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Sample records for action potentials

  1. Perfect Actions with Chemical Potential

    Bietenholz, W

    1998-01-01

    We show how to include a chemical potential \\mu in perfect lattice actions. It turns out that the standard procedure of multiplying the quark fields \\Psi, an example, the case of free fermions with chemical potential is worked out explicitly. Even after truncation, cut-off effects in the pressure and the baryon density are small. Using a (quasi-)perfect action, numerical QCD simulations for non-zero chemical potential become more powerful, because coarse lattices are sufficient for extracting continuum physics.

  2. Action Principle for Potential Flows

    Frønsdal, Christian

    2014-01-01

    The restriction of hydrodynamics to non-viscous, potential (gradient, irrotational) flows is a theory both simple and elegant; a favorite topic of introductory textbooks. It is known that this theory (under the stated limitations) can be formulated as an action principle. It finds its principle application to adiabatic systems and cannot account for viscosity or dissipation. However, it can be generalized to include non-potential flows, as this paper shows. The new theory is a combination of Eulerian and Lagrangian hydrodynamics, with an extension to thermodynamics. It describes adiabatic phenomena but does not account for viscosity or dissipation. Nevertheless, it is an approach within which quasi-static processes can be described. In the adiabatic context it appears to be an improvement of the Navier-Stokes equation, the principal advantage being a natural concept of energy in the form of a first integral of the motion, conserved by virtue of the Euler-Lagrange equations.

  3. Light-triggered action potentials in plants

    Kazimierz Trębacz

    2014-01-01

    Special attention is paid in this paper to the criteria of the light-triggered action potential, namely the all-or-none law, propagation, the occurrence of refractory periods. Such action potentials have been recorded in Acetabularia mediterranea, Asplenium trichomanes, Bryum pseudotriquetrum, Eremosphaera viridis and Concephalum conicum. In Acetabularia, action potentials are generated after sudden cessation of light stimuli of sufficient intensity. The depolarization phase of the action pot...

  4. Improved Lattice Actions with Chemical Potential

    Bietenholz, W

    1998-01-01

    We give a prescription how to include a chemical potential \\mu into a general lattice action. This inclusion does not cause any lattice artifacts. Hence its application to an improved - or even perfect - action at \\mu =0 yields an improved resp. perfect action at arbitrary \\mu. For short-ranged improved actions, a good scaling behavior holds over a wide region, and the upper bound for the baryon density - which is known for the standard lattice actions - can be exceeded.

  5. Abstract Action Potential Models for Toxin Recognition

    Peterson, James; Khan, Taufiquar

    2005-01-01

    In this paper, we present a robust methodology using mathematical pattern recognition schemes to detect and classify events in action potentials for recognizing toxins in biological cells. We focus on event detection in action potential via abstraction of information content into a low dimensional feature vector within the constrained computational environment of a biosensor. We use generated families of action potentials from a classic Hodgkin–Huxley model to verify our methodology and build...

  6. Screening action potentials: The power of light

    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.

  7. Introducing the Action Potential to Psychology Students

    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…

  8. expression, physiological actions and therapeutic potential

    Steckelings, Ulrike

    2012-01-01

    Angiotensin II mediates its action via 2 receptor subtypes: the AT1- and AT2-receptor. The existence of more than one receptor for angiotensin II has been discovered not earlier than 1989. This "Habilitationsschrift" is based on six publications which represent mosaic stones within the growing picture of AT2-receptor expression, regulation of expression, physiological and patho-physiological function as well as potential therapeutic use. The first part is dealing with tissue specific ex...

  9. The Potential of Deweyan-Inspired Action Research

    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 separation between action and reflection or theory and practice. This paper considers the potential of action research informed specifically by Deweyan pragm...

  10. Action potential broadening in a presynaptic channelopathy

    Begum, Rahima; Bakiri, Yamina; Volynski, Kirill E.; Kullmann, Dimitri M.

    2016-07-01

    Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory terminals have not been characterized, and it is not known whether developmental plasticity compensates for the effects of Kv1.1 dysfunction. Here we use visually targeted patch-clamp recordings from basket cell terminals of mice harbouring an ataxia-associated mutation and their wild-type littermates. Presynaptic spikes are followed by a pronounced afterdepolarization, and are broadened by pharmacological blockade of Kv1.1 or by a dominant ataxia-associated mutation. Somatic recordings fail to detect such changes. Spike broadening leads to increased Ca2+ influx and GABA release, and decreased spontaneous Purkinje cell firing. We find no evidence for developmental compensation for inherited Kv1.1 dysfunction.

  11. Teachers in Action Research: Assumptions and Potentials

    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.…

  12. Action potential initiation in the hodgkin-huxley model.

    Colwell, Lucy J; Brenner, Michael P.

    2009-01-01

    A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span) and the rapidity of action potential initiation (the onset rapidity). This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or in...

  13. Spectral action, Weyl anomaly and the Higgs-Dilaton potential

    Andrianov, A.A.(V.A. Fock Department of Theoretical Physics, Saint-Petersburg State University, 1 ul. Ulyanovskaya, St. Petersburg, 198504, Russia); Kurkov, M.A.; Lizzi, Fedele

    2011-01-01

    We show how the bosonic spectral action emerges from the fermionic action by the renormalization group flow in the presence of a dilaton and the Weyl anomaly. The induced action comes out to be basically the Chamseddine-Connes spectral action introduced in the context of noncommutative geometry. The entire spectral action describes gauge and Higgs fields coupled with gravity. We then consider the effective potential and show, that it has the desired features of a broken and an unbroken phase,...

  14. Action potentials reliably invade axonal arbors of rat neocortical neurons

    Cox, Charles L.; Denk, Winfried; Tank, David W.; Svoboda, Karel

    2000-01-01

    Neocortical pyramidal neurons have extensive axonal arborizations that make thousands of synapses. Action potentials can invade these arbors and cause calcium influx that is required for neurotransmitter release and excitation of postsynaptic targets. Thus, the regulation of action potential invasion in axonal branches might shape the spread of excitation in cortical neural networks. To measure the reliability and extent of action potential invasion into axonal arbors, we have used two-photon...

  15. Critical Utopian Action Research: The Potential of Action Research in the Democratization of Society

    Nielsen, Birger Steen; Nielsen, Kurt Aagaard

    The specific concept of critical utopian action research is presented and discussed, as to its origin, use and potentials. The inspiration from Robert Jungk and his future creating workshops is elaborated.......The specific concept of critical utopian action research is presented and discussed, as to its origin, use and potentials. The inspiration from Robert Jungk and his future creating workshops is elaborated....

  16. [Individualised medicine - potentials and need for action].

    Hüsing, Bärbel

    2010-01-01

    Individualised medicine aims to classify seemingly homogenous patient groups into smaller clinically relevant subgroups (stratification) in order to be able to treat them differently, thus contributing to the improvement of health care services, to the prevention of inappropriate treatments and to the reduction of adverse effects. This article summarises a report to the Office of Technology Assessment at the German Bundestag and points out the need for action for transferring individualised medicine from research to clinical application: significant incentives are required in order to prove the clinical validity of newly identified biomarkers of complex diseases. Sustainable business models for the joint development of new applications by research institutions, biotechnology companies, pharmaceuticals and medical devices companies are required. Instruments for transferring knowledge from bench to bedside (translational research) and the existing regulatory framework should be further developed in order to strike an appropriate balance between incentives for accelerating the transfer of innovative technology to the health care sector while, at the same time, ensuring patient safety, high quality and clinical utility. PMID:21147435

  17. Angle-action estimation in a general axisymmetric potential

    Sanders, Jason

    2012-01-01

    The usefulness of angle-action variables in galaxy dynamics is well known, but their use is limited due to the difficulty of their calculation in realistic galaxy potentials. Here we present a method for estimating angle-action variables in a realistic Milky Way axisymmetric potential by locally fitting a St\\"ackel potential over the region an orbit probes. The quality of the method is assessed by comparison with other known methods for estimating angle-action variables of a range of disc and...

  18. Radial propagation of muscle action potential along the tubular system examined by potential-sensitive dyes

    Nakajima, S.; Gilai, A.

    1980-01-01

    Isolated single (Xenopus) muscle fibers were stained with a non-permeant potential-probing dye, merocyanine rhodanine (WW375) or merocyanine oxazolone (NK2367). When the fiber was massively stimulated, an absorption change (wave a), which seemed to reflect the action potential, occurred. Simultaneous recording of optical changes and intracellular action potentials revealed that the time-course of wave a was slower than the action potential: the peak of wave a was attained at 1 ms, and the pea...

  19. Intracellular recording of action potentials by nanopillar electroporation

    Xie, Chong; Lin, Ziliang; Hanson, Lindsey; Cui, Yi; Cui, Bianxiao

    2012-03-01

    Action potentials have a central role in the nervous system and in many cellular processes, notably those involving ion channels. The accurate measurement of action potentials requires efficient coupling between the cell membrane and the measuring electrodes. Intracellular recording methods such as patch clamping involve measuring the voltage or current across the cell membrane by accessing the cell interior with an electrode, allowing both the amplitude and shape of the action potentials to be recorded faithfully with high signal-to-noise ratios. However, the invasive nature of intracellular methods usually limits the recording time to a few hours, and their complexity makes it difficult to simultaneously record more than a few cells. Extracellular recording methods, such as multielectrode arrays and multitransistor arrays, are non-invasive and allow long-term and multiplexed measurements. However, extracellular recording sacrifices the one-to-one correspondence between the cells and electrodes, and also suffers from significantly reduced signal strength and quality. Extracellular techniques are not, therefore, able to record action potentials with the accuracy needed to explore the properties of ion channels. As a result, the pharmacological screening of ion-channel drugs is usually performed by low-throughput intracellular recording methods. The use of nanowire transistors, nanotube-coupled transistors and micro gold-spine and related electrodes can significantly improve the signal strength of recorded action potentials. Here, we show that vertical nanopillar electrodes can record both the extracellular and intracellular action potentials of cultured cardiomyocytes over a long period of time with excellent signal strength and quality. Moreover, it is possible to repeatedly switch between extracellular and intracellular recording by nanoscale electroporation and resealing processes. Furthermore, vertical nanopillar electrodes can detect subtle changes in action

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

    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...

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

    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.

  2. Theophylline-induced potentiation of the antinociceptive action of baclofen.

    Sawynok, J

    1983-01-01

    1--Theophylline (35, 50 mg/kg) potentiated the antinociceptive action of intraperitoneally administered baclofen in the tail flick and hot plate tests. Potentiation was most marked when the pretreatment time was 1 h, but some potentiation was still apparent following a 2 h pretreatment. 2--Theophylline alone (50 mg/kg) produced only slight alterations in reaction latency in the two tests. 3--When baclofen was applied directly into the spinal subarachnoid space, a 1 h pretreatment with theophy...

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

    Przybylski, Aleksander T.; Stratten, Wilford P.; Syren, Robert M.; Fox, Sidney W.

    1982-12-01

    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.

  4. Numerical investigation of action potential transmission in plants

    Mariusz Pietruszka

    2014-02-01

    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.

  5. Far-field potentials recorded from action potentials and from a tripole in a hemicylindrical volume.

    Jewett, D L; Deupree, D L

    1989-05-01

    There is growing evidence in support of the hypothesis that far-field potentials are recorded when action potentials encounter discontinuities in the surrounding volume. The present study found further support for this hypothesis using two methods of experimentation. The first method recorded potentials when the action potential from an isolated bullfrog sciatic nerve in a hemicylindrical volume (i) encountered a change in the shape of the surrounding volume, (ii) crossed a boundary between 2 volumes of differing resistivities, (iii) reached a bend in the nerve, or (iv) reached the functional end of the nerve. In the second method, potentials were recorded when an electrical tripole, constructed in a way to produce the electrical equivalent of an action potential, encountered the same discontinuities as well as when it was configured to simulate a curved nerve. These results are consistent with the hypothesis that dipole components of an action potential predominant in far-field recordings. PMID:2469568

  6. Action prediction based on anticipatory brain potentials during simulated driving

    Khaliliardali, Zahra; Chavarriaga, Ricardo; Gheorghe, Lucian Andrei; Millán, José del R.

    2015-12-01

    Objective. The ability of an automobile to infer the driver’s upcoming actions directly from neural signals could enrich the interaction of the car with its driver. Intelligent vehicles fitted with an on-board brain-computer interface able to decode the driver’s intentions can use this information to improve the driving experience. In this study we investigate the neural signatures of anticipation of specific actions, namely braking and accelerating. Approach. We investigated anticipatory slow cortical potentials in electroencephalogram recorded from 18 healthy participants in a driving simulator using a variant of the contingent negative variation (CNV) paradigm with Go and No-go conditions: count-down numbers followed by ‘Start’/‘Stop’ cue. We report decoding performance before the action onset using a quadratic discriminant analysis classifier based on temporal features. Main results. (i) Despite the visual and driving related cognitive distractions, we show the presence of anticipatory event related potentials locked to the stimuli onset similar to the widely reported CNV signal (with an average peak value of -8 μV at electrode Cz). (ii) We demonstrate the discrimination between cases requiring to perform an action upon imperative subsequent stimulus (Go condition, e.g. a ‘Red’ traffic light) versus events that do not require such action (No-go condition; e.g. a ‘Yellow’ light); with an average single trial classification performance of 0.83 ± 0.13 for braking and 0.79 ± 0.12 for accelerating (area under the curve). (iii) We show that the centro-medial anticipatory potentials are observed as early as 320 ± 200 ms before the action with a detection rate of 0.77 ± 0.12 in offline analysis. Significance. We show for the first time the feasibility of predicting the driver’s intention through decoding anticipatory related potentials during simulated car driving with high recognition rates.

  7. Propagation of Action Potentials: An Active Participation Exercise.

    Felsten, Gary

    1998-01-01

    Describes an active participation exercise that demonstrates the propagation of action potentials (the ability to transmit information through the neural network, dependent upon chemical interactions in the brain). Students assume the structure and function of the network by lining up around the room and communicating through hand signals and…

  8. Compound muscle action potentials in newborn infants with spina bifida.

    Geerdink, N.; Pasman, J.W.; Rotteveel, J.J.; Roeleveld, N.; Mullaart, R.A.

    2008-01-01

    The aim of this study was to investigate the relationship between compound muscle action potentials (CMAPs) and neurological impairment in newborn infants with spina bifida. Thirty-one newborn infants (17 males, 14 females, mean gestational age 39 wks [SD 2]; mean birthweight 3336 g [SD 496]) with s

  9. Sodium and potassium conductance changes during a membrane action potential.

    Bezanilla, F; Rojas, E; Taylor, R E

    1970-12-01

    1. A method for turning a membrane potential control system on and off in less than 10 musec is described. This method was used to record membrane currents in perfused giant axons from Dosidicus gigas and Loligo forbesi after turning on the voltage clamp system at various times during the course of a membrane action potential.2. The membrane current measured just after the capacity charging transient was found to have an almost linear relation to the controlled membrane potential.3. The total membrane conductance taken from these current-voltage curves was found to have a time course during the action potential similar to that found by Cole & Curtis (1939).4. The instantaneous current voltage curves were linear enough to make it possible to obtain a good estimate of the individual sodium and potassium channel conductances, either algebraically or by clamping to the sodium, or potassium, reversal potentials. Good general agreement was obtained with the predictions of the Hodgkin-Huxley equations.5. We consider these results to constitute the first direct experimental demonstration of the conductance changes to sodium and potassium during the course of an action potential. PMID:5505231

  10. Action potential initiation in the hodgkin-huxley model.

    Lucy J Colwell

    2009-01-01

    Full Text Available A recent paper of B. Naundorf et al. described an intriguing negative correlation between variability of the onset potential at which an action potential occurs (the onset span and the rapidity of action potential initiation (the onset rapidity. This correlation was demonstrated in numerical simulations of the Hodgkin-Huxley model. Due to this antagonism, it is argued that Hodgkin-Huxley-type models are unable to explain action potential initiation observed in cortical neurons in vivo or in vitro. Here we apply a method from theoretical physics to derive an analytical characterization of this problem. We analytically compute the probability distribution of onset potentials and analytically derive the inverse relationship between onset span and onset rapidity. We find that the relationship between onset span and onset rapidity depends on the level of synaptic background activity. Hence we are able to elucidate the regions of parameter space for which the Hodgkin-Huxley model is able to accurately describe the behavior of this system.

  11. Click- and chirp-evoked human compound action potentials

    Chertoff, Mark; Lichtenhan, Jeffery; Willis, Marie

    2010-01-01

    In the experiments reported here, the amplitude and the latency of human compound action potentials (CAPs) evoked from a chirp stimulus are compared to those evoked from a traditional click stimulus. The chirp stimulus was created with a frequency sweep to compensate for basilar membrane traveling wave delay using the O-Chirp equations from Fobel and Dau [(2004). J. Acoust. Soc. Am. 116, 2213–2222] derived from otoacoustic emission data. Human cochlear traveling wave delay estimates were obta...

  12. Action potentials of curved nerves in finite limbs.

    Xiao, S; McGill, K C; Hentz, V R

    1995-06-01

    Previous simulations of volume-conducted nerve-fiber action-potentials have modeled the limb as semi-infinite or circularly cylindrical, and the fibers as straight lines parallel to the limb surface. The geometry of actual nerves and limbs, however, can be considerably more complicated. This paper presents a general method for computing the potentials of fibers with arbitrary paths in arbitrary finite limbs. It involves computing the propagating point-source response (PPSR), which is the potential arising from a single point source (dipole or tripole) travelling along the fiber. The PPSR can be applied to fibers of different conduction velocities by simple dilation or compression. The method is illustrated for oblique and spiralling nerve fibers. Potentials from oblique fibers are shown to be different for orthodromic and antidromic propagation. Such results show that the straight-line models are not always adequate for nerves with anatomical amounts of curvature. PMID:7790016

  13. Numerical simulation of antiarrhythmic drugs effects on cardiac action potential

    Převorovská, Světlana; Maršík, František

    Brno : Brno University of Technology, 2006 - (Burša, J.; Fuis, V.), s. 170-171 ISBN 80-214-3232-2. [ Human Biomechanics 2006. Hrotovice (CZ), 13.11.2006-16.11.2006] R&D Projects: GA ČR(CZ) GA106/03/1073; GA ČR(CZ) GA106/03/0958 Institutional research plan: CEZ:AV0Z20760514 Keywords : human cardiovascular system * cardiac action potential * antiarrhytmmic drugs-cell channel interaction Subject RIV: BK - Fluid Dynamics

  14. Flexible graphene transistors for recording cell action potentials

    Blaschke, Benno M.; Lottner, Martin; Drieschner, Simon; Bonaccini Calia, Andrea; Stoiber, Karolina; Rousseau, Lionel; Lissourges, Gaëlle; Garrido, Jose A.

    2016-06-01

    Graphene solution-gated field-effect transistors (SGFETs) are a promising platform for the recording of cell action potentials due to the intrinsic high signal amplification of graphene transistors. In addition, graphene technology fulfills important key requirements for in-vivo applications, such as biocompability, mechanical flexibility, as well as ease of high density integration. In this paper we demonstrate the fabrication of flexible arrays of graphene SGFETs on polyimide, a biocompatible polymeric substrate. We investigate the transistor’s transconductance and intrinsic electronic noise which are key parameters for the device sensitivity, confirming that the obtained values are comparable to those of rigid graphene SGFETs. Furthermore, we show that the devices do not degrade during repeated bending and the transconductance, governed by the electronic properties of graphene, is unaffected by bending. After cell culture, we demonstrate the recording of cell action potentials from cardiomyocyte-like cells with a high signal-to-noise ratio that is higher or comparable to competing state of the art technologies. Our results highlight the great capabilities of flexible graphene SGFETs in bioelectronics, providing a solid foundation for in-vivo experiments and, eventually, for graphene-based neuroprosthetics.

  15. Metabolic syndrome potentiates the cardiac action potential-prolonging action of drugs: a possible 'anti-proarrhythmic' role for amlodipine.

    Caillier, Bertrand; Pilote, Sylvie; Patoine, Dany; Levac, Xavier; Couture, Christian; Daleau, Pascal; Simard, Chantale; Drolet, Benoit

    2012-03-01

    Type II diabetes was shown to prolong the QT interval on the ECG and to promote cardiac arrhythmias. This is not so clear for metabolic syndrome, a precursor state of type II diabetes. The objectives of the present study were to generate a guinea pig model of metabolic syndrome by long-term exposure to diabetogenic diets, and to evaluate the monophasic action potential duration (MAPD)-modulating effects of drugs in these animals. Male Hartley guinea pigs were fed with either the control, the High Fat High Sucrose (HFHS) or the High Fat High Fructose (HFHF) diet for 150 days. Evolution of weight, blood cholesterol, triglycerides, urea and glucose tolerance were regularly monitored. Histopathological evolution was also evaluated in target organs such as pancreas, heart, liver and kidneys. Ex vivo experiments using the Langendorff retroperfusion technique, isolated hearts from guinea pigs either fed with the control, the HFHS or the HFHF diet were exposed to dofetilide 20 nM (D), chromanol 293B 10 μM (C) and amlodipine 100 nM (A) in different drug combinations and monophasic action potential duration was measured at 90% repolarization (MAPD₉₀). Our data show that it is possible to generate a guinea pig model of metabolic syndrome by chronic exposure to diabetogenic diets. Minor histopathological abnormalities were observed, mainly in the pancreas and the liver. Metabolic syndrome potentiates the MAPD-prolonging actions of I(Kr)-blocking (dofetilide) and I(Ks)-blocking (chromanol 293B) drugs, an effect that is reversible upon administration of the calcium channel blocker amlodipine. PMID:22154802

  16. The Potential of Deweyan-Inspired Action Research

    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…

  17. Pressure wave model for action potential propagation in excitable cells

    Rvachev, M M

    2003-01-01

    Speed of propagation of small-amplitude pressure waves through the cytoplasmic interior of myelinated and unmyelinated axons of different diameters is theoretically estimated and is found to generally agree with the action potential (AP) conduction velocities. This remarkable coincidence allows to surmise a model in which AP spread along axon is propelled not by straggling ionic currents as in the widely accepted local circuit theory, but by mechanoactivation of the membrane ion channels by a traveling pressure pulse. Hydraulic pulses propagating in the viscous axoplasm are calculated to decay over ~1 mm distances, and it is further hypothesized that it is the role of influxing during the AP calcium ions to activate membrane skeletal protein network attached to the membrane cytoplasmic side for a brief radial contraction amplifying the pressure pulse and preventing its decay. The model correctly predicts that the AP conduction velocity should vary as the one-half power of axon diameter for large unmyelinated ...

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

    Krarup, Christian

    2004-01-01

    at different conduction distances are determined by summation of SFAPs of varying fiber diameters, and differ in this respect, also, from the compound muscle action potential (CMAP) for which conduction velocities are determined by the very fastest fibers in the nerve. The effect and extent of temporal...... 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...... in different polyneuropathies. In this review, different factors that characterize sensory fibers and set the SNAP apart from the CMAP are discussed to emphasize the supplementary and complementary information that can be obtained from sensory conduction studies. Sensory conduction studies require particular...

  19. Map-based model of the cardiac action potential

    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.

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

    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.

  1. Modelling Action Potential Generation and Propagation in Fibroblastic Cells

    Torres, J. J.; Cornelisse, L. N.; Harks, E. G. A.; Theuvenet, A. P. R.; Ypey, D. L.

    2003-04-01

    Using a standard Hodgkin-Huxley (HH) formalism, we present a mathematical model for action potential (AP) generation and intercellular AP propagation in quiescent (serum-deprived) normal rat kidney (NRK) fibroblasts [1], based on the recent experimental identification of the ion channels involved [2]. The principal ion channels described are those of an inwardly rectifying K+ conductance (GKIR), an L-type calcium conductance (GCaL), an intracellular calcium activated Cl- conductance (GCl(Ca)), a residual leak conductance Gleak, and gap junctional channels between the cells (Ggj). The role of each one of these components in the particular shape of the AP wave-form has been analyzed and compared with experimental observations. In addition, we have studied the role of subcellular processes like intracellular calcium dynamics and calcium buffering in AP generation. AP propagation between cells was reconstructed in a hexagonal model of cells coupled by Ggj with physiological conductance values. The model revealed an excitability mechanism of quiescent NRK cells with a particular role of intracellular calcium dynamics. It allows further explorations of the mechanism of signal generation and transmission in NRK cell cultures and its dependence on growth conditions.

  2. Pharmacological actions of statins: potential utility in COPD

    T. E. Eaton

    2009-12-01

    Full Text Available Chronic obstructive pulmonary disease (COPD is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-B mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1 Inhibition of cytokine production (tumour necrosis factor-, interleukin (IL-6 and IL-8 and neutrophil infiltration into the lung; 2 inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3 antioxidant and anti-inflammatory (IL-6 mediated effects on skeletal muscle; 4 reduced inflammatory response to pulmonary infection; and 5 inhibition of the development (or reversal of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD.

  3. Pharmacological actions of statins: potential utility in COPD.

    Young, R P; Hopkins, R; Eaton, T E

    2009-12-01

    Chronic obstructive pulmonary disease (COPD) is characterised by minimally reversible airflow limitation and features of systemic inflammation. Current therapies for COPD have been shown to reduce symptoms and infective exacerbations and to improve quality of life. However, these drugs have little effect on the natural history of the disease (progressive decline in lung function and exercise tolerance) and do not improve mortality. The anti-inflammatory effects of statins on both pulmonary and systemic inflammation through inhibition of guanosine triphosphatase and nuclear factor-κB mediated activation of inflammatory and matrix remodelling pathways could have substantial benefits in patients with COPD due to the following. 1) Inhibition of cytokine production (tumour necrosis factor-α, interleukin (IL)-6 and IL-8) and neutrophil infiltration into the lung; 2) inhibition of the fibrotic activity in the lung leading to small airways fibrosis and irreversible airflow limitation; 3) antioxidant and anti-inflammatory (IL-6 mediated) effects on skeletal muscle; 4) reduced inflammatory response to pulmonary infection; and 5) inhibition of the development (or reversal) of epithelial-mesenchymal transition, a precursor event to lung cancer. This review examines the pleiotropic pharmacological action of statins which inhibit key inflammatory and remodelling pathways in COPD and concludes that statins have considerable potential as adjunct therapy in COPD. PMID:20956147

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

    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. ...

  5. Acute nerve compression and the compound muscle action potential

    Baylor Kelly

    2008-01-01

    Full Text Available Abstract Detecting acute nerve compression using neurophysiologic studies is an important part of the practice of clinical intra-operative neurophysiology. The goal of this paper was to study the changes in the compound muscle action potential (CMAP during acute mechanical compression. This is the type of injury most likely to occur during surgery. Thus, understanding the changes in the CMAP during this type of injury will be useful in the detection and prevention using intra-operative neurophysiologic monitoring. The model involved compression of the hamster sciatic nerve over a region of 1.3 mm with pressures up to 2000 mmHg for times on the order of 3 minutes. In this model CMAP amplitude dropped to 50% of its baseline value when a pressure of roughly 1000 mmHg is applied while, at the same time, nerve conduction velocities decline by only 5%. The ability to detect statistically significant changes in the CMAP at low force levels using other descriptors of the CMAP including duration, latency variation, etc alone or in conjunction with amplitude and velocity measures was investigated. However, these other parameters did not allow for earlier detection of significant changes. This study focused on a model in which nerve injury on a short time scale is purely mechanical in origin. It demonstrated that a pure compression injury produced large changes in CMAP amplitude prior to large changes in conduction velocity. On the other hand, ischemic and stretch injuries are associated with larger changes in conduction velocity for a given value of CMAP amplitude reduction.

  6. Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions

    Karch, Susanne; Loy, Fabian; Krause, Daniela; Schwarz, Sandra; Kiesewetter, Jan; Segmiller, Felix; Chrobok, Agnieszka I.; Keeser, Daniel; Pogarell, Oliver

    2016-01-01

    Objective: Internally guided actions are defined as being purposeful, self-generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we ...

  7. The membrane actions of estrogens can potentiate their lordosis behavior-facilitating genomic actions

    Kow, Lee-Ming; Pfaff, Donald W.

    2004-01-01

    The membrane actions of estrogens can facilitate their genomic actions. To determine whether this facilitation bears on CNS mechanisms for estrogen-dependent behaviors, ovariectomized rats were subjected to a two-pulse treatment of estrogen directly in the hypothalamic ventromedial nucleus. Two days later, each rat was given progesterone and then tested for lordosis behavior, the induction of which requires the genomic actions of estrogen. When estrogen was given in both pulses (15 min to 2 h...

  8. Circadian- and Light-Dependent Regulation of Resting Membrane Potential and Spontaneous Action Potential Firing of Drosophila Circadian Pacemaker Neurons

    Sheeba, Vasu; Gu, Huaiyu; Sharma, Vijay K.; O'Dowd, Diane K.; Holmes, Todd C.

    2007-01-01

    The ventral lateral neurons (LNvs) of adult Drosophila brain express oscillating clock proteins and regulate circadian behavior. Whole cell current-clamp recordings of large LNvs in freshly dissected Drosophila whole brain preparations reveal two spontaneous activity patterns that correlate with two underlying patterns of oscillating membrane potential: tonic and burst firing of sodium-dependent action potentials. Resting membrane potential and spontaneous action potential firing are rapidly ...

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

    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.)

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

    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,…

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

    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.

  12. Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle

    Seong-Jin Cho; Sang-Hun Lee; Wenji Zhang; Sae-Bhom Lee; Kwang-Ho Choi; Sun-Mi Choi; Yeon-Hee Ryu

    2012-01-01

    We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid de...

  13. Distribution of Action Potential Duration and T-wave Morphology: a Simulation Study

    Ryzhii, Elena; Ryzhii, Maxim; Wei, Daming

    2009-01-01

    The results of a simulation study of the action potential duration (APD) distribution and T-wave morphology taking into account the midmyocardial cells (M-cells) concept are described. To investigate the effect of M-cells we present a computer model in which ion channel action potential formulations are incorporated into three-dimensional whole heart model. We implemented inhomogeneous continuous action potential duration distribution based on different distributions of maximal slow delayed r...

  14. A Rabbit Ventricular Action Potential Model Replicating Cardiac Dynamics at Rapid Heart Rates

    Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G.; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N.

    2008-01-01

    Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Cai) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ven...

  15. On the excitation of action potentials by protons and its potential implications for cholinergic transmission

    Fillafer, Christian

    2014-01-01

    One of the most conserved mechanisms for transmission of a nerve pulse across a synapse relies on acetylcholine. Ever since the Nobel-prize winning works of Dale and Loewi, it has been assumed that acetylcholine - subsequent to its action on a postsynaptic cell - is split into inactive by-products by acetylcholinesterase. Herein, this widespread assumption is falsified. Excitable cells (Chara australis internodes), which had previously been unresponsive to acetylcholine, became acetylcholine-sensitive in presence of acetylcholinesterase. The latter was evidenced by a striking difference in cell membrane depolarisation upon exposure to 10 mM intact acetylcholine (deltaV=-2plus/minus5 mV) and its hydrolysate respectively (deltaV=81plus/minus19 mV) for 60 sec. This pronounced depolarization, which also triggered action potentials, was clearly attributed to one of the hydrolysis products: acetic acid (deltaV=87plus/minus9 mV at pH 4.0; choline ineffective in range 1-10 mM). In agreement with our findings, numerou...

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

    Fabián Muñoz

    Full Text Available 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.

  17. Potential involvement of serotonergic signaling in ketamine's antidepressant actions

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina;

    2016-01-01

    A single i.v. infusion of ketamine, classified as an N-methyl-D-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic...... properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5......-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms...

  18. Characteristics of action potentials and their underlying outward currents in rat taste receptor cells.

    Chen, Y; Sun, X D; Herness, S

    1996-02-01

    1. Taste receptor cells produce action potentials as a result of transduction mechanisms that occur when these cells are stimulated with tastants. These action potentials are thought to be key signaling events in relaying information to the central nervous system. We explored the ionic basis of action potentials from dissociated posterior rat taste cells using the patch-clamp recording technique in both voltage-clamp and current-clamp modes. 2. Action potentials were evoked by intracellular injection of depolarizing current pulses from a holding potential of -80 mV. The threshold potential for firing of action potentials was approximately -35 mV; the input resistance of these cells averaged 6.9 G omega. With long depolarizing pulses, two or three action potentials could be elicited with successive attenuation of the spike height. Afterhyperpolarizations were observed often. 3. Both sodium and calcium currents contribute to depolarizing phases of the action potential. Action potentials were blocked completely in the presence of the sodium channel blocker tetrodotoxin. Calcium contributions could be visualized as prolonged calcium plateaus when repolarizing potassium currents were blocked and barium was used as a charge carrier. 4. Outward currents were composed of sustained delayed rectifier current, transient potassium current, and calcium-activated potassium current. Transient and sustained potassium currents activated close to -30 mV and increased monotonically with further depolarization. Up to half the outward current inactivated with decay constants on the order of seconds. Sustained and transient currents displayed steep voltage dependence in conductance and inactivation curves. Half inactivation occurred at -20 +/- 3.1 mV (mean +/- SE) with a decrease of 11.2 +/- 0.5 mV per e-fold. Half maximal conductance occurred at 3.6 +/- 1.8 mV and increased 12.2 +/- 0.6 mV per e-fold. Calcium-activated potassium current was evidenced by application of apamin and the

  19. Analysis of toxin induced changes in action potential shape for drug development

    Akanda, Nesar; Molnar, Peter; Stancescu, Maria; Hickman, James J.

    2009-01-01

    The generation of an action potential is a complex process in excitable cells which involves the temporal opening and closing of several voltage-dependent ion channels in the cell membrane. The shape of an action potential can carry information concerning the state of the involved ion channels and their relationship to cellular processes. Alteration of these ion channels by the administration of toxins, drugs, and biochemicals can change the action potential’s shape in a specific way which ca...

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

    A.O. Verkerk; H.M. den Ruijter; N. de Jonge; R. Coronel

    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 pre

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

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

    2012-01-01

    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 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 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. © 2012 CCAL....

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

    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.

  3. Time-Dependent Action in φ~6 Potential

    Hatem Widyan; Mashhoor Al-Wardat

    2012-01-01

    The false vacuum decay in field theory from a coherently oscillating initial state is studied for φ6 potential. An oscillating bubble solution is obtained. The instantaneous bubble nucleation rate is calculated.

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

    Crago, Patrick E.; Makowski, Nathaniel S.

    2014-10-01

    Objective. 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. Approach. 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. Main results. 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. Significance. 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

  5. A model for thermal exchange in axons during action potential propagation.

    Masson, Jean-Baptiste; Gallot, Guilhem

    2008-01-01

    International audience Several experiments have shown that during propagation of the action potential in axons, thermal energy is locally exchanged. In this paper, we use a simple model based on statistical physics to show that an important part of this exchange comes from the physics of the effusion. We evaluate, during the action potential propagation, the variation of internal energy and of the energy associated with the chemical potential of the effusion of water and ions to extract th...

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

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

    Objective. 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. Approach. 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. Main results. 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. Significance. 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.

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

    Dimitrios Zikos; Andreas Thiel

    2013-01-01

    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 determi...

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

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

    2006-01-01

    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......--permitted accurate discernment of up to 1,000 different stimuli. At low oscillation frequencies, stimulus discrimination showed a clear phase dependence whereby inputs arriving during the trough and the early rising phase of an oscillation cycle were most robustly discriminated. Thus, by ensuring AP precision...

  9. More evidence for a refined Gribov-Zwanziger action based on an effective potential approach

    Vandersickel, N.; Dudal, D.; Sorella, S.P.

    2011-01-01

    The purpose of this proceeding is twofold. Firstly, we shall make the refining of the Gribov-Zwanziger action more complete by taking into account more condensates than considered so far. Secondly, we shall provide more evidence for the refined Gribov-Zwanziger action based on an effective potential approach.

  10. Synaptically evoked dendritic action potentials in rat neocortical pyramidal neurons.

    Schwindt, P C; Crill, W E

    1998-05-01

    In a previous study iontophoresis of glutamate on the apical dendrite of layer 5 pyramidal neurons from rat neocortex was used to identify sites at which dendritic depolarization evoked small, prolonged Ca2+ spikes and/or low-threshold Na+ spikes recorded by an intracellular microelectrode in the soma. These spikes were identified as originating in the dendrite. Here we evoke similar dendritic responses by electrical stimulation of presynaptic elements near the tip of the iontophoretic electrode with the use of a second extracellular electrode. In 9 of 12 recorded cells, electrically evoked excitatory postsynaptic potentials (EPSPs) above a minimum size triggered all-or-none postsynaptic responses similar to those evoked by dendritic glutamate iontophoresis at the same site. Both the synaptically evoked and the iontophoretically evoked depolarizations were abolished reversibly by blockade of glutamate receptors. In all recorded cells, the combination of iontophoresis and an EPSP, each of which was subthreshold for the dendritic spike when given alone, evoked a dendritic spike similar to that evoked by a sufficiently large iontophoresis. In one cell tested, dendritic spikes could be evoked by the summation of two independent subthreshold EPSPs evoked by stimulation at two different locations. We conclude that the dendritic spikes are not unique to the use of glutamate iontophoresis because similar spikes can be evoked by EPSPs. We discuss the implications of these results for synaptic integration and for the interpretation of recorded synaptic potentials. PMID:9582218

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

    Vinding, Mikkel Christoffer; 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. Action potential detection by non-linear microscopy

    Sacconi, Leonardo; Lotti, Jacopo; O'Connor, Rodney P.; Mapelli, Jonathan; Gandolfi, Daniela; D'Angelo, Egidio; Pavone, Francesco S.

