using state-of-the-art electrophysiological and optical techniques in single muscle fibers from biopsies of the locomotive vastus lateralis muscle, we measured the action potential (AP-evoked Ca2+ release in 4 HF patients and 4 age-matched healthy controls. The mean peak Ca2+ release flux in fibers obtained from HF patients (10±1.2 µM/ms was markedly (2.6-fold and significantly (p<0.05 smaller than in fibers from healthy volunteers (28±3.3 µM/ms. This impairment in AP-evoked Ca2+ release was ubiquitous and was not explained by differences in the excitability mechanisms since single APs were indistinguishable between HF patients and healthy volunteers.These findings prove the feasibility of performing electrophysiological experiments in single fibers from human skeletal muscle, and offer a new approach for investigations of myopathies due to HF and other diseases. Importantly, we have demonstrated that one step in the ECC process, AP-evoked Ca2+ release, is impaired in single muscle fibers in HF patients.

  16. Assessing transformational change potential: the case of the Tunisian cement Nationally Appropriate Mitigation Action (NAMA)

    DEFF Research Database (Denmark)

    Boodoo, Zyaad; Olsen, Karen Holm

    2018-01-01

    and documentation gathered during field work in Tunisia 2014–2015. The study finds that the NAMA design is not likely to lead to transformational change of the cement sector, since underlying factors accounting for lock-in are not properly tackled. Although the NAMA has enabled new and promising sectoral......To effectively address the root causes of carbon lock-in across developing countries, Nationally Appropriate Mitigation Actions (NAMAs) with transformational change characteristics are being supported by donors and finance mechanisms as a means to achieve ambitious nationally determined...... contributions (NDCs). However, there is still a scarcity of empirical studies on how transformational change policies and actions are designed and supported in practice. This article addresses such a gap in knowledge by combining theoretical insights from the multi-level perspective and transitions management...

  17. Biosynthesis of silver nanoparticles using Sida acuta extract for antimicrobial actions and corrosion inhibition potential.

    Science.gov (United States)

    Idrees, Muhammad; Batool, Saima; Kalsoom, Tanzila; Raina, Sadaf; Sharif, Hafiz Muhammad Adeel; Yasmeen, Summera

    2018-02-12

    Nanotechnology exhibits a multidisciplinary area and gained interests for researchers. Nanoparticles produced via physical and chemical methods affects ecosystem drastically. Green synthesis is the charming technique that is inexpensive and safe for the environment. This study aimed to explore the antibacterial actions of as-synthesized silver nanoparticles (Ag-NPs) against Escherichia coli, Staphylococcus aureus and Streptococcus faecalis. Also, the anti-corrosion actions confirmed that the Ag-NPs proved as good inhibitors. In this way, Ag-NPs were prepared via biosynthesis technique by consuming the ground leaves and stem of 'Sida acuta' as a capping agent. The Ag-NPs were formed by irradiation of the aqueous solution of silver nitrate (AgNO 3 ) with extract of S. acuta stem and leaves. The as-synthesized reaction mixture of Ag-NPs was found to exhibit an absorbance band at 446-447 nm, by an UV/VIS spectrophotometer, which is a characteristic of Ag-NPs due to the surface plasmon resonance absorption band. The X-ray diffraction and transmission electron microscopy (TEM) were used for the confirmation of Ag-NPs' variety dimension, morphology and dispersion. The infrared spectra confirmed the bio-fabrication of the Ag-NPs displayed the existence of conceivable functional groups responsible for the bio-reduction and capping. The antimicrobial actions were measured and the zone of inhibition was compared with standard antibiotics.

  18. Diosgenin, 4-hydroxyisoleucine, and fiber from fenugreek: mechanisms of actions and potential effects on metabolic syndrome.

    Science.gov (United States)

    Fuller, Scott; Stephens, Jacqueline M

    2015-03-01

    Metabolic syndrome and its complications continue to rise in prevalence and show no signs of abating in the immediate future. Therefore, the search for effective treatments is a high priority in biomedical research. Products derived from botanicals have a time-honored history of use in the treatment of metabolic diseases including type 2 diabetes. Trigonella foenum-graecum, commonly known as fenugreek, is an annual herbaceous plant that has been a staple of traditional herbal medicine in many cultures. Although fenugreek has been studied in both clinical and basic research settings, questions remain about its efficacy and biologic mechanisms of action. Diosgenin, 4-hydroxyisoleucine, and the fiber component of the plant are the most intensively studied bioactive constituents present in fenugreek. These compounds have been demonstrated to exert beneficial effects on several physiologic markers including glucose tolerance, inflammation, insulin action, liver function, blood lipids, and cardiovascular health. Although insights into the molecular mechanisms underlying the favorable effects of fenugreek have been gained, we still do not have definitive evidence establishing its role as a therapeutic agent in metabolic disease. This review aims to summarize the currently available evidence on the physiologic effects of the 3 best-characterized bioactive compounds of fenugreek, with particular emphasis on biologic mechanisms of action relevant in the context of metabolic syndrome. © 2015 American Society for Nutrition.

  19. [A Structural Equation Model of Pressure Ulcer Prevention Action in Clinical Nurses].

    Science.gov (United States)

    Lee, Sook Ja; Park, Ok Kyoung; Park, Mi Yeon

    2016-08-01

    The purpose of this study was to construct and test a structural equation model for pressure ulcer prevention action by clinical nurses. The Health Belief Model and the Theory of Planned Behavior were used as the basis for the study. A structured questionnaire was completed by 251 clinical nurses to analyze the relationships between concepts of perceived benefits, perceived barriers, attitude, subjective norm, perceived control, intention to perform action and behavior. SPSS 22.0 and AMOS 22.0 programs were used to analyze the efficiency of the hypothesized model and calculate the direct and indirect effects of factors affecting pressure ulcer prevention action among clinical nurses. The model fitness statistics of the hypothetical model fitted to the recommended levels. Attitude, subjective norm and perceived control on pressure ulcer prevention action explained 64.2% for intention to perform prevention action. The major findings of this study indicate that it is essential to recognize improvement in positive attitude for pressure ulcer prevention action and a need for systematic education programs to increase perceived control for prevention action.

  20. Potential of mathematical modeling in fruit quality

    African Journals Online (AJOL)

    ONOS

    2010-01-18

    Jan 18, 2010 ... successful mathematical model, the modeler needs to chose what .... equations. In the SUCROS models, the rate of CO2 assimilation is .... insect ecology. ... García y García A, Ingram KT, Hatch U, Hoogenboom G, Jones JW,.

  1. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    Science.gov (United States)

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  2. Teachers’ individual action theories about competence-based education: the value of the cognitive apprenticeship model

    NARCIS (Netherlands)

    Seezink, Audrey; Poell, Rob; Kirschner, Paul A.

    2009-01-01

    Seezink, A., Poell, R. F., & Kirschner, P. A. (2009). Teachers' individual action theories about competence-based education: The value of the cognitive apprenticeship model. Journal of Vocational Education & Training, 61, 203-215.

  3. A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration.

    Science.gov (United States)

    Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R

    2014-04-01

    The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    International Nuclear Information System (INIS)

    Franzellitti, Silvia; Buratti, Sara; Capolupo, Marco; Du, Bowen; Haddad, Samuel P.; Chambliss, C. Kevin; Brooks, Bryan W.; Fabbri, Elena

    2014-01-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  5. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    Energy Technology Data Exchange (ETDEWEB)

    Franzellitti, Silvia, E-mail: silvia.franzellitti@unibo.it [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Buratti, Sara; Capolupo, Marco [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Du, Bowen; Haddad, Samuel P. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Chambliss, C. Kevin [Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798 (United States); Brooks, Bryan W. [Department of Environmental Science, Baylor University, Waco, TX 76798 (United States); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy)

    2014-06-01

    Highlights: • Mode of action (MOA) related endpoints and biomarkers of toxicity were assessed in mussels exposed to fluoxetine (FX). • Significant FX bioaccumulation was observed in tissues of mussels exposed to 30 and 300 ng/L FX. • Alterations of cAMP-related cell signaling were observed in exposed mussels as part of the MOA of FX. • FX reduced the health status of mussels inducing lysosomal effects in digestive gland and antioxidant responses in gills. • The importance of considering additional MOAs and adverse outcome pathways for FX impacts on mussels is highlighted. - Abstract: The present study investigated possible adverse outcome pathways (AOPs) of the antidepressant fluoxetine (FX) in the marine mussel Mytilus galloprovincialis. An evaluation of molecular endpoints involved in modes of action (MOAs) of FX and biomarkers for sub-lethal toxicity were explored in mussels after a 7-day administration of nominal FX concentrations encompassing a range of environmentally relevant values (0.03–300 ng/L). FX bioaccumulated in mussel tissues after treatment with 30 and 300 ng/L FX, resulting in bioconcentration factor (BCF) values ranging from 200 to 800, which were higher than expected based solely on hydrophobic partitioning models. Because FX acts as a selective serotonin (5-HT) re-uptake inhibitor increasing serotonergic neurotransmission at mammalian synapses, cell signaling alterations triggered by 5-HT receptor occupations were assessed. cAMP levels and PKA activities were decreased in digestive gland and mantle/gonads of FX-treated mussels, consistent with an increased occupation of 5-HT1 receptors negatively coupled to the cAMP/PKA pathway. mRNA levels of a ABCB gene encoding the P-glycoprotein were also significantly down-regulated. This membrane transporter acts in detoxification towards xenobiotics and in altering pharmacokinetics of antidepressants; moreover, it is under a cAMP/PKA transcriptional regulation in mussels. Potential stress

  6. pH Dependent Antimicrobial Peptides and Proteins, Their Mechanisms of Action and Potential as Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Erum Malik

    2016-11-01

    Full Text Available Antimicrobial peptides (AMPs are potent antibiotics of the innate immune system that have been extensively investigated as a potential solution to the global problem of infectious diseases caused by pathogenic microbes. A group of AMPs that are increasingly being reported are those that utilise pH dependent antimicrobial mechanisms, and here we review research into this area. This review shows that these antimicrobial molecules are produced by a diverse spectrum of creatures, including vertebrates and invertebrates, and are primarily cationic, although a number of anionic examples are known. Some of these molecules exhibit high pH optima for their antimicrobial activity but in most cases, these AMPs show activity against microbes that present low pH optima, which reflects the acidic pH generally found at their sites of action, particularly the skin. The modes of action used by these molecules are based on a number of major structure/function relationships, which include metal ion binding, changes to net charge and conformational plasticity, and primarily involve the protonation of histidine, aspartic acid and glutamic acid residues at low pH. The pH dependent activity of pore forming antimicrobial proteins involves mechanisms that generally differ fundamentally to those used by pH dependent AMPs, which can be described by the carpet, toroidal pore and barrel-stave pore models of membrane interaction. A number of pH dependent AMPs and antimicrobial proteins have been developed for medical purposes and have successfully completed clinical trials, including kappacins, LL-37, histatins and lactoferrin, along with a number of their derivatives. Major examples of the therapeutic application of these antimicrobial molecules include wound healing as well as the treatment of multiple cancers and infections due to viruses, bacteria and fungi. In general, these applications involve topical administration, such as the use of mouth washes, cream formulations

  7. Rodent Models of Non-classical Progesterone Action Regulating Ovulation

    Directory of Open Access Journals (Sweden)

    Melinda A. Mittelman-Smith

    2017-07-01

    Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

  8. Nongenomic actions of cortisol in the teleost lactotroph model

    DEFF Research Database (Denmark)

    Borski, Russell J; Tipsmark, Christian Kølbæk; Mita, M

    2006-01-01

    of the present study was to investigate the role of phospholipase C (PLC)-IP3 in mediating cortisol's actions. During 30 min and 4-hour incubation, chicken GnRH-II induces a 2-4 fold increase in PRL release from the tilapia pituitary. The stimulatory effect of cGnRH-II was reduced by cortisol, cortisol-21......-hemisuccinate (HEF) and its membrane impermeant analog, HEF-BSA. Since GnRH induces PRL release, in part, via activation of PLC this suggests that cortisol may rapidly inhibit GnRH-induced PRL release by suppressing PLC activity. We also found that cortisol rapidly inhibits IP3 accumulation in tilapia RPD under...... stimulation by angiotensin II, a factor known to exert its cellular effects through stimulation of the PLC-IP3 pathway. Further studies demonstrate that cortisol reduces PLC activity (measured by the hydrolysis of 3H-PIP2) in a dose dependent manner from crude tilapia lactotroph membrane preparations. SRIF...