    2009-02-01

    In this work, we combined the advantages of second-harmonic generation (SHG) with a random access (RA) excitation scheme to realize a new microscope (RA-SHG) capable of optically recording fast membrane potential events occurring in a wide-field configuration. The RA-SHG microscope in combination with a bulk staining method with FM4-64 was used to simultaneously record electrical activity from clusters of Purkinje cells (PCs) in acute cerebellar slices. Spontaneous electrical activity was also monitored simultaneously in pairs of neurons, where APs were recorded in a single trial without averaging. These results show the strength of this technique to describe the temporal dynamics of neuronal assemblies.

  13. Control of Secretion by Encodes of Action Potentials in Neuronal Cells

    Kailai Duan; Zhuan Zhou

    2003-01-01

    @@ Action potentials (APs) are principle physiological stimuli of neurotransmitter secretion or synaptic transmis sion. Most studies on stimulus-secretion-coupling have been performed under voltage clamp using artificial electric stimulations.

  14. Dynamics of Action Potential Initiation in the GABAergic Thalamic Reticular Nucleus In Vivo

    Fabián Muñoz; Pablo Fuentealba

    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 th...

  15. Cortical Action Potential Backpropagation Explains Spike Threshold Variability and Rapid-Onset Kinetics

    Yu, Yuguo; Shu, Yousheng; McCormick, David A.

    2008-01-01

    Neocortical action potential responses in vivo are characterized by considerable threshold variability, and thus timing and rate variability, even under seemingly identical conditions. This finding suggests that cortical ensembles are required for accurate sensorimotor integration and processing. Intracellularly, trial-to-trial variability results not only from variation in synaptic activities, but also in the transformation of these into patterns of action potentials. Through simultaneous ax...

  16. NeuroGrid: recording action potentials from the surface of the brain

    Khodagholy, Dion; Gelinas, Jennifer N.; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G.; Buzsáki, György

    2014-01-01

    Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultra-conformable, biocompatible and scalable neural interface array (the ‘NeuroGrid’) that can record both LFP and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneous...

  17. Pharmacological actions and potential uses of Momordica charantia: a review.

    Grover, J K; Yadav, S P

    2004-07-01

    Since ancient times, plants and herbal preparations have been used as medicine. Research carried out in last few decades has certified several such claims of use of several plants of traditional medicine. Popularity of Momordica charantia (MC) in various systems of traditional medicine for several ailments (antidiabetic, abortifacient, anthelmintic, contraceptive, dysmenorrhea, eczema, emmenagogue, antimalarial, galactagogue, gout, jaundice, abdominal pain, kidney (stone), laxative, leprosy, leucorrhea, piles, pneumonia, psoriasis, purgative, rheumatism, fever and scabies) focused the investigator's attention on this plant. Over 100 studies using modern techniques have authenticated its use in diabetes and its complications (nephropathy, cataract, insulin resistance), as antibacterial as well as antiviral agent (including HIV infection), as anthelmintic and abortifacient. Traditionally it has also been used in treating peptic ulcers, interestingly in a recent experimental studies have exhibited its potential against Helicobacter pylori. Most importantly, the studies have shown its efficacy in various cancers (lymphoid leukemia, lymphoma, choriocarcinoma, melanoma, breast cancer, skin tumor, prostatic cancer, squamous carcinoma of tongue and larynx, human bladder carcinomas and Hodgkin's disease). There are few reports available on clinical use of MC in diabetes and cancer patients that have shown promising results. PMID:15182917

  18. Detection of Variability of the Motor Unit Action Potential Shape by Means of the Firing Patterns

    Krarup, Christian; Nikolic, Mile; Dahl, Kristian;

    1997-01-01

    The motor unit action potential is a summation of the potentials of the individual muscle fibers from the same motor unit.By using a newly developed automatic EMG decomposition system, variability of the firing patterns of the muscle fibers are analyzed.......The motor unit action potential is a summation of the potentials of the individual muscle fibers from the same motor unit.By using a newly developed automatic EMG decomposition system, variability of the firing patterns of the muscle fibers are analyzed....

  19. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    2011-04-19

    ... Federal Aviation Administration Potential Environmental Impacts of the Proposed Runway 13 Extension and... Administration (FAA), Department of Transportation (DOT). ACTION: Notice of availability of a final EA and FONSI/ROD for the evaluation of the potential environmental impacts associated with the proposed Runway...

  20. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    2010-01-01

    ... assessment of agricultural production losses resulting from a potential natural disaster. These councils are...) Actions to be taken. Immediately after the occurrence of a potential natural disaster: (1) When physical... Administrator will decide whether a natural disaster has occurred. If it has, the Administrator will make...

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

    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.

  2. Initiation and blocking of the action potential in the axon in a weak ultrasonic field

    Shneider, M N

    2013-01-01

    It is shown that the longitudinal standing ultrasonic wave of low intensity leads to the lateral drift and to redistribution of the transmembrane ion channels in the initial segment of the myelinated axon of a neuron. The analysis is based on the Hodgkin - Huxley model of an axon. Redistribution of the density of transmembrane sodium channels, caused by ultrasound, may reduce the threshold of the action potential, up to its spontaneous initiation. At significant redistribution of sodium channels in membrane, the zones of rarefaction of the transmembrane channels density are formed blocking the propagation of the action potential. After switching the ultrasound off, the unperturbed uniform distribution of transmembrane channels in the axon recovers due to lateral diffusion. The blocking effect of the action potential can be used in anesthesia.

  3. DBI potential, DBI inflation action and general Lagrangian relative to phantom, K-essence and quintessence

    We derive a Dirac-Born-Infeld (DBI) potential and DBI inflation action by rescaling the metric. The determinant of the induced metric naturally includes the kinetic energy and the potential energy. In particular, the potential energy and kinetic energy can convert into each other in any order, which is in agreement with the limit of classical physics. This is quite different from the usual DBI action. We show that the Taylor expansion of the DBI action can be reduced into the form in the non-linear classical physics. These investigations are the support for the statement that the results of string theory are consistent with quantum mechanics and classical physics. We deduce the Phantom, K-essence, Quintessence and Generalized Klein-Gordon Equation from the DBI model

  4. Modeling and simulation of ion channels and action potentials in taste receptor cells

    2009-01-01

    Based on patch clamp data on the ionic currents of rat taste receptor cells, a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components, including voltage-gated Na+ currents and outward delayed rectifier K+ currents. Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants. The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed. Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.

  5. Modeling and simulation of ion channels and action potentials in taste receptor cells

    CHEN PeiHua; LIU Xiaodong; ZHANG Wei; ZHOU Jun; WANG Ping; YANG Wei; LUO JianHong

    2009-01-01

    Based on patch clamp data on the ionic currents of rat taste receptor cells,a mathematical model of mammalian taste receptor cells was constructed to simulate the action potentials of taste receptor cells and their corresponding ionic components,including voltage-gated Na~+ currents and outward delayed rectifier K~+ currents.Our simulations reproduced the action potentials of taste receptor cells in response to electrical stimuli or sour tastants.The kinetics of ion channels and their roles in action potentials of taste receptor cells were also analyzed.Our prototype model of single taste receptor cell and simulation results presented in this paper provide the basis for the further study of taste information processing in the gustatory system.

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

    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...

  7. Phase lagging model of brain response to external stimuli - modeling of single action potential

    Seetharaman, Karthik; Kulish, Vladimir V

    2012-01-01

    In this paper we detail a phase lagging model of brain response to external stimuli. The model is derived using the basic laws of physics like conservation of energy law. This model eliminates the paradox of instantaneous propagation of the action potential in the brain. The solution of this model is then presented. The model is further applied in the case of a single neuron and is verified by simulating a single action potential. The results of this modeling are useful not only for the fundamental understanding of single action potential generation, but also they can be applied in case of neuronal interactions where the results can be verified against the real EEG signal.

  8. Optical magnetic detection of single-neuron action potentials using NV-diamond

    Turner, Matthew; Barry, John; Schloss, Jennifer; Glenn, David; Walsworth, Ron

    2016-05-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential dynamics in whole organisms with single-neuron resolution. Here, we report a new approach to this problem: using nitrogen-vacancy (NV) color centers in diamond to measure the time-dependent magnetic fields produced by single-neuron action potentials. We demonstrate our method using excised single neurons from two invertebrate species, marine worm and squid; and then by single-neuron action potential magnetic sensing exterior to whole, live, opaque marine worms for extended periods with no adverse effect. The results lay the groundwork for real-time, noninvasive 3D magnetic mapping of functional mammalian neuronal networks.

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

    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 %. PMID:27016364

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

    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.

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

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

    2015-01-01

    (+)-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...

  12. Wogonin potentiates the antitumor action of etoposide and ameliorates its adverse effects.

    Enomoto, Riyo; Koshiba, Chika; Suzuki, Chie; Lee, Eibai

    2011-05-01

    Wogonin, a flavone in the roots of Scutellaria baicalensis, reduced etoposide-induced apoptotic cell death in normal cells, such as bone marrow cells and thymocytes. On the other hand, wogonin potentiated the proapoptotic or cytotoxic action of etoposide in tumor cells, such as Jurkat, HL-60, A549, and NCI-H226. These contradictory actions of wogonin on apoptosis are distinguished by normal or cancer cell types. Wogonin had no effect on apoptosis induced by other anticancer agents in the tumor cells. Thus, the potentiation effect of wogonin was observed only in etoposide-induced apoptosis in tumor cells. In a functional assay for P-glycoprotein (P-gp), wogonin suppressed excretion of calcein, a substrate for P-gp, in these tumor cells. Moreover, wogonin decreased the excretion of radiolabeled etoposide and accordingly increased intracellular content of this agent in the cells. P-gp inhibitors showed a similar potentiation effect on etoposide-induced apoptosis in these tumor cells. Thus, wogonin is likely to potentiate the anticancer action of etoposide due to P-gp inhibition and accumulation of this agent. These findings suggest that wogonin may be a useful chemotherapeutic adjuvant to potentiate the pharmacological action of etoposide and ameliorate its adverse effects. PMID:20658136

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

    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. PMID:26686984

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

    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.

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

    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 IC50 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; IC50 = 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

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

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

    2016-01-01

    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....

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

    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 intracellu

  18. ACTION OF PROGESTERONE ON THE DEPOLARIZATION OF THE MEMBRANE POTENTIAL IN TOAD OOCYTES INDUCED BY LEUCINE

    WANGYu-Feng

    1989-01-01

    The depolarization of the membrane potential in toad oocytes induced by leucine was found in our previous experiment. In this paper, a possible action or progesterone in the process was further investigated. After oocytes had been incubated for 16 to 24 hours with

  19. Preservation of cardiac function by prolonged action potentials in mice deficient of KChIP2

    Grubb, Søren Jahn; Aistrup, Gary L; Koivumäki, Jussi T;

    2015-01-01

    Inherited ion channelopathies and electrical remodeling in heart disease alter the cardiac action potential with important consequences for excitation-contraction coupling. Potassium channel-interacting protein 2 (KChIP2) is reduced in heart failure and interacts under physiological conditions with...

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

    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…

  1. Effect of ethanol on action potential in ventricular cardiomyocytes: experimental and computational approach

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

    London: The Physiological Society, 2014. 208P. [Physiology 2014. 30.06.2014-02.07.2014, London] R&D Projects: GA MZd(CZ) NT14301-3/2013 Institutional support: RVO:61388998 Keywords : rat ventricular cardiomyocyte * action potential * ethanol * rat ventricular cell model Subject RIV: BO - Biophysics

  2. Effects of benactyzine on action potentials and contractile force of guinea pig papillary muscles

    2000-01-01

    Aim:To explore the effects of benactyzine (BEN) on the action potential and contractile force in guinea pig papillary muscles.Methods:Conventional microelectrode technique was used to record the fast action potentials (FAP) and slow action potentials (SAP) of guinea pig papillary muscles.Results:Benactyzine 5,10,50 μmol·L-1 suppressed the maximal upstroke velocity (vmax) of FAP and contractile force (Fc) concentration-dependently while prolonged the action potential duration at 50%,90% repolarization (APD50,APD90) and effective refractory period (ERP) of FAP.The suppression on the vmax was frequency-dependent.Benactyzine 5,10,50μmol·L-1 lengthened the APD50,APD90 of SAP induced by isoprenaline or histamine when perfused with KCl 22 mmol·L-1 Tyrode's solution.The vmax of the SAP was not decreased by benactyzine 5,10 μmol·L-1 but by 50 μmol·L-1.The effects on the SAP were antagonized by elevation of the extracellular calcium from 2.0 to 5.6 mmol·L-1.The effects of benactyzine on SAP elicited by tetrodotoxin resembled that by isoprenaline or histamine except the more pronounced suppression on vmax and action potential amplitude (APA).The persistent rapid spontaneous activity and triggered tachyarrhythmia induced by ouabain were also abolished immediately by benactyzine 5 μmol·L-1.Conclusion:Benactyzine can inhibit Na+,K+,Ca2+ transmembrane movement and intracellular Ca2+ mobilization in the myocardium,and this may be the electrophysiological basis of its effects against experimental arrhythmias.

  3. Axonal sodium channel distribution shapes the depolarized action potential threshold of dentate granule neurons.

    Kress, Geraldine J; Dowling, Margaret J; Eisenman, Lawrence N; Mennerick, Steven

    2010-04-01

    Intrinsic excitability is a key feature dictating neuronal response to synaptic input. Here we investigate the recent observation that dentate granule neurons exhibit a more depolarized voltage threshold for action potential initiation than CA3 pyramidal neurons. We find no evidence that tonic GABA currents, leak or voltage-gated potassium conductances, or the expression of sodium channel isoform differences can explain this depolarized threshold. Axonal initial segment voltage-gated sodium channels, which are dominated by the Na(V)1.6 isoform in both cell types, distribute more proximally and exhibit lower overall density in granule neurons than in CA3 neurons. To test possible contributions of sodium channel distributions to voltage threshold and to test whether morphological differences participate, we performed simulations of dentate granule neurons and of CA3 pyramidal neurons. These simulations revealed that cell morphology and sodium channel distribution combine to yield the characteristic granule neuron action potential upswing and voltage threshold. Proximal axon sodium channel distribution strongly contributes to the higher voltage threshold of dentate granule neurons for two reasons. First, action potential initiation closer to the somatodendritic current sink causes the threshold of the initiating axon compartment to rise. Second, the proximity of the action potential initiation site to the recording site causes somatic recordings to more faithfully reflect the depolarized threshold of the axon than in cells like CA3 neurons, with distally initiating action potentials. Our results suggest that the proximal location of axon sodium channels in dentate granule neurons contributes to the intrinsic excitability differences between DG and CA3 neurons and may participate in the low-pass filtering function of dentate granule neurons. PMID:19603521

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

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

    2016-05-01

    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 D p-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.

  5. Acute NMDA receptor antagonism disrupts synchronization of action potential firing in rat prefrontal cortex.

    Leonardo A Molina

    Full Text Available Antagonists of N-methyl-D-aspartate receptors (NMDAR have psychotomimetic effects in humans and are used to model schizophrenia in animals. We used high-density electrophysiological recordings to assess the effects of acute systemic injection of an NMDAR antagonist (MK-801 on ensemble neural processing in the medial prefrontal cortex of freely moving rats. Although MK-801 increased neuron firing rates and the amplitude of gamma-frequency oscillations in field potentials, the synchronization of action potential firing decreased and spike trains became more Poisson-like. This disorganization of action potential firing following MK-801 administration is consistent with changes in simulated cortical networks as the functional connections among pyramidal neurons become less clustered. Such loss of functional heterogeneity of the cortical microcircuit may disrupt information processing dependent on spike timing or the activation of discrete cortical neural ensembles, and thereby contribute to hallucinations and other features of psychosis induced by NMDAR antagonists.

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

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

    2012-01-01

    Abstract Background 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. Result...

  7. Simulation and calculation of the contribution of hyperpolarization-activated cyclic nucleotide-gated channels to action potentials

    Liao Liping; Lin Xianguang; Hu Jielin; Wu Xin; Yang Xiaofei; Wang Wei; Li Chenhong

    2016-01-01

    The hyperpolarization-activated cyclic nucleotide-gated (HCN) channel, which mediates the influx of cations, has an important role in action potential generation. In this article, we describe the contribution of the HCN channel to action potential generation. We simulated several common ion channels in neuron membranes based on data from rat dorsal root ganglion cells and modeled the action potential. The ion channel models employed in this paper were based...

  8. The DBI Action, Higher-derivative Supergravity, and Flattening Inflaton Potentials

    Bielleman, Sjoerd; 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 D$p$-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 K\\"ahler potential. We identify the supersymmetric dimension-eight operators describing the $\\alpha'$ 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 $\\mathcal N = 1$ 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 monomia...

  9. Potentiators of Defective ΔF508-CFTR Gating that Do Not Interfere with Corrector Action.

    Phuan, Puay-Wah; Veit, Guido; Tan, Joseph A; Finkbeiner, Walter E; Lukacs, Gergely L; Verkman, A S

    2015-10-01

    Combination drug therapies under development for cystic fibrosis caused by the ∆F508 mutation in cystic fibrosis transmembrane conductance regulator (CFTR) include a "corrector" to improve its cellular processing and a "potentiator" to improve its chloride channel function. Recently, it was reported that the approved potentiator N-(2,4-di-tert-butyl-5-hydroxyphenyl)-4-oxo-1,4-dihydroquinoline-3-carboxamide (Ivacaftor) reduces ∆F508-CFTR cellular stability and the efficacy of investigational correctors, including 3-(6-[([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl) amino]-3-methyl-2-pyridinyl)-benzoic acid and 1-(2,2-difluoro-1,3-benzodioxol-5-yl)-N-(1-[(2R)-2,3-dihydroxypropyl]-6-fluoro-2-(2-hydroxy-1,1-dimethylethyl)-1H-indol-5-yl), which might contribute to the modest reported efficacy of combination therapy in clinical trials. Here, we report the identification and characterization of potentiators that do not interfere with ∆F508-CFTR stability or corrector action. High-throughput screening and structure-activity analysis identified several classes of potentiators that do not impair corrector action, including tetrahydrobenzothiophenes, thiooxoaminothiazoles, and pyrazole-pyrrole-isoxazoles. The most potent compounds have an EC(50) for ∆F508-CFTR potentiation down to 18 nM and do not reduce corrector efficacy in heterologous ∆F508-CFTR-expressing cells or primary cultures of ∆F508/∆F508 human bronchial epithelia. The ΔF508-CFTR potentiators also activated wild-type and G551D CFTR, albeit weakly. The efficacy of combination therapy for cystic fibrosis caused by the ∆F508 mutation may be improved by replacement of Ivacaftor with a potentiator that does not interfere with corrector action. PMID:26245207

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

    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...... examples 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....

  11. Real-time imaging of action potentials in nerves using changes in birefringence.

    Badreddine, Ali H; Jordan, Tomas; Bigio, Irving J

    2016-05-01

    Polarized light can be used to measure the electrical activity associated with action potential propagation in nerves, as manifested in simultaneous dynamic changes in their intrinsic optical birefringence. These signals may serve as a tool for minimally invasive neuroimaging in various types of neuroscience research, including the study of neuronal activation patterns with high spatiotemporal resolution. A fast linear photodiode array was used to image propagating action potentials in an excised portion of the lobster walking leg nerve. We show that the crossed-polarized signal (XPS) can be reliably imaged over a ≥2 cm span in our custom nerve chamber, by averaging multiple-stimulation signals, and also in single-scan real-time "movies". This demonstration paves the way toward utilizing changes in the optical birefringence to image more complex neuronal activity in nerve fibers and other organized neuronal tissue. PMID:27231635

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

    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

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

    Kim, Jongsoo; Lee, Goan Yub; Lee, Hae Choi; Kim, Bong Suk [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    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.

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

    Biswa Sengupta; Martin Stemmler; Simon B Laughlin; 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 ...

  15. Correlation of compound action potential and electromyography with facial muscle tension

    Goodnight, J W; Dulguerov, Pavel; Berke, G S; Lesavoy, M; Hoffman, L. F.

    1995-01-01

    Functional electric stimulation is a new method for dynamic rehabilitation of paralyzed muscles. The output of such prosthetic devices needs to be modulated by some index of the muscle movement. In facial paralysis a measure of the muscle contractions of the normal contralateral side seems to be an appropriate input. In the rabbit, we simultaneously measured the compound action potential of the buccal branch of the facial nerve, the electromyogram of the zygomaticus major muscle, and the musc...

  16. Depth-Resolved Measurement of Transient Structural Changes during Action Potential Propagation

    Akkin, T.; Joo, C.; Boer

    2007-01-01

    We report noncontact optical measurement of fast transient structural changes in the crustacean nerve during action potential propagation without the need for exogenous chemicals or reflection coatings. The technique, spectral domain optical coherence tomography, provides real-time cross-sectional images of the nerve with micron-scale resolution to select a specific region for functional assessment and interferometric phase sensitivity for subnanometer-scale motion detection. Noncontact optic...

  17. Bimodal action of menthol on the transient receptor potential channel TRPA1

    Karashima, Yuji; Damann, Nils; Prenen, Jean; Talavera Pérez, Karel; Segal Stanciu, Andrei; Voets, Thomas; Nilius, Bernd

    2007-01-01

    TRPA1 is a calcium-permeable nonselective cation transient receptor potential (TRP) channel that functions as an excitatory ionotropic receptor in nociceptive neurons. TRPA1 is robustly activated by pungent substances in mustard oil, cinnamon, and garlic and mediates the inflammatory actions of environmental irritants and proalgesic agents. Here, we demonstrate a bimodal sensitivity of TRPA1 to menthol, a widely used cooling agent and known activator of the related cold receptor TRPM8. In who...

  18. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells

    Renjun Zhu; Millrod, Michal A.; Zambidis, Elias T.; Leslie Tung

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to re...

  19. Action Potential Morphology Influences Intracellular Calcium Handling Stability and the Occurrence of Alternans

    Jordan, Peter N; Christini, David J

    2005-01-01

    Instability in the intracellular Ca2+ handling system leading to Ca2+ alternans is hypothesized to be an underlying cause of electrical alternans. The highly coupled nature of membrane voltage and Ca2+ regulation suggests that there should be reciprocal effects of membrane voltage on the stability of the Ca2+ handling system. We investigated such effects using a mathematical model of the cardiac intracellular Ca2+ handling system. We found that the morphology of the action potential has a sig...

  20. Relation of recurrent laryngeal nerve compound action potential to laryngeal biomechanics

    Nasri, S.; Dulguerov, Pavel; Damrose, E J; Ye, M.; Kreiman, J; Berke, G S

    1995-01-01

    This study was designed to investigate the compound action potential (CAP) of the recurrent laryngeal nerve (RLN) and to correlate this electrophysiologic signal to laryngeal biomechanics and phonatory function. Four adult mongrel canines were anesthetized. The RLN was isolated and stimulated, and recording electrodes were applied. The electromyographic (EMG) electrode was placed in the thyroarytenoid (TA) muscle. The RLN CAP and the EMG of the TA muscle were recorded and compared to the stim...

  1. Human sensory nerve compound action potential amplitude: variation with sex and finger circumference.

    Bolton, C F; Carter, K M

    1980-01-01

    The amplitude of human, antidromic, sensory compound action potentials (CAP) recorded from median and ulnar digital nerves is greater in females than males. This sex difference is probably due entirely to females having digits of smaller circumference, resulting in digital nerves being closer to the recording ring electrode enclosing the digit. The negative linear correlation between CAP amplitude and circumference holds true for persons of the same sex.

  2. Axonal sodium channel distribution shapes the depolarized action potential threshold of dentate granule neurons

    Kress, Geraldine J.; Dowling, Margaret; Eisenman, Lawrence N.; Mennerick, Steven

    2010-01-01

    Intrinsic excitability is a key feature dictating neuronal response to synaptic input. Here we investigate the recent observation that dentate granule neurons exhibit a more depolarized voltage threshold for action potential initiation than CA3 pyramidal neurons. We find no evidence that tonic GABA currents, leak or voltage-gated potassium conductances, or the expression of sodium channel isoform differences can explain this depolarized threshold. Axonal initial segment voltage-gated sodium c...

  3. Variety of the Wave Change in Compound Muscle Action Potential in an Animal Model

    ITO, ZENYA; Imagama, Shiro; Ando, Kei; Muramoto, Akio; Kobayashi, Kazuyoshi; Hida, Tetsuro; Ito, Kenyu; Ishikawa, Yoshimoto; Tsushima, Mikito; Matsumoto, Akiyuki; Tanaka, Satoshi; Morozumi, Masayoshi; Matsuyama, Yukihiro; Ishiguro, Naoki

    2015-01-01

    Study Design Animal study. Purpose To review the present warning point criteria of the compound muscle action potential (CMAP) and investigate new criteria for spinal surgery safety using an animal model. Overview of Literature Little is known about correlation palesis and amplitude of spinal cord monitoring. Methods After laminectomy of the tenth thoracic spinal lamina, 2-140 g force was delivered to the spinal cord with a tension gage to create a bilateral contusion injury. The study morpho...

  4. Effect of ethanol on action potential and ionic membrane currents in rat ventricular myocytes

    Bébarová, M.; Matejovič, P.; Pásek, Michal; Ohlídalová, D.; Jansová, D.; Šimurdová, M.; Šimurda, J.

    2010-01-01

    Roč. 200, č. 4 (2010), s. 301-314. ISSN 1748-1708 Institutional research plan: CEZ:AV0Z20760514 Keywords : action potential * ethanol * rat ventricular myocyte Subject RIV: BO - Biophysics Impact factor: 3.138, year: 2010 http:// apps .isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=15&SID=Y1pmpi@7k2HPEc8ehEE&page=1&doc=1&colname=WOS

  5. Experimental determination of compound action potential direction and propagation velocity from multi-electrode nerve cuffs.

    Rieger, R; Taylor, J; Comi, E; Donaldson, N; Russold, M; Mahony, C M O; McLaughlin, J A; McAdams, E; Demosthenous, A; Jarvis, J C

    2004-07-01

    Information extracted from whole-nerve electroneurograms, recorded using electrode cuffs, can provide signals to neuroprostheses. However, the amount of information that can be extracted from a single tripole is limited. This communication demonstrates how previously unavailable information about the direction of action potential propagation and velocity can be obtained using a multi-electrode cuff and that the arrangement acts as a velocity-selective filter. Results from in vitro experiments on frog nerves are presented. PMID:15234689

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

    Frey, Scott H.; POVINELLI, DANIEL J.

    2012-01-01

    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 ...

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

    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.

  8. Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

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

    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 s...

  9. Effects of Potassium Currents upon Action Potential of Cardiac Cells Exposed to External Electric fields

    An-Ying Zhang; Xiao-Feng Pang

    2008-01-01

    Previous studies show that exposure to high-voltage electric fields would influence the electro cardiogram both in experimental animate and human beings. The effects of the external electric fields upon action potential of cardiac cells are studied in this paper based on the dynamical model, LR91. Fourth order Runger-Kuta is used to analyze the change of potassium ion channels exposed to external electric fields in detail. Results indicate that external electric fields could influence the current of potassium ion by adding an induced component voltage on membrane. This phenomenon might be one of the reasons of heart rate anomaly under the high-voltage electric fields.

  10. Ranolazine inhibits shear sensitivity of endogenous Na+ current and spontaneous action potentials in HL-1 cells

    Strege, Peter; Beyder, Arthur; Bernard, Cheryl; Crespo-Diaz, Ruben; Behfar, Atta; Terzic, Andre; Ackerman, Michael; Farrugia, Gianrico

    2012-01-01

    NaV1.5 is a mechanosensitive voltage-gated Na+ channel encoded by the gene SCN5A, expressed in cardiac myocytes and required for phase 0 of the cardiac action potential (AP). In the cardiomyocyte, ranolazine inhibits depolarizing Na+ current and delayed rectifier (IKr) currents. Recently, ranolazine was also shown to be an inhibitor of NaV1.5 mechanosensitivity. Stretch also accelerates the firing frequency of the SA node, and fluid shear stress increases the beating rate of cultured cardiomy...

  11. On modelling of physical effects accompanying the propagation of action potentials in nerve fibres

    Engelbrecht, Jüri; Tamm, Kert; Laasmaa, Martin; Vendelin, Marko

    2016-01-01

    The recent theoretical and experimental studies have revealed many details of signal propagation in nervous systems. In this paper an attempt is made to unify various mathematical models which describe the signal propagation in nerve fibres. The analysis of existing single models permits to select the leading physiological effects. As a result, a more general mathematical model is described based on the coupling of action potentials with mechanical waves in a nerve fibre. The crucial issue is how to model coupling effects which are strongly linked to the ion currents through biomembranes.

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

    M.R. Moreira; G.M.P. Cruz; Lopes, M S; A.A.C. Albuquerque; J.H. Leal-Cardoso

    2001-01-01

    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 con...

  13. The optimal distance between two electrode tips during recording of compound nerve action potentials in the rat median nerve

    Yongping Li; Jie Lao; Xin Zhao; Dong Tian; Yi Zhu; Xiaochun Wei

    2014-01-01

    The distance between the two electrode tips can greatly inlfuence the parameters used for record-ing compound nerve action potentials. To investigate the optimal parameters for these recordings in the rat median nerve, we dissociated the nerve using different methods and compound nerve action potentials were orthodromically or antidromically recorded with different electrode spac-ings. Compound nerve action potentials could be consistently recorded using a method in which the middle part of the median nerve was intact, with both ends dissociated from the surrounding fascia and a ground wire inserted into the muscle close to the intact part. When the distance be-tween two stimulating electrode tips was increased, the threshold and supramaximal stimulating intensity of compound nerve action potentials were gradually decreased, but the amplitude was not changed signiifcantly. When the distance between two recording electrode tips was increased, the amplitude was gradually increased, but the threshold and supramaximal stimulating intensity exhibited no signiifcant change. Different distances between recording and stimulating sites did not produce signiifcant effects on the aforementioned parameters. A distance of 5 mm between recording and stimulating electrodes and a distance of 10 mm between recording and stimulating sites were found to be optimal for compound nerve action potential recording in the rat median nerve. In addition, the orthodromic compound action potential, with a biphasic waveform that was more stable and displayed less interference (however also required a higher threshold and higher supramaximal stimulus), was found to be superior to the antidromic compound action potential.

  14. Characterization of action potential-triggered [Ca2+]i transients in single smooth muscle cells of guinea-pig ileum

    Kohda, M.; Komori, S.; Unno, T; Ohashi, H

    1997-01-01

    To characterize increases in cytosolic free Ca2+ concentration ([Ca2+]i) associated with discharge of action potentials, membrane potential and [Ca2+]i were simultaneously recorded from single smooth muscle cells of guinea-pig ileum by use of a combination of nystatin-perforated patch clamp and fura-2 fluorimetry techniques.A single action potential in response to a depolarizing current pulse elicited a transient rise in [Ca2+]i. When the duration of the current pulse was prolonged, action po...

  15. Action of hallucinogens on raphe-evoked dorsal root potentials (DRPs) in the cat.

    Larson, A A; Anderson, E G

    1986-02-01

    The dorsal root potential (DRP) evoked by stimulation of the inferior central nucleus (ICN) of the cat is affected by administration of a variety of hallucinogenic agents. It has been previously shown that a single low dose of LSD is unique in that it potentiates this DRP, while injections of 5-methoxy-N,N- dimethyltryptamine (5-MeODMT), ketamine or phencyclidine (PCP) inhibit its production. Tolerance develops to the facilitatory effect of low doses of LSD on the DRP, but not to the inhibitory action of 5-MeODMT. Repeated injections of ketamine every 30 minutes also fail to produce tachyphylaxis to the inhibitory effect of this dissociative anesthetic. The raphe-evoked DRP is a long latency potential that is inhibited by a wide variety of putative serotonin antagonists and has therefore been traditionally thought to be mediated by serotonin. However, in light of the inability of either tryptophan or fluoxetine to potentiate this DRP, and the resistance of this DRP to blockade by parachlorophenylalanine, reserpine or intrathecally administered 5,7-dihydroxytryptamine, it appears that this potential may in fact be mediated, at least in part, by a non-serotonergic transmitter. PMID:3952125

  16. Quantitative assessment of the distributions of membrane conductances involved in action potential backpropagation along basal dendrites.

    Acker, Corey D; Antic, Srdjan D

    2009-03-01

    Basal dendrites of prefrontal cortical neurons receive strong synaptic drive from recurrent excitatory synaptic inputs. Synaptic integration within basal dendrites is therefore likely to play an important role in cortical information processing. Both synaptic integration and synaptic plasticity depend crucially on dendritic membrane excitability and the backpropagation of action potentials. We carried out multisite voltage-sensitive dye imaging of membrane potential transients from thin basal branches of prefrontal cortical pyramidal neurons before and after application of channel blockers. We found that backpropagating action potentials (bAPs) are predominantly controlled by voltage-gated sodium and A-type potassium channels. In contrast, pharmacologically blocking the delayed rectifier potassium, voltage-gated calcium, or I(h) conductance had little effect on dendritic AP propagation. Optically recorded bAP waveforms were quantified and multicompartmental modeling was used to link the observed behavior with the underlying biophysical properties. The best-fit model included a nonuniform sodium channel distribution with decreasing conductance with distance from the soma, together with a nonuniform (increasing) A-type potassium conductance. AP amplitudes decline with distance in this model, but to a lesser extent than previously thought. We used this model to explore the mechanisms underlying two sets of published data involving high-frequency trains of APs and the local generation of sodium spikelets. We also explored the conditions under which I(A) down-regulation would produce branch strength potentiation in the proposed model. Finally, we discuss the hypothesis that a fraction of basal branches may have different membrane properties compared with sister branches in the same dendritic tree. PMID:19118105

  17. The characteristics of action potential and nonselective cation current of cardiomyocytes in rabbit superior vena cava

    WANG Pan; YANG XinChun; LIU XiuLan; BAO RongFeng; LIU TaiFeng

    2008-01-01

    As s special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cavs (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may increase or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can increase or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyocytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

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

    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

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

    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.

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

    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.

  1. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  2. Action potential-simulated weak electric fields can directly initiate myelination

    Lei Liu; Shifu Zhao; Haiming Wang

    2008-01-01

    BACKGROUND: Myelination is a process whereby glial cells identify, adhere, wrap and enclose axons to form a spiral myelin sheath.OBJECTIVE: To investigate the effects of action potential-simulated weak electric fields on myelination in the central nervous system.DESIGN AND SETTING: This single-sample observation study was performed at the 324 Hospital of Chinese PLA.MATERIALS: Two 5 μm carbon fibers were provided by the Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. One Sprague Dawley rat, aged 1 day, was used.METHODS: Cerebral cortex was harvested from the rat to prepare a suspension [(1-2)×105/mL] containing neurons and glial cells. To simulate the axon, carbon fibers were placed at the bottom of the neuron-glial cell coculture dish, and were electrified with a single phase square wave current, 1×10-2, 1×10-3, 1×10-4, and 1×10-5 seconds, 1 Hz, 40 mV, and 10 μA, 30 minutes each, once aday for 10 consecutive days to simulate weak negative electric fields during action potential conduction.MAIN OUTCOME MEASURES: Glial cell growth and wrapping of carbon fibers were observed by phase contrast microscopy and immunohistochemistry.RESULTS: On culture day 7, cell groups were found to adhere to negative carbon fibers in the 1×10-3 seconds square wave group. Cell membrane-like substances grew out of cell groups, wrapped the carbon fibers, and stretched to the ends of carbon fibers. Only some small and round cells close to negative carbon fibers were found on culture day 12. In the 1×10-4 and 1×10-3 seconds square wave groups, the negative carbon fibers were wrapped by oligodendrocytes or their progenitor cells.CONCLUSION: The local negative electric field which is generated by action potentials at 1×(10-4-10-3)seconds, 40 mV can directly initiate and participate in myelination in the central nervous system.

  3. Intracellular recordings of action potentials by an extracellular nanoscale field-effect transistor

    Duan, Xiaojie; Gao, Ruixuan; Xie, Ping; Cohen-Karni, Tzahi; Qing, Quan; Choe, Hwan Sung; Tian, Bozhi; Jiang, Xiaocheng; Lieber, Charles M.

    2012-03-01

    The ability to make electrical measurements inside cells has led to many important advances in electrophysiology. The patch clamp technique, in which a glass micropipette filled with electrolyte is inserted into a cell, offers both high signal-to-noise ratio and temporal resolution. Ideally, the micropipette should be as small as possible to increase the spatial resolution and reduce the invasiveness of the measurement, but the overall performance of the technique depends on the impedance of the interface between the micropipette and the cell interior, which limits how small the micropipette can be. Techniques that involve inserting metal or carbon microelectrodes into cells are subject to similar constraints. Field-effect transistors (FETs) can also record electric potentials inside cells, and because their performance does not depend on impedance, they can be made much smaller than micropipettes and microelectrodes. Moreover, FET arrays are better suited for multiplexed measurements. Previously, we have demonstrated FET-based intracellular recording with kinked nanowire structures, but the kink configuration and device design places limits on the probe size and the potential for multiplexing. Here, we report a new approach in which a SiO2 nanotube is synthetically integrated on top of a nanoscale FET. This nanotube penetrates the cell membrane, bringing the cell cytosol into contact with the FET, which is then able to record the intracellular transmembrane potential. Simulations show that the bandwidth of this branched intracellular nanotube FET (BIT-FET) is high enough for it to record fast action potentials even when the nanotube diameter is decreased to 3 nm, a length scale well below that accessible with other methods. Studies of cardiomyocyte cells demonstrate that when phospholipid-modified BIT-FETs are brought close to cells, the nanotubes can spontaneously penetrate the cell membrane to allow the full-amplitude intracellular action potential to be

  4. Cancer Driver Log (CanDL): Catalog of Potentially Actionable Cancer Mutations.

    Damodaran, Senthilkumar; Miya, Jharna; Kautto, Esko; Zhu, Eliot; Samorodnitsky, Eric; Datta, Jharna; Reeser, Julie W; Roychowdhury, Sameek

    2015-09-01

    Massively parallel sequencing technologies have enabled characterization of genomic alterations across multiple tumor types. Efforts have focused on identifying driver mutations because they represent potential targets for therapy. However, because of the presence of driver and passenger mutations, it is often challenging to assign the clinical relevance of specific mutations observed in patients. Currently, there are multiple databases and tools that provide in silico assessment for potential drivers; however, there is no comprehensive resource for mutations with functional characterization. Therefore, we created an expert-curated database of potentially actionable driver mutations for molecular pathologists to facilitate annotation of cancer genomic testing. We reviewed scientific literature to identify variants that have been functionally characterized in vitro or in vivo as driver mutations. We obtained the chromosome location and all possible nucleotide positions for each amino acid change and uploaded them to the Cancer Driver Log (CanDL) database with associated literature reference indicating functional driver evidence. In addition to a simple interface, the database allows users to download all or selected genes as a comma-separated values file for incorporation into their own analysis pipeline. Furthermore, the database includes a mechanism for third-party contributions to support updates for novel driver mutations. Overall, this freely available database will facilitate rapid annotation of cancer genomic testing in molecular pathology laboratories for mutations. PMID:26320871

  5. Electrophysiological Motor Unit Number Estimation (MUNE) Measuring Compound Muscle Action Potential (CMAP) in Mouse Hindlimb Muscles.

    Arnold, W David; Sheth, Kajri A; Wier, Christopher G; Kissel, John T; Burghes, Arthur H; Kolb, Stephen J

    2015-01-01

    Compound muscle action potential (CMAP) and motor unit number estimation (MUNE) are electrophysiological techniques that can be used to monitor the functional status of a motor unit pool in vivo. These measures can provide insight into the normal development and degeneration of the neuromuscular system. These measures have clear translational potential because they are routinely applied in diagnostic and clinical human studies. We present electrophysiological techniques similar to those employed in humans to allow recordings of mouse sciatic nerve function. The CMAP response represents the electrophysiological output from a muscle or group of muscles following supramaximal stimulation of a peripheral nerve. MUNE is an electrophysiological technique that is based on modifications of the CMAP response. MUNE is a calculated value that represents the estimated number of motor neurons or axons (motor control input) supplying the muscle or group of muscles being tested. We present methods for recording CMAP responses from the proximal leg muscles using surface recording electrodes following the stimulation of the sciatic nerve in mice. An incremental MUNE technique is described using submaximal stimuli to determine the average single motor unit potential (SMUP) size. MUNE is calculated by dividing the CMAP amplitude (peak-to-peak) by the SMUP amplitude (peak-to-peak). These electrophysiological techniques allow repeated measures in both neonatal and adult mice in such a manner that facilitates rapid analysis and data collection while reducing the number of animals required for experimental testing. Furthermore, these measures are similar to those recorded in human studies allowing more direct comparisons. PMID:26436455

  6. Optical magnetic detection of single-neuron action potentials using quantum defects in diamond

    Barry, J F; Schloss, J M; Glenn, D R; Song, Y; Lukin, M D; Park, H; Walsworth, R L

    2016-01-01

    A key challenge for neuroscience is noninvasive, label-free sensing of action potential (AP) dynamics in whole organisms with single-neuron resolution. Here, we present a new approach to this problem: using nitrogen-vacancy (NV) quantum defects in diamond to measure the time-dependent magnetic fields produced by single-neuron APs. Our technique has a unique combination of features: (i) it is noninvasive, as the light that probes the NV sensors stays within the biocompatible diamond chip and does not enter the organism, enabling activity monitoring over extended periods; (ii) it is label-free and should be widely applicable to most organisms; (iii) it provides high spatial and temporal resolution, allowing precise measurement of the AP waveforms and conduction velocities of individual neurons; (iv) it directly determines AP propagation direction through the inherent sensitivity of NVs to the associated AP magnetic field vector; (v) it is applicable to neurons located within optically opaque tissue or whole org...

  7. Anthropomorphizing the Mouse Cardiac Action Potential via a Novel Dynamic Clamp Method

    Ahrens-Nicklas, Rebecca C.; Christini, David J.

    2009-01-01

    Abstract Interspecies differences can limit the translational value of excitable cells isolated from model organisms. It can be difficult to extrapolate from a drug- or mutation-induced phenotype in mice to human pathophysiology because mouse and human cardiac electrodynamics differ greatly. We present a hybrid computational-experimental technique, the cell-type transforming clamp, which is designed to overcome such differences by using a calculated compensatory current to convert the macroscopic electrical behavior of an isolated cell into that of a different cell type. We demonstrate the technique's utility by evaluating drug arrhythmogenicity in murine cardiomyocytes that are transformed to behave like human myocytes. Whereas we use the cell-type transforming clamp in this work to convert between mouse and human electrodynamics, the technique could be adapted to convert between the action potential morphologies of any two cell types of interest. PMID:19917221

  8. Effect of sampling frequency on the measurement of phase-locked action potentials.

    Go eAshida

    2010-09-01

    Full Text Available Phase-locked spikes in various types of neurons encode temporal information. To quantify the degree of phase-locking, the metric called vector strength (VS has been most widely used. Since VS is derived from spike timing information, error in measurement of spike occurrence should result in errors in VS calculation. In electrophysiological experiments, the timing of an action potential is detected with finite temporal precision, which is determined by the sampling frequency. In order to evaluate the effects of the sampling frequency on the measurement of VS, we derive theoretical upper and lower bounds of VS from spikes collected with finite sampling rates. We next estimate errors in VS assuming random sampling effects, and show that our theoretical calculation agrees with data from electrophysiological recordings in vivo. Our results provide a practical guide for choosing the appropriate sampling frequency in measuring VS.

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

    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. Modulation of hERG potassium channel gating normalizes action potential duration prolonged by dysfunctional KCNQ1 potassium channel

    Zhang, Hongkang; Zou, Beiyan; Yu, Haibo; Moretti, Alessandra; Wang, Xiaoying; Yan, Wei; Babcock, Joseph J.; Bellin, Milena; McManus, Owen B.; Tomaselli, Gordon; Nan, Fajun; Laugwitz, Karl-Ludwig; Li, Min

    2012-01-01

    Long QT syndrome (LQTS) is a genetic disease characterized by a prolonged QT interval in an electrocardiogram (ECG), leading to higher risk of sudden cardiac death. Among the 12 identified genes causal to heritable LQTS, ∼90% of affected individuals harbor mutations in either KCNQ1 or human ether-a-go-go related genes (hERG), which encode two repolarizing potassium currents known as IKs and IKr. The ability to quantitatively assess contributions of different current components is therefore important for investigating disease phenotypes and testing effectiveness of pharmacological modulation. Here we report a quantitative analysis by simulating cardiac action potentials of cultured human cardiomyocytes to match the experimental waveforms of both healthy control and LQT syndrome type 1 (LQT1) action potentials. The quantitative evaluation suggests that elevation of IKr by reducing voltage sensitivity of inactivation, not via slowing of deactivation, could more effectively restore normal QT duration if IKs is reduced. Using a unique specific chemical activator for IKr that has a primary effect of causing a right shift of V1/2 for inactivation, we then examined the duration changes of autonomous action potentials from differentiated human cardiomyocytes. Indeed, this activator causes dose-dependent shortening of the action potential durations and is able to normalize action potentials of cells of patients with LQT1. In contrast, an IKr chemical activator of primary effects in slowing channel deactivation was not effective in modulating action potential durations. Our studies provide both the theoretical basis and experimental support for compensatory normalization of action potential duration by a pharmacological agent. PMID:22745159

  11. Calcium Transients Closely Reflect Prolonged Action Potentials in iPSC Models of Inherited Cardiac Arrhythmia

    C. Ian Spencer

    2014-08-01

    Full Text Available Long-QT syndrome mutations can cause syncope and sudden death by prolonging the cardiac action potential (AP. Ion channels affected by mutations are various, and the influences of cellular calcium cycling on LQTS cardiac events are unknown. To better understand LQTS arrhythmias, we performed current-clamp and intracellular calcium ([Ca2+]i measurements on cardiomyocytes differentiated from patient-derived induced pluripotent stem cells (iPS-CM. In myocytes carrying an LQT2 mutation (HERG-A422T, APs and [Ca2+]i transients were prolonged in parallel. APs were abbreviated by nifedipine exposure and further lengthened upon releasing intracellularly stored Ca2+. Validating this model, control iPS-CM treated with HERG-blocking drugs recapitulated the LQT2 phenotype. In LQT3 iPS-CM, expressing NaV1.5-N406K, APs and [Ca2+]i transients were markedly prolonged. AP prolongation was sensitive to tetrodotoxin and to inhibiting Na+-Ca2+ exchange. These results suggest that LQTS mutations act partly on cytosolic Ca2+ cycling, potentially providing a basis for functionally targeted interventions regardless of the specific mutation site.

  12. Variability of Action Potentials Within and Among Cardiac Cell Clusters Derived from Human Embryonic Stem Cells.

    Zhu, Renjun; Millrod, Michal A; Zambidis, Elias T; Tung, Leslie

    2016-01-01

    Electrophysiological variability in cardiomyocytes derived from pluripotent stem cells continues to be an impediment for their scientific and translational applications. We studied the variability of action potentials (APs) recorded from clusters of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) using high-resolution optical mapping. Over 23,000 APs were analyzed through four parameters: APD30, APD80, triangulation and fractional repolarization. Although measures were taken to reduce variability due to cell culture conditions and rate-dependency of APs, we still observed significant variability in APs among and within the clusters. However, similar APs were found in spatial locations with close proximity, and in some clusters formed distinct regions having different AP characteristics that were reflected as separate peaks in the AP parameter distributions, suggesting multiple electrophysiological phenotypes. Using a recently developed automated method to group cells based on their entire AP shape, we identified distinct regions of different phenotypes within single clusters and common phenotypes across different clusters when separating APs into 2 or 3 subpopulations. The systematic analysis of the heterogeneity and potential phenotypes of large populations of hESC-CMs can be used to evaluate strategies to improve the quality of pluripotent stem cell-derived cardiomyocytes for use in diagnostic and therapeutic applications and in drug screening. PMID:26729331

  13. Optimisation of Ionic Models to Fit Tissue Action Potentials: Application to 3D Atrial Modelling

    Amr Al Abed

    2013-01-01

    Full Text Available A 3D model of atrial electrical activity has been developed with spatially heterogeneous electrophysiological properties. The atrial geometry, reconstructed from the male Visible Human dataset, included gross anatomical features such as the central and peripheral sinoatrial node (SAN, intra-atrial connections, pulmonary veins, inferior and superior vena cava, and the coronary sinus. Membrane potentials of myocytes from spontaneously active or electrically paced in vitro rabbit cardiac tissue preparations were recorded using intracellular glass microelectrodes. Action potentials of central and peripheral SAN, right and left atrial, and pulmonary vein myocytes were each fitted using a generic ionic model having three phenomenological ionic current components: one time-dependent inward, one time-dependent outward, and one leakage current. To bridge the gap between the single-cell ionic models and the gross electrical behaviour of the 3D whole-atrial model, a simplified 2D tissue disc with heterogeneous regions was optimised to arrive at parameters for each cell type under electrotonic load. Parameters were then incorporated into the 3D atrial model, which as a result exhibited a spontaneously active SAN able to rhythmically excite the atria. The tissue-based optimisation of ionic models and the modelling process outlined are generic and applicable to image-based computer reconstruction and simulation of excitable tissue.

  14. Optophysiological approach to resolve neuronal action potentials with high spatial and temporal resolution in cultured neurons

    Stephane ePages

    2011-10-01

    Full Text Available Cell to cell communication in the central nervous system is encoded into transient and local membrane potential changes (ΔVm. Deciphering the rules that govern synaptic transmission and plasticity entails to be able to perform Vm recordings throughout the entire neuronal arborization. Classical electrophysiology is, in most cases, not able to do so within small and fragile neuronal subcompartments. Thus, optical techniques based on the use of fluorescent voltage-sensitive dyes (VSDs have been developed. However, reporting spontaneous or small ΔVm from neuronal ramifications has been challenging, in part due to the limited sensitivity and phototoxicity of VSD-based optical measurements. Here we demonstrate the use of water soluble VSD, ANNINE-6plus, with laser scanning microscopy to optically record ΔVm in cultured neurons. We show that the sensitivity (> 10 % of fluorescence change for 100 mV depolarization and time response (submillisecond of the dye allows the robust detection of action potentials (APs even without averaging, allowing the measurement of spontaneous neuronal firing patterns. In addition, we show that back-propagating APs can be recorded, along distinct dendritic sites and within dendritic spines. Importantly, our approach does not induce any detectable phototoxic effect on cultured neurons. This optophysiological approach provides a simple, minimally invasive and versatile optical method to measure electrical activity in cultured neurons with high temporal (ms resolution and high spatial (µm resolution.

  15. Small-conductance calcium-activated potassium (SK) channels contribute to action potential repolarization in human atria

    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...

  16. Potential involvement of serotonergic signaling in ketamine's antidepressant actions: A critical review.

    du Jardin, Kristian Gaarn; Müller, Heidi Kaastrup; Elfving, Betina; Dale, Elena; Wegener, Gregers; Sanchez, Connie

    2016-11-01

    A single i.v. infusion of ketamine, classified as an N-methyl-d-aspartate (NMDA) receptor antagonist, may alleviate depressive symptoms within hours of administration in treatment resistant depressed patients, and the antidepressant effect may last for several weeks. These unique therapeutic properties have prompted researchers to explore the mechanisms mediating the antidepressant effects of ketamine, but despite many efforts, no consensus on its antidepressant mechanism of action has been reached. Recent preclinical reports have associated the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) with the antidepressant-like action of ketamine. Here, we review the current evidence for a serotonergic role in ketamine's antidepressant effects. The pharmacological profile of ketamine may include equipotent activity on several non-NMDA targets, and the current hypotheses for the mechanisms responsible for ketamine's antidepressant activity do not appear to preclude the possibility that non-glutamate neurotransmitters are involved in the antidepressant effects. At multiple levels, the serotonergic and glutamatergic systems interact, and such crosstalk could support the notion that changes in serotonergic neurotransmission may impact ketamine's antidepressant potential. In line with these prospects, ketamine may increase 5-HT levels in the prefrontal cortex of rats, plausibly via hippocampal NMDA receptor inhibition and activation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. In addition, a number of preclinical studies suggest that the antidepressant-like effects of ketamine may depend on endogenous activation of 5-HT receptors. Recent imaging and behavioral data predominantly support a role for 5-HT1A or 5-HT1B receptors, but the full range of 5-HT receptors has currently not been systematically investigated in this context. Furthermore, the nature of any 5-HT dependent mechanism in ketamine's antidepressant effect is currently not

  17. CLINICAL AND EXPERIMENTAL STUDIES OF LARGE AMPLITUDE ACTION POTENTIAL OF THE SUFFERED FACIAL MUSCLES IN INTRATEMPORAL FACIAL NERVE PARALYSIS

    1999-01-01

    Ojective. To testify the phenomenon that large amplitude action potential appears at the early stage of facial paralysis, and to search for the mechanism through clinical and experimental studies. Patients(animals) and methods. The action potentials of the orbicular ocular and oral muscles were recorded in 34 normal persons by electromyogram instruments. The normal range of amplitude percentage was found out according to he normal distribution. One hundred patients with facial paralysis were also studied. The action potentials of facial muscles were recorded in 17 guinea pigs before and after the facial nerve was compressed and the facial nerve was examined under electromicroscope before and after the compression.Results. The amplitude percentage of the suffered ide to the healthy side was more than 153 percent in 6 of the 100 patients. Lare amplitude action potential ocured in 35 per cent guinea pigs which were performed the experiment of facial nrve compression. Electromicroscopic examination revealed separation of the lammae of the facial nerve's myelin sheath in the guinea pigs which exhibited large amplitude action potential.Conclusion. The facial nerve exhibited a temporary over-exciability at the early stage of facial nerve injury in some patients and guinea pigs. If the injury waslimited in the myelin sheath, te prognosis was relatively good.

  18. CLINICAL AND EXPERIMENTAL STUDIES OF LARGE AMPLITUDE ACTION POTENTIAL OF THE SUFFERED FACIAL MUSCLES IN INTRATEMPORAL FACIAL NERVE PARALYSIS

    任重; 惠莲

    1999-01-01

    Objctive. To testify the phenomenon that large amplitude action potential appears at the early stage oil facial paralysis, and to search for the mechanism through clinical and experimental studies. Patients(aninmls) and methods. The action potentials of the orbicular ocular and oral museles were recorded in 34 normal persons by electromyogram instrtiments. The normal range of amplitude percentage was found out according to the normal distribution, One hundred patients with facial paralysis were also studied. The action potentials of facial muscles were recorded ia 17 guinea pigs before and after the facial nerve was comp~ and the facial nerve was examined under electromicroscope before and after the compression.Results. The amplitude percentage of the suffered side to the healthy side was more than 153 percent in 6 of the 100 patients. Large amplitude action potential occured in 35 per cent guinea pigs which were performed the experiment of facial nerve compression. Electromicroscopic examination revealed separation of the lammae of the facial nerve's myelin sheath in the guinea pigs which exhibited large amplitude action potential Conclusion. The facial nerve exhibited a temporary over-excitability at the early stage of facial nerve injury in scane patients and guinea pigs. If the injury was limited in the myelin sheath, the prognods was relatively good.

  19. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

    2009-01-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead II) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by floating microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5 ± 4.2), (45.5 ± 6.9) and (43.8 ± 7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6 ± 2.9), (38.7 ± 5.6) and (38.2 ± 7.3) ms, P<0.05). The atrial ventricular heart block type II and III only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17 ± 10.56) and (101.89 ± 9.54) mV/s) vs those in wild-type mice (vs (110.51 ± 10.38) and (109.53 ± 10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83 ± 11.17) and (195.43 ± 16.41) ms) vs that in wild-type mice ((108.27 ± 10.85) and (171.00 ± 15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80 ± 0.92) nA vs that in wild-type mice ((-5.98 ± 1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

  20. Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

    MENG Yan; ZHAO ChunYan; ZHANG XueXin; ZHAO HuaShan; GUO LiRong; Lü Bin; ZHAO XueJian; YANG BaoXue

    2009-01-01

    UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead Ⅱ) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by float-ing microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5±4.2), (45.5±6.9) and (43.8±7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6±2.9), (38.7±5.6) and (38.2±7.3) ms, P<0.05). The atrial ventricular heart block type Ⅱ and Ⅲ only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17±10.56) and (101.89±9.54) mV/s) vs those in wild-type mice (vs (110.51±10.38) and (109.53±10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83±11.17) and (195.43±16.41) ms) vs that in wild-type mice ((108.27±10.85) and (171.00±15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80±0.92) nA vs that in wild-type mice ((-5.98±1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

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

    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

    2016-01-01

    Summary 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. Video Abstract PMID:26804557

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

    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.

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

    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

    2016-02-01

    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. PMID:26804557

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

    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.

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

    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

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

    Biswa Sengupta

    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.

  7. Sensitivity analysis of potential events affecting the double-shell tank system and fallback actions

    Knutson, B.J.

    1996-09-27

    Sensitivity analyses were performed for fall-back positions (i.e., management actions) to accommodate potential off-normal and programmatic change events overlaid on the waste volume projections and their uncertainties. These sensitivity analyses allowed determining and ranking tank system high-risk parameters and fall- back positions that will accommodate the respective impacts. This quantification of tank system impacts shows periods where tank capacity is sensitive to certain variables that must be carefully managed and/or evaluated. Identifying these sensitive variables and quantifying their impact will allow decision makers to prepare fall-back positions and focus available resources on the highest impact parameters where technical data are needed to reduce waste projection uncertainties. For noncomplexed waste, the period of capacity vulnerability occurs during the years of single-shell tank (SST) retrieval (after approximately 2009) due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate and 200-East SST solids transfer volume. For complexed waste, the period of capacity vulnerability occurs during the period after approximately 2005 due to the sensitivity to several variables. Ranked by importance these variables include the pretreatment rate. 200-East SST solids transfer volume. complexed waste reduction factor using evaporation, and 200-west saltwell liquid porosity.

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

    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.

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

    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.

  10. Modeling the action-potential-sensitive nonlinear-optical response of myelinated nerve fibers and short-term memory

    Shneider, M. N.; Voronin, A. A.; Zheltikov, A. M.

    2011-11-01

    The Goldman-Albus treatment of the action-potential dynamics is combined with a phenomenological description of molecular hyperpolarizabilities into a closed-form model of the action-potential-sensitive second-harmonic response of myelinated nerve fibers with nodes of Ranvier. This response is shown to be sensitive to nerve demyelination, thus enabling an optical diagnosis of various demyelinating diseases, including multiple sclerosis. The model is applied to examine the nonlinear-optical response of a three-neuron reverberating circuit—the basic element of short-term memory.

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

    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

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

    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

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

    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.…

  14. Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.

    Manzini, S; Parlani, M; Martucci, E; Maggi, C A; Meli, A

    1986-01-01

    The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents. PMID:2430855

  15. Effect of knockout of α2δ-1 on action potentials in mouse sensory neurons.

    Margas, Wojciech; Ferron, Laurent; Nieto-Rostro, Manuela; Schwartz, Arnold; Dolphin, Annette C

    2016-08-01

    Gene deletion of the voltage-gated calcium channel auxiliary subunit α2δ-1 has been shown previously to have a cardiovascular phenotype, and a reduction in mechano- and cold sensitivity, coupled with delayed development of neuropathic allodynia. We have also previously shown that dorsal root ganglion (DRG) neuron calcium channel currents were significantly reduced in α2δ-1 knockout mice. To extend our findings in these sensory neurons, we have examined here the properties of action potentials (APs) in DRG neurons from α2δ-1 knockout mice in comparison to their wild-type (WT) littermates, in order to dissect how the calcium channels that are affected by α2δ-1 knockout are involved in setting the duration of individual APs and their firing frequency. Our main findings are that there is reduced Ca(2+) entry on single AP stimulation, particularly in the axon proximal segment, reduced AP duration and reduced firing frequency to a 400 ms stimulation in α2δ-1 knockout neurons, consistent with the expected role of voltage-gated calcium channels in these events. Furthermore, lower intracellular Ca(2+) buffering also resulted in reduced AP duration, and a lower frequency of AP firing in WT neurons, mimicking the effect of α2δ-1 knockout. By contrast, we did not obtain any consistent evidence for the involvement of Ca(2+)-activation of large conductance calcium-activated potassium (BK) and small conductance calcium-activated potassium (SK) channels in these events. In conclusion, the reduced Ca(2+) elevation as a result of single AP stimulation is likely to result from the reduced duration of the AP in α2δ-1 knockout sensory neurons.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377724

  16. Natural cures for type 1 diabetes: a review of phytochemicals, biological actions, and clinical potential.

    Chang, C L T; Chen, Yi-Ching; Chen, Hui-Ming; Yang, Ning-Sun; Yang, Wen-Chin

    2013-01-01

    Autoimmune diseases are the third largest category of illness in the industrialized world, following cardiovascular diseases and cancers. Among them, type 1 diabetes, also named autoimmune diabetes, afflicts 10 million people worldwide. This disease is caused by autoimmunity-mediated destruction of pancreatic β-cells, leading to insulin deficiency, hyperglycemia and complications. Currently, there is no cure for type 1 diabetes. Insulin injection is the only medication; however, it accompanies serious medical complications. Current strategies to cure type 1 diabetes include immunotherapy, replacement therapy, and combination therapy. Despite recent advances in anti-diabetic strategies, no strategy is clinically successful. How to cure type 1 diabetes without undesirable side effects still remains a formidable challenge in drug research and development. Plants provide an extraordinary source of natural medicines for different diseases. Moreover, secondary metabolites of plant origin serve as an invaluable chemical library for drug discovery and current medicinal chemistry in the pharmaceutical industry. Over the past 25 years, 50% of prescription drugs have been developed from natural products and their derivatives. In this article, we review more than 20 plant compounds and extracts reported in the literature to prevent and treat type-1 diabetes. Emphasis is placed on their chemistry and biology in terms of regulation of immune cells and pancreatic β-cells. We summarize recent progress in understanding the biological actions, mechanisms and therapeutic potential of the compounds and extracts of plant origin in type 1 diabetes. New views on phytocompound-based strategies for prevention and treatment of type 1 diabetes are also discussed. PMID:23210779

  17. Effects of estragole on the compound action potential of the rat sciatic nerve

    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.

  18. Contribution of auditory nerve fibers to compound action potential of the auditory nerve.

    Bourien, Jérôme; Tang, Yong; Batrel, Charlène; Huet, Antoine; Lenoir, Marc; Ladrech, Sabine; Desmadryl, Gilles; Nouvian, Régis; Puel, Jean-Luc; Wang, Jing

    2014-09-01

    Sound-evoked compound action potential (CAP), which captures the synchronous activation of the auditory nerve fibers (ANFs), is commonly used to probe deafness in experimental and clinical settings. All ANFs are believed to contribute to CAP threshold and amplitude: low sound pressure levels activate the high-spontaneous rate (SR) fibers, and increasing levels gradually recruit medium- and then low-SR fibers. In this study, we quantitatively analyze the contribution of the ANFs to CAP 6 days after 30-min infusion of ouabain into the round window niche. Anatomic examination showed a progressive ablation of ANFs following increasing concentration of ouabain. CAP amplitude and threshold plotted against loss of ANFs revealed three ANF pools: 1) a highly ouabain-sensitive pool, which does not participate in either CAP threshold or amplitude, 2) a less sensitive pool, which only encoded CAP amplitude, and 3) a ouabain-resistant pool, required for CAP threshold and amplitude. Remarkably, distribution of the three pools was similar to the SR-based ANF distribution (low-, medium-, and high-SR fibers), suggesting that the low-SR fiber loss leaves the CAP unaffected. Single-unit recordings from the auditory nerve confirmed this hypothesis and further showed that it is due to the delayed and broad first spike latency distribution of low-SR fibers. In addition to unraveling the neural mechanisms that encode CAP, our computational simulation of an assembly of guinea pig ANFs generalizes and extends our experimental findings to different species of mammals. Altogether, our data demonstrate that substantial ANF loss can coexist with normal hearing threshold and even unchanged CAP amplitude. PMID:24848461

  19. Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

    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

  20. Flattening of the electrocardiographic T-wave is a sign of proarrhythmic risk and a reflection of action potential triangulation

    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...

  1. Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

    Cotel, Florence; Exley, Richard; Cragg, Stephanie;

    2013-01-01

    --as during motor exercise--activated 5-HT1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential...

  2. Synthesis of a dendritic estrogen cluster: A potential tool for studies of nuclear versus extranuclear pathways of estrogen actions

    Jian Chen; Hu Zheng; Yan Song; Yu Feng Liang; Qing Rong Qi

    2012-01-01

    A novel estrogen dendrimer has been synthesized through a combination of divergent and convergent approaches in 9 practical steps and in good yields.It was characterized and confirmed by elemental analysis,FT-IR,MS,1H NMR,13C NMR.The dendrimer contains 16 estrone units and is potentially a useful tool for the studies of estrogen actions.

  3. Assessing the Potential Impact of a Nationwide Class-Based Affirmative Action System

    Xiang, Alice; Rubin, Donald B.

    2015-01-01

    We examine the possible consequences of a change in law school admissions in the United States from an affirmative action system based on race to one based on socioeconomic class. Using data from the 1991-1996 Law School Admission Council Bar Passage Study, students were reassigned attendance by simulation to law school tiers by transferring the affirmative action advantage for black students to students from low socioeconomic backgrounds. The hypothetical academic outcomes for the students w...

  4. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control

    Bravo, Alejandra; Gill, Sarjeet S.; Soberón, Mario

    2006-01-01

    Bacillus thuringiensis Cry and Cyt protein families are a diverse group of proteins with activity against insects of different orders - Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some...

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

    Desbois, Andrew Paul; Smith, Valerie Jane

    2010-01-01

    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 ...

  6. Effects of nerve growth factor on the action potential duration and repolarizing currents in a rabbit model of myocardial infarction

    Yun-Feng Lan; Yang Li; Jian-Cheng Zhang; Jin-Lao Gao; Xue-Ping Wang; Zhou Fang; Yi-Cheng Fu; Mei-Yan Chen; Min Lin; Qiao Xue

    2013-01-01

    Objectives To investigate the effect of nerve growth factor (NGF) on the action potential and potassium currents of non-infarcted myocardium in the myocardial infarcted rabbit model. Methods Rabbits with occlusion of the left anterior descending coronary artery were prepared and allowed to recover for eight weeks (healed myocardial infarction, HMI). During ligation surgery of the left coronary artery, a polyethylene tube was placed near the left stellate ganglion in the subcutis of the neck for the purpose of administering NGF 400 U/d for eight weeks (HMI + NGF group). Cardiomyocytes were isolated from regions of the non-infarcted left ventricular wall and the action potentials and ion currents in these cells were recorded using whole-cell patch clamps. Results Compared with HMI and control cardiomyocytes, significant prolongation of APD50 or APD90 (Action potential duration (APD) measured at 50% and 90% of repolarization) in HMI + NGF cardiomyocytes was found. The results showed that the 4-aminopyridine sensitive transient outward potassium current (Ito), the rapidly activated omponent of delayed rectifier potassium current (IKr), the slowly activated component of delayed rectifier potassium current (IKs), and the L-type calcium current (ICaL) were significantly altered in NGF + HMI cardiomyocytes compared with HMI and control cells. Conclusions Our results suggest that NGF treatment significantly prolongs APD in HMI cardiomyocytes and that a decrease in outward potassium currents and an increase of inward Ca2+ current are likely the underlying mechanism of action.

  7. Governance issues, potentials and failures of participative collective action in the Kafue Flats, Zambia

    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.

  8. Preparing Social Justice Oriented Teachers: The Potential Role of Action Research in the PDS

    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.…

  9. Mode of action of Bacillus thuringiensis Cry and Cyt toxins and their potential for insect control.

    Bravo, Alejandra; Gill, Sarjeet S; Soberón, Mario

    2007-03-15

    Bacillus thuringiensis Crystal (Cry) and Cytolitic (Cyt) protein families are a diverse group of proteins with activity against insects of different orders--Lepidoptera, Coleoptera, Diptera and also against other invertebrates such as nematodes. Their primary action is to lyse midgut epithelial cells by inserting into the target membrane and forming pores. Among this group of proteins, members of the 3-Domain Cry family are used worldwide for insect control, and their mode of action has been characterized in some detail. Phylogenetic analyses established that the diversity of the 3-Domain Cry family evolved by the independent evolution of the three domains and by swapping of domain III among toxins. Like other pore-forming toxins (PFT) that affect mammals, Cry toxins interact with specific receptors located on the host cell surface and are activated by host proteases following receptor binding resulting in the formation of a pre-pore oligomeric structure that is insertion competent. In contrast, Cyt toxins directly interact with membrane lipids and insert into the membrane. Recent evidence suggests that Cyt synergize or overcome resistance to mosquitocidal-Cry proteins by functioning as a Cry-membrane bound receptor. In this review we summarize recent findings on the mode of action of Cry and Cyt toxins, and compare them to the mode of action of other bacterial PFT. Also, we discuss their use in the control of agricultural insect pests and insect vectors of human diseases. PMID:17198720

  10. The Potential of General Classroom Observation: Turkish EFL Teachers' Perceptions, Sentiments, and Readiness for Action

    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…

  11. Doubts about actions and flanker incongruity-related potentials and performance

    Tops, Mattie; Wijers, Albertus A.

    2012-01-01

    The brain networks that are involved in flanker incongruity and error processing are also consistently implicated in mental disorders such as obsessive compulsive disorder (OCD) that feature increased "Doubts about Actions" (DaA) scores. In the present study we investigated whether DaA scores, simil

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

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

    2011-01-01

    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...

  13. Neural Networks for Template Matching: Application to Real-Time Classification of the Action Potentials of Real Neurons

    Wong, Yiu-fai; Banik, Jashojiban; Bower, James M.

    1988-01-01

    Much experimental study of real neural networks relies on the proper classification of extracellulary sampled neural signals (i .e. action potentials) recorded from the brains of experimental animals. In most neurophysiology laboratories this classification task is simplified by limiting investigations to single, electrically well-isolated neurons recorded one at a time. However, for those interested in sampling the activities of many single neurons simultaneously, waveform cla...

  14. Back-propagation of physiological action potential output in dendrites of slender-tufted L5A pyramidal neurons

    Grewe, Benjamin F.; Audrey Bonnan; Andreas Frick

    2010-01-01

    Pyramidal neurons of layer 5A are a major neocortical output type and clearly distinguished from layer 5B pyramidal neurons with respect to morphology, in vivo firing patterns, and connectivity; yet knowledge of their dendritic properties is scant. We used a combination of whole-cell recordings and Ca2+ imaging techniques in vitro to explore the specific dendritic signalling role of physiological action potential patterns recorded in vivo in layer 5A pyramidal neurons of the whisker-related &...

  15. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy:an analysis of 500 cases

    Yunqian Zhang; Jintao Li; Tingjuan Wang; Jianlin Wang

    2014-01-01

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Afifl-iated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control sub-jects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were signiifcantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. More-over, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The ampli-tude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, as-ymptomatic stage of diabetic peripheral neuropathy.

  16. Potential pathways of pesticide action on erectile function-a contributory factor in male infertility

    RP Kaur; V Gupta; AF Christopher; P Bansal

    2015-01-01

    One of the important objectives of this manuscript is to focus on the place of erectile dysfunction as an important factor for infertility. The review is about correlating the indiscriminate use of pesticides and to find out and highlight the evidences for mechanism of action of these pesticides for erectile dysfunction and find out the most used and most dangerous pesticide from erectile dysfunction point of view. The review suggests that erectile dysfunction is having a significant place as a causal factor for infertility. Study infers that pesticides are having multiple mechanisms of action through which these cause erectile dysfunction. It also reflects that acetamiprid is having most devastating effect causing erectile dysfunction as it acts through multiple inhibitory pathways. The review successfully highlights the indiscriminate regional use of pesticides.

  17. Evaluation of the potential carcinogenic action of radiocalcium internal irradiation in Swiss albino mice

    The carcinogenic action of 45Ca on inducing hepatocelluar carcinoma (HCC) in Swiss albino mice has been statistically evaluated. HCC proved to be radiation-induced and not due to spontaneous origin. Also, the higher incidence of male hepatocarcinogenesis due to internal irradiation has been found to be significant. The precise possible mechanism regarding the higher male susceptibility to liver cancer has been discussed in the light of available literature. (author)

  18. Reading Humboldt through the theory of communicative action: the democratic potential of symbolic interaction

    McLuskie, Ed

    2015-01-01

    Wilhelm von Humboldt's studies of language during the nineteenth century anticipated twentieth-century symbolic interactionism, suggesting a two-century intellectual history stressing the communicating subject as an intersubjective actor. Jürgen Habermas's theory of communicative action, well known for its inclusion of George Herbert Mead's symbolic interactionism, appeals in the same breath to von Humboldt's work, thus inviting a critical re-appropriation of Mead beyond the social-psychologi...

  19. Reading Humboldt through the theory of communicative action: the democratic potential of symbolic interaction:

    McLuskie, Ed

    2003-01-01

    Wilhelm von Humboldt's studies of language during the nineteenth century anticipated twentieth-century symbolic interactionism, suggesting a two-century intellectual history stressing the communicating subject as an intersubjective actor. Jürgen Habermas's theory of communicative action, well known for its inclusion of George Herbert Mead's symbolic interactionism, appeals in the same breath to von Humboldt's work, thus inviting a critical re-appropriation of Mead beyond the social-psychologi...

  20. Carnosine: can understanding its actions on energy metabolism and protein homeostasis inform its therapeutic potential?

    Hipkiss, Alan R; Cartwright, Stephanie P.; Bromley, Clare; Gross, Stephane R.; Bill, Roslyn M.

    2013-01-01

    The dipeptide carnosine (β-alanyl-L-histidine) has contrasting but beneficial effects on cellular activity. It delays cellular senescence and rejuvenates cultured senescent mammalian cells. However, it also inhibits the growth of cultured tumour cells. Based on studies in several organisms, we speculate that carnosine exerts these apparently opposing actions by affecting energy metabolism and/or protein homeostasis (proteostasis). Specific effects on energy metabolism include the dipeptide’s ...

  1. Conservation laws of wave action and potential enstrophy for Rossby waves in a stratified atmosphere

    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.

  2. Waveform Similarity Analysis: A Simple Template Comparing Approach for Detecting and Quantifying Noisy Evoked Compound Action Potentials.

    Jason Robert Potas

    Full Text Available Experimental electrophysiological assessment of evoked responses from regenerating nerves is challenging due to the typical complex response of events dispersed over various latencies and poor signal-to-noise ratio. Our objective was to automate the detection of compound action potential events and derive their latencies and magnitudes using a simple cross-correlation template comparison approach. For this, we developed an algorithm called Waveform Similarity Analysis. To test the algorithm, challenging signals were generated in vivo by stimulating sural and sciatic nerves, whilst recording evoked potentials at the sciatic nerve and tibialis anterior muscle, respectively, in animals recovering from sciatic nerve transection. Our template for the algorithm was generated based on responses evoked from the intact side. We also simulated noisy signals and examined the output of the Waveform Similarity Analysis algorithm with imperfect templates. Signals were detected and quantified using Waveform Similarity Analysis, which was compared to event detection, latency and magnitude measurements of the same signals performed by a trained observer, a process we called Trained Eye Analysis. The Waveform Similarity Analysis algorithm could successfully detect and quantify simple or complex responses from nerve and muscle compound action potentials of intact or regenerated nerves. Incorrectly specifying the template outperformed Trained Eye Analysis for predicting signal amplitude, but produced consistent latency errors for the simulated signals examined. Compared to the trained eye, Waveform Similarity Analysis is automatic, objective, does not rely on the observer to identify and/or measure peaks, and can detect small clustered events even when signal-to-noise ratio is poor. Waveform Similarity Analysis provides a simple, reliable and convenient approach to quantify latencies and magnitudes of complex waveforms and therefore serves as a useful tool for

  3. Adaptation decision-making in the Nordic Countries: assessing the potential for joint action

    Juhola, Sirkku; Goodsite, Michael Evan; Davis, Marion;

    2014-01-01

    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...... and weaknesses of a Nordic strategy for adaptation? In order to answer these two questions, this paper examines reviews the current national adaptation policies of each Nordic country and discusses the challenges facing a Nordic strategy and finally assesses the potential for common Nordic adaptation...