  9. Enhancing the Action Research Capacity of the International Model ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... the UNCED (United Nations Conference on Environment and Development) Rio ... an international network of working models of sustainable forest management ... countries in Africa, Asia, Canada, Europe, Latin America and the Caribbean, ...

  10. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin

    2014-01-01

    (+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

  11. Comment on "Penetration of Action Potentials During Collision in the Median and Lateral Giant Axons of Invertebrates"

    Science.gov (United States)

    Berg, Rune W.; Stauning, Marius Tving; Sørensen, Jakob Balslev; Jahnsen, Henrik

    2017-04-01

    The action potential (AP) is an electrical impulse elicited by depolarization of the neuronal membrane from the resting membrane potential (around -70 mV ). It propagates along the axon, allowing for rapid and distant communication. Recently, it was claimed that two APs traveling in opposite direction will pass unhindered through each other (penetrate) upon collision [Gonzalez-Perez et al.Phys. Rev. X 4, 031047 (2014), 10.1103/PhysRevX.4.031047]. We tested this claim under carefully controlled conditions and found that we cannot reproduce penetration. Instead, APs consistently annihilated upon collision. This is consistent with a vast body of literature.

  12. What’s Needed from Climate Modeling to Advance Actionable Science for Water Utilities?

    Science.gov (United States)

    Barsugli, J. J.; Anderson, C. J.; Smith, J. B.; Vogel, J. M.

    2009-12-01

    “…perfect information on climate change is neither available today nor likely to be available in the future, but … over time, as the threats climate change poses to our systems grow more real, predicting those effects with greater certainty is non-discretionary. We’re not yet at a level at which climate change projections can drive climate change adaptation.” (Testimony of WUCA Staff Chair David Behar to the House Committee on Science and Technology, May 5, 2009) To respond to this challenge, the Water Utility Climate Alliance (WUCA) has sponsored a white paper titled “Options for Improving Climate Modeling to Assist Water Utility Planning for Climate Change. ” This report concerns how investments in the science of climate change, and in particular climate modeling and downscaling, can best be directed to help make climate projections more actionable. The meaning of “model improvement” can be very different depending on whether one is talking to a climate model developer or to a water manager trying to incorporate climate projections in to planning. We first surveyed the WUCA members on present and potential uses of climate model projections and on climate inputs to their various system models. Based on those surveys and on subsequent discussions, we identified four dimensions along which improvement in modeling would make the science more “actionable”: improved model agreement on change in key parameters; narrowing the range of model projections; providing projections at spatial and temporal scales that match water utilities system models; providing projections that water utility planning horizons. With these goals in mind we developed four options for improving global-scale climate modeling and three options for improving downscaling that will be discussed. However, there does not seem to be a single investment - the proverbial “magic bullet” -- which will substantially reduce the range of model projections at the scales at which utility

  13. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    Science.gov (United States)

    Straus, D. M.

    1983-01-01

    The evolution of wave energy, enstrophy, and wave motion for atmospheric Rossby waves in a variable mean flow are discussed from a theoretical and pedagogic standpoint. In the absence of mean flow gradients, the wave energy density satisfies a local conservation law, with the appropriate flow velocity being the group velocity. In the presence of mean flow variations, wave energy is not conserved, but wave action is, provided the mean flow is independent of longitude. Wave enstrophy is conserved for arbitrary variations of the mean flow. Connections with Eliassen-Palm flux are also discussed.

  14. Adaptation decision-making in the Nordic Countries: assessing the potential for joint action

    DEFF Research Database (Denmark)

    Juhola, Sirkku; Goodsite, Michael Evan; Davis, Marion

    2014-01-01

    on the issue. This paper explores the potential for Nordic cooperation on adaptation; specifically, for the development of a regional adaptation strategy. In particular, it addresses two questions (1) What is the current state of adaptation in the Nordic countries? and (2) What are the potential benefits...

  15. Acting in solidarity: Testing an extended dual pathway model of collective action by bystander group members.

    Science.gov (United States)

    Saab, Rim; Tausch, Nicole; Spears, Russell; Cheung, Wing-Yee

    2015-09-01

    We examined predictors of collective action among bystander group members in solidarity with a disadvantaged group by extending the dual pathway model of collective action, which proposes one efficacy-based and one emotion-based path to collective action (Van Zomeren, Spears, Fischer, & Leach, 2004). Based on two proposed functions of social identity performance (Klein, Spears, & Reicher, 2007), we distinguished between the efficacy of collective action at consolidating the identity of a protest movement and its efficacy at achieving social change (political efficacy). We expected identity consolidation efficacy to positively predict collective action tendencies directly and indirectly via political efficacy. We also expected collective action tendencies to be positively predicted by moral outrage and by sympathy in response to disadvantaged outgroup's suffering. These hypotheses were supported in two surveys examining intentions to protest for Palestine in Britain (Study 1), and intentions to attend the June 4th vigil in Hong Kong to commemorate the Tiananmen massacre among a sample of Hong Kong citizens (Study 2). The contributions of these findings to research on the dual pathway model of collective action and the different functions of collective action are discussed. © 2014 The British Psychological Society.

  16. A Trusted Host's Authentication Access and Control Model Faced on User Action

    Institute of Scientific and Technical Information of China (English)

    ZHANG Miao; XU Guoai; HU Zhengming; YANG Yixian

    2006-01-01

    The conception of trusted network connection (TNC) is introduced, and the weakness of TNC to control user's action is analyzed. After this, the paper brings out a set of secure access and control model based on access, authorization and control, and related authentication protocol. At last the security of this model is analyzed. The model can improve TNC's security of user control and authorization.

  17. Role of suppression of the inward rectifier current in terminal action potential repolarization in the failing heart.

    Science.gov (United States)

    Klein, Michael G; Shou, Matie; Stohlman, Jayna; Solhjoo, Soroosh; Haigney, Myles; Tidwell, Richard R; Goldstein, Robert E; Flagg, Thomas P; Haigney, Mark C

    2017-08-01

    The failing heart exhibits an increased arrhythmia susceptibility that is often attributed to action potential (AP) prolongation due to significant ion channel remodeling. The inwardly rectifying K + current (I K1 ) has been reported to be reduced, but its contribution to shaping the AP waveform and cell excitability in the failing heart remains unclear. The purpose of this study was to define the effect of I K1 suppression on the cardiac AP and excitability in the normal and failing hearts. We used electrophysiological and pharmacological approaches to investigate I K1 function in a swine tachy-pacing model of heart failure (HF). Terminal repolarization of the AP (TRAP; the time constant of the exponential fit to terminal repolarization) was markedly prolonged in both myocytes and arterially perfused wedges from animals with HF. TRAP was increased by 54.1% in HF myocytes (P < .001) and 26.2% in HF wedges (P = .014). The increase in TRAP was recapitulated by the potent and specific I K1 inhibitor, PA-6 (pentamidine analog 6), indicating that I K1 is the primary determinant of the final phase of repolarization. Moreover, we find that I K1 suppression reduced the ratio of effective refractory period to AP duration at 90% of repolarization, permitting re-excitation before full repolarization, reduction of AP upstroke velocity, and likely promotion of slow conduction. Using an objective measure of terminal repolarization, we conclude that I K1 is the major determinant of the terminal repolarization time course. Moreover, suppression of I K1 prolongs repolarization and reduces postrepolarization refractoriness without marked effects on the overall AP duration. Collectively, these findings demonstrate how I K1 suppression may contribute to arrhythmogenesis in the failing heart. Published by Elsevier Inc.

  18. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate.

    Science.gov (United States)

    Child, Nicholas; Hanson, Ben; Bishop, Martin; Rinaldi, Christopher A; Bostock, Julian; Western, David; Cooklin, Michael; O'Neil, Mark; Wright, Matthew; Razavi, Reza; Gill, Jaswinder; Taggart, Peter

    2014-06-01

    Mental stress and emotion have long been associated with ventricular arrhythmias and sudden death in animal models and humans. The effect of mental challenge on ventricular action potential duration (APD) in conscious healthy humans has not been reported. Activation recovery intervals measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady-state pacing, whilst subjects watched an emotionally charged film clip. To assess the possible modulating role of altered respiration on APD, the subjects then repeated the same breathing pattern they had during the stress, but without the movie clip. Hemodynamic parameters (mean, systolic, and diastolic blood pressure, and rate of pressure increase) and respiration rate increased during the stressful part of the film clip (P=0.001). APD decreased during the stressful parts of the film clip, for example, for global right ventricular activation recovery interval at end of film clip 193.8 ms (SD, 14) versus 198.0 ms (SD, 13) during the matched breathing control (end film left ventricle 199.8 ms [SD, 16] versus control 201.6 ms [SD, 15]; P=0.004). Respiration rate increased during the stressful part of the film clip (by 2 breaths per minute) and was well matched in the respective control period without any hemodynamic or activation recovery interval changes. Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular APD in conscious humans. The effect of mental challenge on APD was not secondary to emotionally induced altered respiration or heart rate. © 2014 American Heart Association, Inc.

  19. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    Directory of Open Access Journals (Sweden)

    V. Tamara Perchyonok

    2014-11-01

    Full Text Available Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM, release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.

  20. Spatial modeling of potential woody biomass flow

    Science.gov (United States)

    Woodam Chung; Nathaniel Anderson

    2012-01-01

    The flow of woody biomass to end users is determined by economic factors, especially the amount available across a landscape and delivery costs of bioenergy facilities. The objective of this study develop methodology to quantify landscape-level stocks and potential biomass flows using the currently available spatial database road network analysis tool. We applied this...

  1. Modeling the Clarification Potential of Instructions

    DEFF Research Database (Denmark)

    Benotti, Luciana; Blackburn, Patrick

    2017-01-01

    We hypothesize that conversational implicatures are a rich source of clarification requests, and in this paper we do two things. First, we motivate the hypothesis in theoretical, practical and empirical terms and formulate it as a concrete Clarification Potential Principle: implicatures may becom...

  2. Biphasic response of action potential duration to metabolic inhibition in rabbit and human ventricular myocytes: role of transient outward current and ATP-regulated potassium current

    NARCIS (Netherlands)

    Verkerk, A. O.; Veldkamp, M. W.; van Ginneken, A. C.; Bouman, L. N.

    1996-01-01

    Inhibition of cell metabolism is associated with significant changes in action potential duration. The aim of this study was to investigate the time course of the changes in action potential duration during metabolic inhibition and to determine what changes in membrane currents are responsible. The

  3. Matrix metalloproteinase-13 downregulation and potential cartilage protective action of the Korean Red Ginseng preparation

    Directory of Open Access Journals (Sweden)

    Je Hyeong Lee

    2015-01-01

    Conclusion: Some preparations from Korean Red Ginseng and ginseng leaves, particularly GDF/F4, may possess the protective activity against cartilage degradation in joint disorders, and may have potential as new therapeutic agents.

  4. The Use of Evolution in a Central Action Selection Model

    Directory of Open Access Journals (Sweden)

    F. Montes-Gonzalez

    2007-01-01

    Full Text Available The use of effective central selection provides flexibility in design by offering modularity and extensibility. In earlier papers we have focused on the development of a simple centralized selection mechanism. Our current goal is to integrate evolutionary methods in the design of non-sequential behaviours and the tuning of specific parameters of the selection model. The foraging behaviour of an animal robot (animat has been modelled in order to integrate the sensory information from the robot to perform selection that is nearly optimized by the use of genetic algorithms. In this paper we present how selection through optimization finally arranges the pattern of presented behaviours for the foraging task. Hence, the execution of specific parts in a behavioural pattern may be ruled out by the tuning of these parameters. Furthermore, the intensive use of colour segmentation from a colour camera for locating a cylinder sets a burden on the calculations carried out by the genetic algorithm.

  5. Modelling adversary actions against a nuclear material accounting system

    International Nuclear Information System (INIS)

    Lim, J.J.; Huebel, J.G.

    1979-01-01

    A typical nuclear material accounting system employing double-entry bookkeeping is described. A logic diagram is used to model the interactions of the accounting system and the adversary when he attempts to thwart it. Boolean equations are derived from the logic diagram; solution of these equations yields the accounts and records through which the adversary may disguise a SSNM theft and the collusion requirements needed to accomplish this feat. Some technical highlights of the logic diagram are also discussed

  6. Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

    Science.gov (United States)

    Terazima, E; Yoshino, M

    2010-12-01

    Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Assessing potential targets of calcium action in light-modulated gravitropism

    Science.gov (United States)

    Roux, S. J.

    1995-01-01

    Light, through the mediation of the pigment phytochrome, modulates the gravitropic response of the shoots and roots of many plants. The transduction of both light and gravity stimuli appears to involve Ca(2+)-regulated steps, one or more of which may represent points of intersection between the two transduction chains. To be confident that Ca2+ plays a critical role in stimulus-response coupling for gravitropism, it will be important to identify specific targets of Ca2+ action whose function can be clearly linked to the regulation of growth. Calcium typically exerts its influence on cell metabolism through binding to and activating key regulatory proteins. The three best characterized of these proteins in plants are the calmodulins, calcium-dependent protein kinases, and annexins. In this review we summarize what is known about the structure and function of these proteins and speculate on how their activation by Ca2+ could influence the differential growth response of gravitropism.

  8. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    Science.gov (United States)

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-04-01

    Sepsis, also known as systemic inflammatory response syndrome, is a life-threatening condition caused by a pathogenic agent and leading to multiple organ dysfunction syndrome. One of the factors responsible for the excessive intensification of the inflammatory response in the course of inflammation is high-mobility group protein B1 (HMGB1). HMG-1 is a nuclear protein which, after being released to the intercellular space, has a highly pro-inflammatory effect and acts as a late mediator of lethal damage. The purpose of this study was to examine whether the anti-inflammatory action of riboflavin is accompanied by inhibition of HMGB1 release during peritoneal inflammation and zymosan stimulation of macrophages. Peritonitis was induced in male BALB/c and C57BL/6J mice via intraperitoneal injection of zymosan (40 mg/kg). RAW 264.7 macrophages were activated with zymosan (250 µg/ml). Riboflavin (mice, 50 mg/kg; RAW 264.7, 25 µg/ml) was administered 30 min before zymosan, simultaneously with, or 2, 4, 6 h after zymosan. Additionally, mRNA expression of HMGB1 and its intracellular and serum levels were evaluated. The research showed that riboflavin significantly reduces both the expression and the release of HMGB1; however, the effect of riboflavin was time-dependent. The greatest efficacy was found when riboflavin was given 30 min prior to zymosan, and also 2 and 4 h (C57BL/6J; RAW 264.7) or 4 and 6 h (BALB/c) after zymosan. Research showed that riboflavin influences the level of HMGB1 released in the course of inflammation; however, further study is necessary to determine its mechanisms of action.

  9. Computational Model of Primary Visual Cortex Combining Visual Attention for Action Recognition.

    Directory of Open Access Journals (Sweden)

    Na Shu

    Full Text Available Humans can easily understand other people's actions through visual systems, while computers cannot. Therefore, a new bio-inspired computational model is proposed in this paper aiming for automatic action recognition. The model focuses on dynamic properties of neurons and neural networks in the primary visual cortex (V1, and simulates the procedure of information processing in V1, which consists of visual perception, visual attention and representation of human action. In our model, a family of the three-dimensional spatial-temporal correlative Gabor filters is used to model the dynamic properties of the classical receptive field of V1 simple cell tuned to different speeds and orientations in time for detection of spatiotemporal information from video sequences. Based on the inhibitory effect of stimuli outside the classical receptive field caused by lateral connections of spiking neuron networks in V1, we propose surround suppressive operator to further process spatiotemporal information. Visual attention model based on perceptual grouping is integrated into our model to filter and group different regions. Moreover, in order to represent the human action, we consider the characteristic of the neural code: mean motion map based on analysis of spike trains generated by spiking neurons. The experimental evaluation on some publicly available action datasets and comparison with the state-of-the-art approaches demonstrate the superior performance of the proposed model.

  10. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    Science.gov (United States)

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Potential Molecular Mechanisms on the Role of the Sigma-1 Receptor in the Action of Cocaine and Methamphetamine

    Science.gov (United States)

    Yasui, Yuko; Su, Tsung-Ping

    2016-01-01

    The sigma-1 receptor (Sig-1R) is an endoplasmic reticulum membrane protein that involves a wide range of physiological functions. The Sig-1R has been shown to bind psychostimulants including cocaine and methamphetamine (METH) and thus has been implicated in the actions of those psychostimulants. For example, it has been demonstrated that the Sig-1R antagonists mitigate certain behavioral and cellular effects of psychostimulants including hyperactivity and neurotoxicity. Thus, the Sig-1R has become a potential therapeutic target of medication development against drug abuse that differs from traditional monoamine-related strategies. In this review, we will focus on the molecular mechanisms of the Sig-1R and discuss in such a manner with a hope to further understand or unveil unexplored relations between the Sig-1R and the actions of cocaine and METH, particularly in the context of cellular biological relevance. PMID:27088037

  12. Applicability of linear and non-linear potential flow models on a Wavestar float

    DEFF Research Database (Denmark)

    Bozonnet, Pauline; Dupin, Victor; Tona, Paolino

    2017-01-01

    as a model based on non-linear potential flow theory and weakscatterer hypothesis are successively considered. Simple tests, such as dip tests, decay tests and captive tests enable to highlight the improvements obtained with the introduction of nonlinearities. Float motion under wave actions and without...... control action, limited to small amplitude motion with a single float, is well predicted by the numerical models, including the linear one. Still, float velocity is better predicted by accounting for non-linear hydrostatic and Froude-Krylov forces.......Numerical models based on potential flow theory, including different types of nonlinearities are compared and validated against experimental data for the Wavestar wave energy converter technology. Exact resolution of the rotational motion, non-linear hydrostatic and Froude-Krylov forces as well...

  13. Risk Communication Emergency Response Preparedness: Contextual Assessment of the Protective Action Decision Model.

    Science.gov (United States)

    Heath, Robert L; Lee, Jaesub; Palenchar, Michael J; Lemon, Laura L

    2018-02-01

    Studies are continuously performed to improve risk communication campaign designs to better prepare residents to act in the safest manner during an emergency. To that end, this article investigates the predictive ability of the protective action decision model (PADM), which links environmental and social cues, predecision processes (attention, exposure, and comprehension), and risk decision perceptions (threat, alternative protective actions, and stakeholder norms) with protective action decision making. This current quasi-longitudinal study of residents (N = 400 for each year) in a high-risk (chemical release) petrochemical manufacturing community investigated whether PADM core risk perceptions predict protective action decision making. Telephone survey data collected at four intervals (1995, 1998, 2002, 2012) reveal that perceptions of protective actions and stakeholder norms, but not of threat, currently predict protective action decision making (intention to shelter in place). Of significance, rather than threat perceptions, perception of Wally Wise Guy (a spokes-character who advocates shelter in place) correlates with perceptions of protective action, stakeholder norms, and protective action decision making. Wally's response-efficacy advice predicts residents' behavioral intentions to shelter in place, thereby offering contextually sensitive support and refinement for PADM. © 2017 Society for Risk Analysis.

  14. Partial differential equations in action from modelling to theory

    CERN Document Server

    Salsa, Sandro

    2016-01-01

    The book is intended as an advanced undergraduate or first-year graduate course for students from various disciplines, including applied mathematics, physics and engineering. It has evolved from courses offered on partial differential equations (PDEs) over the last several years at the Politecnico di Milano. These courses had a twofold purpose: on the one hand, to teach students to appreciate the interplay between theory and modeling in problems arising in the applied sciences, and on the other to provide them with a solid theoretical background in numerical methods, such as finite elements. Accordingly, this textbook is divided into two parts. The first part, chapters 2 to 5, is more elementary in nature and focuses on developing and studying basic problems from the macro-areas of diffusion, propagation and transport, waves and vibrations. In turn the second part, chapters 6 to 11, concentrates on the development of Hilbert spaces methods for the variational formulation and the analysis of (mainly) linear bo...

  15. Bessel functions in mass action modeling of memories and remembrances

    Energy Technology Data Exchange (ETDEWEB)

    Freeman, Walter J. [Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3206 (United States); Capolupo, Antonio [Dipartimento di Fisica, E.R. Caianiello Universitá di Salerno, and INFN Gruppo collegato di Salerno, Fisciano 84084 (Italy); Kozma, Robert [Department of Mathematics, Memphis University, Memphis, TN 38152 (United States); Olivares del Campo, Andrés [The Blackett Laboratory, Imperial College London, Prince Consort Road, London SW7 2BZ (United Kingdom); Vitiello, Giuseppe, E-mail: vitiello@sa.infn.it [Dipartimento di Fisica, E.R. Caianiello Universitá di Salerno, and INFN Gruppo collegato di Salerno, Fisciano 84084 (Italy)

    2015-10-02

    Data from experimental observations of a class of neurological processes (Freeman K-sets) present functional distribution reproducing Bessel function behavior. We model such processes with couples of damped/amplified oscillators which provide time dependent representation of Bessel equation. The root loci of poles and zeros conform to solutions of K-sets. Some light is shed on the problem of filling the gap between the cellular level dynamics and the brain functional activity. Breakdown of time-reversal symmetry is related with the cortex thermodynamic features. This provides a possible mechanism to deduce lifetime of recorded memory. - Highlights: • We consider data from observations of impulse responses of cortex to electric shocks. • These data are fitted by Bessel functions which may be represented by couples of damped/amplified oscillators. • We study the data by using couples of damped/amplified oscillators. • We discuss lifetime and other properties of the considered brain processes.

  16. Partial differential equations in action from modelling to theory

    CERN Document Server

    Salsa, Sandro

    2015-01-01

    The book is intended as an advanced undergraduate or first-year graduate course for students from various disciplines, including applied mathematics, physics and engineering. It has evolved from courses offered on partial differential equations (PDEs) over the last several years at the Politecnico di Milano. These courses had a twofold purpose: on the one hand, to teach students to appreciate the interplay between theory and modeling in problems arising in the applied sciences, and on the other to provide them with a solid theoretical background in numerical methods, such as finite elements. Accordingly, this textbook is divided into two parts. The first part, chapters 2 to 5, is more elementary in nature and focuses on developing and studying basic problems from the macro-areas of diffusion, propagation and transport, waves and vibrations. In turn the second part, chapters 6 to 11, concentrates on the development of Hilbert spaces methods for the variational formulation and the analysis of (mainly) linear bo...

  17. The application of an action system model to destructive behaviour: the examples of arson and terrorism.

    Science.gov (United States)

    Fritzon, K; Canter, D; Wilton, Z

    2001-01-01

    This article argues that criminal and deviant behaviour can be productively viewed through an action system framework. The idea is developed by considering two forms of destructive behaviour: arson and barricade-hostage terrorist incidents. Two studies are presented. The first study tests the hypothesis that different forms of arson will reflect the four dominant states that an action system can take; integrative, expressive, conservative, and adaptive. A smallest space analysis was performed on 46 variables describing 230 cases of arson and the results identified the four themes of action system functioning. An examination of the personal characteristics of the arsonists also produced four variable groupings and a combined analysis of the four action scales and four characteristics scales also supported the structural hypothesis of the action system model. The second study applied the action system model to the study acts of terrorist barricade-hostage incidents. A smallest space analysis of 44 variables coded from 41 incidents again revealed four distinct forms of activity, which were psychologically similar to the four modes of arson identified in study one. Overall, these two studies provide support for the appropriateness of the action system framework as a way of classifying different forms of deviant behaviour. Copyright 2001 John Wiley & Sons, Ltd.

  18. Action Prediction Allows Hypothesis Testing via Internal Forward Models at 6 Months of Age

    Directory of Open Access Journals (Sweden)

    Gustaf Gredebäck

    2018-03-01

    Full Text Available We propose that action prediction provides a cornerstone in a learning process known as internal forward models. According to this suggestion infants’ predictions (looking to the mouth of someone moving a spoon upward will moments later be validated or proven false (spoon was in fact directed toward a bowl, information that is directly perceived as the distance between the predicted and actual goal. Using an individual difference approach we demonstrate that action prediction correlates with the tendency to react with surprise when social interactions are not acted out as expected (action evaluation. This association is demonstrated across tasks and in a large sample (n = 118 at 6 months of age. These results provide the first indication that infants might rely on internal forward models to structure their social world. Additional analysis, consistent with prior work and assumptions from embodied cognition, demonstrates that the latency of infants’ action predictions correlate with the infant’s own manual proficiency.