  4. A model of the magnetic fields created by single motor unit compound action potentials in skeletal muscle.

    Parker, K K; Wikswo, J P

    1997-10-01

    We have developed a computationally simple model for calculating the magnetic-field strength at a point due to a single motor unit compound action potential (SMUCAP). The motor unit is defined only in terms of its anatomical features, and the SMUCAP is approximated using the tripole model. The distributed current density J is calculated within the volume defined by the motor unit. The law of Biot and Savart can then be cast in a form necessitating that J be integrated only over the region containing current sources or conductivity boundaries. The magnetic-field strength is defined as the summation of the contributions to the field made by every muscle fiber in the motor unit. Applying this model to SMUCAP measurements obtained using a high-resolution SUper Conducting Quantum Interference Device (SQUID) magnetometer may yield information regarding the distribution of action currents (AC's) and the anatomical properties of single motor units within a muscle bundle. PMID:9311164

  5. Opposing actions of chronic Δ9-tetrahydrocannabinol and cannabinoid antagonists on hippocampal long-term potentiation

    Hoffman, Alexander F; Oz, Murat; Yang, Ruiqin; Lichtman, Aron H.; Carl R Lupica

    2007-01-01

    Memory deficits produced by marijuana arise partly via interaction of the psychoactive component, Δ9-tetrahydrocannabinol (Δ9-THC), with cannabinoid receptors in the hippocampus. Although cannabinoids acutely reduce glutamate release and block hippocampal long-term potentiation (LTP), a potential substrate for learning and memory, the consequences of prolonged exposure to Δ9-THC for hippocampal function are poorly understood. Rats were injected with Δ9-THC (10 mg/kg, i.p., q.d.) for 1, 3, or ...

  6. Characterising action potential in virtual game worlds applied with the mind module

    Eladhari, Mirjam Palosaari

    2009-01-01

    Because games set in persistent virtual game worlds (VGWs) have massive numbers of players, these games need methods of characterisation for playable characters (PCs) that differ from the methods used in traditional narrative media. VGWs have a number of particularly interesting qualities. Firstly, VGWs are places where players interact with and create elements carrying narrative potential. Secondly, players add goals, motives and driving forces to the narrative potential of a VGW, which some...

  7. Computational modeling of voltage-gated Ca channels inhibition: identification of different effects on uterine and cardiac action potentials

    Wing Chiu eTong

    2014-10-01

    Full Text Available The uterus and heart share the important physiological feature whereby contractile activation of the muscle tissue is regulated by the generation of periodic, spontaneous electrical action potentials (APs. Preterm birth arising from premature uterine contractions is a major complication of pregnancy and there remains a need to pursue avenues of research that facilitate the use of drugs, tocolytics, to limit these inappropriate contractions without deleterious actions on cardiac electrical excitation. A novel approach is to make use of mathematical models of uterine and cardiac APs, which incorporate many ionic currents contributing to the AP forms, and test the cell-specific responses to interventions. We have used three such models – of uterine smooth muscle cells (USMC, cardiac sinoatrial node cells (SAN and ventricular cells – to investigate the relative effects of reducing two important voltage-gated Ca currents – the L-type (ICaL and T-type (ICaT Ca currents. Reduction of ICaL (10% alone, or ICaT (40% alone, blunted USMC APs with little effect on ventricular APs and only mild effects on SAN activity. Larger reductions in either current further attenuated the USMC APs but with also greater effects on SAN APs. Encouragingly, a combination of ICaL and ICaT reduction did blunt USMC APs as intended with little detriment to APs of either cardiac cell type. Subsequent overlapping maps of ICaL and ICaT inhibition profiles from each model revealed a range of combined reductions of ICaL and ICaT over which an appreciable diminution of USMC APs could be achieved with no deleterious action on cardiac SAN or ventricular APs. This novel approach illustrates the potential for computational biology to inform us of possible uterine and cardiac cell-specific mechanisms. Incorporating such computational approaches in future studies directed at designing new, or repurposing existing, tocolytics will be beneficial for establishing a desired uterine

  8. Potential mechanisms of action of lithium in bipolar disorder. Current understanding.

    Malhi, Gin S; Tanious, Michelle; Das, Pritha; Coulston, Carissa M; Berk, Michael

    2013-02-01

    Lithium has been used for over half a century for the treatment of bipolar disorder as the archetypal mood stabilizer, and has a wealth of empirical evidence supporting its efficacy in this role. Despite this, the specific mechanisms by which lithium exerts its mood-stabilizing effects are not well understood. Given the inherently complex nature of the pathophysiology of bipolar disorder, this paper aims to capture what is known about the actions of lithium ranging from macroscopic changes in mood, cognition and brain structure, to its effects at the microscopic level on neurotransmission and intracellular and molecular pathways. A comprehensive literature search of databases including MEDLINE, EMBASE and PsycINFO was conducted using relevant keywords and the findings from the literature were then reviewed and synthesized. Numerous studies report that lithium is effective in the treatment of acute mania and for the long-term maintenance of mood and prophylaxis; in comparison, evidence for its efficacy in depression is modest. However, lithium possesses unique anti-suicidal properties that set it apart from other agents. With respect to cognition, studies suggest that lithium may reduce cognitive decline in patients; however, these findings require further investigation using both neuropsychological and functional neuroimaging probes. Interestingly, lithium appears to preserve or increase the volume of brain structures involved in emotional regulation such as the prefrontal cortex, hippocampus and amygdala, possibly reflecting its neuroprotective effects. At a neuronal level, lithium reduces excitatory (dopamine and glutamate) but increases inhibitory (GABA) neurotransmission; however, these broad effects are underpinned by complex neurotransmitter systems that strive to achieve homeostasis by way of compensatory changes. For example, at an intracellular and molecular level, lithium targets second-messenger systems that further modulate neurotransmission. For

  9. Cardiovascular Actions and Therapeutic Potential of Tetramethylpyrazine (Active Component Isolated from Rhizoma Chuanxiong): Roles and Mechanisms

    Guo, Ming; Liu, Yue; Shi, Dazhuo

    2016-01-01

    Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use. PMID:27314011

  10. Assessing potential targets of calcium action in light-modulated gravitropism

    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.

  11. Metal-organic frameworks: mechanisms of antibacterial action and potential applications.

    Wyszogrodzka, Gabriela; Marszałek, Bartosz; Gil, Barbara; Dorożyński, Przemysław

    2016-06-01

    The growing resistance of pathogens to conventional antibiotics has become a public health problem and raises the need to seek new effective solutions. Metal-organic frameworks (MOFs) are porous, hybrid materials comprising metal ions linked by organic binding ligands. The possibility of using a variety of chemical building components in MOFs enables the formation of structures with desired properties. They can act as a reservoir of metal ions, providing their gradual release and resulting in a sustained antibacterial action analogous to that proposed for metal/metal oxide nanoparticles (NPs) but different to that of antibiotics. These features make MOFs promising candidates for pharmaceutical and biomedical applications, as illustrated by examples discussed in this review. PMID:27091434

  12. HMGB1 Inhibition During Zymosan-Induced Inflammation: The Potential Therapeutic Action of Riboflavin.

    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. PMID:26445809

  13. Bursting regimes in a reaction-diffusion system with action potential-dependent equilibrium.

    Stephen R Meier

    Full Text Available The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this paper we explore time-dependent ionic concentrations by allowing the ion-specific Nernst potentials to vary with developing transmembrane potential. As a specific implementation, we incorporate the potential-dependent Nernst shift into a one-dimensional Morris-Lecar reaction-diffusion model. Our main findings result from a region in parameter space where self-sustaining oscillations occur without external forcing. Studying the system close to the bifurcation boundary, we explore the vulnerability of the system with respect to external stimulations which disrupt these oscillations and send the system to a stable equilibrium. We also present results for an extended, one-dimensional cable of excitable tissue tuned to this parameter regime and stimulated, giving rise to complex spatiotemporal pattern formation. Potential applications to the emergence of neuronal bursting in similar two-variable systems and to pathophysiological seizure-like activity are discussed.

  14. Novel experimental results in human cardiac electrophysiology: measurement of the Purkinje fibre action potential from the undiseased human heart.

    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. PMID:26320996

  15. Potentiation of bradykinin action on smooth muscle by a scorpion venom extract.

    Araujo, R L; Gomez, M V

    1976-08-01

    Gel filtration of the water extract of the venom of the scorpion T. serrulatus showed four peaks; the first peak (P1) is devoid of toxic activity but increases the bradykinin-induced contraction of isolated rat uterus and guinea-pig ileum. The stepwise fractionation of the pooled P1 peak was performed in a DEAE-cellulose column and the bradykinin potentiating activity was found in the second protein peak. Finger-printing of this material showed that the bradykinin potentiating material migrates to the anode, giving two spots when submitted to chromatography, the activity being found in the spot that presents the greatest Rf. The potentiator is destroyed by heating at 97 degrees C, is not dialysable and is destroyed by incubation with pronase. Some of these properties differentiate it from the BPF's from snake venoms. PMID:976731

  16. EFFECTS OF DESENSITIZATION AND REBOUND TO ADENOSINE ON ACTION POTENTIAL AND CONTRACTILITY IN ATRIAL CELLS IN GUINEA-PIGS

    张凤杰; 臧伟进; 于晓江; 胡浩; 张春虹; 孙强; 吕军

    2002-01-01

    Objective To investigate the effects of desensitization and rebound to adenosine(Ado) on action potential duration(APD) and contractility in guinea-pig atrial cells. Methods Electrical activity was recorded using standard intracellular microelectrode technique and contractility was recorded using. We studied the effects of adenosine on the action potential and desensitization of contractility and rebound of contractility. Results The results showed that action potential duration were shortened by 1,10,100μmol*L-1Ado, the ratio of shortened APD was (9.58±1.40)%,(13.80±2.26)%,(24.80±3.19)%, respectively. 1μmol*L-1Ado had no desensitization (P>0.05), but the time of desensitization of 10μmol*L-1 Ado and 100μmol*L-1 Ado was 1 minute(P<0.05) and 5 minutes(P<0.05), respectively. The desensitization of contractility of 10*!μmol*L-1 Ado was obvious in atrial cells, the decrease of contractility of 10*!μmol*L-1 Ado was obvious in atrial cells, the decrease of contractility was changed from (31.4±16.04)%(2 minutes) to (50.60±15.87)% (4 minutes), compared with control. After washing out Ado, contractility was shown to rebound, the ratio of increase of contractility by 1,10,100μmol*L-1 Ado was (12.38±7.50)%,(19.00±8.14)% and (27.60±13.44)%, respectively. Conclusion Ado can abbreviate APD in atrial cells. The desensitization of Ado on APD is characterized by concentration-dependent and time-dependent in atrial cells, and the desensitization of contractility of Ado is obvious and contractility was shown to rebound after washing out Ado.

  17. Action potential generation in the small intestine of W mutant mice that lack interstitial cells of Cajal

    Malysz, J; Thuneberg, L; Mikkelsen, Hanne Birte; Huizinga, J D

    , K+ channel blockade evoked the typical spikelike action potentials. Electron microscopy identified few methylene blue-positive cells in the W/Wv small intestine associated with Auerbach's plexus as individual ICC. Numbers of resident macrophage-like cells (MLC) and fibroblast-like cells (FLC) were...... significantly changed. Neither FLC nor MLC were part of a network nor did they form specialized junctions with neighboring cells as ICC do. Hence no cell type had replaced ICC at their normal morphological position associated with Auerbach's plexus. ICC were present in W/Wv mice at the deep muscular plexus in...

  18. Potential need for re-definition of the highest priority recovery action in the Krsko SAG-1

    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)

  19. Motor unit action potential topography and its use in motor unit number estimation.

    Blok, J.H.; Dijk, J.P. van; Zwarts, M.J.; Stegeman, D.F.

    2005-01-01

    High-density multichannel electromyography (EMG) recordings add spatial information to the temporal information content of the surface EMG (sEMG) signal. This study explores the potential value of such multichannel information at a single motor unit level, in particular for the improvement of motor

  20. Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish.

    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. PMID:25619798

  1. Immunomodulatory effects of fluoxetine: A new potential pharmacological action for a classic antidepressant drug?

    Di Rosso, María Emilia; Palumbo, María Laura; Genaro, Ana María

    2016-07-01

    Selective serotonin reuptake inhibitors are frequently used antidepressants. In particular, fluoxetine is usually chosen for the treatment of the symptoms of depression, obsessive-compulsive, panic attack and bulimia nervosa. Antidepressant therapy has been associated with immune dysfunction. However, there is contradictory evidence about the effect of fluoxetine on the immune system. Experimental findings indicate that lymphocytes express the serotonin transporter. Moreover it has been shown that fluoxetine is able to modulate the immune function through a serotonin-dependent pathway and through a novel independent mechanism. In addition, several studies have shown that fluoxetine can alter tumor cell viability. Thus, it was recently demonstrated in vivo that chronic fluoxetine treatment inhibits tumor growth by increasing antitumor T-cell activity. Here we briefly review some of the literature referring to how fluoxetine is able to modify, for better or worse, the functionality of the immune system. These results of our analysis point to the relevance of the novel pharmacological action of this drug as an immunomodulator helping to treat several pathologies in which immune deficiency and/or deregulation is present. PMID:26644208

  2. Bursting Regimes in a Reaction-Diffusion System with Action Potential-Dependent Equilibrium

    Meier, Stephen R.; Lancaster, Jarrett L.; Starobin, Joseph M.

    2015-01-01

    The equilibrium Nernst potential plays a critical role in neural cell dynamics. A common approximation used in studying electrical dynamics of excitable cells is that the ionic concentrations inside and outside the cell membranes act as charge reservoirs and remain effectively constant during excitation events. Research into brain electrical activity suggests that relaxing this assumption may provide a better understanding of normal and pathophysiological functioning of the brain. In this pap...

  3. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders

    Chiu, Chi-Tso; Chuang, De-Maw

    2010-01-01

    Lithium has been used clinically to treat bipolar disorder for over half a century, and remains a fundamental pharmacological therapy for patients with this illness. Although lithium’s therapeutic mechanisms are not fully understood, substantial in vitro and in vivo evidence suggests that it has neuroprotective/neurotrophic properties against various insults, and considerable clinical potential for the treatment of several neurodegenerative conditions. Evidence from pharmacological and gene m...

  4. HDL-replacement therapy: mechanism of action, types of agents and potential clinical indications

    Remaley, Alan T.; Amar, Marcelo; Sviridov, Dmitri

    2008-01-01

    HDL-replacement therapy is a promising new treatment strategy involving the acute administration of HDL to rapidly stabilize patients at imminent risk for developing a myocardial infarction, such as those with acute coronary syndrome. This review will first focus on the anti-atherogenic mechanisms for HDL, such as the stimulation of the reverse cholesterol transport pathway, and then discuss the other potential beneficial biological effects of HDL on atherosclerosis. The various types of HDL-...

  5. Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

    YangLI; QiaoXUE; JieMA; Cun-taiZHANG; PingQIU; LinWANG; WeiGAO; ReiCHENG; Zai-yinLU; Shi-wenWANG

    2004-01-01

    AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks. Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique. RESULTS: The action potential duration of repolarization 90 % (APD90) was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of/Ca-L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measured. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

  6. Effects of imidapril on heterogeneity of action potential and calcium current of ventriclar myocytes in infarcted rabbits

    Yang LI; Shi-wen WANG; Qiao XUE; Jie MA; Cun-tai ZHANG; Ping QIU; Lin WANG; Wei GAO; Rei CHENG; Zai-ying LU

    2004-01-01

    AIM: To investigate the effects of chronic treatment with imidapril on the electrophysiologic heterogeneous change of the noninfarcted myocardium of rabbits after myocardial infarction and the mechanism of its antiarrhythmic efficacy. METHODS: Rabbits with left coronary artery ligation were prepared and allowed to recover for 8 weeks.Myocytes were isolated from subendocardial, midmyocardial, and subepicardial regions of the noninfarcted left ventricular wall. Action potentials and calcium current were recorded using whole-cell patch clamp technique.RESULTS: The action potential duration of repolarization 90 % (APD90)was more prolonged in midmyocardium rather than in subepicardium and subendocardium with healed myocardial infarction. The transmural dispersion of repolarization (TDR) was increased in the three ventricular regions. The amplitude of ICa-L was enhanced but its density was decreased in noninfarcted ventricular myocytes due to increased cell membrane capacitance. The increased differences of calcium currents among subepicardium, midmyocardium, and subendocardium were also discovered. Normalization of heterogeneous changes in repolarization after treatment with imidapril was observed and decrease of TDR in noninfarcted area was measvred. Early after depolarization (EAD) events of noninfarcted midmyocardium were markedly decreased by imidapril. CONCLUSION: Imidapril reduced the electrophysiologic heterogeneities in noninfarcted area in rabbits after myocardial infarction. This ability of imidapril may contribute to its antiarrhythmic efficacy.

  7. The characteristics of action potential and nonselec-tive cation current of cardiomyocytes in rabbit superior vena cava

    2008-01-01

    As a special focus in initiating and maintaining atrial fibrillation (AF), cardiomyocytes in superior vena cava (SVC) have distinctive electrophysiological characters. In this study, we found that comparing with the right atrial (RA) cardiomyoctyes, the SVC cardiomyoctyes had longer APD90 at the different basic cycle lengths; the conduction block could be observed on both RA and SVC cardiomyoctyes. A few of SVC cardiomyoctyes showed slow response action potentials with automatic activity and some others showed early afterdepolarization (EAD) spontaneously. Further more, we found that there are nonselective cation current (INs) in both SVC and RA cardiomyocytes. The peak density of INs in SVC cardiomyocytes was smaller than that in RA cardiomyocytes. Removal of extracellular divalent cation and glucose could increase INs in SVC cardiomyocytes. The agonist or the antagonist of INs may in-crease or decrease APD. To sum up, some SVC cardiomyocytes possess the ability of spontaneous activity; the difference of transmembrane action potentials between SVC and RA cardiomyocytes is partly because of the different density of INs between them; the agonist or the antagonist of INs can in-crease or decrease APD leading to the enhancement or reduction of EAD genesis in SVC cardiomyo-cytes. INs in rabbit myocytes is fairly similar to TRPC3 current in electrophysiological property, which might play an important role in the mechanisms of AF.

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

    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.

  9. Effects of rapid and slow potassium repolarization currents and calcium dynamics on hysteresis in restitution of action potential duration.

    Wu, Runze; Patwardhan, Abhijit

    2007-04-01

    We used a mathematical model to investigate effects of repolarizing currents I(kr) and I(ks), calcium (Ca) current I(CaL), and Ca dynamics in network sarcoplasmic reticulum and junctional sarcoplasmic reticulum (JSR) on hysteresis in restitution of action potential duration. Enhanced I(kr) increased slope of restitution, hysteresis loop thickness, and delay between peaks of diastolic intervals and action potential duration. Increase in I(ks) decreased loop thickness and peak delay. Decrease in I(CaL) had effects similar to increasing I(kr), except slope of restitution decreased markedly. Uptake of Ca into the network sarcoplasmic reticulum had less effect on hysteresis than transfer of Ca into JSR. Faster transfer of Ca into JSR markedly decreased loop thickness and peak delay. Our results provide insight into mechanisms responsible for this newly identified property of restitution. Such information will be valuable in studies where modification of hysteresis is used to investigate its role in arrhythmogenesis. PMID:16895773

  10. Whey protein potentiates the intestinotrophic action of glucagon-like peptide-2 in parenterally fed rats

    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 and...... 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 < 0.05. The ability of whey protein to induce greater mucosal surface area was...

  11. Adjuvant potential of resiquimod with inactivated Newcastle disease vaccine and its mechanism of action in chicken.

    Sachan, Swati; Ramakrishnan, Saravanan; Annamalai, Arunsaravanakumar; Sharma, Bal Krishan; Malik, Hina; Saravanan, B C; Jain, Lata; Saxena, Meeta; Kumar, Ajay; Krishnaswamy, Narayanan

    2015-08-26

    Resiquimod (R-848), an imidazoquinoline compound, is a potent synthetic Toll-like receptor (TLR) 7 agonist. Although the solitary adjuvant potential of R-848 is well established in mammals, such reports are not available in avian species hitherto. Hence, the adjuvant potential of R-848 was tested in SPF chicken in this study. Two week old chicks were divided into four groups (10 birds/group) viz., control (A), inactivated Newcastle disease virus (NDV) vaccine prepared from velogenic strain (B), commercial oil adjuvanted inactivated NDV vaccine prepared from lentogenic strain (C) and inactivated NDV vaccine prepared from velogenic strain with R-848 (D). Booster was given two weeks post primary vaccination. Humoral immune response was assessed by haemagglutination inhibition (HI) test and ELISA while the cellular immune response was quantified by lymphocyte transformation test (LTT) and flow cytometry post-vaccination. Entire experiment was repeated twice to check the reproducibility. Highest HI titre was observed in group D at post booster weeks 1 and 2 that corresponds to mean log2 HI titre of 6.4 ± 0.16 and 6.8 ± 0.13, respectively. The response was significantly higher than that of group B or C (Pstimulation index (P ≤ 0.01) as well as CD4(+) and CD8(+) cells in flow cytometry (P<0.05) were significantly high and maximum in group D. Group D conferred complete protection against virulent NDV challenge, while it was only 80% in group B and C. To understand the effects of R-848, the kinetics of immune response genes in spleen were analyzed using quantitative real-time PCR after R-848 administration (50 μg/bird, i.m. route). Resiquimod significantly up-regulated the expression of IFN-α, IFN-β, IFN-γ, IL-1β, IL-4, iNOS and MHC-II genes (P<0.01). In conclusion, the study demonstrated the adjuvant potential of R-848 when co-administered with inactivated NDV vaccine in SPF chicken which is likely due to the up-regulation of immune response genes. PMID:26192354

  12. Potential food applications of biobased materials. An EU- concerted action project

    Haugaard, V.K.; Udsen, A.M.; Mortensen, G.;

    2001-01-01

    films 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......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...

  13. Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers.

    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. PMID:25365774

  14. Potassium conductances mediate bidirectional state-dependent modulation of action potential evoked dendritic calcium signals in dentate gyrus granule cells

    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

  15. Methanol extract of Tephrosia vogelii leaves potentiates the contractile action of acetylcholine on isolated rabbit jejunum

    Tavershima Dzenda; Joseph Olusegun Ayo; Alexander Babatunde Adelaiye; Ambrose Osemattah Adaudi

    2015-01-01

    To investigate the modulating role of methanol extract of Tephrosia vogelii leaves on acetylcholine (ACh)-induced contraction of isolated rabbit jejunum. Methods: Rabbit jejunum segment was removed and placed in an organ bath containing Tyrode’s solution, and its contractions were recorded isometrically. Results: ACh (2.0 × 10-10 g/mL) and the extract (2.0 × 10-4 g/mL) individually increased the frequency of contraction (mean ± SEM) of the isolated smooth muscle tissue by 47.6% ± 9.5%and 77.8% ± 66.5%, respectively. When ACh and the extract were combined, the frequency of contraction of the tissue was increased by 222.2% ± 25.9%, representing a 366.7% increase (P < 0.001) over the effect of ACh alone. Similarly, ACh (2.0 × 10-9 g/mL) and the extract individually increased significantly (P < 0.001) the amplitude of contraction of the tissue by 685.7% ± 61.1% and 455.2% ± 38.1%, respectively. When ACh and the extract were combined, the amplitude of contraction of the tissue rose by 1263.8% ± 69.0%, representing 84.3% increase over the effect of ACh alone. Conclusions: The findings demonstrate that methanol extract of Tephrosia vogelii leaves potentiates the contractile effect of ACh on intestinal smooth muscle, supporting the traditional claim that the plant is purgative.

  16. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action.

    Jeong, Rae-Dong; Chu, Eun-Hee; Park, Duck Hwan; Park, Hae-Jun

    2016-04-01

    Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika. PMID:27147935

  17. Anthocyanins in obesity-associated thrombogenesis: a review of the potential mechanism of action.

    Thompson, Kiara; Pederick, Wayne; Santhakumar, Abishek Bommannan

    2016-05-18

    Platelet dysfunction, oxidative stress and dyslipidemia are important contributors to pro-thrombotic progression particularly in obese and hyper-cholesterolemic populations. Becoming an increasingly widespread endemic, obesity causes a dysfunction in the metabolic system by initiating endothelial dysfunction; increasing free radical production; lipid peroxidation; platelet hyperactivity and aggregation; thereby accelerating thrombogenesis. In the event of increased free radical generation under pro-thrombotic conditions, antioxidants act as scavengers in reducing physiological oxidative stress; free radical-mediated thrombosis and hemostatic function. Anthocyanin, a subclass of the polyphenol family flavonoids has been shown to exhibit anti-dyslipidemic and anti-thrombotic properties by virtue of its antioxidant activity. Current anti-platelet/coagulant therapeutics target specific receptor pathways to relieve the extent of dysfunction and plaque acceleration in pro-thrombotic individuals. Though effective, they have been associated with high bleeding risk and increased response variability. The following review focuses on the potential role of natural dietary anthocyanins in targeting simultaneous mechanistic pathways in alleviating platelet activation, dyslipidemia, and oxidative stress-associated thrombus acceleration in obese pro-thrombotic populations. PMID:27043127

  18. Control of Postharvest Bacterial Soft Rot by Gamma Irradiation and its Potential Modes of Action

    Jeong, Rae-Dong; Chu, Eun-Hee; Park, Duck Hwan; Park, Hae-Jun

    2016-01-01

    Gamma irradiation was evaluated for its in vitro and in vivo antibacterial activity against a postharvest bacterial pathogen, Erwinia carotovora subsp. carotovora (Ecc). Gamma irradiation in a bacteria cell suspension resulted in a dramatic reduction of the viable counts as well as an increase in the amounts of DNA and protein released from the cells. Gamma irradiation showed complete inactivation of Ecc, especially at a dose of 0.6 kGy. In addition, scanning electron microscopy of irradiated cells revealed severe damage on the surface of most bacterial cells. Along with the morphological changes of cells by gamma irradiation, it also affected the membrane integrity in a dose-dependent manner. The mechanisms by which the gamma irradiation decreased the bacterial soft rot can be directly associated with the disruption of the cell membrane of the bacterial pathogen, along with DNA fragmentation, results in dose-dependent cell inactivation. These findings suggest that gamma irradiation has potential as an antibacterial approach to reduce the severity of the soft rot of paprika. PMID:27147935

  19. Exploring potential mechanisms of action of natalizumab in secondary progressive multiple sclerosis.

    Sellebjerg, Finn; Cadavid, Diego; Steiner, Deborah; Villar, Luisa Maria; Reynolds, Richard; Mikol, Daniel

    2016-01-01

    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 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, 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, including persistent microglial activation that may lead to chronic demyelination and neurodegeneration associated with irreversible disability. In patients with relapsing forms of MS, natalizumab therapy is known to significantly reduce intrathecal inflammatory responses which results in reductions in brain lesions and brain atrophy as well as beneficial effects on clinical measures, such as reduced frequency and severity of relapse and reduced accumulation of disability. Natalizumab treatment also reduces levels of cerebrospinal fluid chemokines and other biomarkers of intrathecal inflammation, axonal damage and demyelination, and has demonstrated the ability to reduce innate immune activation and intrathecal immunoglobulin synthesis in patients with MS. The efficacy of natalizumab therapy in SPMS is currently being investigated in a randomized, double-blind, placebo-controlled trial. PMID:26788129

  20. Microelectrode array recordings of cardiac action potentials as a high throughput method to evaluate pesticide toxicity.

    Natarajan, A; Molnar, P; Sieverdes, K; Jamshidi, A; Hickman, J J

    2006-04-01

    The threat of environmental pollution, biological warfare agent dissemination and new diseases in recent decades has increased research into cell-based biosensors. The creation of this class of sensors could specifically aid the detection of toxic chemicals and their effects in the environment, such as pyrethroid pesticides. Pyrethroids are synthetic pesticides that have been used increasingly over the last decade to replace other pesticides like DDT. In this study we used a high-throughput method to detect pyrethroids by using multielectrode extracellular recordings from cardiac cells. The data from this cell-electrode hybrid system was compared to published results obtained with patch-clamp electrophysiology and also used as an alternative method to further understand pyrethroid effects. Our biosensor consisted of a confluent monolayer of cardiac myocytes cultured on microelectrode arrays (MEA) composed of 60 substrate-integrated electrodes. Spontaneous activity of these beating cells produced extracellular field potentials in the range of 100 microV to nearly 1200 microV with a beating frequency of 0.5-4 Hz. All of the tested pyrethroids; alpha-Cypermethrin, Tetramethrin and Tefluthrin, produced similar changes in the electrophysiological properties of the cardiac myocytes, namely reduced beating frequency and amplitude. The sensitivity of our toxin detection method was comparable to earlier patch-clamp studies, which indicates that, in specific applications, high-throughput extracellular methods can replace single-cell studies. Moreover, the similar effect of all three pyrethroids on the measured parameters suggests, that not only detection of the toxins but, their classification might also be possible with this method. Overall our results support the idea that whole cell biosensors might be viable alternatives when compared to current toxin detection methods. PMID:16198528

  1. Potential Causes of Significant Inventory Differences at Bulk Handling Facilities and the Importance of Inventory Difference Action Levels

    Accountancy for nuclear material can be split into two categories. Firstly, where possible, accountancy should be in terms of items that can be transferred as discrete packages and their contents fixed at the time of their creation. All items must remain accounted for at all times, and a single missing item is considered significant. Secondly, where nuclear material is unconstrained, for example in a reprocessing plant where it can change form, there is an uncertainty that relates to the amount of material present in any location. Cumulatively, these uncertainties can be summed and provide a context for any estimate of material in a process. Any apparent loss or gain between what has been physically measured within a facility during its physical inventory take and what is reported within its nuclear material accounts is known as an inventory difference. The cumulative measurement uncertainties can be used to set an action level for the inventory difference so that if an inventory difference is observed outside of such action levels, the difference is classified as significant and an investigation to find the root cause(s) is required. The purpose of this paper is to explore the potential causes of significant inventory differences and to provide a framework within which an inventory difference investigation can be carried out.

  2. Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

    Galati Gaspare

    2009-07-01

    Full Text Available Abstract Background Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of Vitis vinifera. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA. Methods The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols. Results Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6 as well as a tumor-line (HL60. Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA. Conclusion Resveratrol is

  3. Effect of mental challenge induced by movie clips on action potential duration in normal human subjects independent of heart rate

    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

    2014-01-01

    Background 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. Methods and Results Activation recovery intervals (ARI) measured from unipolar electrograms as a surrogate for APD (n=19) were recorded from right and left ventricular endocardium during steady state pacing while 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. Haemodynamic 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, eg for global RV ARI at end of film clip 193.8ms (SD 14) vs 198.0ms (SD13) during the matched breathing control (end film LV 199.8ms (SD16) vs control 201.6ms (SD15), p=0.004. Respiration rate increased during the stressful part of the film clip (by 2 breaths/minute), and was well matched in the respective control period without any haemodynamic or ARI changes. Conclusions Our results document for the first time direct recordings of the effect of a mental challenge protocol on ventricular action potential duration in conscious humans. The effect of mental challenge on APD was not secondary to emotionally-induced altered respiration or heart rate. PMID:24833641

  4. The effects of propofol on local field potential spectra, action potential firing rate, and their temporal relationship in humans and felines

    Sara Hanrahan

    2013-04-01

    Full Text Available Propofol is an intravenous sedative hypnotic, which, acting as a GABAA agonist, results in neocortical inhibition. While propofol has been well studied at the molecular and clinical level, less is known about the effects of propofol at the level of individual neurons and local neocortical networks. We used Utah Electrode Arrays (UEAs to investigate the effects of propofol anesthesia on action potentials (APs and local field potentials (LFPs. UEAs were implanted into the neocortex of two humans and three felines. The two human patients and one feline received propofol by bolus injection, while the other two felines received target-controlled infusions. We examined the changes in LFP power spectra and AP firing at different levels of anesthesia. Increased propofol concentration correlated with decreased high-frequency power in LFP spectra and decreased AP firing rates, and the generation of large amplitude spike-like LFP activity; however, the temporal relationship between APs and LFPs remained relatively consistent at all levels of propofol. The probability that an AP would fire at this local minimum of the LFP increased with propofol administration. The propofol-induced suppression of neocortical network activity allowed LFPs to be dominated by low-frequency spike-like activity, and correlated with sedation and unconsciousness. As the low-frequency spike-like activity increased and the AP-LFP relationship became more predictable firing rate encoding capacity is impaired. This suggests a mechanism for decreased information processing in the neocortex that accounts for propofol-induced unconsciousness.

  5. Effect of microbial action on the corrosion potential of austenitic alloy containers for high-level nuclear waste

    The safe disposal of high-level nuclear waste (HLW) entails the ability to ensure the integrity of waste containers for prolonged time periods. It is generally accepted that under certain conditions, microbial action may change local benign environments to those in which localized corrosion can be actively promoted. The use of repassivation potential (Erp) in relation to the value of the corrosion potential (Ecorr) has been proposed as a means of assessing the propensity of a metallic material to localized corrosion. Microbial activity is known to influence Ecorr however, the precise mechanism is unresolved. Shewanella putrefaciens, a bacteria with many of the characteristics of sulfate-reducing bacteria (SRB), are being grown under controlled conditions on 316L stainless steel (SS) surfaces to understand the relationship between Ecorr and metabolic activity. It has been observed that the growth of the bacteria under aerobic conditions, without the production of metabolic sulfide, leads to only minor variation in Ecorr. These changes possibly correlate to the periods of active bacterial growth

  6. Effect of microbial action on the corrosion potential of austenitic alloy containers for high-level nuclear waste

    Angell, P.; Dunn, D.S.; Cragnolino, G.A. [Southwest Research Inst., San Antonio, TX (United States). Center for Nuclear Waste Regulatory Analyses

    1996-08-01

    The safe disposal of high-level nuclear waste (HLW) entails the ability to ensure the integrity of waste containers for prolonged time periods. It is generally accepted that under certain conditions, microbial action may change local benign environments to those in which localized corrosion can be actively promoted. The use of repassivation potential (E{sub rp}) in relation to the value of the corrosion potential (E{sub corr}) has been proposed as a means of assessing the propensity of a metallic material to localized corrosion. Microbial activity is known to influence E{sub corr} however, the precise mechanism is unresolved. Shewanella putrefaciens, a bacteria with many of the characteristics of sulfate-reducing bacteria (SRB), are being grown under controlled conditions on 316L stainless steel (SS) surfaces to understand the relationship between E{sub corr} and metabolic activity. It has been observed that the growth of the bacteria under aerobic conditions, without the production of metabolic sulfide, leads to only minor variation in E{sub corr}. These changes possibly correlate to the periods of active bacterial growth.

  7. Sources of actual and potential radioactive contamination at the Dnieper River basin with regard to preparation of strategic action plan

    Full text: The Dnieper River basin is one of the largest drainage areas in Europe. The modern Dnieper is a cascade of large artificial reservoirs (Kiev, Kanev, Kremenchug, Dniprodzerzhinsk, Zaporozhie, Kakhovske) carrying its water to the Black Sea. It is largest water artery of Ukraine where more then 20 million of peoples live, and which water extensively use for water supply, fishery, irrigation and recreation in the region. At the same time the Dnieper basin is the most important industrial, agricultural congested area. About 20 units of Nuclear Reactors are in operation of 6 NPP situated on the territory of Ukraine (4) and Russia (2) as well. This area was also heavy contaminated mainly with long-lived radionuclides such as Cs 137 and Sr 90 and Pu due to Chernobyl releases in 1986. In the central part of Ukraine Uranium mining and uranium ores re-processing industry are developed. At the moment most of these facilities are suspended their activity because economical reason. However the problem of uranium tailing of liquid and solid wastes are remain to be one of the serious sources for the Environmental contamination and uncertainties with its impact to the human health in the region (Zheltie Vodi town and Dnieprodzerzhinsk). The Radiation Risk Assessment of the environmental impacts of these sources ('Hot spots') in the basin and Priorities for potential actions to reduce the ecological Risks of its impacts are considering. The Results of this study are the basis for Strategic Action Plan recommended for three countries (Ukraine, Russia and Belarus) at the Dnieper River Basin obtained using Optimization Procedures and experience of Radiation Protection Practice

  8. Effectiveness of elite female basketball players’ technical-tactic actions and ways for their improvement at stage of maximal realization of individual potentials

    Sushko R.A.

    2015-08-01

    Full Text Available Purpose: study effectiveness of elite female basketball players’ technical-tactic actions and determine the ways for their improvement at stage of maximal realization of individual potentials. Material: the authors analyzed competition functioning’s indicators of female basketball players of national combined team of Ukraine and their age characteristics. Results: effectiveness of technical-tactic actions in structure of national female basketball players’ combined team of Ukraine competition functioning at European championship. The authors present: indicators of team composition; roles in team; won and lost games; quantity of scored and skipped points; technical-tactic actions; age of sportswomen. Age indicators of elite female basketball players at stage of maximal realization have been given. Conclusions: we have composed a list of the most important technical-tactic actions in competition functioning. We also outlined ways for their perfection at stage of maximal realization of individual potentials of elite female basketball players of different game roles.