  19. Metabotropic action of postsynaptic kainate receptors triggers hippocampal long-term potentiation

    Czech Academy of Sciences Publication Activity Database

    Petrovič, Miloš; da Silva, S. V.; Clement, J. P.; Vyklický ml., Ladislav; Mulle, C.; González-González, I. M.; Henley, J. M.

    2017-01-01

    Roč. 20, č. 4 (2017), s. 529-539 ISSN 1097-6256 R&D Projects: GA ČR(CZ) GA17-02300S Institutional support: RVO:67985823 Keywords : hippocampus * long-term potentiation * membrane proteins Subject RIV: FH - Neurology OBOR OECD: Neuroscience s (including psychophysiology Impact factor: 17.839, year: 2016

  20. Virtual Burglary: Exploring the Potential of Virtual Reality to Study Burglary in Action

    NARCIS (Netherlands)

    van Sintemaartensdijk, I.; van Prooijen, J-W.; van Gelder, J-L.; Otte, M.; Nee, Claire; Demetriou, Andrew

    2016-01-01

    Objectives: This article explores the potential of virtual reality (VR) to study burglary by measuring user responses on the subjective, physiological, and behavioral levels. Furthermore, it examines the influence of individual dispositions, such as sensation seeking and self-control, on behavior

  1. Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias.

    Science.gov (United States)

    Lu, H R; Hortigon-Vinagre, M P; Zamora, V; Kopljar, I; De Bondt, A; Gallacher, D J; Smith, G

    2017-09-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (T rise ) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with I Ca -antagonists, I Kr -activator or ATP-sensitive K + channel (K ATP )-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free effective therapeutic plasma levels or effective concentrations by other studies. The results of this blinded study indicate that OAP is a sensitive method to accurately detect drug-induced effects (i.e., duration/QT-prolongation, shortening, beat rate, and incidence of early after depolarizations) in hiPS-CMs; therefore, this technique will potentially be useful in predicting drug-induced arrhythmogenic liabilities in early de-risking within the drug discovery phase. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Monoamine Oxidase-A Inhibition and Associated Antioxidant Activity in Plant Extracts with Potential Antidepressant Actions

    Directory of Open Access Journals (Sweden)

    Tomás Herraiz

    2018-01-01

    Full Text Available Monoamine oxidase (MAO catalyzes the oxidative deamination of amines and neurotransmitters and is involved in mood disorders, depression, oxidative stress, and adverse pharmacological reactions. This work studies the inhibition of human MAO-A by Hypericum perforatum, Peganum harmala, and Lepidium meyenii, which are reported to improve and affect mood and mental conditions. Subsequently, the antioxidant activity associated with the inhibition of MAO is determined in plant extracts for the first time. H. perforatum inhibited human MAO-A, and extracts from flowers gave the highest inhibition (IC50 of 63.6 μg/mL. Plant extracts were analyzed by HPLC-DAD-MS and contained pseudohypericin, hypericin, hyperforin, adhyperforin, hyperfirin, and flavonoids. Hyperforin did not inhibit human MAO-A and hypericin was a poor inhibitor of this isoenzyme. Quercetin and flavonoids significantly contributed to MAO-A inhibition. P. harmala seed extracts highly inhibited MAO-A (IC50 of 49.9 μg/L, being a thousand times more potent than H. perforatum extracts owing to its content of β-carboline alkaloids (harmaline and harmine. L. meyenii root (maca extracts did not inhibit MAO-A. These plants may exert protective actions related to antioxidant effects. Results in this work show that P. harmala and H. perforatum extracts exhibit antioxidant activity associated with the inhibition of MAO (i.e., lower production of H2O2.

  3. Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv

    Directory of Open Access Journals (Sweden)

    Aldo F. Clemente-Soto

    2014-12-01

    Full Text Available The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

  4. Barriers, facilitators, and potential strategies for increasing HPV vaccination: A statewide assessment to inform action

    Directory of Open Access Journals (Sweden)

    Kathleen B. Cartmell

    2018-06-01

    Full Text Available Objective: The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. Design: An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. Results: Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1 addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2 advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3 coordination of efforts. Discussion: A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state. Keywords: HPV, HPV vaccines, Cervical cancer, Prevention, Health systems, Barriers, Facilitators, Strategies, South Carolina

  5. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    Science.gov (United States)

    Nagy, Norbert; Szél, Tamás; Jost, Norbert; Tóth, András; Gy Papp, Julius; Varró, András

    2015-09-01

    Data obtained from canine cardiac electrophysiology studies are often extrapolated to the human heart. However, it has been previously demonstrated that because of the lower density of its K(+) currents, the human ventricular action potential has a less extensive repolarization reserve. Since the relevance of canine data to the human heart has not yet been fully clarified, the aim of the present study was to determine for the first time the action potentials of undiseased human Purkinje fibres (PFs) and to compare them directly with those of dog PFs. All measurements were performed at 37 °C using the conventional microelectrode technique. At a stimulation rate of 1 Hz, the plateau potential of human PFs is more positive (8.0 ± 1.8 vs 8.6 ± 3.4 mV, n = 7), while the amplitude of the spike is less pronounced. The maximal rate of depolarization is significantly lower in human PKs than in canine PFs (406.7 ± 62 vs 643 ± 36 V/s, respectively, n = 7). We assume that the appreciable difference in the protein expression profiles of the 2 species may underlie these important disparities. Therefore, caution is advised when canine PF data are extrapolated to humans, and further experiments are required to investigate the characteristics of human PF repolarization and its possible role in arrhythmogenesis.

  6. Loss of Local Astrocyte Support Disrupts Action Potential Propagation and Glutamate Release Synchrony from Unmyelinated Hippocampal Axon Terminals In Vitro.

    Science.gov (United States)

    Sobieski, Courtney; Jiang, Xiaoping; Crawford, Devon C; Mennerick, Steven

    2015-08-05

    Neuron-astrocyte interactions are critical for proper CNS development and function. Astrocytes secrete factors that are pivotal for synaptic development and function, neuronal metabolism, and neuronal survival. Our understanding of this relationship, however, remains incomplete due to technical hurdles that have prevented the removal of astrocytes from neuronal circuits without changing other important conditions. Here we overcame this obstacle by growing solitary rat hippocampal neurons on microcultures that were comprised of either an astrocyte bed (+astrocyte) or a collagen bed (-astrocyte) within the same culture dish. -Astrocyte autaptic evoked EPSCs, but not IPSCs, displayed an altered temporal profile, which included increased synaptic delay, increased time to peak, and severe glutamate release asynchrony, distinct from previously described quantal asynchrony. Although we observed minimal alteration of the somatically recorded action potential waveform, action potential propagation was altered. We observed a longer latency between somatic initiation and arrival at distal locations, which likely explains asynchronous EPSC peaks, and we observed broadening of the axonal spike, which likely underlies changes to evoked EPSC onset. No apparent changes in axon structure were observed, suggesting altered axonal excitability. In conclusion, we propose that local astrocyte support has an unappreciated role in maintaining glutamate release synchrony by disturbing axonal signal propagation. Certain glial cell types (oligodendrocytes, Schwann cells) facilitate the propagation of neuronal electrical signals, but a role for astrocytes has not been identified despite many other functions of astrocytes in supporting and modulating neuronal signaling. Under identical global conditions, we cultured neurons with or without local astrocyte support. Without local astrocytes, glutamate transmission was desynchronized by an alteration of the waveform and arrival time of axonal

  7. The modeling and solution of course of action generation based on IN-DEA

    Science.gov (United States)

    Wan, Lujun; Li, Wen; Dai, Jiangbin; Huang, Aqian

    2017-08-01

    The course of action (COA) generation is the course of designing the task planning flow, which is one of the key supporting techniques while the military organization executing aerial operation. Due to the outstanding advantage of influence nets (IN), describing the causal logic between random variable, this proposal will introduce IN into the fast building mechanism of COA model. The COA generation model utilize influence nets is established. The probability propagation method is designed, which is based on influence intensity. An improved differential evolution algorithm (IDEA) is designed to solve the action policy optimized selected model. At last, the simulated result of aerial arrack campaign case show the action policy optimized selected in variety influence constants can improve the capability of cause-effect modeling, and the improved differential evolution algorithm has fine convergent and optimized capability.

  8. A code to compute the action-angle transformation for a particle in an abritrary potential well

    International Nuclear Information System (INIS)

    Berg, J.S.; Warnock, R.L.

    1995-01-01

    For a Vlasov treatment of longitudinal stability under an arbitrary wake field, with the solution of the Haiessinski equation as the unperturbed distribution, it is important to have the action-angle transformation for the distorted potential well in a convenient form. The authors have written a code that gives the transformation q,p → J, φ, with q(J,φ) as a Fourier series in φ, the Fourier coefficients and the Hamiltonian H(J) being spline functions of J in C 2 (having continuous second derivatives)

  9. Potential need for re-definition of the highest priority recovery action in the Krsko SAG-1

    International Nuclear Information System (INIS)

    Bilic Zabric, T.; Basic, I.

    2005-01-01

    Replacement of old SG (Steam Generators) [7] and the characteristic of new ones throws the question of proper accident management strategy, which leans on philosophy that repair and recovery actions have first priority. In the current NPP Krsko SAMGs (Severe Accident Management Guidelines), water supply to the SG has priority over re-injection water into the core. NPP Krsko reconsidered the highest priority of SAG-1 (inject water to the SG), against the WOG (Westinghouse Owners Group) generic approach (inject water into the core) and potential revision of Severe Accident Phenomenology Evaluations using MAAP (Modular accident Analysis Program) 4.0.5 code. (author)

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

    Science.gov (United States)

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  11. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    DEFF Research Database (Denmark)

    Liu, Xiaowen; Murali, Sangita G; Holst, Jens J

    2009-01-01

    protein component, casein, soy, or whey protein, potentiates the intestinal growth response to GLP-2 in rats with PN-induced mucosal hypoplasia. Rats received PN and continuous intravenous infusion of GLP-2 (100 microg/kg/day) for 7 days. Six EN groups received PN+GLP-2 for days 1-3 and partial PN+GLP-2...... plus EN for days 4-7. EN was provided by ad libitum intake of a semielemental liquid diet with different protein sources: casein, hydrolyzed soy, whey protein concentrate (WPC), and hydrolyzed WPC+casein. Controls received PN+GLP-2 alone. EN induced significantly greater jejunal sucrase activity...... whey protein, and not casein or soy, potentiated the ability of GLP-2 to reverse PN-induced mucosal hypoplasia and further increase ileal villus height, crypt depth, and mucosa cellularity compared with PN+GLP-2 alone, P whey protein to induce greater mucosal surface area...

  12. Navy Ship Maintenance: Action Needed to Maximize New Contracting Strategys Potential Benefits

    Science.gov (United States)

    2016-11-01

    implementation of the new strategy, the Navy conducted market research and pilot-tested attributes of the strategy with pilot maintenance periods for a...readiness strategy and, in 2015, introduction of a new contracting strategy for ship repair, referred to as MAC-MO. House Report 114-102 accompanying the...Maintenance Letter 1 Background 3 Market Research and Piloting Helped Inform Roll-out of MAC-MO Strategy, Which Offers Potential Benefits

  13. THE MODEL CHARACTERISTICS OF JUMP ACTIONS STRUCTURE OF HIGH PERFORMANCE FEMALE VOLLEYBALL PLAYERS

    Directory of Open Access Journals (Sweden)

    Stech M.

    2012-12-01

    Full Text Available The purpose of this study was to develop generalized and individual models of the jump actions of skilled female volleyball players. The main prerequisite for the development of the jump actions models were the results of our earlier studies of factor structure of jump actions of 10 sportswomen of the Polish volleyball team "Gedania" (Premier League in the preparatory and competitive periods of the annual cycle of preparation. The athletes age was 22.0 +- 2.9 years, the sports experience - 8.1 +- 3.1 years, body height - 181.9 +- 8.4 years and body weight - 72.8 +- 10.8 kg. Mathematical and statistical processing of the data (the definition of M ± SD and significant differences between the samples was performed using a standard computer program "STATISTICA 7,0". Based on the analysis of the factor structure of 20 jump actions of skilled women volleyball players determined to within 5 of the most informative indexes and their tentative values recommended for the formation of a generalized model of this structure. Comparison of individual models of jump actions of skilled women volleyball players with their generalized models in different periods of preparation can be used for the rational choice of means and methods for the increasing of the training process efficiency.

  14. Nurses' intention to leave: critically analyse the theory of reasoned action and organizational commitment model.

    Science.gov (United States)

    Liou, Shwu-Ru

    2009-01-01

    To systematically analyse the Organizational Commitment model and Theory of Reasoned Action and determine concepts that can better explain nurses' intention to leave their job. The Organizational Commitment model and Theory of Reasoned Action have been proposed and applied to understand intention to leave and turnover behaviour, which are major contributors to nursing shortage. However, the appropriateness of applying these two models in nursing was not analysed. Three main criteria of a useful model were used for the analysis: consistency in the use of concepts, testability and predictability. Both theories use concepts consistently. Concepts in the Theory of Reasoned Action are defined broadly whereas they are operationally defined in the Organizational Commitment model. Predictability of the Theory of Reasoned Action is questionable whereas the Organizational Commitment model can be applied to predict intention to leave. A model was proposed based on this analysis. Organizational commitment, intention to leave, work experiences, job characteristics and personal characteristics can be concepts for predicting nurses' intention to leave. Nursing managers may consider nurses' personal characteristics and experiences to increase their organizational commitment and enhance their intention to stay. Empirical studies are needed to test and cross-validate the re-synthesized model for nurses' intention to leave their job.

  15. Operationalizing the Concept of Value--An Action Research-Based Model

    Science.gov (United States)

    Naslund, Dag; Olsson, Annika; Karlsson, Sture

    2006-01-01

    Purpose: While the importance of measuring customer satisfaction levels is well established, less research exists on how organizations operationalize such knowledge. The purpose of this paper is to describe an action research (AR) case study resulting in a workshop model to operationalize the concept of value. The model facilitates organizational…

  16. A dynamic texture based approach to recognition of facial actions and their temporal models

    NARCIS (Netherlands)

    Koelstra, Sander; Pantic, Maja; Patras, Ioannis (Yannis)

    2010-01-01

    In this work, we propose a dynamic texture-based approach to the recognition of facial Action Units (AUs, atomic facial gestures) and their temporal models (i.e., sequences of temporal segments: neutral, onset, apex, and offset) in near-frontal-view face videos. Two approaches to modeling the

  17. The potential role of cotinine in the cognitive and neuroprotective actions of nicotine.

    Science.gov (United States)

    Buccafusco, Jerry J; Terry, Alvin V

    2003-05-16

    Cotinine is a primary metabolite of nicotine that has been suggested in many studies in animals and in humans to exert measurable effects on aspects of on-going behavior or on cognitive function. Much of the interest in cotinine derives from its long pharmacological half-life (15-19 hours) relative to nicotine (2-3 hours). Despite decades of study focusing on nicotine as the predominant behaviorally active component of tobacco, there continue to be aspects of the pharmacology of the drug that have yet to be explained. For example, nicotine can evoke a protracted behavioral response, i.e., in great excess of the presence of the drug in the plasma. Also, there is often a striking differential between the potency for nicotine-induced behavioral responses in humans and animals, and its potency as a cholinergic agonist, neurochemically. One possibility that may explain one or more of these properties of nicotine is the presence of a long-lived bioactive metabolite or breakdown product of nicotine such as cotinine. Preliminary data in support of this hypothesis are consistent with the ability of cotinine to improve performance accuracy on delayed matching task by macaque monkeys, and in reversing apomorphine-induced deficits in prepulse inhibition of acoustic startle in rats. The drug also was shown to be as potent as nicotine in the ability to act as a cytoprotective agent in cells that express a neuronal cholinergic phenotype. This new appreciation for the role of cotinine in nicotine's actions, and as a pharmacological agent in its own right, particularly in aspects of cognitive function and for neuroprotection, ultimately may be applied towards the treatment of Alzheimer's disease and related disorders, and for various psychiatric syndromes.

  18. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    Science.gov (United States)

    Opler, Lewis A; Opler, Mark G A; Arnsten, Amy F T

    2016-02-01

    This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.

  19. AMELIORATING TREATMENT-REFRACTORY DEPRESSION WITH INTRANASAL KETAMINE: POTENTIAL NMDA RECEPTOR ACTIONS IN THE PAIN CIRCUITRY REPRESENTING MENTAL ANGUISH

    Science.gov (United States)

    Opler, Lewis A.; Opler, Mark G.; Arnsten, Amy F.T.

    2014-01-01

    This paper reviews the anti-depressant actions of the N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, ketamine, and offers a potential neural mechanism for intranasal ketamine’s ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5–40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (e.g. Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia. PMID:25619798

  20. Review article: potential mechanisms of action of rifaximin in the management of irritable bowel syndrome with diarrhoea.

    Science.gov (United States)

    Pimentel, M

    2016-01-01

    The role of gut microbiota in the pathophysiology of irritable bowel syndrome (IBS) is supported by various lines of evidence, including differences in mucosal and faecal microbiota between patients with IBS and healthy individuals, development of post-infectious IBS, and the efficacy of some probiotics and nonsystemic antibiotics (e.g. rifaximin). To review the literature regarding the role of rifaximin in IBS and its potential mechanism(s) of action. A literature search was conducted using the terms 'rifaximin', 'irritable bowel syndrome' and 'mechanism of action'. Rifaximin was approved in 2015 for the treatment of IBS with diarrhoea. In contrast to other currently available IBS therapies that require daily administration to maintain efficacy, 2-week rifaximin treatment achieved symptom improvement that persisted ≥12 weeks post-treatment. The mechanisms of action of rifaximin, therefore, may extend beyond direct bactericidal effects. Data suggest that rifaximin may decrease host proinflammatory responses to bacterial products in patients with IBS. In some cases, small intestinal bacterial overgrowth (SIBO) may play a role in the clinical symptoms of IBS. Because of the high level of solubility of rifaximin in the small intestine, rifaximin may reset microbial diversity in this environment. Consistent with this hypothesis, rifaximin has antibiotic efficacy against isolates derived from patients with SIBO. Resetting microbial diversity via rifaximin use may lead to a decrease in bacterial fermentation and a reduction in the clinical symptoms of IBS. © 2015 John Wiley & Sons Ltd.

  1. Model Dependency of TMAO's Counteracting Effect Against Action of Urea: Kast Model versus Osmotic Model of TMAO.

    Science.gov (United States)

    Borgohain, Gargi; Paul, Sandip

    2016-03-10

    Classical molecular dynamics simulation of GB1 peptide (a 16-residue β-hairpin) in different osmotic environments is studied. Urea is used for denaturation of the peptide, and trimethylamine-N-oxide (TMAO) is used to offset the effect of urea. Protein-urea electrostatic interactions are found to play a major role in protein-denaturation. To emphasize on protein protecting action of TMAO against urea, two different models of TMAO are used, viz., the Kast model and the Osmotic model. We observe that the Osmotic model of TMAO gives the best protection to counteract urea's action when used in ratio 1:2 of urea:TMAO (i.e., reverse ratio). This is because the presence of TMAO makes urea-protein electrostatic interactions more unfavorable. Preferential solvation of TMAO molecules by urea (and water) molecules is also observed, which causes depletion in the number of urea molecules in the vicinity of the protein. The calculations of intraprotein hydrogen bonds between different residues of protein further reveal the breaking of backbone hydrogen bonds of residues 2 and 15 in the presence of urea, and the same is preserved in the presence of TMAO. Free energy landscapes show that the narrowest distribution is obtained for the osmotic TMAO model when used in reverse ratio.

  2. CO, Pb++ and SO2 effects on L-type calcium channel and action potential in human atrial myocytes. In silico study

    Directory of Open Access Journals (Sweden)

    Diana C. Pachajoa

    2017-09-01

    Full Text Available Exposure to air pollutants like carbon monoxide (CO, lead (Pb++ and sulfur dioxide (SO2 promotes the occurrence of cardiovascular diseases. Experimental studies have shown that CO, Pb++ and SO2 block L-type calcium channels, reducing the calcium current (ICaL and the action potential duration (APD, which favors the initiation of atrial arrhythmias. The goal is to study the effects of CO, Pb++ and SO2 at different concentrations on ICaL and action potential using computational simulation. For this purpose, models of the effects of the air pollutants on the atrial L-type calcium channel were developed and were incorporated into a mathematical model of a human atrial cell. The results suggest that CO, Pb++ and SO2 block the ICaL current in a fraction that increases along with the concentration, generating an APD shortening. These results are consistent with experimental studies. The combined effect of the three air pollutants produced an APD shortening, which is considered to be a pro-arrhythmic effect.

  3. Modelling of potentially promising SARS protease inhibitors

    International Nuclear Information System (INIS)

    Plewczynski, Dariusz; Hoffmann, Marcin; Grotthuss, Marcin von; Knizewski, Lukasz; Rychewski, Leszek; Eitner, Krystian; Ginalski, Krzysztof

    2007-01-01

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation

  4. APPROXIMATING INNOVATION POTENTIAL WITH NEUROFUZZY ROBUST MODEL

    Directory of Open Access Journals (Sweden)

    Kasa, Richard

    2015-01-01

    Full Text Available In a remarkably short time, economic globalisation has changed the world’s economic order, bringing new challenges and opportunities to SMEs. These processes pushed the need to measure innovation capability, which has become a crucial issue for today’s economic and political decision makers. Companies cannot compete in this new environment unless they become more innovative and respond more effectively to consumers’ needs and preferences – as mentioned in the EU’s innovation strategy. Decision makers cannot make accurate and efficient decisions without knowing the capability for innovation of companies in a sector or a region. This need is forcing economists to develop an integrated, unified and complete method of measuring, approximating and even forecasting the innovation performance not only on a macro but also a micro level. In this recent article a critical analysis of the literature on innovation potential approximation and prediction is given, showing their weaknesses and a possible alternative that eliminates the limitations and disadvantages of classical measuring and predictive methods.

  5. Modelling of potentially promising SARS protease inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Plewczynski, Dariusz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Hoffmann, Marcin [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Grotthuss, Marcin von [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Knizewski, Lukasz [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland); Rychewski, Leszek [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Eitner, Krystian [BioInfoBank Institute, Limanowskiego 24A/16, 60-744 Poznan (Poland); Ginalski, Krzysztof [Interdisciplinary Centre for Mathematical and Computational Modelling, ICM, Warsaw University, Pawinskiego 5a Street, 02-106 Warsaw (Poland)

    2007-07-18

    In many cases, at the beginning of a high throughput screening experiment some information about active molecules is already available. Active compounds (such as substrate analogues, natural products and inhibitors of related proteins) are often identified in low throughput validation studies on a biochemical target. Sometimes the additional structural information is also available from crystallographic studies on protein and ligand complexes. In addition, the structural or sequence similarity of various protein targets yields a novel possibility for drug discovery. Co-crystallized compounds from homologous proteins can be used to design leads for a new target without co-crystallized ligands. In this paper we evaluate how far such an approach can be used in a real drug campaign, with severe acute respiratory syndrome (SARS) coronavirus providing an example. Our method is able to construct small molecules as plausible inhibitors solely on the basis of the set of ligands from crystallized complexes of a protein target, and other proteins from its structurally homologous family. The accuracy and sensitivity of the method are estimated here by the subsequent use of an electronic high throughput screening flexible docking algorithm. The best performing ligands are then used for a very restrictive similarity search for potential inhibitors of the SARS protease within the million compounds from the Ligand.Info small molecule meta-database. The selected molecules can be passed on for further experimental validation.