  9. Assessing the Electrode-Neuron Interface with the Electrically Evoked Compound Action Potential, Electrode Position, and Behavioral Thresholds.

    DeVries, Lindsay; Scheperle, Rachel; Bierer, Julie Arenberg

    2016-06-01

    Variability in speech perception scores among cochlear implant listeners may largely reflect the variable efficacy of implant electrodes to convey stimulus information to the auditory nerve. In the present study, three metrics were applied to assess the quality of the electrode-neuron interface of individual cochlear implant channels: the electrically evoked compound action potential (ECAP), the estimation of electrode position using computerized tomography (CT), and behavioral thresholds using focused stimulation. The primary motivation of this approach is to evaluate the ECAP as a site-specific measure of the electrode-neuron interface in the context of two peripheral factors that likely contribute to degraded perception: large electrode-to-modiolus distance and reduced neural density. Ten unilaterally implanted adults with Advanced Bionics HiRes90k devices participated. ECAPs were elicited with monopolar stimulation within a forward-masking paradigm to construct channel interaction functions (CIF), behavioral thresholds were obtained with quadrupolar (sQP) stimulation, and data from imaging provided estimates of electrode-to-modiolus distance and scalar location (scala tympani (ST), intermediate, or scala vestibuli (SV)) for each electrode. The width of the ECAP CIF was positively correlated with electrode-to-modiolus distance; both of these measures were also influenced by scalar position. The ECAP peak amplitude was negatively correlated with behavioral thresholds. Moreover, subjects with low behavioral thresholds and large ECAP amplitudes, averaged across electrodes, tended to have higher speech perception scores. These results suggest a potential clinical role for the ECAP in the objective assessment of individual cochlear implant channels, with the potential to improve speech perception outcomes. PMID:26926152

  10. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 (125I-Crotoxin) and iodine-131 (131I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL50 in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. 125I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented Kd=24.98 nmol/L and Bmax=16,570 sites/cell for low affinity binding sites and Kd=0.06 nmol/L and Bmax=210 sites/cell high affinity binding sites; moreover, the

  11. Effects of Ginkgolide B on action potential and calcium,potassium current in guinea pig ventricular myocytes

    Xiao-yan QI; Zhi-xiong ZHANG; You-qiu XU

    2004-01-01

    AIM: To investigate the effect of Ginkgolide B (GB) on action potential (AP), delayed rectifier potassium current (IK), and L-type calcium current (ICa-L) in guinea pig ventricular myocytes. METHODS: Single ventricular myocytes were isolated by an enzymatic dissociation method. AP, IK, ICa-L were recorded by whole-cell patch-clamp technique in either current or voltage clamp mode. RESULTS: GB shortened APD in a concentration-dependent manner. GB 0.1, 1, and 10 μmol/L shortened APD50 by 7.9 % (n=5, P>0.05), 18.4 % (n=5, P<0.01), and 28.9 % (n=6, P<0.01), respectively; APD90 by 12.4 % (n=5, P>0.05), 17.6 % (n=5, P<0.01), 26.4 % (n=5, P<0.01),respectively. GB increased IK in a concentration-dependent manner. GB 0.1, 1, and l0 μmol/L increased IK by 20.1% (n=6, P<0.05), 43.1% (n=6, P<0.01), 55.6 % (n=6, P<0.05); increased IKtail by 10.7 % (n=6, P<0.05),25.1% (n=6, P<0.05), and 37.7 % (n=6, P<0.05), respectively at testing potential of +50 mV and shift the I-V curve of Ik upward. But GB had no significant effect on ICa-L at above concentrations. CONCLUSION: GB significantly shortened APD in a concentration-dependent manner which mainly due to increase of IK.

  12. Percutaneous method for single-catheter multiple monophasic action potential recordings during magnetocardiographic mapping in spontaneously breathing rodents

    To test the feasibility of a novel method to combine magnetocardiographic (MCG) estimate of ventricular repolarization (VR) and multiple monophasic action potential (MultiMAP) recording in spontaneously breathing rodents with percutaneous sub-xyphoid epicardial placement of a MCG-compatible amagnetic catheter (AC), ten Wistar rats (WRs) and ten guinea pigs (GPs) were studied. Under fluoroscopic control, the AC was moved until four stable MAPs were recorded (fixed inter-electrode distance of 1.2 mm). 36-channel DC-SQUID (sensitivity 20 fT Hz–½) were used for MCG mapping. MAPs, differentially amplified (BW: DC-500 Hz), were digitized at 1 kHz. AC pacing provided local ventricular effective refractory period (VERP) estimate. MAP duration (MAPd) was measured at 50% and 90% levels of repolarization. Simultaneous MCG mapping and MultiMAP recording were successful in all animals. Average MAPd50% and MAPd90% were shorter in WRs than in GPs (26.4 ± 2.9 ms versus 110.6 ± 14.3 ms and 60.7 ± 5.4 ms versus 127.7 ± 15.3 ms, respectively). VERP was 51 ± 4.8 ms in WRs and 108.4 ± 12.9 ms in GPs, respectively. The MAP amplitude was 16.9 ± 4.5 in WRs and 16.2 ± 4.2 in GPs. MAP and MCG parameters of VR were in good agreement. All animals survived the procedure. Two also survived a second invasive study; one was followed up until natural death at 52 months. Percutaneous MultiMAP recording is minimally invasive, usually avoids animal sacrifice, is compatible with simultaneous surface MCG mapping and might be used for experimental validation of MCG VR abnormality, to study the arrhythmogenic potential of new drugs and/or animal models of ventricular arrhythmias. (paper)

  13. Copper(II)-Bis(Thiosemicarbazonato) Complexes as Antibacterial Agents: Insights into Their Mode of Action and Potential as Therapeutics.

    Djoko, Karrera Y; Goytia, Maira M; Donnelly, Paul S; Schembri, Mark A; Shafer, William M; McEwan, Alastair G

    2015-10-01

    There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria gonorrhoeae showed that Cu(btsc) complexes may act as inhibitors of respiratory dehydrogenases in the electron transport chain. We now show that these complexes are also toxic against pathogens that lack a respiratory chain. Respiration in Escherichia coli was slightly affected by Cu(btsc) complexes, but our results indicate that, in this model bacterium, the complexes act primarily as agents that deliver toxic Cu ions efficiently into the cytoplasm. Although the chemistry of Cu(btsc) complexes may dictate their mechanism of action, their efficacy depends heavily on bacterial physiology. This is linked to the ability of the target bacterium to tolerate Cu and, additionally, the susceptibility of the respiratory chain to direct inhibition by Cu(btsc) complexes. The physiology of N. gonorrhoeae, including multidrug-resistant strains, makes it highly susceptible to damage by Cu ions and Cu(btsc) complexes, highlighting the potential of Cu(btsc) complexes (and Cu-based therapeutics) as a promising treatment against this important bacterial pathogen. PMID:26239980

  14. Liénard-type models for the simulation of the action potential of cardiac nodal cells

    Podziemski, P.; Żebrowski, J. J.

    2013-10-01

    Existing models of cardiac cells which include multi-variable cardiac transmembrane current are too complex to simulate the long time dynamical properties of the heart rhythm. The large number of parameters that need to be defined and set for such models make them not only cumbersome to use but also require a large computing power. Consequently, the application of such models for the bedside analysis of heart rate of a specific patient may be difficult. Other ways of modelling need to be investigated. We consider the general problem of developing a model of cardiac pacemaker tissue that allows to combine the investigation of phenomena at a time scale of thousands of heart beats with the ability to reproduce realistic tissue-level characteristics of cell dynamics. We propose a modified van der Pol-Duffing equation-a Liénard-type oscillator-as a phenomenological model for cardiac nodal tissue, with certain important physiological similarities to ion-channel models of cardiac pacemaker cells. The model presented here is specifically designed to qualitatively reproduce mesoscopic characteristics of cell dynamics, including action potential duration (APD) restitution properties, phase response characteristics, and phase space structure. We show that these characteristics agree qualitatively with the extensive ionic models and experimental results in the literature [Anumonwo et al., 1991, [33], Cao et al., 1999, [49], Coster and Celler, 2003, [31], Qu, 2004, [45], Tsalikakis et al., 2007, [32], Inada et al., 2009, [14], Qu et al., 2010, [50

  15. Theoretical study of L-type Ca(2+) current inactivation kinetics during action potential repolarization and early afterdepolarizations.

    Morotti, Stefano; Grandi, Eleonora; Summa, Aurora; Ginsburg, Kenneth S; Bers, Donald M

    2012-09-15

    Sarcoplasmic reticulum (SR) Ca(2+) release mediates excitation–contraction coupling (ECC) in cardiac myocytes. It is triggered upon membrane depolarization by entry of Ca(2+) via L-type Ca(2+) channels (LTCCs), which undergo both voltage- and Ca(2+)-dependent inactivation (VDI and CDI, respectively). We developed improved models of L-type Ca(2+) current and SR Ca(2+) release within the framework of the Shannon-Bers rabbit ventricular action potential (AP) model. The formulation of SR Ca(2+) release was modified to reproduce high ECC gain at negative membrane voltages. An existing LTCC model was extended to reflect more faithfully contributions of CDI and VDI to total inactivation. Ba(2+) current inactivation included an ion-dependent component (albeit small compared with CDI), in addition to pure VDI. Under physiological conditions (during an AP) LTCC inactivates predominantly via CDI, which is controlled mostly by SR Ca(2+) release during the initial AP phase, but by Ca(2+) through LTCCs for the remaining part. Simulations of decreased CDI or K(+) channel block predicted the occurrence of early and delayed after depolarizations. Our model accurately describes ECC and allows dissection of the relative contributions of different Ca(2+) sources to total CDI, and the relative roles of CDI and VDI, during normal and abnormal repolarization. PMID:22586219

  16. Electrophysiological evaluation of nerve function in inferior alveolar nerve injury: relationship between nerve action potentials and histomorphometric observations.

    Murayama, M; Sasaki, K; Shibahara, T

    2015-12-01

    The objective of this study was to improve the accuracy of diagnosis of inferior alveolar nerve (IAN) injury by determining degrees of nerve disturbance using the sensory nerve action potential (SNAP) and sensory nerve conduction velocity (SCV). Crush and partial and complete nerve amputation injuries were applied to the IAN of rabbits, then SNAPs and histomorphometric observations were recorded at 1, 5, and 10 weeks. For crush injury, most nerves were smaller in diameter at 5 weeks than at 1 week, however after 10 weeks, extensive nerve regeneration was observed. The SNAP showed a decrease in SCV at weeks 1 and 5, followed by an increase at week 10. For partial nerve amputation, small to medium-sized nerve fibres were observed at weeks 1 and 5, then larger nerves were seen at week 10. Minimal changes in SCV were observed at weeks 1 and 5, however SCV increased at week 10. For complete nerve amputation, nerve fibres were sparse at week 1, but gradual nerve regeneration was observed at weeks 5 and 10. SNAPs were detectable from week 10, however the SCV was extremely low. This study showed SCV to be an effective factor in the evaluation of nerve injury and regeneration. PMID:26433750

  17. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    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

  18. An exploratory investigation of various modes of action and potential adverse outcomes of fluoxetine in marine mussels

    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

  19. Heeding a Call to Action for U.S. Coral Reefs: the Untapped Potential of the Clean Water Act

    A recently published call to action by Dodge et al. (2008) identifies nine actions needed to protect coral reefs. The authors identify several management goals that cannot be accomplished with MPAs alone, the traditional approach to coral reef protection. For U.S. waters, the Cle...

  20. Action potential-evoked calcium release is impaired in single skeletal muscle fibers from heart failure patients.

    Marino DiFranco

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  1. Elevated heart rate triggers action potential alternans and sudden death. translational study of a homozygous KCNH2 mutation.

    Ulrich Schweigmann

    Full Text Available BACKGROUND: Long QT syndrome (LQTS leads to arrhythmic events and increased risk for sudden cardiac death (SCD. Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness. METHODS AND RESULTS: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q in the index patient (QTc ∼506 ms with notched T waves. Parents were I° cousins - both heterozygous for the mutation and clinically unremarkable (QTc ∼447 ms, father and ∼396 ms, mother. Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q. CONCLUSION: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.

  2. Evaluation of nystatin containing chitosan hydrogels as potential dual action bio-active restorative materials: in vitro approach.

    Perchyonok, V Tamara; Reher, Vanessa; Zhang, Shengmiao; Basson, Nicki; Grobler, Sias

    2014-01-01

    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. PMID:25459982

  3. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    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.

  4. Problems, Prescriptions and Potential in Actionable Climate Change Science - A Case Study from California Coastal Marsh Research

    MacDonald, G. M.; Ambrose, R. F.; Thorne, K.; Takekawa, J.; Brown, L. N.; Fejtek, S.; Gold, M.; Rosencranz, J.

    2015-12-01

    Frustrations regarding the provision of actionable science extend to both producers and consumers. Scientists decry the lack of application of their research in shaping policy and practices while decision makers bemoan the lack of applicability of scientific research to the specific problems at hand or its narrow focus relative to the plethora of engineering, economic and social considerations that they must also consider. Incorporating climate change adds additional complexity due to uncertainties in estimating many facets of future climate, the inherent variability of climate and the decadal scales over which significant changes will develop. Recently a set of guidelines for successful science-policy interaction was derived from the analysis of transboundary water management. These are; 1 recognizing that science is a crucial but bounded input into the decision-making processes, 2 early establishment of conditions for collaboration and shared commitment among participants, 3 understanding that science-policy interactions are enhanced through greater collaboration and social or group-learning processes, 4 accepting that the collaborative production of knowledge is essential to build legitimate decision-making processes, and 5 engaging boundary organizations and informal networks as well as formal stakeholders. Here we present as a case study research on California coastal marshes, climate change and sea-level that is being conducted by university and USGS scientists under the auspices of the Southwest Climate Science Center. We also present research needs identified by a seperate analysis of best practices for coastal marsh restoration in the face of climate change that was conducted in extensive consultation with planners and managers. The initial communication, scientific research and outreach-dissemination of the marsh scientfic study are outlined and compared to best practices needs identified by planners and the science-policy guidelines outlined above

  5. Biophysical characterization of inwardly rectifying potassium currents (I(K1) I(K,ACh), I(K,Ca)) using sinus rhythm or atrial fibrillation action potential waveforms

    Tang, Chuyi; Skibsbye, Lasse; Yuan, Lei; Bentzen, Bo H; Jespersen, Thomas

    2015-01-01

    voltage protocols adapted from atrial action potentials recorded in human tissue at 1 and 3 Hz. The current recordings were performed in the HEK-293 heterologous cell system expressing either I(K1), I(K,ACh) or I(K,Ca) to establish the individual contribution of each of these currents during the voltage...

  6. Sensitivity of action potential to changes of inward rectifier potassium current IK1 is different in recent models of human ventricular cardiomyocytes

    Pásek, Michal; Šimurda, J.; Christé, G.

    Brno: Brno University of Technology, 2014 - (Fuis, V.), s. 476-479 ISBN 978-80-214-4871-1. ISSN 1805-8248. [Engineering Mechanics 2014. Svratka (CZ), 12.05.2014-15.05.2014] Institutional support: RVO:61388998 Keywords : human ventricular cardiomyocyte * action potential * inward rectifier potassium current * human ventricular cell model Subject RIV: BO - Biophysics

  7. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    Kampa, Marilena; Alexaki, Vassilia-Ismini; Notas, George; Nifli, Artemissia-Phoebe; Nistikaki, Anastassia; Hatzoglou, Anastassia; Bakogeorgou, Efstathia; Kouimtzoglou, Elena; Blekas, George; Boskou, Dimitrios; Gravanis, Achille; Castanas, Elias

    2003-01-01

    Introduction The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. Methods This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatech...

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

    Wing-Chiu Tong

    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

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

    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

  10. A Comparative Study On The Action Potential Simulation (APS Therapy And The Routine Physiotherapy Protocol In Knee Osteoarthritisin Elderly People

    Abbas Rahimi

    2012-04-01

    Full Text Available Background and Aim: Knee osteoarthritis is the most common cause for which the elderly people refere to physiotherapy outpatient clinics. This study aimed to investigate the effects of the Action Potential Stimulation (APS Therapy and the routine physiotherapy (PT protocol on relieving pain and swelling as well as the duration of the relief period in patients with knee osteoarthritis. Materials and Methods: 69 patients (62 females & 7 males with knee osteoarthritis were recruited in this study. The subjects were divided into two groups including APS Therapy (n=37, mean age: 55±13 years old and the routine PT protocol (n=32, mean age: 61±14 years old groups. A 10-session treatment period was carried out for each group; and their pain and swelling were measured at the first, fifth and tenth sessions and also one-month after the last session (follow up. The swelling was measured using measuring the circumference of the knee on the patella, 5 Cm above and 5 Cm below the patella. The routine PT protocol consisted of hot pack, ultrasound, TENS and exercise; and the APS therapy protocol included hot pack, APS Therapy and the same exercise. During the follow up, 50 out of 61 subjects were called on the phone and any pain changes were recorded.Results: In terms of swelling, the results showed significant reduction just on the patella only in the APS Therapy group (P<0.05. Visual Analogue Pain Scale (VAPS indicated a significant pain reduction in both groups. However, the APS Therapy group showed significantly pain reduction at the end of sessions five, ten and the follow up session (P<0.05. It was also revealed that while routine PT subjects showed no significant pain changes between the tenth and the follow up session, a gradual pain reduction was seen in the APS therapy group during this period (P<0.05. A gradual dosage reduction was recorded only in the APS therapy group, indicating a slight correlation with pain reduction (r=0.4.Conclusion: The

  11. Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle

    Treebak, Jonas Thue; Frøsig, Christian; Pehmøller, Christian;

    2009-01-01

    AIMS/HYPOTHESIS: TBC1 domain family, member 4 (TBC1D4; also known as AS160) is a cellular signalling intermediate to glucose transport regulated by insulin-dependent and -independent mechanisms. Skeletal muscle insulin sensitivity is increased after acute exercise by an unknown mechanism that doe...... insulin action after exercise....

  12. Action-potential duration and the modulation of transmitter release from the sensory neurons of Aplysia in presynaptic facilitation and behavioral sensitization

    Hochner, Binyamin; Klein, Marc; Schacher, Samuel; Kandel, Eric R.

    1986-01-01

    Presynaptic facilitation of transmitter release from Aplysia sensory neurons is an important contributor to behavioral sensitization of the gill and siphon withdrawal reflex. The enhanced release is accompanied by reduction of the serotonin-sensitive S current in the sensory neurons and a consequent increase in duration of the presynaptic action potential (ranging from 10% to 30%). We find that changes of similar magnitude in the duration of depolarizing voltage-clamp steps in sensory neurons...

  13. Anti-cancer and potential chemopreventive actions of ginseng by activating Nrf2 (NFE2L2) anti-oxidative stress/anti-inflammatory pathways

    Wu Qing; Saw Constance; Kong Ah-Ng Tony

    2010-01-01

    Abstract This article reviews recent basic and clinical studies of ginseng, particularly the anti-cancer effects and the potential chemopreventive actions by activating the transcriptional factor, nuclear factor (erythroid-derived 2)-like 2 (Nrf2 or NFE2L2)-mediated anti-oxidative stress or anti-inflammatory pathways. Nrf2 is a novel target for cancer prevention as it regulates the antioxidant responsive element (ARE), a critical regulatory element in the promoter region of genes encoding cel...

  14. Early Afterdepolarizations with Growing Amplitudes via Delayed Subcritical Hopf Bifurcations and Unstable Manifolds of Saddle Foci in Cardiac Action Potential Dynamics

    Kügler, Philipp

    2016-01-01

    Early afterdepolarizations (EADs) are pathological oscillations in cardiac action potentials during the repolarization phase and may be caused by drug side effects, ion channel disease or oxidative stress. The most widely observed EAD pattern is characterized by oscillations with growing amplitudes. So far, its occurence has been explained in terms of a supercritical Hopf bifurcation in the fast subsystem of the action potential dynamics from which stable limit cycles with growing amplitudes emerge. The novel contribution of this article is the introduction of two alternative explanations of EAD genesis with growing amplitudes that do not involve stable limit cycles in fast subsystems. In particular, we demonstrate that EAD patterns with growing amplitudes may alternatively arise due to a delayed subcritical Hopf bifurcation or an unstable manifold of a saddle focus fixed point in the full fast-slow system modelling the action potential. Our work extends the list of possible dynamical EAD mechanisms and may contribute to a classification of drug effects in preclinical cardiotoxicity testing. PMID:26977805

  15. Evaluation of Nystatin Containing Chitosan Hydrogels as Potential Dual Action Bio-Active Restorative Materials: in Vitro Approach

    V. Tamara Perchyonok; Vanessa Reher; Shengmiao Zhang; Nicki Basson; Sias Grobler

    2014-01-01

    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 i...

  16. Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action

    The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action

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

    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 o...

  18. Deleting the accessory subunit KChIP2 results in loss of I(to,f) and increased I(K,slow) that maintains normal action potential configuration

    Thomsen, Morten B; Sosunov, Eugene A; Anyukhovsky, Evgeny P; Ozgen, Nazira; Boyden, Penelope A; Rosen, Michael R

    2008-01-01

    potential duration (APD) is maintained in KChIP2 knockout mice. OBJECTIVE: We tested the role of KChIP2 in regulating APD and studied the underlying ionic currents. METHODS: We used microelectrode techniques, whole-cell patch clamp studies, and real-time polymerase chain reaction amplification to...... characterize ventricular repolarization and its determinants in wild-type and KChIP2(-/-) mice. RESULTS: Despite comparable baseline action potentials, APD was more markedly prolonged by 4-aminopyridine (4-AP) in KChIP2(-/-) preparations. Peak K(+) current densities were similar in wild-type and KChIP2...

  19. Differential expression of hERG1 channel isoforms reproduces properties of native I(Kr) and modulates cardiac action potential characteristics

    Larsen, Anders Peter; Olesen, Søren-Peter

    2010-01-01

    The repolarizing cardiac rapid delayed rectifier current, I(Kr), is composed of ERG1 channels. It has been suggested that two isoforms of the ERG1 protein, ERG1a and ERG1b, both contribute to I(Kr). Marked heterogeneity in the kinetic properties of native I(Kr) has been described. We hypothesized...... that the heterogeneity of native I(Kr) can be reproduced by differential expression of ERG1a and ERG1b isoforms. Furthermore, the functional consequences of differential expression of ERG1 isoforms were explored as a potential mechanism underlying native heterogeneity of action potential duration (APD...

  20. Reactor safety and energy policy in Eastern Europe. Hazard potentials and possibilities for action. Lectures and discussions

    The eleven lectures given at the meeting attempt an interim statement on the safety of eastern European nuclear power stations and deal with the Chernobyl reactor accident and its consequences as well as with the energy-political constraints and perspectives for eastern European states that were brought about especially by the collapse of the USSR and the associated infra-structural changes. A further six statements made at the panel discussion describe possibilities of action for the West in order to enhance reactor safety in eastern Europe. (DG)

  1. Dopamine modulates Spike Timing-Dependent Plasticity and action potential properties in CA1 pyramidal neurons of acute rat hippocampal slices

    Elke eEdelmann

    2011-11-01

    Full Text Available Spike Timing-Dependent Plasticity (STDP is a cellular model of hebbian synaptic plasticity which is believed to underlie memory formation. In an attempt to establish a STDP paradigm in CA1 of acute hippocampal slices from juvenile rats (P15-20, we found that changes in excitability resulting from different slice preparation protocols correlate with the success of STDP induction. Slice preparation with sucrose containing ACSF prolonged rise time, reduced frequency adaptation, and decreased latency of action potentials in CA1 pyramidal neurons compared to preparation in conventional ASCF, while other basal electrophysiological parameters remained unaffected. Whereas we observed prominent timing-dependent (t-LTP to 171 ± 10% of controls in conventional ACSF, STDP was absent in sucrose prepared slices. This sucrose-induced STDP deficit could not be rescued by stronger STDP paradigms, applying either more pre- and/or postsynaptic stimuli, or by a higher stimulation frequency. Importantly, slice preparation with sucrose containing ACSF did not eliminate theta-burst stimulation induced LTP in CA1 in field potential recordings in our rat hippocampal slices. Application of dopamine (for 10-20 min to sucrose prepared slices completely rescued t-LTP and recovered action potential properties back to levels observed in ACSF prepared slices. Conversely, acute inhibition of D1 receptor signaling impaired t-LTP in ACSF prepared slices. No similar restoring effect for STDP as seen with dopamine was observed in response to the β-adrenergic agonist isoproterenol. ELISA measurements demonstrated a significant reduction of endogenous dopamine levels (to 61.9 ± 6.9% of ACSF values in sucrose prepared slices. These results lead us to suggest that dopamine dependent regulation of action potential properties correlates with the efficiency to elicit STDP in CA1 pyramidal neurons.

  2. Potentiation of Sulfonylurea Action by an EPAC-selective cAMP Analog in INS-1 Cells: Comparison of Tolbutamide and Gliclazide and a Potential Role for EPAC Activation of a 2-APB-sensitive Ca2+ Influx

    Jarrard, Rachel E.; Wang, Yuchen; Salyer, Amy E.; Pratt, Evan P. S.; Soderling, Ian M.; Guerra, Marcy L.; Lange, Allison M.; Broderick, Hilary J.; Hockerman, Gregory H.

    2013-01-01

    Tolbutamide and gliclazide block the KATP channel Kir6.2/Sur1, causing membrane depolarization and stimulating insulin secretion in pancreatic beta cells. We examined the ability of the EPAC-selective cAMP analog 8-pCPT-2′-O-Me-cAMP-AM to potentiate the action of these drugs and the mechanism that might account for it. Insulin secretion stimulated by both 200 μM tolbutamide and 20 μM gliclazide, concentrations that had equivalent effects on membrane potential, was inhibited by thapsigargin (1...

  3. Remarkable relations for the expectation values of simultaneous action of the kinetic and potential energy operators on Schrodinger wavefunctions

    Joubert, D

    2001-01-01

    For Psi an eigenfunction of the Hamiltonian operator H = T + V, where T is the kinetic energy operator and V the potential energy operator, the following relations between expectation values are satisfied: = , ^2 = , ^2 = .

  4. Long term cardioprotective action of trimetazidine and potential effect on the inflammatory process in patients with ischaemic dilated cardiomyopathy

    Di Napoli, P; Taccardi, A A; Barsotti, A

    2005-01-01

    Objective: To investigate the long term effects of trimetazidine in patients with dilated ischaemic cardiomyopathy. The effects of trimetazidine on left ventricular function as well as its tolerability profile and potential anti-inflammatory effects were studied.

  5. Donnan effect on chloride ion distribution as a determinant of body fluid composition that allows action potentials to spread via fast sodium channels

    Kurbel Sven

    2011-05-01

    Full Text Available Abstract Proteins in any solution with a pH value that differs from their isoelectric point exert both an electric Donnan effect (DE and colloid osmotic pressure. While the former alters the distribution of ions, the latter forces water diffusion. In cells with highly Cl--permeable membranes, the resting potential is more dependent on the cytoplasmic pH value, which alters the Donnan effect of cell proteins, than on the current action of Na/K pumps. Any weak (positive or negative electric disturbances of their resting potential are quickly corrected by chloride shifts. In many excitable cells, the spreading of action potentials is mediated through fast, voltage-gated sodium channels. Tissue cells share similar concentrations of cytoplasmic proteins and almost the same exposure to the interstitial fluid (IF chloride concentration. The consequence is that similar intra- and extra-cellular chloride concentrations make these cells share the same Nernst value for Cl-. Further extrapolation indicates that cells with the same chloride Nernst value and high chloride permeability should have similar resting membrane potentials, more negative than -80 mV. Fast sodium channels require potassium levels >20 times higher inside the cell than around it, while the concentration of Cl- ions needs to be >20 times higher outside the cell. When osmotic forces, electroneutrality and other ions are all taken into account, the overall osmolarity needs to be near 280 to 300 mosm/L to reach the required resting potential in excitable cells. High plasma protein concentrations keep the IF chloride concentration stable, which is important in keeping the resting membrane potential similar in all chloride-permeable cells. Probable consequences of this concept for neuron excitability, erythrocyte membrane permeability and several features of circulation design are briefly discussed.

  6. Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects on Leishmania amazonensis and Possible Mechanisms of Action

    Klinger Antonio da Franca Rodrigues; Layane Valéria Amorim; Jamylla Mirck Guerra de Oliveira; Clarice Noleto Dias; Denise Fernandes Coutinho Moraes; Eloisa Helena de Aguiar Andrade; Jose Guilherme Soares Maia; Sabrina Maria Portela Carneiro; Fernando Aécio de Amorim Carvalho

    2013-01-01

    Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components...

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

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

    2015-01-01

    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters of...

  8. 4-Phenylselenyl-7-chloroquinoline, a new quinoline derivative containing selenium, has potential antinociceptive and anti-inflammatory actions.

    Pinz, Mikaela; Reis, Angélica S; Duarte, Vanessa; da Rocha, Márcia J; Goldani, Bruna S; Alves, Diego; Savegnago, Lucielli; Luchese, Cristiane; Wilhelm, Ethel A

    2016-06-01

    The development of new drugs to treat painful and inflammatory clinical conditions continues to be of great interest. The present study evaluated the antinociceptive and anti-inflammatory effects of 4-phenylselenyl-7-chloroquinoline (4-PSQ). Mice were orally (p.o.) pretreated with 4-PSQ (0.1-25mg/kg), meloxicam (25mg/kg, a reference drug) or vehicle, 30min prior to the acetic acid, formalin, hot-plate and open-field tests. 4-PSQ reduced abdominal writhing induced by acetic acid and it caused an increase in latency time in the hot-plate test. 4-PSQ inhibited early and late phases of nociception and reduced the paw edema caused by formalin. Locomotor and exploratory activities in the open field test were not altered by treatments. In addition, a time-response curve was carried out by administration of 4-PSQ (25mg/kg; p.o.) at different times before the acetic acid injection. The antinociceptive effect in inhibiting acetic acid-induced abdominal writhing of 4-PSQ started at 0.5h and remained significant up to 4h after administration. Indeed, the anti-inflammatory and antioxidant properties of 4-PSQ were investigated. 4-PSQ diminished the edema formation and decreased the myeloperoxidase activity and reactive species levels induced by croton oil in the ear tissue. 4-PSQ partially protected against the decrease of the 2,2'-Azinobis-3-ethylbenzothiazoline 6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) levels induced by croton oil. Meloxicam presented similar results for 4-PSQ in tests evaluated. These results demonstrated that 4-PSQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies. PMID:27020552

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

    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.

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

    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

  11. Sustained Exocytosis after Action Potential-Like Stimulation at Low Frequencies in Mouse Chromaffin Cells Depends on a Dynamin-Dependent Fast Endocytotic Process

    Moya-Díaz, José; Álvarez, Yanina D.; Montenegro, Mauricio; Bayonés, Lucas; Belingheri, Ana V.; González-Jamett, Arlek M.; Cárdenas, Ana M.; Marengo, Fernando D.

    2016-01-01

    Under basal conditions the action potential firing rate of adrenal chromaffin cells is lower than 0.5 Hz. The maintenance of the secretory response at such frequencies requires a continuous replenishment of releasable vesicles. However, the mechanism that allows such vesicle replenishment remains unclear. Here, using membrane capacitance measurements on mouse chromaffin cells, we studied the mechanism of replenishment of a group of vesicles released by a single action potential-like stimulus (APls). The exocytosis triggered by APls (ETAP) represents a fraction (40%) of the immediately releasable pool, a group of vesicles highly coupled to voltage dependent calcium channels. ETAP was replenished with a time constant of 0.73 ± 0.11 s, fast enough to maintain synchronous exocytosis at 0.2–0.5 Hz stimulation. Regarding the mechanism involved in rapid ETAP replenishment, we found that it depends on the ready releasable pool; indeed depletion of this vesicle pool significantly delays ETAP replenishment. On the other hand, ETAP replenishment also correlates with a dynamin-dependent fast endocytosis process (τ = 0.53 ± 0.01 s). In this regard, disruption of dynamin function markedly inhibits the fast endocytosis and delays ETAP replenishment, but also significantly decreases the synchronous exocytosis during repetitive APls stimulation at low frequencies (0.2 and 0.5 Hz). Considering these findings, we propose a model in where both the transfer of vesicles from ready releasable pool and fast endocytosis allow rapid ETAP replenishment during low stimulation frequencies. PMID:27507935

  12. Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

    The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21Cip1/Waf1, cyclin D1, Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G0/G1 arrest, which involved increased expression of p53 and p21Cip1/Waf1, and decreased expression of cyclin D1. CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system

  13. Identification of sodium channel isoforms that mediate action potential firing in lamina I/II spinal cord neurons

    Smith Paula L

    2011-09-01

    Full Text Available Abstract Background Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of sodium channel function in nociceptive signaling have primarily focused on recombinant channels or peripheral nociceptors. Here, we utilize recordings from lamina I/II neurons withdrawn from the surface of spinal cord slices to systematically determine the functional properties of sodium channels expressed within the superficial dorsal horn. Results Sodium channel currents within lamina I/II neurons exhibited relatively hyperpolarized voltage-dependent properties and fast kinetics of both inactivation and recovery from inactivation, enabling small changes in neuronal membrane potentials to have large effects on intrinsic excitability. By combining biophysical and pharmacological channel properties with quantitative real-time PCR results, we demonstrate that functional sodium channel currents within lamina I/II neurons are predominantly composed of the NaV1.2 and NaV1.3 isoforms. Conclusions Overall, lamina I/II neurons express a unique combination of functional sodium channels that are highly divergent from the sodium channel isoforms found within peripheral nociceptors, creating potentially complementary or distinct ion channel targets for future pain therapeutics.

  14. The role of dietary coconut for the prevention and treatment of Alzheimer's disease: potential mechanisms of action.

    Fernando, W M A D B; Martins, Ian J; Goozee, K G; Brennan, Charles S; Jayasena, V; Martins, R N

    2015-07-14

    Coconut, Cocos nucifera L., is a tree that is cultivated to provide a large number of products, although it is mainly grown for its nutritional and medicinal values. Coconut oil, derived from the coconut fruit, has been recognised historically as containing high levels of saturated fat; however, closer scrutiny suggests that coconut should be regarded more favourably. Unlike most other dietary fats that are high in long-chain fatty acids, coconut oil comprises medium-chain fatty acids (MCFA). MCFA are unique in that they are easily absorbed and metabolised by the liver, and can be converted to ketones. Ketone bodies are an important alternative energy source in the brain, and may be beneficial to people developing or already with memory impairment, as in Alzheimer's disease (AD). Coconut is classified as a highly nutritious 'functional food'. It is rich in dietary fibre, vitamins and minerals; however, notably, evidence is mounting to support the concept that coconut may be beneficial in the treatment of obesity, dyslipidaemia, elevated LDL, insulin resistance and hypertension - these are the risk factors for CVD and type 2 diabetes, and also for AD. In addition, phenolic compounds and hormones (cytokinins) found in coconut may assist in preventing the aggregation of amyloid-β peptide, potentially inhibiting a key step in the pathogenesis of AD. The purpose of the present review was to explore the literature related to coconut, outlining the known mechanistic physiology, and to discuss the potential role of coconut supplementation as a therapeutic option in the prevention and management of AD. PMID:25997382

  15. Healthy universities--time for action: a qualitative research study exploring the potential for a national programme.

    Dooris, Mark; Doherty, Sharon

    2010-03-01

    Despite the absence of national or international steers, there is within England growing interest in the Healthy University approach. This article introduces Healthy Universities; reports on a qualitative study exploring the potential for a national programme contributing to health, well-being and sustainable development; and concludes with reflections and recommendations. The study used questionnaires and interviews with key informants from English higher education institutions and national stakeholder organizations. The findings confirmed that higher education offers significant potential to impact positively on the health and well-being of students, staff and wider communities through education, research, knowledge exchange and institutional practice. There was strong support for extending the healthy settings approach beyond schools and further education, through a National Healthy Higher Education Programme that provides a whole system Healthy University Framework. Informants argued that although there are important public health drivers, it will also be necessary to show how a Healthy Universities can help achieve core business objectives and contribute to related agendas such as sustainability. Two models were discussed: an accreditation scheme with externally assessed standardized achievement criteria; and a flexible and light-touch framework focusing on change-related processes and utilizing self-assessment. While highlighting the appeal of league tables, many informants feared that a top-down approach could backfire, generating resistance and resulting in minimal compliance. In contrast, the majority felt that a process-focused aspirational model would be more likely to win hearts and minds and facilitate system-level change. Key recommendations relate to national programme development, research and evaluation and international collaboration and networking. PMID:20167825

  16. PDE type-4 inhibition increases L-type Ca(2+) currents, action potential firing, and quantal size of exocytosis in mouse chromaffin cells.