  6. The Things You Do: Internal Models of Others' Expected Behaviour Guide Action Observation.

    Directory of Open Access Journals (Sweden)

    Kimberley C Schenke

    Full Text Available Predictions allow humans to manage uncertainties within social interactions. Here, we investigate how explicit and implicit person models-how different people behave in different situations-shape these predictions. In a novel action identification task, participants judged whether actors interacted with or withdrew from objects. In two experiments, we manipulated, unbeknownst to participants, the two actors action likelihoods across situations, such that one actor typically interacted with one object and withdrew from the other, while the other actor showed the opposite behaviour. In Experiment 2, participants additionally received explicit information about the two individuals that either matched or mismatched their actual behaviours. The data revealed direct but dissociable effects of both kinds of person information on action identification. Implicit action likelihoods affected response times, speeding up the identification of typical relative to atypical actions, irrespective of the explicit knowledge about the individual's behaviour. Explicit person knowledge, in contrast, affected error rates, causing participants to respond according to expectations instead of observed behaviour, even when they were aware that the explicit information might not be valid. Together, the data show that internal models of others' behaviour are routinely re-activated during action observation. They provide first evidence of a person-specific social anticipation system, which predicts forthcoming actions from both explicit information and an individuals' prior behaviour in a situation. These data link action observation to recent models of predictive coding in the non-social domain where similar dissociations between implicit effects on stimulus identification and explicit behavioural wagers have been reported.

  7. Deferred Action: Theoretical model of process architecture design for emergent business processes

    Directory of Open Access Journals (Sweden)

    Patel, N.V.

    2007-01-01

    Full Text Available E-Business modelling and ebusiness systems development assumes fixed company resources, structures, and business processes. Empirical and theoretical evidence suggests that company resources and structures are emergent rather than fixed. Planning business activity in emergent contexts requires flexible ebusiness models based on better management theories and models . This paper builds and proposes a theoretical model of ebusiness systems capable of catering for emergent factors that affect business processes. Drawing on development of theories of the ‘action and design’class the Theory of Deferred Action is invoked as the base theory for the theoretical model. A theoretical model of flexible process architecture is presented by identifying its core components and their relationships, and then illustrated with exemplar flexible process architectures capable of responding to emergent factors. Managerial implications of the model are considered and the model’s generic applicability is discussed.

  8. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    DEFF Research Database (Denmark)

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T

    2015-01-01

    to the preservation of contractile function. Detailed analysis of current kinetics shows that only ICa,L density is reduced, and immunoblots demonstrate unaltered CaV1.2 and CaVβ2 protein levels. Computer modeling suggests that delayed repolarization would prolong the period of Ca(2+) entry into the cell, thereby...

  9. In situ vitrification - A potential remedial action technique for hazardous wastes

    International Nuclear Information System (INIS)

    Fitzpatrick, V.F.; Buelt, J.L.; Oma, K.H.; Timmerman, C.L.

    1984-01-01

    In situ vitrification (ISV) is an innovative technology being developed as a potential method for stabilizing transuranic (TRU) contaminated wastes in place. Although the process is being developed for TRU contaminated wastes, it is envisioned that the process could also be applied to hazardous chemical wastes. In situ vitrification (ISV) is the conversion of contaminated soil into a durable glass and crystalline wastes form through melting by joule heating. The technology for in situ vitrification is based upon electric melter technology developed at the Pacific Northwest Laboratory (PNL) for the immobilization of high-level nuclear waste. In situ vitrification was initially tested by researchers at PNL in August, 1980 (U.S. Patent 4,376,598). Since then, ISV has grown from a concept to an emerging technology through a series of 21 engineering-scale (laboratory) tests and 7 pilot-scale (field) tests. A large-scale system is currently being fabricated for testing. The program has been sponsored by the U.S. Department of Energy's (DOE) Richland Operations Office for potential application to Hanford TRU contaminated soil sites. A more detailed description outlining the power system design and the off-gas treatment system follows

  10. Use of Chemical Mixtures to Differentiate Mechanisms of Endocrine Action in a Small Fish Model

    Science.gov (United States)

    Various assays with adult fish have been developed to identify potential endocrine-disrupting chemicals (EDCs) which may cause toxicity via alterations in the hypothalamic-pituitary-gonadal (HPG) axis via different mechanisms/modes of action (MOA). These assays can be sensitive ...

  11. HiTEC: a connectionist model of the interaction between perception and action planning.

    Science.gov (United States)

    Haazebroek, Pascal; Raffone, Antonino; Hommel, Bernhard

    2017-11-01

    Increasing evidence suggests that perception and action planning do not represent separable stages of a unidirectional processing sequence, but rather emerging properties of highly interactive processes. To capture these characteristics of the human cognitive system, we have developed a connectionist model of the interaction between perception and action planning: HiTEC, based on the Theory of Event Coding (Hommel et al. in Behav Brain Sci 24:849-937, 2001). The model is characterized by representations at multiple levels and by shared representations and processes. It complements available models of stimulus-response translation by providing a rationale for (1) how situation-specific meanings of motor actions emerge, (2) how and why some aspects of stimulus-response translation occur automatically and (3) how task demands modulate sensorimotor processing. The model is demonstrated to provide a unitary account and simulation of a number of key findings with multiple experimental paradigms on the interaction between perception and action such as the Simon effect, its inversion (Hommel in Psychol Res 55:270-279, 1993), and action-effect learning.

  12. An evaluation of the utility and limitations of counting motor unit action potentials in the surface electromyogram

    Science.gov (United States)

    Zhou, Ping; Zev Rymer, William

    2004-12-01

    The number of motor unit action potentials (MUAPs) appearing in the surface electromyogram (EMG) signal is directly related to motor unit recruitment and firing rates and therefore offers potentially valuable information about the level of activation of the motoneuron pool. In this paper, based on morphological features of the surface MUAPs, we try to estimate the number of MUAPs present in the surface EMG by counting the negative peaks in the signal. Several signal processing procedures are applied to the surface EMG to facilitate this peak counting process. The MUAP number estimation performance by this approach is first illustrated using the surface EMG simulations. Then, by evaluating the peak counting results from the EMG records detected by a very selective surface electrode, at different contraction levels of the first dorsal interosseous (FDI) muscles, the utility and limitations of such direct peak counts for MUAP number estimation in surface EMG are further explored.

  13. The Einstein action for algebras of matrix valued functions - Toy models

    International Nuclear Information System (INIS)

    Hajac, P.M.

    1995-10-01

    Two toy models are considered within the framework of noncommutative differential geometry. In the first one, the Einstein action of the Levi-Civita connection is computed for the algebra of matrix valued functions on a torus. It is shown that, assuming some constraints on the metric, this action splits into a classical-like, a quantum-like and a mixed term. In the second model, an analogue of the Palatini method of variation is applied to obtain critical points of the Einstein action functional for M 4 (R). It is pointed out that a solution to the Palatini variational problem is not necessarily a Levi-Civita connection. In this model, no additional assumptions regarding metrics are made. (author). 14 refs

  14. The Einstein action for algebras of matrix valued functions - Toy models

    Energy Technology Data Exchange (ETDEWEB)

    Hajac, P M

    1995-10-01

    Two toy models are considered within the framework of noncommutative differential geometry. In the first one, the Einstein action of the Levi-Civita connection is computed for the algebra of matrix valued functions on a torus. It is shown that, assuming some constraints on the metric, this action splits into a classical-like, a quantum-like and a mixed term. In the second model, an analogue of the Palatini method of variation is applied to obtain critical points of the Einstein action functional for M{sub 4}(R). It is pointed out that a solution to the Palatini variational problem is not necessarily a Levi-Civita connection. In this model, no additional assumptions regarding metrics are made. (author). 14 refs.

  15. Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

    Science.gov (United States)

    Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

    2018-01-01

    Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14 Neurons

    Directory of Open Access Journals (Sweden)

    Chin-Wei Huang

    2018-05-01

    Full Text Available Background/Aims: Rotenone (Rot is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39.3 µM; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization with an EC50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

  17. Intraoperative observation of changes in cochlear nerve action potentials during exposure to electromagnetic fields generated by mobile phones.

    Science.gov (United States)

    Colletti, Vittorio; Mandalà, Marco; Manganotti, Paolo; Ramat, Stefano; Sacchetto, Luca; Colletti, Liliana

    2011-07-01

    The rapid spread of devices generating electromagnetic fields (EMF) has raised concerns as to the possible effects of this technology on humans. The auditory system is the neural organ most frequently and directly exposed to electromagnetic activity owing to the daily use of mobile phones. In recent publications, a possible correlation between mobile phone usage and central nervous system tumours has been detected. Very recently a deterioration in otoacoustic emissions and in the auditory middle latency responses after intensive and long-term magnetic field exposure in humans has been demonstrated. To determine with objective observations if exposure to mobile phone EMF affects acoustically evoked cochlear nerve compound action potentials, seven patients suffering from Ménière's disease and undergoing retrosigmoid vestibular neurectomy were exposed to the effects of mobile phone placed over the craniotomy for 5 min. All patients showed a substantial decrease in amplitude and a significant increase in latency of cochlear nerve compound action potentials during the 5 min of exposure to EMF. These changes lasted for a period of around 5 min after exposure. The possibility that EMF can produce relatively long-lasting effects on cochlear nerve conduction is discussed and analysed in light of contrasting previous literature obtained under non-surgical conditions. Limitations of this novel approach, including the effects of the anaesthetics, craniotomy and surgical procedure, are presented in detail.

  18. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

    Science.gov (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

    2017-10-04

    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

  19. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah

    2016-01-01

    progressive MS (SPMS), for which approved disease-modifying therapies are limited. In this review, we summarize the pathophysiological mechanisms involved in the development of SPMS and the rationale and clinical potential for natalizumab, which is currently approved for the treatment of relapsing forms of MS......Multiple sclerosis (MS) is a common and chronic central nervous system (CNS) demyelinating disease and a leading cause of permanent disability. Patients most often present with a relapsing-remitting disease course, typically progressing over time to a phase of relentless advancement in secondary......, to exert beneficial effects in reducing disease progression unrelated to relapses in SPMS. In both forms of MS, active brain-tissue injury is associated with inflammation; but in SPMS, the inflammatory response occurs at least partly behind the blood-brain barrier and is followed by a cascade of events...

  20. Potential food applications of biobased materials. An EU- concerted action project

    DEFF Research Database (Denmark)

    Haugaard, V.K.; Udsen, A.M.; Mortensen, G.

    2001-01-01

    and coatings to food but novel commercial applications of these are scarce. Based on information currently available on the properties of biobased packaging materials the study identified products in the fresh meat, dairy, ready meal, beverage, fruit and vegetable, snack, frozen food and dry food categories......The objective of the study was to ascertain the state of the art with regard to the applicability of biobased packaging materials to foods and to identify potential food applications for biobased materials. The study revealed relatively few examples of biobased materials used as primary, secondary...... or tertiary packaging materials for foods. This is due to the fact that published investigations on the use of biobased materials are still scarce, and results obtained remain unpublished because of commercial pressures. The scientific literature contains numerous reports on applications of edible films...

  1. Analyzing the greenhouse gas impact potential of smallholder development actions across a global food security program

    Science.gov (United States)

    Grewer, Uwe; Nash, Julie; Gurwick, Noel; Bockel, Louis; Galford, Gillian; Richards, Meryl; Costa Junior, Ciniro; White, Julianna; Pirolli, Gillian; Wollenberg, Eva

    2018-04-01

    This article analyses the greenhouse gas (GHG) impact potential of improved management practices and technologies for smallholder agriculture promoted under a global food security development program. Under ‘business-as-usual’ development, global studies on the future of agriculture to 2050 project considerable increases in total food production and cultivated area. Conventional cropland intensification and conversion of natural vegetation typically result in increased GHG emissions and loss of carbon stocks. There is a strong need to understand the potential greenhouse gas impacts of agricultural development programs intended to achieve large-scale change, and to identify pathways of smallholder agricultural development that can achieve food security and agricultural production growth without drastic increases in GHG emissions. In an analysis of 134 crop and livestock production systems in 15 countries with reported impacts on 4.8 million ha, improved management practices and technologies by smallholder farmers significantly reduce GHG emission intensity of agricultural production, increase yields and reduce post-harvest losses, while either decreasing or only moderately increasing net GHG emissions per area. Investments in both production and post-harvest stages meaningfully reduced GHG emission intensity, contributing to low emission development. We present average impacts on net GHG emissions per hectare and GHG emission intensity, while not providing detailed statistics of GHG impacts at scale that are associated to additional uncertainties. While reported improvements in smallholder systems effectively reduce future GHG emissions compared to business-as-usual development, these contributions are insufficient to significantly reduce net GHG emission in agriculture beyond current levels, particularly if future agricultural production grows at projected rates.

  2. Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers.