    Marcantoni, A; Carabelli, V; Vandael, D H; Comunanza, V; Carbone, E

    2009-03-01

    We studied the effects of the cAMP-hydrolyzing enzyme phosphodiesterase type-4 (PDE4) on the L-type Ca(2+) channels (LTCCs) and Ca(2+)-dependent secretion in mouse chromaffin cells (MCCs). The selective PDE4 inhibitor rolipram (3 microM) had a specific potentiating action on Ca(2+) currents of MCCs (40% increase within 3 min). A similar effect was produced by the selective beta(1)-AR agonist denopamine (1 microM) and by the unselective PDEs inhibitor IBMX (100 microM). Rolipram and denopamine actions were selective for LTCCs, and the Ca(2+) current increase remained unchanged if the two compounds were applied simultaneously. This suggests that at rest, LTCCs in MCCs are down-regulated by the low levels of cAMP determined by PDE4 activity and that LTCCs can be up-regulated by either inhibiting PDE4 or activating beta(1)-AR. No other PDEs are likely involved in this specific action. PDE4 inhibition had also a marked effect on the spontaneous firing of resting MCCs and catecholamine secretion. Rolipram up-regulated the LTCCs contributing to the "pace-maker" current underlying action potential (AP) discharges and accelerated the firing rate, with no significant effects on AP waveform. Acceleration of AP firing was also induced by the LTCC-agonist Bay K (1 microM), while nifedipine (3 microM) reduced the firing frequency, suggesting that LTCCs and intracellular cAMP play a key role in setting the pace-maker current regulating MCCs excitability. Rolipram increased also the size of the ready-releasable pool and the quantal content of secretory vesicles without affecting their probability of release. Thus, rolipram acts on MCCs by up-regulating both exocytosis and AP firings. These two processes are effectively down-regulated by PDE4 at rest and can dramatically increase the quantity of released catecholamines when PDE4 is inhibited and/or cAMP is raised. PMID:18779976

  17. Recent actions taken on methyl bromide under the Montreal Protocol: Their potential economic implications on international trade

    Methyl bromide (MB) produced and used by man is a versatile, highly effective, fastacting fumigant employed in a number of important ways to kill organisms destructive to plants. A wide spectrum of commodities is treated with MB. The compound is unique in that it provides a wide range of pest control, may be applied to a broad spectrum of both food and non-food commodities, can be used for fumigation of large and small quantities of materials, and, when applied properly, leaves no residues of toxicological significance. Recently, this compound has come under scientific scrutiny and has been identified as a potentially potent ozone depleting chemical. As a result, countries operating under the Montreal Protocol will be restricting its use, and, in some cases, eliminating its use altogether. To date there are no alternative chemical fumigants to replace methyl bromide. Non-chemical treatments such as irradiation, hot and cold treatments, modified atmosphere, etc., are the most promising. The paper focuses on the magnitude of the economic consequences on international trade and the necessity to have available alternative treatments that are highly effective, fast-acting, and practical. 8 refs, 12 tabs

  18. [Algorithm study on the three-dimensional cardiac tissue based on the model of ventricular action potential].

    Zhang, Hong; Ming, Lequn; Jin, Yinbin; Li, Mingjun; Zhang, Zhenxi; Lin, Yang

    2010-02-01

    Cardiac reentry is one of the important factors to induce arrhythmias. It could lead to ventricular tachycardia (VT) or even fibrillation (VF), resulting in sudden cardiac death. With the wide use of computer in the quantitative study of electrophysiology, the three-dimensional virtual heart for simulations needs to be developed imminently in computer. In this paper, numerical algorithm of the model was studied. The three-dimensional model was constructed by integrating Luo-Rudy 1991 ventricular cell model and diffusion equation. The operator splitting method was employed to solve the model. The alternate direction iterative (ADI) format and seven-point centered difference method were used for the partial differential equation. And the discrete format with second-order accuracy was taken for the boundary conditions. The results showed that the ADI format and seven-point centered difference method both could successfully figure out the membrane potential and electrical activities with good numerical stability. However, computing consumption could be greatly reduced with the ADI format, implying that the ADI method with large time step was more powerful in numerical simulations. PMID:20337013

  19. The angiogenic effect of dracorhodin perchlorate on human umbilical vein endothelial cells and its potential mechanism of action.

    Li, Feng; Jiang, Tao; Liu, Wei; Hu, Quan; Yin, Huinan

    2016-08-01

    Hyperglycemia is the key clinical feature of diabetes, and may induce refractory wound lesions and impaired angiogenesis. Dracorhodin perchlorate (Dra) is the major ingredient of dragon's blood and it has been used as a medicine to treat chronic wounds, such as diabetic foot, since ancient times in many cultures. The current study aimed to investigate the effect of Dra on human umbilical vein endothelial cells (HUVECs) under high‑glucose (HG) stimulation and its potential mechanism. Dra was observed to increase the multiplication capacity of HUVECs both under low glucose (LG) and HG concentrations. Additionally, migration and tube formation in HUVECs was facilitated by Dra. The expression levels of Ras, mitogen‑activated protein kinase (MAPK) and vascular endothelial growth factor, which are key components of the Ras/MAPK pathway, were upregulated following Dra treatment. The present study is the first report, to the best of our knowledge, of the effects of Dra on wound healing, and the association with the Ras/MAPK signaling pathway. PMID:27357516

  20. Molecular mechanisms of action and potential biomarkers of growth inhibition of dasatinib (BMS-354825) on hepatocellular carcinoma cells

    Molecular targeted therapy has emerged as a promising treatment of Hepatocellular carcinoma (HCC). One potential target is the Src family Kinase (SFK). C-Src, a non-receptor tyrosine kinase is a critical link of multiple signal pathways that regulate proliferation, invasion, survival, metastasis, and angiogenesis. In this study, we evaluated the effects of a novel SFK inhibitor, dasatinib (BMS-354825), on SFK/FAK/p130CAS, PI3K/PTEN/Akt/mTOR, Ras/Raf/MAPK and Stats pathways in 9 HCC cell lines. Growth inhibition was assessed by MTS assay. EGFR, Src and downstream proteins FAK, Akt, MAPK42/44, Stat3 expressions were measured by western blot. Cell adhesion, migration and invasion were performed with and without dasatinib treatment. The IC50 of 9 cell lines ranged from 0.7 μM ~ 14.2 μM. In general the growth inhibition by dasatinib was related to total Src (t-Src) and the ratio of activated Src (p-Src) to t-Src. There was good correlation of the sensitivity to dasatinib and the inhibition level of p-Src, p-FAK576/577 and p-Akt. No inhibition was found on Stat3 and MAPK42/44 in all cell lines. The inhibition of cell adhesion, migration and invasion were correlated with p-FAK inhibition. Dasatinib inhibits the proliferation, adhesion, migration and invasion of HCC cells in vitro via inhibiting of Src tyrosine kinase and affecting SFK/FAK and PI3K/PTEN/Akt, but not Ras/Raf/MEK/ERK and JAK/Stat pathways. T-Src and p-Src/t-Src may be useful biomarkers to select HCC patients for dasatinib treatment

  1. Addictive evaluation of cholic acid-verticinone ester, a potential cough therapeutic agent with agonist action of opioid receptor

    Jiu-liang ZHANG; Hui WANG; Chang CHEN; Hui-fang PI; Han-li RUAN; Peng ZHANG; Ji-zhou WU

    2009-01-01

    Aim: The purpose of this work was to search for potential drugs with potent antitussive and expectorant activities as well as a low toxicity, but without addictive properties. Cholic acid-verticinone ester (CA-Ver) was synthesized based on the clearly elucidated antitussive and expectorant activities of verticinone in bulbs of Fritillaria and different bile acids in Snake Bile. In our previous study, CA-Vet showed a much more potent activity than codeine phosphate. This study was carried out to investigate the central antitussive mechanism and the addictive evaluation of CA-Ver.Methods: Testing on a capsaicin-induced cough model of mice pretreated with naloxone, a non-selective opioid receptor antagonist, was performed for the observation of CA-Ver's central antitussive mechanism. We then took naloxone-induced withdrawal tests of mice for the judgment of CA-Ver's addiction. Lastly, we determined the opioid dependence of CA-Ver in the guinea pig ileum. Results: The test on the capsaicin-induced cough model showed that naloxone could block the antitussive effect of CA-Ver,suggesting the antitussive mechanism of CA-Ver was related to the central opioid receptors. The naloxone-urged withdrawal tests of the mice showed that CA-Ver was not addictive, and the test of the opioid dependence in the guinea pig ileum showed that CA-Ver had no withdrawal response.Conclusion: These findings suggested that CA-Ver deserved attention for its potent antitussive effects related to the central opioid receptors, but without addiction, and had a good development perspective.

  2. Remote Monitoring of the Heart Condition of Athletes by Measuring the Cardiac Action Potential Propagation Time Using a Wireless Sensor Network

    Amang Sudarsono

    2016-04-01

    Full Text Available Highly performing athletes are susceptible to cardiac damage of several kinds which may be irreversible. The monitoring of heart rate and ECG waveforms from such subjects by wireless sensor networks has been reported in health and sports care documents. However, a more decisive parameter for instant to instant changes would be the time of Cardiac Action Potential Propagation. This time, which can be between 15-20 ms would shoot suddenly in acute stress in highly performing athletes for short durations. Repeated incidents of such rising values will tend to cause irreversible damage to the heart. We developed the technique of measuring this time and reporting it through a wireless sensor network to monitoring station.

  3. Action potential initial dynamical control and analysis of a minimum neuron model%最小神经元模型放电起始动态控制与分析

    金淇涛; 王江; 魏熙乐; 邓斌; 车艳秋

    2011-01-01

    本文采用最小神经元模型,从生理学角度设计wash-out滤波器,实现了不同放电起始动态机理之间的转换,并证明wash-out滤波器控制通过影响阈下电流的竞争结果改变了神经元的放电起始动态机理.%Neuron is a basic unit of information transmission in the nervous system . Neuron encodes the information input from the dendrites by generating action potential sequences of different firing patterns. The different firing patterns result from different action potential initial dynamic mechanisms for neurons to generate spikes. The result of competition between neuron ion currents with different dynamic features in the sub threshold potential determines the action potential initial dynamic mechanism. In this paper, we adopt a minimum neuron model to design the wash-out filter from a physiological view for achieving the transition between different action potential initial dynamic mechanisms and for verifying that the wash-out filter control changes the action potential initial dynamic mechanism of neuron by affecting the result of competition between currents with different dynamic features in the sub-threshold potential.

  4. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry: A case study on bile salts.

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

    2015-09-01

    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters 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 numbers, as those of bile salts, are interesting because such small aggregates cannot be characterized as a separate macroscopic phase and the widely applied pseudo-phase model (PPM) is inaccurate. In the present work it was demonstrated that the aggregation number of micelles was constant at low concentrations enabling determination of the thermodynamic potentials by the MAM. A correlation between the aggregation number and the heat capacity was found, which implies that the dehydrated surface area of bile salts increases with the aggregation number. This is in accordance with Tanford's principles of opposing forces where neighbouring molecules in the aggregate are better able to shield from the surrounding hydrophilic environment when the aggregation number increases. PMID:25978555

  5. Character of diaphragm compound muscle action potential and phrenic nerve conduction time in patients with obstructive sleep apnea-hypopnea syndrome

    Yuhong Hou; Rongchang Chen; Jinbing Pan; Yuanming Luo; Nanshan Zhong

    2008-01-01

    BACKGROUND: Both hypoxia and carbon dioxide retention can damage phrenic nerve and muscle conduction, as well as diaphragm function. Diaphragm compound muscle action potential and phrenic nerve conduction time are reliable indicators for measuring phrenic nerve and diaphragm function.OBJECTIVES: To verify the hypothesis that changes of phrenic nerve conduction time (PNCT) and diaphragm compound muscle action potential (CMAP) in obstructive sleep apnea-hypopnea syndrome (OSAHS) patients might contribute to the decline of phrenic nerve and diaphragm function. PNCT and CMAP were measured with multipair esophageal electrodes combined with unilateral magnetic stimulation.DESIGN, TIME AND SETTING: Case controlled study. The experiment was carried out in Guangzhou Institute of Respiratory Disease, Guangzhou Medical College, from June 2005 to April 2006.PARTICIPANTS: Twenty seven OSAHS patients and eight primary snoring subjects from Guangzhou Institute of Respiratory Disease, Guangzhou Medical College were recruited and all subjects were diagnosed by polysomnography (PSG). Sixteen healthy, non-snoring subjects in the hospital for medical examination during the same time period were selected as the control group.METHODS: Esophageal electrodes, made by Guangzhou Institute of Respiratory Disease, combined with unilateral magnetic stimulation, were used to measure PNCT and CMAP of all subjects. PNCT was defined as the time from stimulation artifact to the onset of CMAP and diaphragm CMAP amplitude was measured from peak to peak. Oxygen desaturation index and apnea-hypopnea index were measured using PSG, and their relevance to PNCT and CMAP were analyzed. PNCT and CMAP in five OSAHS patients were repeatedly measured after effective nasal continuous positive airway pressure treatment for more than 2 months.MAIN OUTCOME MEAAURES: (1) PNCT and diaphragm CMAP of suhjects in each group. (2) Relevance of oxygen desaturation index and apnea-hypopnea index to PNCT and CMAP. (3

  6. A novel method for the description of voltage-gated ionic currents based on action potential clamp results - Application to hippocampal mossy fiber boutons

    John R Clay

    2016-01-01

    Full Text Available Action potential clamp (AP-clamp recordings of the delayed rectifier K+ current IK and the fast-activated Na+ current INa in rat hippocampal mossy fiber boutons (MFBs are analyzed using a computational technique recently reported. The method is implemented using a digitized AP from an MFB and computationally applying that that data set to published models of IK and INa. These numerical results are compared with experimental AP-clamp recordings. The INa result is consistent with experiment; the IK result is not. The difficulty with the IK model concerns the fully activated current-voltage relation, which is described here by the Goldman-Hodgkin-Katz dependence of the driving force (V-EK rather than (V-EK itself, the standard model for this aspect of ion permeation. That revision leads to the second - a much steeper voltage dependent activation curve for IK than the one obtained from normalization of a family of IK records by (V-EK. The revised model provides an improved description of the AP-clamp measurement of IK in MFBs compared with the standard approach The method described here is general. It can be used to test models of ionic currents in any excitable cell. In this way it provides a novel approach to the relationship between ionic currents and membrane excitability in neurons.

  7. Simultaneous recording of the action potential and its whole-cell associated ion current on NG108-15 cells cultured over a MWCNT electrode

    Morales-Reyes, I.; Seseña-Rubfiaro, A.; Acosta-García, M. C.; Batina, N.; Godínez-Fernández, R.

    2016-08-01

    It is well known that, in excitable cells, the dynamics of the ion currents (I i) is extremely important to determine both the magnitude and time course of an action potential (A p). To observe these two processes simultaneously, we cultured NG108-15 cells over a multi-walled carbon nanotubes electrode (MWCNTe) surface and arranged a two independent Patch Clamp system configuration (Bi-Patch Clamp). The first system was used in the voltage or current clamp mode, using a glass micropipette as an electrode. The second system was modified to connect the MWCNTe to virtual ground. While the A p was recorded through the micropipette electrode, the MWCNTe was used to measure the underlying whole-cell current. This configuration allowed us to record both the membrane voltage (V m) and the current changes simultaneously. Images acquired by atomic force microscopy (AFM) and scanning electron microscopy (SEM) indicate that cultured cells developed a complex network of neurites, which served to establish the necessary close contact and strong adhesion to the MWCNTe surface. These features were a key factor to obtain the recording of the whole-cell I i with a high signal to noise ratio (SNR). The experimental results were satisfactorily reproduced by a theoretical model developed to simulate the proposed system. Besides the contribution to a better understanding of the fundamental mechanisms involved in cell communication, the developed method could be useful in cell physiology studies, pharmacology and diseases diagnosis.

  8. Bystander Effects Induced by Continuous Low-Dose-Rate 125I Seeds Potentiate the Killing Action of Irradiation on Human Lung Cancer Cells In Vitro

    Purpose: To investigate bystander effects of low-dose-rate (LDR) 125I seed irradiation on human lung cancer cells in vitro. Methods and Materials: A549 and NCI-H446 cell lines of differing radiosensitivity were directly exposed to LDR 125I seeds irradiation for 2 or 4 Gy and then cocultured with nonirradiated cells for 24 hours. Induction of micronucleus (MN), γH2AX foci, and apoptosis were assayed. Results: After 2 and 4 Gy irradiation, micronucleus formation rate (MFR) and apoptotic rate of A549 and NCI-H446 cells were increased, and the MFR and apoptotic rate of NCI-H446 cells was 2.1-2.8 times higher than that of A549 cells. After coculturing nonirradiated bystander cells with 125I seed irradiated cells for 24 hours, MFR and the mean number of γH2AX foci/cells of bystander A549 and NCI-H446 cells were similar and significantly higher than those of control (p 125I seeds could induce bystander effects, which potentiate the killing action on tumor cells and compensate for the influence of nonuniform distribution of radiation dosage on therapeutic outcomes

  9. Intentional Action and Action Slips.

    Heckhausen, Heinz; Beckmann, Jurgen

    1990-01-01

    An explanation of action slips is offered that examines controlled actions in the context of an intentional behavior theory. Actions are considered guided by mentally represented intentions, subdivided into goal intentions and contingent instrumental intentions. Action slips are categorized according to problem areas in the enactment of goal…

  10. Stochasticity intrinsic to coupled-clock mechanisms underlies beat-to-beat variability of spontaneous action potential firing in sinoatrial node pacemaker cells

    Yaniv, Yael; Lyashkov, Alexey E.; Sirenko, Syevda; Okamoto, Yosuke; Guiriba, Toni-Rose; Ziman, Bruce D.; Morrell, Christopher H.; Lakatta, Edward G.

    2014-01-01

    Recent evidence indicates that the spontaneous action potential (AP) of isolated sinoatrial node cells (SANC) is regulated by a system of stochastic mechanisms embodied within two clocks: ryanodine receptors of the “Ca2+ clock” within the sarcoplasmic reticulum, spontaneously activate during diastole and discharge local Ca2+ releases (LCRs) beneath the cell surface membrane; clock crosstalk occurs as LCRs activate an inward Na+/Ca2+ exchanger current (INCX), which together with If and decay of K+ channels prompts the “M clock,” the ensemble of sarcolemmal-electrogenic molecules, to generate APs. Prolongation of the average LCR period accompanies prolongation of the average AP beating interval (BI). Moreover, prolongation of the average AP BI accompanies increased AP BI variability. We hypothesized that both the average AP BI and AP BI variability are dependent upon stochasticity of clock mechanisms reported by the variability of LCR period. We perturbed the coupled-clock system by directly inhibiting the M clock by ivabradine (IVA) or the Ca2+ clock by cyclopiazonic acid (CPA). When either clock is perturbed by IVA (3, 10 and 30μM), which has no direct effect on Ca2+ cycling, or CPA ( 0.5 and 5μM), which has no direct effect on the M clock ion channels, the clock system failed to achieve the basal AP BI and both AP BI and AP BI variability increased. The changes in average LCR period and its variability in response to perturbations of the coupled-clock system were correlated with changes in AP beating interval and AP beating interval variability. We conclude that the stochasticity within the coupled-clock system affects and is affected by the AP BI firing rate and rhythm via modulation of the effectiveness of clock coupling. PMID:25257916

  11. Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects on Leishmania amazonensis and Possible Mechanisms of Action

    Klinger Antonio da Franca Rodrigues

    2013-01-01

    Full Text Available Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO by using gas chromatography-mass spectrometry (GC-MS and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components were sesquiterpenes (91.92%, with curzerene (47.3%, γ-elemene (14.25%, and trans-β-elemenone (10.4% being the major constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04 μg·mL−1 and amastigotes (IC50, 1.92 μg·mL−1 suggested significant anti-Leishmania activity. In the cytotoxicity determination, EuEO was 20 times more toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the highest concentration tested (400 μg·mL−1; however, there appeared to be no toxicity at 50 μg·mL−1. While the data show that EuEO activity is not mediated by nitric oxide production, they do suggest that macrophage activation may be involved in EuEO anti-Leishmania activity, as evidenced by increases in both the phagocytic capacity and the lysosomal activity. More studies are needed to determine in vivo activity as well as additional mechanisms of the anti-Leishmania activity.

  12. Sevoflurane postconditioning alleviates action potential duration shortening and L-type calcium current suppression induced by ischemia/reperfusion injury in rat epicardial myocytes

    GONG Jun-song; YAO Yun-tai; FANG Neng-xin; HUANG Jian; LI Li-huan

    2012-01-01

    Background It has been proved that sevoflurane postconditioning (SpostC) could protect the heart against myocardial ischemia/reperfusion injury,however,there has been few research focused on the electrophysiological effects of SpostC.The objective of the study was to investigate the effects of SpostC on action potential duration (APD) and L-type calcium current (ICa,L) in isolated cardiomyocytes.Methods Langendorff perfused SD rat hearts were randomly assigned to one of the time control (TC),ischemia/reperfusion (I/R,25 minutes of ischemia followed by 30 minutes of reperfusion),and SpostC (postconditioned with 3% sevoflurane) groups.At the end of reperfusion,epicardial myocytes were dissociated enzymatically for patch clamp studies.Results Sevoflurane directly prolonged APD and decreased peak Ica,L densities in epicardial myocytes of the TC group (P<0.05).I/R injury shortened APD and decreased peak Ica,L densities in epicardial myocytes of the I/R group (P<0.05).SpostC prolonged APD and increased peak Ica,L densities in epicardial myocytes exposed to I/R injury (P<0.05).SpostC decreased intracellular reactive oxygen species (ROS) levels,reduced the incidence of ventricular tachycardia and ventricular fibrillation,and decreased reperfusion arrhythmia scores compared with the I/R group (all P<0.05).Conclusions SpostC attenuates APDshortening and ICa,L suppression induced by I/R injury.The regulation of APD and Ica,L by SpostC might be related with intracellular ROS modulation,which contributes to the alleviation of reperfusion ventricular arrhythmia.Chin Med J 2012;125(19):3485-3491

  13. Eugenia uniflora L. Essential Oil as a Potential Anti-Leishmania Agent: Effects on Leishmania amazonensis and Possible Mechanisms of Action.

    Rodrigues, Klinger Antonio da Franca; Amorim, Layane Valéria; de Oliveira, Jamylla Mirck Guerra; Dias, Clarice Noleto; Moraes, Denise Fernandes Coutinho; Andrade, Eloisa Helena de Aguiar; Maia, Jose Guilherme Soares; Carneiro, Sabrina Maria Portela; Carvalho, Fernando Aécio de Amorim

    2013-01-01

    Eugenia uniflora L. is a member of the Myrtaceae family and is commonly known as Brazilian cherry tree. In this study, we evaluated the chemical composition of Eugenia uniflora L. essential oil (EuEO) by using gas chromatography-mass spectrometry (GC-MS) and assessed its anti-Leishmania activity. We also explored the potential mechanisms of action and cytotoxicity of EuEO. Thirty-two compounds were identified, which constituted 92.65% of the total oil composition. The most abundant components were sesquiterpenes (91.92%), with curzerene (47.3%), γ -elemene (14.25%), and trans- β -elemenone (10.4%) being the major constituents. The bioactivity shown by EuEO against promastigotes (IC50, 3.04  μ g·mL(-1)) and amastigotes (IC50, 1.92  μ g·mL(-1)) suggested significant anti-Leishmania activity. In the cytotoxicity determination, EuEO was 20 times more toxic to amastigotes than to macrophages. Hemolytic activity was 63.22% at the highest concentration tested (400  μ g·mL(-1)); however, there appeared to be no toxicity at 50  μ g·mL(-1). While the data show that EuEO activity is not mediated by nitric oxide production, they do suggest that macrophage activation may be involved in EuEO anti-Leishmania activity, as evidenced by increases in both the phagocytic capacity and the lysosomal activity. More studies are needed to determine in vivo activity as well as additional mechanisms of the anti-Leishmania activity. PMID:23533469

  14. Loss of ATP-Sensitive Potassium Channel Surface Expression in Heart Failure Underlies Dysregulation of Action Potential Duration and Myocardial Vulnerability to Injury.

    Zhan Gao

    Full Text Available The search for new approaches to treatment and prevention of heart failure is a major challenge in medicine. The adenosine triphosphate-sensitive potassium (KATP channel has been long associated with the ability to preserve myocardial function and viability under stress. High surface expression of membrane KATP channels ensures a rapid energy-sparing reduction in action potential duration (APD in response to metabolic challenges, while cellular signaling that reduces surface KATP channel expression blunts APD shortening, thus sacrificing energetic efficiency in exchange for greater cellular calcium entry and increased contractile force. In healthy hearts, calcium/calmodulin-dependent protein kinase II (CaMKII phosphorylates the Kir6.2 KATP channel subunit initiating a cascade responsible for KATP channel endocytosis. Here, activation of CaMKII in a transaortic banding (TAB model of heart failure is coupled with a 35-40% reduction in surface expression of KATP channels compared to hearts from sham-operated mice. Linkage between KATP channel expression and CaMKII is verified in isolated cardiomyocytes in which activation of CaMKII results in downregulation of KATP channel current. Accordingly, shortening of monophasic APD is slowed in response to hypoxia or heart rate acceleration in failing compared to non-failing hearts, a phenomenon previously shown to result in significant increases in oxygen consumption. Even in the absence of coronary artery disease, failing myocardium can be further injured by ischemia due to a mismatch between metabolic supply and demand. Ischemia-reperfusion injury, following ischemic preconditioning, is diminished in hearts with CaMKII inhibition compared to wild-type hearts and this advantage is largely eliminated when myocardial KATP channel expression is absent, supporting that the myocardial protective benefit of CaMKII inhibition in heart failure may be substantially mediated by KATP channels. Recognition of Ca

  15. Regulation of action potential delays via voltage-gated potassium Kv1.1 channels in dentate granule cells during hippocampal epilepsy

    Florian eKirchheim

    2013-12-01

    Full Text Available Action potential (AP responses of dentate gyrus granule (DG cells have to be tightly regulated to maintain hippocampal function. However, which ion channels control the response delay of DG cells is not known. In some neuron types, spike latency is influenced by a dendrotoxin (DTX-sensitive delay current (ID mediated by unidentified combinations of voltage-gated K+ (Kv channels of the Kv1 family Kv1.1-6. In DG cells, the ID has not been characterized and its molecular basis is unknown. The response phenotype of mature DG cells is usually considered homogenous but intrinsic adaptations likely occur in particular in conditions of hyperexcitability, for example during temporal lobe epilepsy (TLE. In this study, we examined response delays of DG cells and underlying ion channel molecules by employing a new combination of gramicidin-perforated patch-clamp recordings in acute brain slices and single-cell reverse transcriptase quantitative polymerase chain reaction (SC RT-qPCR experiments. An in vivo mouse model of TLE consisting of intrahippocampal kainate (KA injection was used to examine epilepsy-related plasticity. Response delays of DG cells were DTX-sensitive and strongly increased in KA-injected hippocampi; Kv1.1 mRNA was elevated 10-fold, and the response delays correlated with Kv1.1 mRNA abundance on the single cell level. Other Kv1 subunits did not show overt changes in mRNA levels. Kv1.1 immunolabeling was enhanced in KA DG cells. The biophysical properties of ID and the delay heterogeneity between inner and outer DG cell layer were characterized. Using organotypic hippocampal slice cultures (OHCs, where KA incubation also induced ID upregulation, reversibility and neuroprotective potential for DG cells were tested. In summary, the AP timing of DG cells is effectively controlled via scaling of Kv1.1 subunit transcription. With this antiepileptic mechanism, DG cells delay their

  16. Effects of Ascorbic Acid on the Amplitude of Ventral Tegmental Area Field Action Potential in Morphine-Exposed Rats (An Electrophysiology Study

    K Saadipour

    2010-07-01

    Full Text Available Introduction & Objective: Evidences have indicated that the Ventral Tegmental Area (VTA is the major source of dopamine (DA neurons projecting to cortical and limbic regions involved in cognitive and motivational aspects of addiction. Also, studies have indicated that the Ascorbic acid (vitamin C can reduce the dependency symptoms of opioids such as morphine via effect of activity on dopaminergic neuron in VTA. For this reason, the aim of this study was to assess the effects of ascorbic acid on the amplitude of Ventral Tegmental Area field action potential in morphine-exposed rats. Materials & Methods: Forty male Wistar’s rats were used in this experimental study conducted at Yasuj University of Medical Sciences in 2010. Animals were randomly divided into four groups after electrode implantation and recovery period: 1. No- Vit C and No-Addicted group (nVitC.nA 2. Vit C and No-Addicted group (VitC.nA 3. No- Vit C and Addicted group (nVitCA 4.Vit C and Addicted (VitC.A, The Vit C groups received 500 mg/kg of Vit C during 20 days. For addicted groups morphine was administrated once daily for 20 days. In the 20th day, the field potential recording was accomplished. Two-way ANOVA was used for data analysis followed by the Tukey test for post hoc analysis. Results were considered significant at P < 0.05. Results: This study shows the exposure to morphine declined the power of Delta and Beta bands (p<0.05 and Vit C solely enhance power of Theta and Beta (p<0.05, p<0.001 in VTA nuclei. Furthermore, Vit C could alter power of some bands which were affected by morphine. Therefore it seems that Vit C has an increasing effects on them (p<0.05. Conclusion: Although the effect of Vit C on power of the VTA bands is not well known, but it is supposed that this phenomenon can be related to alteration in activity of dopaminergic neuron in the brain.

  17. Body posture modulates action perception

    Zimmermann, M; Toni, I.; Lange, F.P. de

    2013-01-01

    Recent studies have highlighted cognitive and neural similarities between planning and perceiving actions. Given that action planning involves a simulation of potential action plans that depends on the actor's body posture, we reasoned that perceiving actions may also be influenced by one's body posture. Here, we test whether and how this influence occurs by measuring behavioral and cerebral (fMRI) responses in human participants predicting goals of observed actions, while manipulating postur...

  18. Action Potential Classification Based on PCA and Improved K-means Algorithm%基于PCA和改进K均值算法的动作电位分类

    师黎; 杨振兴; 王治忠; 王岩

    2011-01-01

    微电极阵列记录的神经元信号往往是电极临近区域数个神经元的动作电位信号以及大量背景噪声的混叠,研究神经系统的信息处理机制以及神经编码、解码机理需了解相关每个神经元的动作电位,因此需从记录信号中分离出每个神经元的动作电位.基于此,提出基于主元分析(PCA)和改进K均值相结合的动作电位分类方法.该方法采用PCA提取动作电位特征,使用改进K均值算法实现动作电位分类.实验结果表明,该方法降低了动作电位的特征维数以及K均值算法对初始分类重心的依赖,提高动作电位分类结果的正确率及稳定性.尤其是在处理低信噪比信号时,分类正确率仍能达到理想水平.%Neural signal recorded by the microelectrode array is often the mixture which is composed of action potentials of several neurons near the electrodes and the background noises. Researches on the nervous system information processing mechanism and neural coding and decoding mechanism need know every related neuron's action potential. Therefore, every neuron's action potential is essential to be separated from the recorded signal. This paper proposes a method based on Principal Component Analysis(PCA) combined with improved K-means for action potential classification. The action potentials' features are extracted by PCA, the action potential classification is implemented by the improved K-means algorithm. Experimental results show that the method brings down action potential's feature dimensions and dependence of the initial classification center for the K-means algorithm, and increases the accuracy and stability of the classification results. Particularly, when processing the low Signal to Noise Ratio(SNR) signals, it can also achieve an expected purpose.

  19. Acute alteration of cardiac ECG, action potential, IKr and the human ether-a-go-go-related gene (hERG) K+ channel by PCB 126 and PCB 77

    Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K+ current (IKr) of guinea pigs' hearts, and hERG K+ current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD90), and 50% of repolarization (APD50) (P 20). PCB 77 decreased APD20 (P 90, and APD50. The PCB 126 increased the IKr in guinea-pig ventricular myocytes held at 36 °C and hERG K+ current amplitude at the end of the voltage steps in voltage-dependent mode (P + current amplitude. The PCB 77 increased the diastolic Ca2+ and decreased Ca2+ transient amplitude (P 90 possibly by increasing IKr, while PCB 77 decreased the APD20 possibly by other modulation related with intracellular Ca2+. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca2+, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K+ current and IKr. ► PCB 77 decreased action potential duration and increased intracellular Ca2+ content. ► PCBs acutely change cardiac electrophysiology and rhythmicity.

  20. Site of cochlear stimulation and its effect on electrically evoked compound action potentials using the MED-EL standard electrode array

    Helbig Silke

    2009-12-01

    Full Text Available Abstract Background The standard electrode array for the MED-EL MAESTRO cochlear implant system is 31 mm in length which allows an insertion angle of approximately 720°. When fully inserted, this long electrode array is capable of stimulating the most apical region of the cochlea. No investigation has explored Electrically Evoked Compound Action Potential (ECAP recordings in this region with a large number of subjects using a commercially available cochlear implant system. The aim of this study is to determine if certain properties of ECAP recordings vary, depending on the stimulation site in the cochlea. Methods Recordings of auditory nerve responses were conducted in 67 subjects to demonstrate the feasibility of ECAP recordings using the Auditory Nerve Response Telemetry (ART™ feature of the MED-EL MAESTRO system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Results Findings show significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function have been observed. The refractory time shows an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusions Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences could be explained by the location of the stimulating electrode with respect to the neural tissue

  1. Effects of sera obtained from electrically charged human body on action potential of giant axon of squid and its relationship to the therapy of the atomic bomb sequela, (2)

    The giant axon of squid was perfused for 20 min with sea water and four kinds of mixture of sera and sea water (1:2), and spike potential of the axon was compared by using a computer. Perfusates used were sea water, sera obtained before electric charge to the human body (pre-sera), sera obtained from the human body electrically charged with -300 volt (negative sera), and sera obtained from the human body electrically charged with +300 volt (positive sera). Negative sera increased action potential of the axon, and positive sera decreased action potential of the axon. These results revealed that negative sera have a greater deal of e-, and positive sera have less quantity of e- than pre-sera, suggesting the involvement of e- in the action potential of the axon. Microtubules in the inner part of the axonal membrane and cell membrane seem to be most greatly related to e-; however, changes in the other axons, cell membrane and protoplasm should also be taken into account. These experimental results seem to be of great value, particularly providing useful information on the treatment for late effects (cell damage) of atomic bombing or burn. (Namekawa, K.)

  2. Learning about goals: development of action perception and action control

    Verschoor, Stephan Alexander

    2014-01-01

    By using innovative paradigms, the present thesis provides convincing evidence that action-effect learning, and sensorimotor processes in general play a crucial role in the development of action- perception and production in infancy. This finding was further generalized to sequential action. Furthermore the thesis suggests that means-selection-, ends-selection information, and action-effect knowledge together feed into a unitary concept of goal. Both these findings have the potential to gener...

  3. Action preparation helps and hinders perception of action

    Press, C; Gherri, E.; Heyes, C; Eimer, M.

    2010-01-01

    Several theories of the mechanisms linking perception and action require that the links are bidirectional, but there is a lack of consensus on the effects that action has on perception. We investigated this by measuring visual event-related brain potentials to observed hand actions while participants prepared responses that were spatially compatible (e.g., both were on the left side of the body) or incompatible and action type compatible (e.g., both were finger taps) or incompatible, with obs...

  4. BODY TEMPERATURE-DEPENDENT AND INDEPENDENT ACTIONS OF CHLORDIMEFORM ON VISUAL EVOKED POTENTIALS AND AXONAL TRANSPORT IN OPTIC SYSTEM OF RAT

    Pattern reversal evoked potentials (PREPs), flash evoked potentials (FEPs), optic nerve axonal transport, and body temperature were measured in hooded rats treated with either saline or the formamidine insecticide/acaricide, chlordimeform (CDM). Rats receiving CDM had low body te...

  5. 牛磺酸对豚鼠乳头状肌慢反应动作电位的影响%Effects of taurine on slow action potentials in papillary muscles of guinea pig

    李萍; 康毅; 王国祥

    1995-01-01

    目的:研究牛磺酸对豚鼠乳头状肌慢反应动作电位的影响.方法:高钾(24 mmol·L-1)或河豚毒素(40μmol·L-1)诱发慢反应动作电位.哇巴因诱发振荡后电位.结果:牛磺酸(20mmol·L-1)减少Vmax,延长APD50并拮抗氯化钙(3 mmol·L-1)增加APA和Vmax及缩短APD的作用,增加哇巴因诱发OAP所需浓度并延长其发生时间.结论:牛磺酸有钙拮抗剂的性质%AIM: To examine the effects of taurine on the slow action potentials induced by KCl 24mmol·L-1 or tetrodotoxin 40 μmol·L-1 in guinea pig papillary muscles. METHODS:The transmembrane AP was recorded by a conventional glass microelectrode filled with to high K+-Tyrode's solution or perfused with Tyrode's solution containing tetrodotoxin.Ouabain was added in order to induce oscillatory afterpotentials. RESULTS: Taurine 20locity of slow action potential and prolonged the action potential duration at 50 % of repolarization. The amplitude of slow action potential and the maximal upstroke velocity both nized by taurine. Taurine increased the concentration of ouabain for oscillatory afterpotential and prolonged the onset time of oscillatory afterpotential. CONCLUSION: Taurine possesses a calcium antagonistic property.

  6. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October - December 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  7. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July - September 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  8. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  9. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. Also included are a number of enforcement actions that had been previously resolved but not published in this NUREG. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  10. Freeman's mass action

    Freeman, Walter J III; Kozma, Robert

    2010-01-01

    Freeman's Mass Action (FMA) refers to the collective synaptic actions that neurons in the cortex exert on each other in vast numbers by synchronizing their firing of action potentials. In the aggregate, FMA is a powerful force that creates bursts of cortical neural activity that resemble the vortices of tornadoes and hurricanes. The bursts rapidly and repeatedly retrieve memories and bind them with sensory information into percepts. In this way, FMA expresses and transmits the meaning of sens...

  11. Analysis of an H1 receptor-mediated, zinc-potentiated vasoconstrictor action of the histidyl dipeptide carnosine in rabbit saphenous vein

    O'Dowd, Anne; Miller, David J.

    1998-01-01

    The contractile action of the dipeptide carnosine (β-alanyl-L-histidine), active as a Zn·carnosine complex (Zn·Carn), was investigated in isolated rings of rabbit saphenous vein (RSV) and was found to be antagonized by the H1 antagonist mepyramine.Mepyramine-sensitive, histamine-induced contractures in RSV, were smaller (73±0.1%) and less well sustained than carnosine-induced contractures.Schild plot values for mepyramine antagonism were, for carnosine-induced contractures; pA2=7.97±0.12, slo...