    Science.gov (United States)

    Dahan, Arik; Wolk, Omri; Yang, Peihua; Mittal, Sachin; Wu, Zhiqian; Landowski, Christopher P; Amidon, Gordon L

    2014-12-01

    The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r(2) = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r(2) = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI₅₀ = 261 μM) compared to that in SK-MEL-5 cells (GI₅₀ = 807 μM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/μg protein) compared to SK-MEL-5 cells (0.68 pmol/min/μg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting.

  3. Palaeohydrogeological modelling for potential future repository sites

    International Nuclear Information System (INIS)

    2001-01-01

    In order to consider the future behaviour of a groundwater system over time scales of relevance to repository safety assessment, it is necessary to develop an understanding of how the groundwater system has changed over time. This can be done through studying the palaeohydrogeology of the groundwater system. The EQUIP project (Evidence from Quaternary Infills for Palaeohydrogeology) set out to develop and evaluate methodologies for obtaining palaeohydrogeological information from fracture infill minerals formed under past groundwater conditions. EQUIP was a collaborative project funded jointly by the European Commission and, in the UK, by the Environment Agency and UK Nirex Limited. The project also involved partners in Finland, France, Spain and Sweden. The fracture infill material chosen for this investigation was calcite, because its reactions in low temperature groundwater environments are fairly well understood and it is fairly ubiquitous in both crystalline and sedimentary rocks. In addition, geochemical modelling suggests that plausible time scales for growth of individual calcite crystals are in the range 10 to 10,000 years, so they may accumulate a record of groundwater evolution over periods of significant climate change. The project was based on four sites, having different climate histories and geological conditions, at which drillcore samples of the deep crystalline rocks, accompanied by hydrogeological and hydrochemical data for the current groundwater conditions, were already available. The principal study sites were Olkiluoto in Finland, Aspo/Laxemar in Sweden, Sellafield in the UK and Vienne in France. The results of the study focus on the morphology and bulk compositions of calcite, compositional zoning of calcite crystals and compositions of fluid inclusions. There are systematic variations in bulk compositions with depth and also in discrete compositional fluctuations (or zones) in individual calcite crystals. These are inferred to reflect

  4. Documentation of a Model Action Plan to Deter Illicit Nuclear Trafficking

    International Nuclear Information System (INIS)

    Smith, D; Kristo, M; Niemeyer, S; Dudder, G

    2006-01-01

    Theft, illegal possession, smuggling, or attempted unauthorized sale of nuclear and radiological materials remains a worldwide problem. The Nuclear Smuggling International Technical Working Group (ITWG) has adopted a model action plan to guide investigation of these cases through a systematic approach to nuclear forensics. The model action plan was recently documented and provides recommendations concerning incident response, collection of evidence in conformance with required legal standards, laboratory sampling and distribution of samples, radioactive materials analysis, including categorization and characterization of samples, forensics analysis of conventional evidence, and case development including interpretation of forensic signatures

  5. Documentation of a model action plan to deter illicit nuclear trafficking

    International Nuclear Information System (INIS)

    Smith, D.K.; Kristo, M.J.; Niemeyer, S.; Dudder, G.B.

    2008-01-01

    Theft, illegal possession, smuggling, or attempted unauthorized sale of nuclear and radiological materials remains a worldwide problem. The Nuclear Smuggling International Technical Working Group (ITWG) has adopted a model action plan to guide investigation of these cases through a systematic approach to nuclear forensics. The model action plan was recently documented and provides recommendations concerning incident response, collection of evidence in conformance with required legal standards, laboratory sampling and distribution of samples, radioactive materials analysis, including categorization and characterization of samples, forensics analysis of conventional evidence, and case development including interpretation of forensic signatures. (author)

  6. Four-parameter analytical local model potential for atoms

    International Nuclear Information System (INIS)

    Fei, Yu; Jiu-Xun, Sun; Rong-Gang, Tian; Wei, Yang

    2009-01-01

    Analytical local model potential for modeling the interaction in an atom reduces the computational effort in electronic structure calculations significantly. A new four-parameter analytical local model potential is proposed for atoms Li through Lr, and the values of four parameters are shell-independent and obtained by fitting the results of X a method. At the same time, the energy eigenvalues, the radial wave functions and the total energies of electrons are obtained by solving the radial Schrödinger equation with a new form of potential function by Numerov's numerical method. The results show that our new form of potential function is suitable for high, medium and low Z atoms. A comparison among the new potential function and other analytical potential functions shows the greater flexibility and greater accuracy of the present new potential function. (atomic and molecular physics)

  7. A continuous time model of the bandwagon effect in collective action

    OpenAIRE

    Arieh Gavious; Shlomo Mizrahi

    2001-01-01

    The paper offers a complex and systematic model of the bandwagon effect in collective action using continuous time equations. The model treats the bandwagon effect as a process influenced by ratio between the mobilization efforts of social activists and the resources invested by the government to counteract this activity. The complex modeling approach makes it possible to identify the conditions for specific types of the bandwagon effect, and determines the scope of that effect. Relying on ce...

  8. Current Government Actions and Potential Policy Options for Reducing Obesity in Queensland Schools

    Directory of Open Access Journals (Sweden)

    Naser A. Alsharairi

    2018-01-01

    Full Text Available School nutrition policies provide promising avenues towards the improvement of children’s eating habits and the prevention of obesity. Childhood obesity rates and related chronic diseases are increasing in Queensland, in part as a result of unhealthy eating habits and lack of physical activity. There is a very high investment by the Queensland government in maintaining healthy weight and promoting nutrition and physical activity among schoolchildren through delivering a range of initiatives across the state. However, there is a lack of evidence concerning the effectiveness of nutrition/physical education and parental involvement programs addressing obesity delivered in Queensland schools. This paper can be used to guide government and policy-makers regarding the most effective policy options that will promote healthy eating and physical activity among Queensland schoolchildren. The aim of this paper is to: (i summarize current evidence on Queensland government responses to obesity; and (ii discuss potential policy options that could support healthy eating and regular physical activity, and examine the evidence base for each option and suggest new areas for future research.

  9. Potentials of Mangifera indica in the treatment of depressive-anxiety disorders: possible mechanisms of action.

    Science.gov (United States)

    Ishola, Ismail O; Awodele, Olufunsho; Eluogu, Chinedum O

    2016-09-01

    Mangifera indica (Anacardiaceae) is an important herb in the traditional African and Ayurvedic medicines. The stem barks are used in the treatment of hypertension, insomnia, tumour, depression, rheumatism and as a tonic. This study was carried out to investigate antidepressant- and anxiolytic-like effect of the hydroethanol stem bark extract of M. indica (HeMI) in mice. HeMI (12.5-100 mg/kg, p.o.) was administered 1 h before subjecting the animal to the forced swim test (FST), tail suspension test (TST) and elevated plus maze tests (EPM). HeMI (12.5-100 mg/kg, p.o.) treatment produced significant reduction in immobility time [F(6.56)=8.35, pindica through interaction with 5-HT2 receptor, α2-adrenoceptor and dopamine D2-receptors. Also, an anxiolytic-like effect through its affinity for 5-HT2 and benzodiazepine receptors. Hence, M. indica could be a potential phytotherapeutic agent in the treatment of mixed anxiety-depressive illness.

  10. When syntax meets action: Brain potential evidence of overlapping between language and motor sequencing.

    Science.gov (United States)

    Casado, Pilar; Martín-Loeches, Manuel; León, Inmaculada; Hernández-Gutiérrez, David; Espuny, Javier; Muñoz, Francisco; Jiménez-Ortega, Laura; Fondevila, Sabela; de Vega, Manuel

    2018-03-01

    This study aims to extend the embodied cognition approach to syntactic processing. The hypothesis is that the brain resources to plan and perform motor sequences are also involved in syntactic processing. To test this hypothesis, Event-Related brain Potentials (ERPs) were recorded while participants read sentences with embedded relative clauses, judging for their acceptability (half of the sentences contained a subject-verb morphosyntactic disagreement). The sentences, previously divided into three segments, were self-administered segment-by-segment in two different sequential manners: linear or non-linear. Linear self-administration consisted of successively pressing three buttons with three consecutive fingers in the right hand, while non-linear self-administration implied the substitution of the finger in the middle position by the right foot. Our aim was to test whether syntactic processing could be affected by the manner the sentences were self-administered. Main results revealed that the ERPs LAN component vanished whereas the P600 component increased in response to incorrect verbs, for non-linear relative to linear self-administration. The LAN and P600 components reflect early and late syntactic processing, respectively. Our results convey evidence that language syntactic processing and performing non-linguistic motor sequences may share resources in the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review

    Directory of Open Access Journals (Sweden)

    Farah Iram

    2017-06-01

    Full Text Available The pentacyclic triterpenic acids isolated from the oleo gum resin of various Boswellia species are collectively called as Boswellic acids (BA. The oleo gum resin obtained from Indian variety i.e. Boswellia serrata (Family – Burseraceae is commonly known as Salai guggal. The resin fraction of Salai guggal is rich in Boswellic acids and its essential oil is composed of a mixture of mono, di and sesquiterpenes while gum fraction chiefly contains pentose and hexose sugars. This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine owing to their wide range of useful biological properties such as anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial anti-fungal, anti-complementary and analgesic activity, etc. It has been used as a herbal medicine since the prehistoric time to cure acute and chronic ailments including inflammatory diseases. Phytochemical investigation of this herbal medicine lead to identification of Boswellic acids which are found to be novel, potent, specific anti-inflammatory agents due to non-redox inhibition of 5-lipoxygenase (5-LO enzyme. However, the other important targets of Boswellic acids also include topoisomerases, angiogenesis, and cytochrome p450 enzymes. This review is a sincere attempt to discuss and present the current status of therapeutic potential, phytochemical as well as pharmacological profile of Boswellic acids primarily obtained from B. serrata.

  12. Efficacy of Morin as a Potential Therapeutic Phytocomponent: Insights into the Mechanism of Action

    Directory of Open Access Journals (Sweden)

    Amarendranath Choudhury

    2017-11-01

    Full Text Available Morin (3,5,7,29,49-pentahydroxyflavone is a yellow colour natural bioflavonoid abundantly available in different species of Moraceae family. Besides this, Morin is also harvested from several other sources like tea, coffee, cereals, fruits and red wine. Anti-oxidant, anti-inflammatory, and antiproliferative potency of Morin is well established in both in vivo and in vitro experiments. Among all major sources of Morin, Almond (Prunus dulcis, Fig (Chlorophora tinctoria, and Indian guava (Psidium guajava contains high quantity of it. Easy availability, less side effects and robust functional properties have encouraged the use of these plants in the traditional herbal medicine. In last few decades, the studies on Morin have opened up a whole new era in the therapeutic medicine. Besides anti-oxidant, anti-inflammatory, and antiproliferative activity, Morin has also been reported as a potential neuroprotective agent against many neurological diseases including Alzheimer’s disease, Parkinson’s disease, and cerebral ischemia. According to published reports, the underlying neuroprotective mechanism of Morin is focused mainly on its capacity to inhibit oxidative stress in brain. However, recent data also supports its efficacy in neuroprotection by effectively interacting in the β‒amyloid pathways, inflammatory pathways, and apoptotic pathways. In the present review, we have accumulated all the protective contributions of Morin and intended to drag a mechanistic pathway containing the molecular events leading to the protection against various anomalies.

  13. Quantitative motor unit action potential analysis of supraspinatus, infraspinatus, deltoideus and biceps femoris muscles in adult Royal Dutch sport horses.

    Science.gov (United States)

    Jose-Cunilleras, E; Wijnberg, I D

    2016-03-01

    Reference values for quantitative electromyography (QEMG) in shoulder and hindlimb muscles of horses are limited. To determine normative data on QEMG analysis of supraspinatus (SS), infraspinatus (IS), deltoideus (DT) and biceps femoris (BF) muscles. Experimental observational study and retrospective case series. Seven adult healthy Royal Dutch sport horses underwent quantitative motor unit action potential analysis of each muscle using commercial electromyography equipment. Measurements were made according to published methods. One-way ANOVA was used to compare quantitative motor unit action potential variables between muscles, with post hoc testing according to Bonferroni, with significance set at Paction potential were 8.7-10.4 ms, 651-867 μV, 3.2-3.7, 3.7-4.7, 1054-1457 μV·ms and 1.1-1.5 for SS, 9.6-11.0 ms, 779-1082 μV, 3.3-3.7, 3.8-4.7, 1349-2204 μV·ms and 1.4-1.9 for IS, 6.0-9.1 ms, 370-691 μV, 2.9-3.7, 2.8-4.5, 380-1374 μV·ms and 0.3-1.3 for DT and 5.7-7.8 ms, 265-385 μV, 2.7-3.2, 2.6-3.1, 296-484 μV·ms and 0.2-0.5 for BF, respectively. Mean duration, amplitude, number of phases and turns, area and size index were significantly (P15% polyphasic motor unit action potentials in SS and IS muscles. Differences between muscles should be taken into account when performing QEMG in order to be able to distinguish normal horses from horses with suspected neurogenic or myogenic disorders. These normal data provide the basis for objective QEMG assessment of shoulder and hindlimb muscles. Quantitative electromyography appears to be helpful in diagnosing neuropathies and discriminating these from myopathies. © 2015 EVJ Ltd.

  14. Evaluation of anticonvulsant actions of dibromophenyl enaminones using in vitro and in vivo seizure models.

    Directory of Open Access Journals (Sweden)

    Mohamed G Qaddoumi

    Full Text Available Epilepsy and other seizure disorders are not adequately managed with currently available drugs. We recently synthesized a series of dibromophenyl enaminones and demonstrated that AK6 and E249 were equipotent to previous analogs but more efficacious in suppressing neuronal excitation. Here we examined the actions of these lead compounds on in vitro and in vivo seizure models. In vitro seizures were induced in the hippocampal slice chemically (zero Mg2+ buffer and picrotoxin and electrically using patterned high frequency stimulation (HFS of afferents. In vivo seizures were induced in rats using the 6 Hz and the maximal electroshock models. AK6 (10 µM and E249 (10 µM depressed the amplitude of population spikes recorded in area CA1 of the hippocampus by -50.5±4.3% and -40.1±3.1% respectively, with partial recovery after washout. In the zero Mg2+ model, AK6 (10 µM depressed multiple population spiking (mPS by -59.3±6.9% and spontaneous bursts (SBs by -65.9±7.2% and in the picrotoxin-model by -43.3±7.2% and -50.0±8.3%, respectively. Likewise, E249 (10 µM depressed the zero-Mg2+-induced mPS by -48.8±9.5% and SBs by -55.8±15.5%, and in the picrotoxin model by -37.1±5.5% and -56.5±11.4%, respectively. They both suppressed post-HFS induced afterdischarges and SBs. AK6 and E249 dose-dependently protected rats in maximal electroshock and 6 Hz models of in vivo seizures after 30 min pretreatment. Their level of protection in both models was similar to that obtained with phenytoin Finally, while AK6 had no effect on locomotion in rats, phenytoin significantly decreased locomotion. AK6 and E249, suppressed in vitro and in vivo seizures to a similar extent. Their in vivo activities are comparable with but not superior to phenytoin. The most efficacious, AK6 produced no locomotor suppression while phenytoin did. Thus, AK6 and E249 may be excellent candidates for further investigation as potential agents for the treatment of epilepsy syndromes

  15. Predicting Individual Action Switching in Passively Experienced and Continuous Interactive Tasks Using the Fluid Events Model

    Directory of Open Access Journals (Sweden)

    Gabriel A. Radvansky

    2016-01-01

    Full Text Available The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience-based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covert event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant’s current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person’s prior experience. Thus, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events.

  16. Predicting Individual Action Switching in Covert and Continuous Interactive Tasks Using the Fluid Events Model.

    Science.gov (United States)

    Radvansky, Gabriel A; D'Mello, Sidney K; Abbott, Robert G; Bixler, Robert E

    2016-01-01

    The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience-based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covert event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant's current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person's prior experience. Thus, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events.

  17. Health belief model and reasoned action theory in predicting water saving behaviors in yazd, iran.

    Science.gov (United States)

    Morowatisharifabad, Mohammad Ali; Momayyezi, Mahdieh; Ghaneian, Mohammad Taghi

    2012-01-01

    People's behaviors and intentions about healthy behaviors depend on their beliefs, values, and knowledge about the issue. Various models of health education are used in deter¬mining predictors of different healthy behaviors but their efficacy in cultural behaviors, such as water saving behaviors, are not studied. The study was conducted to explain water saving beha¬viors in Yazd, Iran on the basis of Health Belief Model and Reasoned Action Theory. The cross-sectional study used random cluster sampling to recruit 200 heads of households to collect the data. The survey questionnaire was tested for its content validity and reliability. Analysis of data included descriptive statistics, simple correlation, hierarchical multiple regression. Simple correlations between water saving behaviors and Reasoned Action Theory and Health Belief Model constructs were statistically significant. Health Belief Model and Reasoned Action Theory constructs explained 20.80% and 8.40% of the variances in water saving beha-viors, respectively. Perceived barriers were the strongest Predictor. Additionally, there was a sta¬tistically positive correlation between water saving behaviors and intention. In designing interventions aimed at water waste prevention, barriers of water saving behaviors should be addressed first, followed by people's attitude towards water saving. Health Belief Model constructs, with the exception of perceived severity and benefits, is more powerful than is Reasoned Action Theory in predicting water saving behavior and may be used as a framework for educational interventions aimed at improving water saving behaviors.

  18. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection.

    Science.gov (United States)

    Baston, Chiara; Ursino, Mauro

    2015-01-01

    The basal ganglia (BG) are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go), indirect (NoGo), and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves) during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges), synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication). Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments.

  19. A Biologically Inspired Computational Model of Basal Ganglia in Action Selection

    Directory of Open Access Journals (Sweden)

    Chiara Baston

    2015-01-01

    Full Text Available The basal ganglia (BG are a subcortical structure implicated in action selection. The aim of this work is to present a new cognitive neuroscience model of the BG, which aspires to represent a parsimonious balance between simplicity and completeness. The model includes the 3 main pathways operating in the BG circuitry, that is, the direct (Go, indirect (NoGo, and hyperdirect pathways. The main original aspects, compared with previous models, are the use of a two-term Hebb rule to train synapses in the striatum, based exclusively on neuronal activity changes caused by dopamine peaks or dips, and the role of the cholinergic interneurons (affected by dopamine themselves during learning. Some examples are displayed, concerning a few paradigmatic cases: action selection in basal conditions, action selection in the presence of a strong conflict (where the role of the hyperdirect pathway emerges, synapse changes induced by phasic dopamine, and learning new actions based on a previous history of rewards and punishments. Finally, some simulations show model working in conditions of altered dopamine levels, to illustrate pathological cases (dopamine depletion in parkinsonian subjects or dopamine hypermedication. Due to its parsimonious approach, the model may represent a straightforward tool to analyze BG functionality in behavioral experiments.

  20. Health Belief Model and Reasoned Action Theory in Predicting Water Saving Behaviors in Yazd, Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Taghi Ghaneian

    2012-12-01

    Full Text Available Background: People's behaviors and intentions about healthy behaviors depend on their beliefs, values, and knowledge about the issue. Various models of health education are used in deter-mining predictors of different healthy behaviors but their efficacy in cultural behaviors, such as water saving behaviors, are not studied. The study was conducted to explain water saving beha-viors in Yazd, Iran on the basis of Health Belief Model and Reasoned Action Theory. Methods: The cross-sectional study used random cluster sampling to recruit 200 heads of households to collect the data. The survey questionnaire was tested for its content validity and reliability. Analysis of data included descriptive statistics, simple correlation, hierarchical multiple regression. Results: Simple correlations between water saving behaviors and Reasoned Action Theory and Health Belief Model constructs were statistically significant. Health Belief Model and Reasoned Action Theory constructs explained 20.80% and 8.40% of the variances in water saving beha-viors, respectively. Perceived barriers were the strongest Predictor. Additionally, there was a sta-tistically positive correlation between water saving behaviors and intention. Conclusion: In designing interventions aimed at water waste prevention, barriers of water saving behaviors should be addressed first, followed by people's attitude towards water saving. Health Belief Model constructs, with the exception of perceived severity and benefits, is more powerful than is Reasoned Action Theory in predicting water saving behavior and may be used as a framework for educational interventions aimed at improving water saving behaviors.

  1. Do we have to take action today in front of climate change? The contribution of integrated models

    International Nuclear Information System (INIS)

    Minh, Ha-Duong; Hourcade, J.Ch.

    2007-03-01

    What shall we do in front of climatic change? Considering the potential seriousness of global risks, shall we start drastic policies of abatement of greenhouse gas emissions? Taking into account the cost of these policies and the uncertainties about the reality of risks, should we postpone the action? Do the efforts of emissions abatement make a good use of rare resources when the stake is only to gain few degrees of temperature and while we need today urgent developments to fight against poverty? One of the priorities of CIRED, a mixed research unit involved in the sustainable development issue, is to clarify the terms of the debate in order to avoid its transformation into a conflict which would paralyze any significant action. To do so, CIRED has elaborated 'integrated' models which allow to study the optimal answer to be adopted considering the size of uncertainties and the forcefulness of the controversies which characterize this subject. (J.S.)

  2. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    Directory of Open Access Journals (Sweden)

    János Brunner

    2014-03-01

    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  3. Community Health Workers-Promotores de Salud in Mexico: History and Potential for Building Effective Community Actions.

    Science.gov (United States)

    Balcazar, Hector; Perez-Lizaur, Ana Bertha; Izeta, Ericka Escalante; Villanueva, Maria Angeles

    2016-01-01

    This article takes a historical perspective combining 3 illustrative examples of the origins of the community health worker (CHW) model in Mexico, as a community-based participatory strategy. Three examples were identified from the sparse literature about CHWs in Mexico emphasizing their key roles and functions in various community settings. The CHW models illustrate what is known of training-development and planning, implementation, and evaluation of the CHWs model in different settings addressing cardiovascular disease and risk factors. The potential exists for integrating CHW projects to expand the health promotion model with new emphasis on municipality and regional participation.

  4. Comparison of potential models through heavy quark effective theory

    International Nuclear Information System (INIS)

    Amundson, J.F.

    1995-01-01

    I calculate heavy-light decay constants in a nonrelativistic potential model. The resulting estimate of heavy quark symmetry breaking conflicts with similar estimates from lattice QCD. I show that a semirelativistic potential model eliminates the conflict. Using the results of heavy quark effective theory allows me to identify and compensate for shortcomings in the model calculations in addition to isolating the source of the differences in the two models. The results lead to a rule as to where the nonrelativistic quark model gives misleading predictions

  5. Artist-Teachers' In-Action Mental Models While Teaching Visual Arts

    Science.gov (United States)

    Russo-Zimet, Gila

    2017-01-01

    Studies have examined the assumption that teachers have previous perceptions, beliefs and knowledge about learning (Cochran-Smith & Villegas, 2015). This study presented the In-Action Mental Model of twenty leading artist-teachers while teaching Visual Arts in three Israeli art institutions of higher Education. Data was collected in two…

  6. On Some Calculations of Effective Action and Fujikawa Regularized Anomaly in the Chiral Schwinger Model

    OpenAIRE

    Mehrdad, GOSHTASBPOUR; Center for Theoretical Physics and Mathematics, AEOI:Department of Physics, Shahid Beheshti University

    1991-01-01

    Extended D^†+D-DD^† Fujikawa regularization of anomaly and a method of integration of fermions for the chiral Schwinger model are criticized. On the basis of the corrected integration method, a new extended version of D^2 is obtained, resulting in the Jackiw-Rajaraman effective action.

  7. Action and Language Mechanisms in the Brain: Data, Models and Neuroinformatics

    Science.gov (United States)

    Bonaiuto, James J.; Bornkessel-Schlesewsky, Ina; Kemmerer, David; MacWhinney, Brian; Nielsen, Finn Årup; Oztop, Erhan

    2014-01-01

    We assess the challenges of studying action and language mechanisms in the brain, both singly and in relation to each other to provide a novel perspective on neuroinformatics, integrating the development of databases for encoding – separately or together – neurocomputational models and empirical data that serve systems and cognitive neuroscience. PMID:24234916

  8. The quench action approach to out-of-equilibrium quantum integrable models

    NARCIS (Netherlands)

    Wouters, B.M.

    2015-01-01

    In this PhD thesis quantum quenches to 1D quantum integrable models are studied by means of the quench action approach. Using the large-system-size scaling of overlaps between the i