  12. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  13. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  14. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  15. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1990) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  16. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  17. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April-June 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  18. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  19. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  20. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (January--March 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  1. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1990) and includes copies of letters, notices, and orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  2. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  3. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1991) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  4. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (July--September 1993) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  5. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (October--December 1989) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  6. Enforcement actions: Significant actions resolved

    This compilation summarizes significant enforcement actions that have been resolved during one quarterly period (April--June 1992) and includes copies of letters, Notices, and Orders sent by the Nuclear Regulatory Commission to licensees with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC, so that actions can be taken to improve safety by avoiding future violations similar to those described in this publication

  7. Malsch toxic waste dump: Potential dangers and impact and goals and concepts for remedial action; Sonderabfalldeponie Malsch: Gefaehrdungspotential, Belastungen, Sanierungsziele und - massnahmen

    Guenther, K. [Sondermuellbetriebsgesellschaft mbH, Fellbach-Schmiden (Germany); Huba, R.P. [wat Wasser- und Abfalltechnik Ingenieurgesellschaft mbH und Co. KG, Karlsruhe (Germany)

    1997-06-01

    The contents of a filled toxic waste dump in Malsch were physically and chemically characterized, and emissions from the dump were quantified. A remedial action plan was subsequently prepared and carried out. The project was completed in the spring of 1996 with a total investment of 100 million German marks. Definition of the project goals is explained using groundwater as an important example of the resources to be protected. (orig.) [Deutsch] Fuer eine verfuellte Sonderabfalldeponie wurde nach chemisch-physikalischer Charakterisierung der Inhaltsstoffe und Quantifizierung der Emissionen ein Sanierungsplan erstellt und bis im Fruehjahr 1996 mit einem Investitionsumfang von 100 Mio. DM umgesetzt. Die Definition der Sanierungsziele wird fuer das massgeblich betroffene Schutzgut Grundwasser dargestellt. (orig.)

  8. O'Hanlon actions by Noether symmetry

    Darabi, F

    2015-01-01

    By using the conformal symmetry between Brans-Dicke action with $\\omega=-\\frac{3}{2}$ and O'Hanlon action, we seek the O'Hanlon actions in Einstein frame respecting the Noether symmetry. Since the Noether symmetry is preserved under conformal transformations, the existence of Noether symmetry in the Brans-Dicke action asserts the Noether symmetry in O'Hanlon action in Einstein frame. Therefore, the potentials respecting Noether symmetry in Brans-Dicke action give the corresponding potentials respecting Noether symmetry in O'Hanlon action in Einstein frame.

  9. Corrective actions

    The variety of corrective actions which have been attempted at many radioactive waste disposal sites points to less than ideal performance by present-day standards at many closed and presently-operating sites. In humid regions, most of the problems have encompassed some kind of water intrusion into the buried waste. In arid regions, the problems have centered on trench subsidence and intrusion by plant roots and animals. It is overwhelmingly apparent that any protective barrier for the buried waste, whether for water or biological intrusion, will depend on stable support from the underlying burial trenches. Trench subsidence must be halted, prevented, or circumscribed in some manner to assure this necessary long-term support. Final corrective actions will differ considerably from site to site, depending on unique geological, pedological, and meteorological environments. In the meantime, many of the shorter-term corrective actions described in this chapter can be implemented as immediate needs dictate

  10. Zoonotic infections in Alaska: disease prevalence, potential impact of climate change and recommended actions for earlier disease detection, research, prevention and control

    Karsten Hueffer

    2013-02-01

    Full Text Available Over the last 60 years, Alaska's mean annual temperature has increased by 1.6°C, more than twice the rate of the rest of the United States. As a result, climate change impacts are more pronounced here than in other regions of the United States. Warmer temperatures may allow some infected host animals to survive winters in larger numbers, increase their population and expand their range of habitation thus increasing the opportunity for transmission of infection to humans. Subsistence hunting and gathering activities may place rural residents of Alaska at a greater risk of acquiring zoonotic infections than urban residents. Known zoonotic diseases that occur in Alaska include brucellosis, toxoplasmosis, trichinellosis, giardiasis/cryptosporidiosis, echinococcosis, rabies and tularemia. Actions for early disease detection, research and prevention and control include: (1 determining baseline levels of infection and disease in both humans and host animals; (2 conducting more research to understand the ecology of infection in the Arctic environment; (3 improving active and passive surveillance systems for infection and disease in humans and animals; (4 improving outreach, education and communication on climate-sensitive infectious diseases at the community, health and animal care provider levels; and (5 improving coordination between public health and animal health agencies, universities and tribal health organisations.

  11. Superoxide dismutase administration, a potential therapy against oxidative stress related diseases: several routes of supplementation and proposal of an original mechanism of action.

    Carillon, Julie; Rouanet, Jean-Max; Cristol, Jean-Paul; Brion, Richard

    2013-11-01

    Oxidative stress, involved in many diseases, is defined as an impaired balance between reactive oxygen species (ROS) production and antioxidant defences. Antioxidant enzymes such as superoxide dismutase (SOD) play a key role in diminishing oxidative stress. Thus, the removal of ROS by exogenous SODs could be an effective preventive strategy against various diseases. The poor bioavailability of exogenous SODs has been criticized. However, improvements in SOD formulation may overcome this limitation and boost interest in its therapeutic properties. Here, we provide a review of animal and human studies about SODs supplementation in order to evaluate their therapeutic value. Protective effects have been observed against irradiation, carcinogenesis, apoptosis and neurodegeneration. SODs administration has also been reported to alleviate inflammatory, infectious, respiratory, metabolic and cardiovascular diseases and genitourinary and fertility disorders, raising the question of its mechanism of action in these diverse situations. Some authors have shown an increase in endogenous antioxidant enzymes after exogenous SODs administration. The induction of endogenous antioxidant defence and, consequently, a decrease in oxidative stress, could explain all the effects observed. Further investigations need to be carried out to test the hypothesis that SODs supplementation acts by inducing an endogenous antioxidant defence. PMID:23793992

  12. Action Research

    Milton-Brkich, Katie Lynn; Shumbera, Kristen; Beran, Becky

    2010-01-01

    Defined as "any systemic inquiry conducted by teachers... for the purpose of gathering information about how their particular schools operate, how they teach, and how their students learn" (Mertler, 2009), "action research" is empowering and professional research done by teachers to inform and improves their own practices. Although there are many…

  13. China's Actions

    2010-01-01

    @@ China's National Development and Reform Commission publicized the country's policies and actions for addressing climate change in a report released on November 26,2009.The report highlighted China's efforts in cutting greenhouse gas emissions in 2009 by: (1)Rigorously checking the blind expansion of its energy-and pollution-intensive industries.

  14. Vasopressin stimulates action potential firing by protein kinase C-dependent inhibition of KCNQ5 in A7r5 rat aortic smooth muscle cells

    Brueggemann, Lioubov I.; Moran, Christopher J.; Barakat, John A.; Yeh, Jay Z.; Cribbs, Leanne L.; Byron, Kenneth L.

    2006-01-01

    [Arg8]-vasopressin (AVP), at low concentrations (10–500 pM), stimulates oscillations in intracellular Ca2+ concentration (Ca2+ spikes) in A7r5 rat aortic smooth muscle cells. Our previous studies provided biochemical evidence that protein kinase C (PKC) activation and phosphorylation of voltage-sensitive K+ (Kv) channels are crucial steps in this process. In the present study, Kv currents (IKv) and membrane potential were measured using patch clamp techniques. Treatment of A7r5 cells with 100...

  15. Use-dependent block of Ca2+ current by moricizine in guinea-pig ventricular myocytes: a possible ionic mechanism of action potential shortening.

    Yamane, T; Sunami, A.; Sawanobori, T.; Hiraoka, M

    1993-01-01

    1. Whole cell patch clamp techniques were used to study the effects of moricizine on membrane currents in guinea-pig ventricular myocytes. 2. Application of moricizine caused reversible depression of the time-dependent outward K+ current. 3. The Na+/Ca2+ exchange current was not directly affected by moricizine. 4. Although moricizine hardly affected the L-type Ca2+ current when cells were stimulated at a frequency of 0.1 Hz, it suppressed the current at depolarized holding potentials in a use...

  16. Willed action and its impairments.

    Jahanshahi, M

    1998-09-01

    Actions are goal-directed behaviours that usually involve movem ent. There is evidence that intentional self-generated actions (willed actions) are controlled differently from routine, stereotyped actions that are externally triggered by environmental stimuli. We review evidence from investigations using positron emission tomography (PET), recordings of movement-related cortical potentials (MRCPs) or transcranial magnetic stimulation (TMS), and conclude that willed actions are controlled by a network of frontal cortical (dorsolateral prefrontal cortex, supplementary motor area, anterior cingulate) and subcortical (thalamus and basal ganglia) areas. We also consider evidence suggesting that some of the cognitive and motor deficits of patients with frontal lesions, Parkinson's disease, or schizophrenia as well as apathy and abulia and rarer phenomena such as primary obsessional slowness can be considered as reflecting im pairment of willed actions. We propose that the concept of a willed action system based on the frontostriatal circuits provides a useful framework for integrating the cognitive, motor, and motivational deficits found in these disorders. Problems remaining to be resolved include: identification of the component processes of willed actions; the specific and differential role played by each of the frontal cortical and subcortical areas in the control of willed actions; the specific mechanisms of impairm ent of willed actions in Parkinson's disease, schizophrenia, and frontal damage; and the precise role of the neurotransmitter dopamine in the willed action system. PMID:22448836

  17. Digital PCR for quantification of recurrent and potentially actionable somatic mutations in circulating free DNA from patients with diffuse large B-cell lymphoma.

    Camus, Vincent; Sarafan-Vasseur, Nasrin; Bohers, Elodie; Dubois, Sydney; Mareschal, Sylvain; Bertrand, Philippe; Viailly, Pierre-Julien; Ruminy, Philippe; Maingonnat, Catherine; Lemasle, Emilie; Stamatoullas, Aspasia; Picquenot, Jean-Michel; Cornic, Marie; Beaussire, Ludivine; Bastard, Christian; Frebourg, Thierry; Tilly, Hervé; Jardin, Fabrice

    2016-09-01

    Diffuse large B-cell lymphoma (DLBCL) is an aggressive and heterogeneous malignancy harboring frequent targetable activating somatic mutations. Emerging evidence suggests that circulating cell-free DNA (cfDNA) can be used to detect somatic variants in DLBCL using Next-Generation Sequencing (NGS) experiments. In this proof-of-concept study, we chose to develop simple and valuable digital PCR (dPCR) assays for the detection of recurrent exportin-1 (XPO1) E571K, EZH2 Y641N, and MYD88 L265P mutations in DLBCL patients, thereby identifying patients most likely to potentially benefit from targeted therapies. We demonstrated that our dPCR assays were sufficiently sensitive to detect rare XPO1, EZH2, and MYD88 mutations in plasma cfDNA, with a sensitivity of 0.05%. cfDNA somatic mutation detection by dPCR seems to be a promising technique in the management of DLBCL, in addition to NGS experiments. PMID:26883583

  18. Action of caffeine on x-irradiated HeLa cells. VII. Evidence that caffeine enhances expression of potentially lethal radiation damage

    HeLa cells irradiated with 2 Gy of 220-kV X rays suffer a 60-70% loss of colony-forming ability which is increased to 90% by postirradiation treatment with 10 mM caffeine for 6 hr. The detailed postirradiation patterns of cell death and sister-cell fusion in such cultures and in cultures in which the colony-forming ability was brought to about the same level by treatment with a larger (4 Gy) X-ray dose alone or by longer (48 hr) treatment with 10 mM caffeine alone were recorded by time-lapse cinemicrography. Because the patterns of cell death and fusion differ radically in irradiated and in caffeine-treated cultures, the response of the additional cells killed by the combined treatment can be identified as X-ray induced rather than caffeine induced. The appearance of cultures after several days of incubation confirms the similarity of the post-treatment patterns of proliferation in cultures suffering enhanced killing to those occurring in cultures treated with larger doses of X rays alone. It is concluded that x rays do not sensitize cells to caffeine, but rather that caffeine enhanced the expression of potentially lethal radiation-induced damage

  19. Specific actions of cyanide on membrane potential and voltage-gated ion currents in rostral ventrolateral medulla neurons in rat brainstem slices.

    Wang, G; Zhou, P; Repucci, M A; Golanov, E V; Reis, D J

    2001-08-24

    The present study examined specific effects of sodium cyanide (CN) on the membrane potential (MP), spontaneous discharge (SD) and voltage-gated ion current of the identified bulbospinal rostral ventrolateral medulla (RVLM) neuron in the rat pup brainstem slice. 125 microM CN rapidly depolarized MP in the RVLM neuron by 11.6 mV as well as enhanced the SD rate by 300%. In contrast, the same dose of CN immediately hyperpolarized unlabeled, non-RVLM neurons by 4.8 mV. 50 microM CN did not significantly affect voltage-gated Ca(++) or A-type K(+) currents. The same concentration of CN, however, rapidly and reversibly suppressed voltage-gated Na(+) currents and sustained outward K(+) currents in the RVLM neuron by 22.5% and 23%, respectively. Tetraethylammonium could mimic the effect of CN on MP, SD and sustained K(+) current in the RVLM neuron. It is concluded that: (1) like that from the adult rat, the rat pup bulbospinal RVLM neuron can be selectively and rapidly excited by CN; (2) the hypoxia-sensitive, sustained outward K(+) channel may play an important role in the acute hypoxia-induced excitation of the RVLM neurons. PMID:11502361

  20. Effect of Zhigancao Decoction on Ventricle Monophasic Action Potential in Rabbits%炙甘草汤对正常家兔心室肌电生理特性的影响

    周承志; 吴成云; 杨波; 张道亮; 王腾

    2015-01-01

    目的:研究炙甘草汤对正常家兔左心室电生理特性的影响,探讨其抗心律失常的作用机制。方法采用单相动作电位(MAP)记录技术,测定空白对照组和炙甘草汤组兔心室肌体表心电图和 MAP 的变化。结果与对照组比较,炙甘草汤组兔心室肌心率减慢,QT 间期延长的同时 Tp -e不增加,Tp -e /QT 缩小;并且炙甘草汤组兔心室肌单相动作电位幅度(MAPA)无明显变化,单相动作电位时程(MAPD)MAPD20、MAPD50、MAPD90均延长。结论炙甘草汤能降低心率,延长 MAPD,并缩小 Tp -e /QT,减少室性心律失常发生,可能是炙甘草汤抗心律失常且相对安全的机制。%Abstracts:Objective To observe the effect of Zhigancao Decoction(ZD) on left ventricular electrophysiology in rabbits.Methods The monophasic action potential recording technique were used to investigate electrocardiogram and the effects of ZD on MAP in control group and ZD group .Results ZD group reduced the heart rate and lengthened QT intervals,and Tp -e /QT was lower than control group.Monopha-sic action potential amplitude (MAPA) of ventricular myocytes had no difference, monophasic action potential duration(MAPD)MAPD20, MAPD50,and MAPD90 were prolonged in ZD group.Conclusion ZD can reduce heart rate , prolong MAPD ,and decrease Tp -e /QT in rab-bits ventricle cardiomyocytes, which may contribute to its antiarhythmic safely effect.

  1. 蝙蝠葛苏林碱对家兔在体心脏单相动作电位的影响%Effect of daurisoline on monophasic action potential of rabbit hearts in vivo

    李真; 林先明; 夏敬生; 杨晓燕; 龚培力; 曾繁典

    2001-01-01

    The use-dependent characteristics of daurisoline on monophasic action potentials (MAP) of the left ventricle of the rabbit heart in situ were recorded with MAP recording technique. The results showed that daurisoline decreased monophasic action potential amplitude (MAPA) and prolonged monophasic action potential duration at the 50% and 90% (MAPD50, MAPD90), effective refractory period (ERP), ERP/MAPD90 at the steady-state cycle lengths of 240, 210, 180 ms. The percent of prolongation of MAPD50 was 12.8±2.9, 9.5±2.6, 9.0±1.6, that of MAPD90 was 10.9±2.6, 7.5±2.4, 6.5±2.7, that of ERP was 25.7±4.3, 18.5±4.1, 24.2±7.2, and that of ERP/MAPD90 was 13.7±4.5, 10.2±2.2, 16.1±5.1, respectively. Its effect showed no relation to frequency (n=6, P>0.05). The effects of sotalol on MAP were similar to that of daurisoline, but it prolonged MAPD90 and ERP in a reverse use-dependent manner (P0.05). 其延长作用均呈非使用依赖性特征. 在所有起搏周长下,索他洛尔亦降低MAPA,延长MAPD50,MAPD90,ERP,ERP/MAPD90,但其延长MAPD90,ERP的作用均呈逆向使用依赖性特征(P<0.05). 结果表明,DS能明显降低家兔在体心脏MAPA,延长MAPD50,MAPD90,ERP,ERP/MAPD90,该作用呈非使用依赖性特征.

  2. Efficacy and safety of Panax notoginseng saponin therapy for acute intracerebral hemorrhage: meta-analysis and mini review of potential mechanisms of action

    Dongying eXu

    2015-01-01

    Full Text Available Intracranial/intracerebral hemorrhage (ICH is a leading cause of death and disability in people with traumatic brain injury (TBI and stroke. No proven drug is available for ICH. Panax notoginseng (total saponin extraction, PNS is one of the most valuable herb medicines for stroke and cerebralvascular disorders in China. We searched for randomized controlled clinical trials (RCTs involving PNS injection to treat cerebral hemorrhage for meta-analysis from various databases including the Chinese Stroke Trials Register, the trials register of the Cochrane Complementary Medicine Field, the Cochrane Central Register of Controlled Trials, MEDLINE, Chinese BioMedical disc, and China Doctorate/Master Dissertations Databases. The quality of the eligible trials was assessed by Jadad’s scale. Twenty (20 of the 24 identified randomized controlled trials matched the inclusive criteria including 984 ICH patients with PNS injection and 907 ICH patients with current treatment (CT. Compared to the CT groups, PNS-treated patients showed better outcomes in the effectiveness rate (ER, neurological deficit score (NDS, intracranial hematoma volume (IHV, intracerebral edema volume (IEV, Barthel Index (BI, the number of patients died (NDP and incidence of adverse events. Conclusion: PNS injection is superior to CT for acute ICH. A review of the literature shows that PNS may exert multiple protective mechanisms against ICH-induced brain damage including hemostasis, anti-coagulation, anti-thromboembolism, cerebral vasodilation, invigorated blood dynamics, anti-inflammation, antioxidation and anti-hyperglycemic effects. As PNS has a long clinical track record in Asia, it could potentially become a therapy option to treat ICH in the US and Europe. Further clinical trials with better experimental design could determine the long-term effects of PNS treatment for TBI and stroke.

  3. Actions and mechanisms of action of novel analogues of sotalol on guinea-pig and rabbit ventricular cells.

    Connors, S. P.; Gill, E. W.; Terrar, D. A.

    1992-01-01

    1. The actions and mechanisms of action of novel analogues of sotalol which prolong cardiac action potentials were investigated in guinea-pig and rabbit isolated ventricular cells. 2. In guinea-pig and rabbit cells the compounds significantly prolonged action potential duration at 20% and 90% repolarization levels without affecting resting membrane potential. In guinea-pig but not rabbit cells there was an increase in action potential amplitude and in rabbit cells there was no change in the s...

  4. Cardiac gap junctions and action potential propagation

    Veen, Antonius Adrianus Bartholomeus van

    2002-01-01

    Described are the results, obtained from experiments on transfected cells to those on intact heart and new data are provided on connexin phosphorylation, expression and distribution. Transfected cells, regarded as the lowest level of complexity, are a very useful and reliable tool to study the effec

  5. Conjugate flow action functionals

    We present a new general framework to construct an action functional for a non-potential field theory. The key idea relies on representing the governing equations relative to a diffeomorphic flow of curvilinear coordinates which is assumed to be functionally dependent on the solution field. Such flow, which will be called the conjugate flow, evolves in space and time similarly to a physical fluid flow of classical mechanics and it can be selected in order to symmetrize the Gâteaux derivative of the field equations with respect to suitable local bilinear forms. This is equivalent to requiring that the governing equations of the field theory can be derived from a principle of stationary action on a Lie group manifold. By using a general operator framework, we obtain the determining equations of such manifold and the corresponding conjugate flow action functional. In particular, we study scalar and vector field theories governed by second-order nonlinear partial differential equations. The identification of transformation groups leaving the conjugate flow action functional invariant could lead to the discovery of new conservation laws in fluid dynamics and other disciplines

  6. Motion Primitives for Action Recognition

    Fihl, Preben; Holte, Michael Boelstoft; Moeslund, Thomas B.

    2007-01-01

    The number of potential applications has made automatic recognition of human actions a very active research area. Different approaches have been followed based on trajectories through some state space. In this paper we also model an action as a trajectory through a state space, but we represent...... the actions as a sequence of temporal isolated instances, denoted primitives. These primitives are each defined by four features extracted from motion images. The primitives are recognized in each frame based on a trained classifier resulting in a sequence of primitives. From this sequence we recognize...... different temporal actions using a probabilistic Edit Distance method. The method is tested on different actions with and without noise and the results show recognition rates of 88.7% and 85.5%, respectively....

  7. Action Recognition using Motion Primitives

    Moeslund, Thomas B.; Fihl, Preben; Holte, Michael Boelstoft

    The number of potential applications has made automatic recognition of human actions a very active research area. Different approaches have been followed based on trajectories through some state space. In this paper we also model an action as a trajectory through a state space, but we represent...... the actions as a sequence of temporal isolated instances, denoted primitives. These primitives are each defined by four features extracted from motion images. The primitives are recognized in each frame based on a trained classifier resulting in a sequence of primitives. From this sequence we recognize...... different temporal actions using a probabilistic Edit Distance method. The method is tested on different actions with and without noise and the results show recognizing rates of 88.7% and 85.5%, respectively....

  8. Efeitos do potencial de ação neural sobre a percepção de fala em usuários de implante coclear Influence of evoked compound action potential on speech perception in cochlear implant users

    Mariana Cardoso Guedes

    2007-08-01

    Full Text Available O Potencial de Ação Composto Evocado Eletricamente reflete a atividade do nervo auditivo, podendo ser registrado através dos eletrodos do implante coclear. A determinação dos elementos neurais estimuláveis pode contribuir para explicar a variabilidade de desempenho entre indivíduos implantados. OBJETIVO: Comparar o desempenho nos testes de percepção da fala entre pacientes que apresentaram e que não apresentaram potencial de ação composto evocado eletricamente no momento intra-operatório. MATERIAL E MÉTODO: Estudo prospectivo no qual 100 indivíduos usuários do implante coclear Nucleus 24 foram divididos em dois grupos de acordo com a presença ou ausência do potencial de ação intra-operatório. Após 6 meses de uso do dispositivo, os resultados dos testes de percepção de fala foram comparados entre os grupos. RESULTADOS: O potencial foi observado em 72% dos pacientes. A percepção no teste de frases em formato aberto foi melhor nos indivíduos com presença de potencial (média 82,8% contra 41,0%, p = 0,005. Houve associação entre ausência do potencial e etiologia da surdez por meningite. CONCLUSÃO: Ausência de potencial neural intraoperatório esteve associada ao pior desempenho na percepção da fala e à etiologia da surdez por meningite. Por outro lado, a presença do potencial de ação intraoperatório sugere ótimo prognóstico.Electrically Evoked Compound Action Potential is a measure of synchronous cochlear nerve fibers activity elicited by electrical stimulation of the cochlear implant. The electrophysiological nerve responses may contribute to explain the variability in individual performance of cochlear implant recipients. AIM: To compare speech perception tests’ performances of cochlear implant users according to the presence or absence of intraoperative neural telemetry responses. MATERIAL AND METHOD: Prospective study design with 100 "Nucleus 24" cochlear implant users divided in two groups according

  9. Affirmative Action and Stereotype Threat

    Cohen, Alma

    2015-01-01

    This paper provides experimental evidence on the effect of affirmative action (AA). In particular, we investigate whether affirmative action has a ”stereotype threat effect” – that is, whether AA cues a negative stereotype that leads individuals to conform to the stereotype and adversely affects their performance. Stereotype threat has been shown in the literature to be potentially significant for individuals who identify strongly with the domain of the stereotype and who engage in complex st...

  10. 29 CFR 1990.147 - Final action.

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Final action. 1990.147 Section 1990.147 Labor Regulations...) IDENTIFICATION, CLASSIFICATION, AND REGULATION OF POTENTIAL OCCUPATIONAL CARCINOGENS Regulation of Potential Occupational Carcinogens § 1990.147 Final action. (a) Within one hundred twenty (120) days from the last day...

  11. Effect of melittin on potassium currents and action potential in ventricular myocytes of guinea pig%蜂毒肽对豚鼠心室肌细胞钾电流和动作电位的影响

    张雪梅; 杨申; 何晓静; 郑平; 江明华

    2000-01-01

    AIM: To examine the effects of melittin (Mel) , the major component of bee venom, on delayed rectifier K + current (Ik), inward rectifier K+ current (Ik1) and action potential (AP) in guinea pig ventricular myocytes. METHODS: Ik, Ikl, and AP were recorded using the whole-cell patch-clamp technique. RESULTS: The action potential duration (APD) was shortened by Mel in a concentration-dependent manner. Mel 0.05, 0.1, 0.2 μmol· L- 1 shortened APD5o from ( 520 ± 55) to (459±91) (n=5, P>0.05), (385±102) (n=5, P<0.01), and (281±81) ms (n=5, P<0.01), respectively; and APD9o from (613±96) to (536±93) (n =5, P>0.05), (467±96)ms (n=5, P<0.01), and (354±95) ms (n=5, P <0.01), respectively. Mel increased the amplitude of Ik alSo in a concentration-dependent manner. Mel 0.05, 0.1, 0.2 μmol· L- 1 increased Ik from (295 ± 109) to (371 ± 142) ( n = 5, P <0.05), (467±180) (n=5, P<0.05), (552±248) pA ( n = 5, P < 0.05), respectively at testing potential of + 40 rmV. But no significant effect of Mci on Ikl was observed at these concentrations. CONCLUSION: Mel significantly increased Ik in a concentration-dependent manner which contributed to shortening of APD.%目的:研究蜂毒肽(Melittin,Mel)对豚鼠心室肌细胞钾电流和动作电位的影响.方法:全细胞膜片箝记录.结果:蜂毒肽可呈浓度依赖性促进延迟整流钾电流(Ik),在测定电压为40mv时,0.05,0.1,0.2μmol·L-1蜂毒肽分别使Ik从(295±109)增大到(371±142)(n=5 P<0.05),(467±180)(n=5,P<0.05),(552±248)pA(n=5,P<0.05).但药物在三个浓度时对内向整流钾电流(Ikl)均无显著影响.蜂毒肽0.05,0.1,0.2 μmol·L-1分别使动作电位APD5o由(520±55)减小到(459±91)(n=5,P>0.05),(385±102)(n=5,P<0.01),(281±81)ms(n=5,P<0.01),使APD9o由(613±96)减小到(536±93)(n=5,P>0.05),(467±96)(n=5,P<0.01),(354±95)ms(n=5,P<0.01).结论:蜂毒肽促进延迟整流钾电流,缩短动作电位时程.

  12. Study of crotoxin mechanism of action to mammary carcinomas and evaluation of its potential as a radiopharmaceutical; Estudo do mecanismo de acao da crotoxina em tumores mamarios e avaliacao do seu potenctial radiofarmaceutico

    Silveira, Marina Bicalho

    2010-07-01

    Crotoxin, the main component of Crotalus durissus terrificus snake venom, has been studied since 1938. It is a natural polypeptidic complex with pharmacological potential because of its antitumoral properties which has attracted great interest for diagnosis and therapy of oncological diseases. However, Crotoxin mechanism of action and sites of specific interaction on tumor cells are still misunderstood. Breast cancer is the second most frequent type in the world and the most common cancer in women. About 30 to 60% of mammary tumors overexpress epidermal growth factor receptor (EGFR), a transmembrane protein related to cell proliferation. Since literature has reported that Crotoxin antitumoral effect is more potent on cells with EGFR overexpression the objectives of this work were to evaluate Crotoxin cytotoxic effects on mammary tumor cells human breast carcinoma (MCF-7) and Ehrlich tumor cells (murine ascitics carcinoma), and to investigate the specific molecular interaction of Crotoxin on Ehrlich tumor cells. Initially, Crotoxin was radiolabelled with iodine-125 ({sup 125}I-Crotoxin) and iodine-131 ({sup 131}I-Crotoxin). Saturation and competition assay were carried out to characterize Crotoxin in vitro interaction; Crotoxin biodistribution studies and singlephoton emission computed tomography (SPECT) of mice bearing Ehrlich tumor have been evaluated to describe in vivo interaction. Our results showed that Crotoxin presented cytotoxic effect against Ehrlich with DL{sub 50} in vitro (concentration of compound which is lethal for 50% of cells) of about one micromolar, but did not present significant effect against MCF-7. Morphological alterations characteristic of apoptosis suggests programmed cell death. {sup 125}I-Crotoxin interaction with Ehrlich tumor cells was saturable with approximately 70% specificity, and presented K{sub d}=24.98 nmol/L and B{sub max}=16,570 sites/cell for low affinity binding sites and K{sub d}=0.06 nmol/L and B{sub max}=210 sites

  13. The Ionic Model of the Canine Left Atrial Action Potential%犬左心房心肌细胞动作电位的计算机建模仿真研究

    孙奇; 唐闽; 夏灵; 张澍

    2013-01-01

    目的 构建犬左心房心肌细胞动作电位的计算机仿真模型.方法 在Ramirez-Nattel-Courtemanche心房肌细胞模型的基础上,根据离子流数据构建左心房心肌细胞的计算机仿真模型.结果 计算机仿真的电流与实验得到的离子流相似,最后得到的动作电位与我们在单个左心房肌细胞记录到的动作电位基本一致.结论 我们根据犬左心房肌细胞离子流数据构建的细胞模型较现有模型更符合左心房细胞的特性,为进一步仿真研究心房颤动的机制打下了良好的基础.%Objective To develop a mathematical model of the left atrial action potential (AP) using experimental data. Methods Using specific formulations of ionic currents, we developed a mathematical model of the left atrial AP. Result The simulated ionic currents in a fashion similar to experimental recordings. The simulated AP resembles AP recorded from canine left atrial myocytes. Conclusion This revised model faithfully reproduced properties of the canine left AP, which would be a useful tool for studying the mechanisms of atrial fibrillation.

  14. Comparison of speech recognition with different speech coding strategies (SPEAK, CIS, and ACE) and their relationship to telemetric measures of compound action potentials in the nucleus CI 24M cochlear implant system.

    Kiefer, J; Hohl, S; Stürzebecher, E; Pfennigdorff, T; Gstöettner, W

    2001-01-01

    Speech understanding and subjective preference for three different speech coding strategies (spectral peak coding [SPEAK], continuous interleaved sampling [CIS], and advanced combination encoders [ACE]) were investigated in 11 post-lingually deaf adult subjects, using the Nucleus CI 24M cochlear implant system. Subjects were randomly assigned to two groups in a balanced crossover study design. The first group was initially fitted with SPEAK and the second group with CIS. The remaining strategies were tested sequentially over 8 to 10 weeks with systematic variations of number of channels and rate of stimulation. Following a further interval of 3 months, during which subjects were allowed to listen with their preferred strategy, they were tested again with all three strategies. Compound action potentials (CAPs) were recorded using neural response telemetry. Input/output functions in relation to increasing stimulus levels and inter-stimulus intervals between masker and probe were established to assess the physiological status of the cochlear nerve. Objective results and subjective rating showed significant differences in favour of the ACE strategy. Ten of the 11 subjects preferred the ACE strategy at the end of the study. The estimate of the refractory period based on the inter-stimulus interval correlated significantly with the overall performance with all three strategies, but CAP measures could not be related to individual preference of strategy or differences in performance between strategies. Based on these results, the ACE strategy can be recommended as an initial choice specifically for the Nucleus CI 24M cochlear implant system. Nevertheless, access to the other strategies may help to increase performance in individual patients. PMID:11296939

  15. Hybrid Action Systems

    Rönnkö, M.; Ravn, Anders Peter; Sere, K.

    2003-01-01

    In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time-derivatives in modell......In this paper we investigate the use of action systems with differential actions in the specifcation of hybrid systems. As the main contribution we generalize the definition of a differential action, allowing the use of arbitrary relations over model variables and their time...... to the differential action, thus, allowing stepwise development of hybrid systems Udgivelsesdato: JAN 1...

  16. Perfect Lattice Actions for Staggered Fermions

    Bietenholz, W; Chandrasekharan, S; Wiese, U J

    1996-01-01

    We construct a perfect lattice action for staggered fermions by blocking from the continuum. The locality, spectrum and pressure of such perfect staggered fermions are discussed. We also derive a consistent fixed point action for free gauge fields and discuss its locality as well as the resulting static quark-antiquark potential. This provides a basis for the construction of (classically) perfect lattice actions for QCD using staggered fermions.

  17. Hybrid Action Systems

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    a differential action, which allows differential equations as primitive actions. The extension allows us to model hybrid systems with both continuous and discrete behaviour. The main result of this paper is an extension of such a hybrid action system with parallel composition. The extension does not change...... the original meaning of the parallel composition, and therefore also the ordinary action systems can be composed in parallel with the hybrid action systems....

  18. Extracellular calcium (Ca2+(o))-sensing receptor in a murine bone marrow-derived stromal cell line (ST2): potential mediator of the actions of Ca2+(o) on the function of ST2 cells

    Yamaguchi, T.; Chattopadhyay, N.; Kifor, O.; Brown, E. M.; O'Malley, B. W. (Principal Investigator)

    1998-01-01

    The calcium-sensing receptor (CaR) is a G protein-coupled receptor that plays key roles in extracellular calcium ion (Ca2+(o)) homeostasis by mediating the actions of Ca2+(o) on parathyroid gland and kidney. Bone marrow stromal cells support the formation of osteoclasts from their progenitors as well as the growth of hematopoietic stem cells by secreting humoral factors and through cell to cell contact. Stromal cells also have the capacity to differentiate into bone-forming osteoblasts. Bone resorption by osteoclasts probably produces substantial local increases in Ca2+(o) that could provide a signal for stromal cells in the immediate vicinity, leading us to determine whether such stromal cells express the CaR. In this study, we used the murine bone marrow-derived, stromal cell line, ST2. Both immunocytochemistry and Western blot analysis, using an antiserum specific for the CaR, detected CaR protein in ST2 cells. We also identified CaR transcripts in ST2 cells by Northern analysis using a CaR-specific probe and by RT-PCR with CaR-specific primers, followed by nucleotide sequencing of the amplified products. Exposure of ST2 cells to high Ca2+(o) (4.8 mM) or to the polycationic CaR agonists, neomycin (300 microM) or gadolinium (100 microM), stimulated both chemotaxis and DNA synthesis in ST2 cells. Therefore, taken together, our data strongly suggest that the bone marrow-derived stromal cell line, ST2, possesses both CaR protein and messenger RNA that are very similar if not identical to those in parathyroid and kidney. Furthermore, as ST2 cells have the potential to differentiate into osteoblasts, the CaR in stromal cells could participate in bone turnover by stimulating the proliferation and migration of such cells to sites of bone resorption as a result of local, osteoclast-mediated release of Ca2+(o) and, thereafter, initiating bone formation after their differentiation into osteoblasts.

  19. Ovarian actions of resveratrol.

    Ortega, Israel; Duleba, Antoni J

    2015-08-01

    Resveratrol, a natural polyphenol found in grapes, berries, and medicinal plants, exhibits antioxidant and anti-inflammatory activities and has been proposed to be a longevity-prolonging agent. There is also growing evidence that resveratrol has cardioprotective properties and beneficial effects on both glucose and lipid metabolism. Recently, several studies have examined the use of resveratrol as a therapeutic agent to treat numerous pathological and metabolic disorders. Herein, we present insights into the mechanisms of action, biological effects, and current evidence of actions of resveratrol on the ovary. In vitro, resveratrol inhibits proliferation and androgen production by theca-interstitial cells. Resveratrol also exerts a cytostatic, but not cytotoxic, effect on granulosa cells, while decreasing aromatization and vascular endothelial growth factor expression. In vivo, resveratrol treatment reduced the size of adipocytes and improved estrus cyclicity in the previously acyclic rat model of polycystic ovary syndrome (PCOS). In addition, resveratrol increased the ovarian follicular reserve and prolonged the ovarian life span in rats. Taken together, resveratrol emerges as a potential therapeutic agent to treat conditions associated with androgen excess, such as PCOS. The efficacy of resveratrol in the treatment of gynecological conditions requires further investigation. PMID:26315293

  20. Corrective Action Decision Document for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada

    The six bunkers included in CAU 204 were primarily used to monitor atmospheric testing or store munitions. The 'Corrective Action Investigation Plan (CAIP) for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada' (NNSA/NV, 2002a) provides information relating to the history, planning, and scope of the investigation; therefore, it will not be repeated in this CADD. This CADD identifies potential corrective action alternatives and provides a rationale for the selection of a recommended corrective action alternative for each CAS within CAU 204. The evaluation of corrective action alternatives is based on process knowledge and the results of investigative activities conducted in accordance with the CAIP (NNSA/NV, 2002a) that was approved prior to the start of the Corrective Action Investigation (CAI). Record of Technical Change (ROTC) No. 1 to the CAIP (approval pending) documents changes to the preliminary action levels (PALs) agreed to by the Nevada Division of Environmental Protection (NDEP) and DOE, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This ROTC specifically discusses the radiological PALs and their application to the findings of the CAU 204 corrective action investigation. The scope of this CADD consists of the following: (1) Develop corrective action objectives; (2) Identify corrective action alternative screening criteria; (3) Develop corrective action alternatives; (4) Perform detailed and comparative evaluations of corrective action alternatives in relation to corrective action objectives and screening criteria; and (5) Recommend and justify a preferred corrective action alternative for each CAS within CAU 204

  1. CLICing into action

    Barbara Warmbein

    2015-01-01

    Putting its acronym into action, the Compact Linear Collider (CLIC) collaboration is testing its first compact accelerator module in the CTF3 test facility. Fed by high-power waveguides, cables and cooling tubes, the module has all the functions of future CLIC modules and allows the experts to test all the features, including frequency, losses, damping, acceleration and deceleration.   The new CLIC module in the CTF3 test facility. CLIC is one of the potential follow-up projects to the LHC, alongside the International Linear Collider (ILC) and the Future Circular Collider (FCC) studies. Instead of smashing protons into protons, it is designed to collide electrons with positrons. Following the publication of its CDR in 2012, the CLIC collaboration entered the project preparation phase - testing its unique technology, making improvements and taking a closer look at the cost of the individual components. This is where the new module comes in. While many of the techniques and technologies neede...

  2. Inferences about Action Engage Action Systems

    Taylor, Lawrence J.; Lev-Ari, Shiri; Zwaan, Rolf A.

    2008-01-01

    Verbal descriptions of actions activate compatible motor responses [Glenberg, A. M., & Kaschak, M. P. (2002). Grounding language in action. "Psychonomic Bulletin & Review, 9", 558-565]. Previous studies have found that the motor processes for manual rotation are engaged in a direction-specific manner when a verb disambiguates the direction of…

  3. Effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials in isolated rabbit hearts%低温联合右美托咪定对兔心肌单相动作电位的影响

    李惠; 高鸿; 赵艳; 龙娟; 张凯强; 刘艳秋

    2015-01-01

    Objective To investigate the effects of hypothermia combined with dexmedetomidine on myocardial monophasic action potentials (MAPs) in isolated rabbit hearts.Methods Adult rabbits,weighing 2.0-2.5 kg,were heparinized and anesthetized with pentobarbital sodium 30 mg/kg.Their hearts were rapidly removed and retrogradely perfused in a Langendorff apparatus at 37 ℃.Eighteen hearts were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C),hypothermia group (group H),and hypothermia+dexmedetomidine group (group HD).The hearts were continuously perfused for 60 min with 37 ℃ K-H solution in group C,with 32 ℃ K-H solution in group H,or with 32 ℃ K-H solution containing dexmedetomidine 25 ng/ml in group HD.At the end of equilibration (T0) and at 15,30 and 60 min of perfusion with K-H solution,HR and MAPs of left ventricular epicardium,mid-myocardium and endocardium were recorded.MAP duration at 50% repolarization (MAPD50) and at 90% repolarization (MAPD90),monophasic action potential amplitude (MAPA) and maximal velocity (Vmax) were calculated.Results Compared with group C,HR was significantly decreased,and MAPD50 and MAPD90 were prolonged at each time of perfusion with K-H solution in H and HD groups.There was no significant difference in HR,MAPD50 and MAPD90 between H group and HD group.There was no significant difference in MAPA and Vmax between the three groups.Conclusion Hypothermia combined with dexmedetomidine can lead to prolongation of myocardial repolarization,and dexmedetomidine exerts no effect on hypothermia-induced change in MAPs in isolated rabbit hearts.%目的 探讨低温联合右美托咪定对兔心肌单相动作电位的影响.方法 成年家兔,体重2.0~ 2.5 kg,制备Langendorff离体心脏灌注模型,取模型制备成功的心脏18个,采用随机数字表法分为3组(n=6):正常对照组(C组)、低温组(H组)和低温+右美托咪定组(HD组).C组继续灌注37℃K-H液60 min

  4. DAPs: Deep Action Proposals for Action Understanding

    Escorcia, Victor

    2016-01-01

    Object proposals have contributed significantly to recent advances in object understanding in images. Inspired by the success of this approach, we introduce Deep Action Proposals (DAPs), an effective and efficient algorithm for generating temporal action proposals from long videos. We show how to take advantage of the vast capacity of deep learning models and memory cells to retrieve from untrimmed videos temporal segments, which are likely to contain actions. A comprehensive evaluation indicates that our approach outperforms previous work on a large scale action benchmark, runs at 134 FPS making it practical for large-scale scenarios, and exhibits an appealing ability to generalize, i.e. to retrieve good quality temporal proposals of actions unseen in training.

  5. All in action

    Annila, Arto

    2010-01-01

    The principle of least action provides a holistic worldview in which nature in its entirety and every detail is pictured in terms of actions. Each and every action is ultimately composed of one or multiples of the most elementary action which corresponds to the Planck's constant. Elements of space are closed actions, known as fermions, whereas elements of time are open actions, known as bosons. The actions span energy landscape, the Universe which evolves irreversibly according to the 2nd law of thermodynamics by diminishing density differences in least time. During the step-by-step evolution densely-curled actions unfold by opening up and expelling one or multiple elementary actions to their surrounding sparser space. The manifold's varieties process from one symmetry group to another until the equivalence to their dual, i.e., the surrounding density has been attained. The scale-free physical portrayal of nature does not recognize any fundamental difference between fundamental particles and fundamental force...

  6. 7 CFR 1940.318 - Completing environmental assessments for Class II actions.

    2010-01-01

    ... action has the potential for significantly affecting the quality of the human environment or will recommend that the action does not have this potential and, therefore, the preparation of an EIS is not... an action or comments or new or changed information relating to the action's potential...

  7. Detecting Emotions from Connected Action Sequences

    Bernhardt, Daniel; Robinson, Peter

    In this paper we deal with the problem of detecting emotions from the body movements produced by naturally connected action sequences. Although action sequences are one of the most common forms of body motions in everyday scenarios their potential for emotion recognition has not been explored in the past. We show that there are fundamental differences between actions recorded in isolation and in natural sequences and demonstrate a number of techniques which allow us to correctly label action sequences with one of four emotions up to 86% of the time. Our results bring us an important step closer to recognizing emotions from body movements in natural scenarios.

  8. Action video game training for cognitive enhancement

    Green, C. Shawn; Bavelier, Daphné

    2015-01-01

    Here we review the literature examining the perceptual, attentional, and cognitive benefits of playing one sub-type of video games known as ‘action video games,’ as well as the mechanistic underpinnings of these behavioral effects. We then outline evidence indicating the potential usefulness of these commercial off-the-shelf games for practical, real-world applications such as rehabilitation or the training of job-related skills. Finally, we discuss potential core characteristics of action vi...

  9. Recovery Action Mapping Tool

    National Oceanic and Atmospheric Administration, Department of Commerce — The Recovery Action Mapping Tool is a web map that allows users to visually interact with and query actions that were developed to recover species listed under the...

  10. Action Rules Mining

    Dardzinska, Agnieszka

    2013-01-01

    We are surrounded by data, numerical, categorical and otherwise, which must to be analyzed and processed to convert it into information that instructs, answers or aids understanding and decision making. Data analysts in many disciplines such as business, education or medicine, are frequently asked to analyze new data sets which are often composed of numerous tables possessing different properties. They try to find completely new correlations between attributes and show new possibilities for users.   Action rules mining discusses some of data mining and knowledge discovery principles and then describe representative concepts, methods and algorithms connected with action. The author introduces the formal definition of action rule, notion of a simple association action rule and a representative action rule, the cost of association action rule, and gives a strategy how to construct simple association action rules of a lowest cost. A new approach for generating action rules from datasets with numerical attributes...

  11. 川芎嗪对兔室性心律失常心外膜单相动作电位的影响%Effects of tetramethylpyrazine on epicardial monophasic action potential in ventricular arrhythmia in rabbits

    张洁; 李想; 沈字玲; 董航; 石俊; 任春晓; 戚晓林

    2011-01-01

    Objective To investigate the effects of tetramethylpyrazine (TMP) on epicardial monophasic action potential(MAP) in ventricular arrhythmia in rabbits. Methods 20 rabbits were randomized into ischemic group ( n = 10 )and TMP group (n= 10 ). The changes of the MAP parameters following myocardial ischemia were observed with the technique for simultaneously recording the epicardial MAP and surface electrocardiogram in rabbits in situ. Results In the ischemic group, both the amplitude ( MAPA) and maximum of depolarization velocity of the zero phase( Vmax) of MAP decreased ( P<0.01 ), MAP duration including MAPD50 and MAPD90 shortened ( P<0. 01 ) after isehemia, compared with those at the baseline. In the TMP group, MAPA, Vmax, MAPD50 and MAPD90 did not change significantly compared with the baseline, whereas compared with the isehemic group, incidence of ventricu-lar arrhythmia decreased (P<0.05), MAPA and Vmax increased (P<0.05), MAPD50 and MAPD90 prolonged (P<0.01). Conclusion TMP could attenuate the changes of MAP in ventricular arrhythmia induced by ischemia, enhance the electrical stability of the heart, avoid forming reentrant movement in the ischemic myocardium and then prevent the ventricular arrhythmogenesis.%目的:探讨川芎嗪(TMP)对兔缺血性室性心律失常时心外膜单相动作电位(MAP)的影响.方法:20只家兔,随机分为单纯缺血组(n=10)和TMP组(n=10),采用闭胸记录心外膜MAP和心电图的改变,观察心肌缺血背景下致心律失常前后MAP参数的变化.结果:在单纯缺血组室性快速性心律失常发生过程中,与缺血前相比,心外膜MAP振幅(MAPA)降低(P<0.01),0相最大上升速率(Vmax)减慢(P<0.01),MAP复极化50%和90%的时程(MAPD50和MAPD90)缩短(P<0.01);而在TMP组,用TMP预处理后,与缺血前相比,心外膜MAPA、Vmax、MAPD50和MAPD90均无明显变化;与单纯缺血组相比,室性心律失常发生率降低(P<0.05),心外膜MAPA和Vnlax增加(P<0.05).MAPD50

  12. Effect of colistin on nerve conduction velocity and motor unit action potential in mice%黏菌素对小鼠神经传导速率及运动单元动作电位的影响

    李继昌; 代重山; 马晶; 蒋红; 李睿; 张德显; 林巍

    2013-01-01

    为探讨黏菌素对小鼠感觉神经传导速率(SNCV)、运动神经传导速率(MNCV)及运动单元动作电位(MUAP)的影响,对50只昆明系小鼠单次尾静脉注射硫酸黏菌素7.5 mg·kg-1,每12h 1次,连续给药7d.分别于第1、3、7、14天(以初次给药当天为第1天计)测定小鼠坐骨神经SNCV、MNCV及MUAP,并对腓肠肌进行病理学检查.结果表明,与对照组相比,黏菌素给药3d后,SNCV降低至(30.67±1.15)m·s-1(p<0.05).给药7d后,神经传导速率(NCv)显著降低,MNCV降低至(24.47±0.41)m·s-1(p<0.05),SNCV降低至(29.67±2.89)m·s-1(P<0.05);此外,腓肠肌MUAP降低至(0.26±0.0153)mV (P<0.05),运动单元动作电位持续时间(MUAPD)降低至(0.3±0.046)s(P<0.01).表明黏菌素可影响小鼠的神经感觉及运动功能,并可导致小鼠肌肉无力.SNCV变化较为敏感,可作为黏菌素诱发神经毒性的早期诊断指标.%To investigate the toxic effect of colistin on sensory and motor nerve conduction velocities (SNCV and MNCV),motor unite action potentials (MUAP) and its duration (MUAPD) in adult mice,50 mice were intravenously given 7.5 mg· kg-1 colistin in normal saline via tail vain twice a day for 7 days.On days 1,3,7 and 14 of the experiment,SNCV-,MNCV-,MUAP-and MUAPD-values were determined.The results showed that,compared with the control,after colistin was given for 3 d,SNCV was significantly decreased to 30.67±1.15 m·s-1 (P<0.05); After colistin was given for 7 d,MNCV and SNCV were significantly decreased to (24.47±0.41) (P<0.05) and (29.67±2.89) m·s-1 (P<0.05),respectively.In addition,MUAP and MUAPD of gastrocnemius muscle was significantly decreased to (0.26±0.015) mV (P<0.05) and (0.3±0.046) s (P<0.01),respectively.The results revealed that colistin decreased the motor and sensory functions,and caused muscle weakness of mice.The SNCV was more sensitive than others,and maybe helpful to detect colistin induced peripheral neurotoxicity.

  13. Effects of pentobarbital sodium on compound muscle action potentials in rats%戊巴比妥钠对大鼠复合肌肉动作电位的影响

    孟祥虎; 臧光辉; 樊龙昌; 李新华; 刘继红; 张传汉; 罗爱林; 田玉科

    2012-01-01

    目的 评价戊巴比妥钠对大鼠复合肌肉动作电位(CMAP)的影响.方法 成年SD大鼠10只,雌、雄各半,8周龄,体重240 ~ 260 g.腹腔注射1%戊巴比妥钠40 mg/kg,给药后8min时开始刺激坐骨神经,记录其所支配的腓肠肌的CMAP,刺激强度为0.50、0.55、0.60 V,每个刺激强度重复3次(刺激间隔1 s),波宽0.05 ms,频率10 Hz.每隔5 min重复上述刺激1次,分别为T1、T2、T3、T4、T5、T6、T7、T8、T9、T10.结果 与T1时比较,0.50、0.55、0.60 V强度下T3-5时CMAP峰值降低,0.50 V强度下T3-6时CMAP潜伏期延长,0.55、0.60V强度下T4,5时CMAP潜伏期延长(P<0.05或0.01).结论 戊巴比妥钠可抑制大鼠CMAP.%Objective To investigate the effects of pentobarbital sodium on compound muscle action potentials (CMAPs) in rats.Methods Ten adult Sprague-Dawley rats (5 males,5 females),aged 8 weeks,weighing 240-260 g,were anesthetized with intraperitoneal 1% pentobarbital sodium 40 mg/kg.The sciatic nerve was stimulated (intensity 0.50,0.55 and 0.60 V,wave length 0.05 ms,frequency 10 Hz) starting from 8 min after administration.Each intensity was repeated three times at 1 s interval.The stimulation mentioned above was repeated every 5 min.CMAPs from the gastrocnemius muscle were recorded starting from 8 min after administration (T1) and then were recorded every 5 min for 9 times (T2-10),Results The peak value of CMAP was significantly decreased at T3-5 when the intensity was 0.50,0.55 and 0.60 V,and CMAP latency was significantly prolonged at T3-6 when the intensity was 0.50 V,and at T4,5 when the intensity was 0.55 and 0.60 V as compared with those at T1 ( P < 0.05 or 0.01 ).Conclusion Pentobarbital sodium can inhibit CMAPs in rats.

  14. Antifungigrama para comprovar o potencial de ação dos extratos vegetais hidroglicólicos sobre Candida sp. (Berkhout Etest to confirm the action potential of plant hydroglycol extracts on Candida sp. (Berkhout

    E.A.V. Glehn

    2012-01-01

    concentration of miconazole is required to eliminate C. glabrata compared to C. albicans. Etest was performed by testing the action potential of plant products on the fungus Candida sp. Inhibition of the fungus occurred when it was in contact with the hydroglycol extracts of plants Arctium lappa L., Calendula officinalis L., Stryphnodendron adstringens (Mart. Coville and Tabebuia avellanedae Lorentz ex Griseb. The importance of this study lies in the possibility of developing a complementary treatment, less aggressive, of lower cost and without toxicity, which would allow better life quality for women with vaginal candidiases that are recurrent or not.

  15. Derivative actions in China

    Lin, Shaowei

    2014-01-01

    The enactment of derivative action was expected to be actively used by shareholders to protect their interests. In fact, it turned out that this reform effort seemed futile as the right to engage in such actions was rarely exercised. This raises a question about the role of derivative actions in China; namely, should a derivative action system play a key role in protecting shareholder interests? If the answer is positive, the next question is how such a system could be improved...

  16. Conservation Action Handbook.

    National Rifle Association, Washington, DC.

    Conservation problems are identified, with some suggestions for action. General areas covered are: Wildlife Conservation, Soil Conservation, Clean Water, Air Pollution Action, and Outdoor Recreation Action. Appendices list private organizations or agencies concerned with natural resource use and/or management, congressional committees considering…

  17. Action and Interactiv research

    Nielsen, Kurt Aagaard; Svensson, Lennart

    The text is written as a first version of editors introduction to a book about action research/interactive research in Nordic countries. You can read abouttrends and contradictions in the history of action research.The authors question the trends and demands a more explicit critical approach to...... actual action research/interactive research....

  18. Putting Action in Perspective

    Lozano, Sandra C.; Hard, Bridgette Martin; Tversky, Barbara

    2007-01-01

    Embodied approaches to cognition propose that our own actions influence our understanding of the world. Do other people's actions also have this influence? The present studies show that perceiving another person's actions changes the way people think about objects in a scene. In Study 1, participants viewed a photograph and answered a question…

  19. Differential Equations as Actions

    Ronkko, Mauno; Ravn, Anders P.

    1997-01-01

    We extend a conventional action system with a primitive action consisting of a differential equation and an evolution invariant. The semantics is given by a predicate transformer. The weakest liberal precondition is chosen, because it is not always desirable that steps corresponding to differential...... actions shall terminate. It is shown that the proposed differential action has a semantics which corresponds to a discrete approximation when the discrete step size goes to zero. The extension gives action systems the power to model real-time clocks and continuous evolutions within hybrid systems....

  20. Creativity as action

    Glaveanu, Vlad Petre; Lubart, Todd; Bonnardel, Nathalie;

    2013-01-01

    The present paper outlines an action theory of creativity and substantiates this approach by investigating creative expression in five different domains. We propose an action framework for the analysis of creative acts built on the assumption that creativity is a relational, inter......, science, scriptwriting, and music. Results point to complex models of action and inter-action specific for each domain and also to interesting patterns of similarity and differences between domains. These findings highlight the fact that creative action takes place not “inside” individual creators but “in...

  1. Action research: Scandinavian Experiences

    Rasmussen, Lauge Baungaard

    2004-01-01

    The article focus on paradigms, methods and ethics of action research in the Scandinavian countries. The special features of the action research paradigm is identified. A historical overview follows of some main action research projects in Norway, Sweden and Denmark. The tendency towards upsclae...... action research projects from organisational or small community projects yo large-scale, regional based network apporaches are also outlined and discussed. Finally, a synthesised approach of the classical, socio-technical action research approach and the large-scale network and holistic approaches is...

  2. Deriving Motor Primitives through Action Segmentation

    PaulE.Hemeren

    2011-01-01

    Full Text Available The purpose of the present experiment is to further understand the effect of levels of processing (top-down vs. bottom-up on the perception of movement kinematics and primitives for grasping actions in order to gain insight into possible primitives used by the mirror system. In the present study, we investigated the potential of identifying such primitives using an action segmentation task. Specifically, we investigated whether or not segmentation was driven primarily by the kinematics of the action, as opposed to high-level top-down information about the action and the object used in the action. Participants in the experiment were shown twelve point-light movies of object-centered hand/arm actions that were either presented in their canonical orientation together with the object in question or upside-down (inverted without information about the object. The results show that (1 despite impaired high-level action recognition for the inverted actions participants were able to reliably segment the actions according to lower-level kinematic variables, (2 segmentation behavior in both groups was significantly related to the kinematic variables of change in direction, velocity and acceleration of the wrist (thumb and finger tips for most of the included actions. This indicates that top-down activation of an action representation leads to similar segmentation behavior for hand/arm actions compared to bottom-up, or local, visual processing when performing a fairly unconstrained segmentation task. Motor primitives as parts of more complex actions may therefore be reliably derived through visual segmentation based on movement kinematics.

  3. Clean Slate 1 corrective action decision document, Corrective Action Unit No. 412. Revision 1

    A Corrective Action Investigation has been completed at the Clean Slate 1 (CS-1) Site, located in the central portion of the Tonopah Test Range. The purpose of this CADD is to identify and evaluate potential correct action alternatives at the CS-1 Site and to evaluate these alternatives with respect to their technical, human health, and environmental benefits and to their cost. Base on this evaluation a corrective action will be recommended for implementation at the CS-1 Site

  4. All in Action

    Arto Annila

    2010-11-01

    Full Text Available The principle of least action provides a holistic worldview in which Nature in its entirety and every detail is described in terms of actions. Each and every action is ultimately composed of one or multiple of the most elementary actions which relates to Planck’s constant. Elements of space are closed actions, known as fermions, whereas elements of time are open actions, known as bosons. The actions span an energy landscape, the Universe, which evolves irreversibly according to the 2nd law of thermodynamics by diminishing energy density differences in least time. During evolution densely-curled actions unfold step-by-step when opening up and expelling one or multiple elementary actions to their surrounding sparser space. The energy landscape will process from one symmetry group to another until the equivalence to its dual, i.e., the surrounding density has been attained. The scale-free physical portrayal of nature in terms of actions does not recognize any fundamental difference between fundamental particles and fundamental forces. Instead a plethora of particles and a diaspora of forces are perceived merely as diverse manifestations of a natural selection for various mechanisms and ways to decrease free energy in the least time.

  5. 异氟醚、七氟醚对心肌单相动作电位的作用%The effects of isoflurane and sevoflurane on monophasic action potential of myocardium

    谷宇; 高鸿; 杨烨

    2012-01-01

    Objective To study the effects of isoflurane and sevoflurane on monophasic action potentials(MAPs) of three-layer myocardium in isolated rabbit hearts. Methods The hearts of fifty-six rabbits were perfused by modified krebs- hens lei t buffer with Langendorff device. All of the rabbits were randomly divided into seven groups (n=8) :0. 65 MAC isoflurane group(group A), 0. 65 MAC isoflurane +enanthol groupfgroup B), 1. 3 MAC isoflurane groupCgroup C), 0. 65 MAC sevoflurane group(group D), 0. 65 MAC sevoflurane +enanthol group (group E), 1. 3 MAC sevoflurane group (group F) and enanthol group (group G). HR, MAP including time course(MAPD100 ) and MAP amplitude of endocardium, mid-layer myocardium and epicardium was recorded at the time of equation perfusion (baseline, T(l) and drug treatment for 15 minutes(T1) Results Compared with To, HR in groups B, E and G was significantly slower at Ti. At T, , HR in group B was slower than those in group A, C, D, E, F and G while HR in group E was slower than that in group D and F(P<0. 01). In group B, MAPDlou in three sites at T1 was shortened compared with To, and was also shorter than that in other groups (P<0. 01). In groups C, E and G, the MAPD100 was lengthened at T, and was longer than those in groups A. B, D and F(P<0. 01 or P<0. 05). Group E showed even longer MAPD100, than groups D and F(P<0. 01). Arrhythmia or even electricity activity stop occurred after administration in group B Conclusion Isoflurane lengthened the lime course of MAPs. Similar to hepianol, isoflurane may affect the MAPs of myocardium through block gap junction. Sevoflurane may have no obviously effect on MAPs of myocardium%目的 在兔离体心脏模型上研究异氟醚、七氟醚对心肌单相动作电位(MAPs)的作用.方法 健康家兔56只,离体Langendorff灌注,随机均分为七组:0.65肺泡最小有效浓度(MAC)异氟醚组(A组),0.65 MAC异氟醚+庚醇组(B组),1.3 MAC异氟醚组(C组),0.65 MAC七氟醚组(D组),0.65MAC

  6. 29 CFR 30.4 - Affirmative action plans.

    2010-07-01

    ... these regulations, sponsors are expected to make appropriate adjustments in goal levels. See 29 CFR 30.8... affirmative action plan. (b) Definition of affirmative action. Affirmative action is not mere passive..., training, and motivation of present and potential minority and female (minority and...

  7. The Characteristics of Action Research in Music Education

    Cain, Tim

    2008-01-01

    This review article discusses the use of action research in music education and its potential for producing knowledge and improving practice. The discussion is situated in an analysis of action research studies in music education. The review demonstrates that action research in music education focuses on a wide variety of subject matter,…

  8. Nuclear emergencies and protective actions

    Although technical improvements have increased the safety of new and old nuclear power plants, many simultaneous component failures and/or human errors are improbable but possible. Both the plant (on-site) and the nearby area (off-site) have emergency plans. Rescue service authorities are responsible of the off-site. The main protective actions are sheltering, evacuation and iodine ingestion. The Loviisa off-site emergency plan assumes that a major part of this population takes care of their own protective actions; Rescue service authorities can then concentrate on the coordination activities and to those people who need help. To be able to carry out the protective actions timely and effectively the people should have information on radiation risk and emergency planning. In case of a potential accident the local population should follow the rescue service information and know how to shelter and how to evacuate themselves. Though there are many stockpiles of iodine pellets in the area the rescue service authorities recommend that each household should purchase iodine pellets for their own need. The utility and the rescue service authorities have distributed information brochures to all homes within 30 km from Loviisa NPP since 1990. This brochure gives information on radiation and protective actions in case of an accident. Because the brochures might not stay available and so also the local telephone book contains this information

  9. Action research and democracy

    Roose, Rudi; De Bie, Maria; Roets, Griet

    2013-01-01

    This contribution explores the relationship between research and learning democracy. Action research is seen as being compatible with the orientation of educational and social work research towards social justice and democracy. Nevertheless, the history of action research is characterized by a tension between democracy and social engineering. In the social-engineering approach, action research is conceptualized as a process of innovation aimed at a specific Bildungsideal. In a democratic appr...

  10. Innovation and action research

    Gustavsen, Bjørn

    2005-01-01

    "In the Western economies there is a growing focus on innovation as the key to economic growth. In spite of its orientation towards transcending the given, and creating something new, action research has so far played a limited role as a resource in innovation. Departing from practice-driven innovation and the need for collaboration between many actors, a key role for action research as promoter of joint inquiries in dialogical form and associated action is described and dis...

  11. Civil Action Exercise Conditions

    Bojinca, Moise

    2010-01-01

    The specialized literature defines civil action as being: “the legal means used by a person in order to ask the court to recognize its right or to fulfil this right, by ending the obstacles put by another person or through an adequate compensation Irrespective of its definition method, civil action is considered a central institution around which the entire activity of the court of law and of the parties gravitates. Next, we will discuss the requirements for exercising civil action: expressio...

  12. Human Actions Made Tangible

    Buur, Jacob; Caglio, Agnese; Jensen, Lars Christian

    2014-01-01

    method developed to engage people from different backgrounds in collaboratively analysing videos with the help of physical objects. We will present one of these tools, Action Scrabble, for analysing temporal organisation of human actions. We work with a case of skilled forklift truck driving. By...... backtracking our design research experiments, we will unfold how and why the tangible tool succeeds in engaging designers with varied analysis experience to collaboratively focus on human action structures – and even find video analysis fun!...

  13. Action in Introductory Physics

    McGinness, Lachlan P

    2015-01-01

    We have investigated the teaching and learning of the stationary action formulation of classical physics in a first-year university class. Instruction proceeded from the many-paths approach to quantum physics through to ray optics, classical mechanics, and relativity. Student learning and misconceptions were studied with quantitative and qualitative techniques. In particular, an action concept inventory was developed through a process of expert consultation and student feedback. Students reported action physics to be accessible, interesting and valuable.

  14. Effective actions near singularities

    We study the heterotic string compactified on K3x T2 near the line T=U, where the effective action becomes singular due to an SU(2) gauge symmetry enhancement. By 'integrating in' the light W± vector multiplets we derive a quantum corrected effective action which is manifestly SU(2) invariant and non-singular. This effective action is found to be consistent with a residual SL(2,Ζ) quantum symmetry on the line T=U. In an appropriate decompactification limit, we recover the known SU(2) invariant action in five dimensions. (author)

  15. Zeta Spectral Action

    Kurkov, Maxim A; Sakellariadou, Mairi; Watcharangkool, Apimook

    2014-01-01

    In this paper we propose a novel definition of the bosonic spectral action using zeta function regularization, in order to address the issues of renormalizability, ultraviolet completeness and spectral dimensions. We compare the zeta spectral action with the usual (cutoff based) spectral action and discuss its purely spectral origin, predictive power, stressing the importance of the issue of the three dimensionful fundamental constants, namely the cosmological constant, the Higgs vacuum expectation value, and the gravitational constant. We emphasize the fundamental role of the neutrino Majorana mass term for the structure of the bosonic action.

  16. Stereoscopically Observing Manipulative Actions.

    Ferri, S; Pauwels, K; Rizzolatti, G; Orban, G A

    2016-08-01

    The purpose of this study was to investigate the contribution of stereopsis to the processing of observed manipulative actions. To this end, we first combined the factors "stimulus type" (action, static control, and dynamic control), "stereopsis" (present, absent) and "viewpoint" (frontal, lateral) into a single design. Four sites in premotor, retro-insular (2) and parietal cortex operated specifically when actions were viewed stereoscopically and frontally. A second experiment clarified that the stereo-action-specific regions were driven by actions moving out of the frontoparallel plane, an effect amplified by frontal viewing in premotor cortex. Analysis of single voxels and their discriminatory power showed that the representation of action in the stereo-action-specific areas was more accurate when stereopsis was active. Further analyses showed that the 4 stereo-action-specific sites form a closed network converging onto the premotor node, which connects to parietal and occipitotemporal regions outside the network. Several of the specific sites are known to process vestibular signals, suggesting that the network combines observed actions in peripersonal space with gravitational signals. These findings have wider implications for the function of premotor cortex and the role of stereopsis in human behavior. PMID:27252350

  17. CHAOTIC GROUP ACTIONS

    ShiEnhui; ZhouLizhen; ZhouYoucheng

    2003-01-01

    It is proved that there is no chaotic group actions on any topological space with free arc.In this paper the chaotic actions of the group like G×F,where F is a finite group,are studied.In particular,under a suitable assumption ,if F is a cyclic group,then the topological space which admits a chaotic action of Z×F must admit a chatotic homeomorphism.A topological space which admits a chaotic group action but admits no chaotic horneomorphism is constructed.

  18. Motion Primitives and Probabilistic Edit Distance for Action Recognition

    Fihl, Preben; Holte, Michael Boelstoft; Moeslund, Thomas B.

    2009-01-01

    The number of potential applications has made automatic recognition of human actions a very active research area. Different approaches have been followed based on trajectories through some state space. In this paper we also model an action as a trajectory through a state space, but we represent t...... different temporal actions using a probabilistic Edit Distance method. The method is tested on different actions with and without noise and the results show recognition rates of 88.7% and 85.5%, respectively....

  19. The characteristics of action research in music education

    Cain, Tim

    2008-01-01

    This review article discusses the use of action research in music education and its potential for producing knowledge and improving practice. The discussion is situated in an analysis of action research studies in music education. The review demonstrates that action research in music education focuses on a wide variety of subject matter, integrates research and action, is collaborative, grounded in a body of existing knowledge, and leads to powerful learning for the participant...

  20. Social Action Art Therapy

    Golub, Deborah

    2005-01-01

    This paper explores intersections among art, action, and community. It describes sociopolitical aspects of the author's art therapy work with survivors of repressive regimes living in Brazil, China, and Denmark and considers ways that unique historical and social processes influenced her conceptualization and practice of social action art therapy.

  1. Talk and Action

    Christensen, Lars Thøger; Morsing, Mette; Thyssen, Ole

    organizational talk and their associated activities, the paper discusses the different ways time shape the relationship between talk and action. Acknowledging that talk gives rise to different expectations over time, we put forward ideal types of organizational strategies for possible talk-action relationships...

  2. Immunization Action Coalition

    ... Contact | A-Z Index | Donate | Shop | SUBSCRIBE Immunization Action Coalition Handouts for Patients & Staff A-Z Screening ... Z Index • Site Map • Disclaimer • Privacy Policy Immunization Action Coalition • 2550 University Avenue West • Suite 415 North • ...

  3. Action spectrum for photocarcinogenesis.

    de Gruijl, F R

    1995-01-01

    The wavelength dependence of the carcinogenicity of ultraviolet (UV) radiation needs to be known in order to assess the carcinogenic risks of various UV sources, most notably the different solar UV spectra at ground level under depleting stratospheric ozone. This wavelength dependence cannot be extracted from human data (e.g., from epidemiology); it can, however, be directly obtained from animal experiments. Precise information on the wavelength dependence, the so-called action spectrum, was not available until recently: erythemal or mutagenic action spectra have been used as substitutes. However, experimental data on skin tumors induced in hairless mice (Skh:HR1) with various polychromatic sources have been building up. Our group has found that none of the substitute action spectra yield a statistically acceptable description of our data, and we have, therefore, derived a new action spectrum, dubbed the SCUP action spectrum (SCUP stands for Skin Cancer Utrecht-Philadelphia, because the action spectrum also fits experimental data from the former Skin and Cancer Hospital in Philadelphia). The SCUP action spectrum has a maximum at 293 nm, and in the UVA region above 340 nm the relative carcinogenicity per J/m2 drops to about 10(-4) of this maximum. The effects of an ozone depletion on solar UV doses weighted with these different action spectra are compared: the erythemal and SCUP weighted dose come out as least sensitive with a 1.3% and 1.4% increase, respectively, for every 1% decrease in ozone. PMID:7597292

  4. Action theory in Habermas and educational practices

    Garland, Paul

    2008-01-01

    In this paper I explore the potential for viewing education as an “unrestricted communication community” (Habermas 1990: 88), using categorisations from Habermas of different kinds of action as analytical tools for examining educational practices. For the paper, I pursue two main themes: 1) how the concept of communicative action in relation to the three forms of knowledge-constitutive interest (Habermas 1987) can be operationalised in educational discourse 2) how the distinguishing of commun...

  5. Action principle for Coulomb collisions in plasmas

    Hirvijoki, Eero

    2015-01-01

    In this letter we derive an action principle for Coulomb collisions in plasmas. Although no natural Lagrangian exists for the Landau-Fokker-Planck equation, an Eulerian variational formulation is found considering the system of partial differential equations that couple the distribution function and the Rosenbluth potentials. Exact conservation laws are derived after generalizing the energy-momentum stress tensor for second order Lagrangians and, in the case of a test-particle population in a given plasma background, the action principle is shown to correspond to the Langevin equation for individual particles. Being suitable for discretization, the presented action allows construction of variational integrators. Numerical implementation is left for a future study.

  6. Perception, Action, and Consciousness

    What is the relationship between perception and action, between an organism and its environment, in explaining consciousness? These are issues at the heart of philosophy of mind and the cognitive sciences. This book explores the relationship between perception and action from a variety of...... the view that perception is an achievement by an agent acting in a complex environment in which sensorimotor dynamics constitute an essential ingredient to perceptual experience. A key focus of the book is on the debate about action-oriented theories of visual perception versus the dual-visual systems...... hypothesis The former champions the role of sensorimotor dynamics in perceptual awareness while the latter favours a functional dichotomy between perception and action. At least on the surface, these two approaches are in conflict. Where one emphasizes the interdependence of action and perception, the other...

  7. Corrective Action Investigation Plan for Corrective Action Unit 563: Septic Systems, Nevada Test Site, Nevada, with Errata Sheet, Revision 0

    Alfred Wickline

    2007-01-01

    Corrective Action Unit 563, Septic Systems, is located in Areas 3 and 12 of the Nevada Test Site, which is 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 563 is comprised of the four corrective action sites (CASs) below: • 03-04-02, Area 3 Subdock Septic Tank • 03-59-05, Area 3 Subdock Cesspool • 12-59-01, Drilling/Welding Shop Septic Tanks • 12-60-01, Drilling/Welding Shop Outfalls These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives. Additional information will be obtained by conducting a corrective action investigation (CAI) before evaluating corrective action alternatives and selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible evaluation of viable corrective action alternatives that will be presented in the Corrective Action Decision Document.

  8. Action spectra again?

    Coohill, T P

    1991-11-01

    Action spectroscopy has a long history and is of central importance to photobiological studies. Action spectra were among the first assays to point to chlorophyll as the molecule most responsible for plant growth and to DNA as the genetic material. It is useful to construct action spectra early in the investigation of new areas of photobiological research in an attempt to determine the wavelength limits of the radiation region causing the studied response. But due to the severe absorption of ultraviolet (UV) radiation by biological samples, UV action spectra were first limited to small cells (bacteria and fungi). Advances in techniques (e.g. single cell culture) and analysis allowed accurate action spectra to be reported even for mammalian cells. But precise analytical action spectra are often difficult to obtain when large, pigmented, or groups of cells are investigated. Here some action spectra are limited in interpretation and merely supply a wavelength vs effect curve. When polychromatic sources are employed, the interpretation of action spectra is even more complex and formidable. But such polychromatic action spectra can be more directly related to ambient responses. Since precise action spectra usually require the completion of a relatively large number of careful experiments using somewhat sophisticated equipment over a range of at least six wavelengths, they are often not pursued. But they remain central to the elucidation of the effect being studied. The worldwide community has agreed that stratospheric ozone is depleting, with the possibility of a consequent rise in the amount of UV-B (290-320 nm) reaching the earth's surface. It is therefore essential that new action spectra be completed for UV-B effects on a large variety of responses of human, animal, and aquatic plant systems. Combining these action spectra with the known amounts of UV-B reaching the biosphere can give rise to solar UV effectiveness spectra that, in turn, can give rise to estimates

  9. Action Research for/as/mindful of Social Justice

    Griffiths, Morwenna

    2009-01-01

    This chapter examines and explores the potential of action research to enhance social justice in education. It discusses different approaches and practices within the field of education in relation to epistemologies and principles underlying research for social justice. Implicit in many characterizations of action research is the potential to work for justice – in small-scale projects or for larger social and educational ends. At the same time, disquiet has been expressed by many action resea...

  10. Faddeev-Niemi Conjecture and Effective Action of QCD

    Cho, Y. M.; Lee, H. W.; Pak, D. G.

    2001-01-01

    We calculate a one loop effective action of SU(2) QCD in the presence of the monopole background, and find a possible connection between the resulting QCD effective action and a generalized Skyrme-Faddeev action of the non-linear sigma model. The result is obtained using the gauge-independent decomposotion of the gauge potential into the topological degrees which describes the non-Abelian monopoles and the local dynamical degrees of the potential, and integrating out all the dynamical degrees...

  11. 大麻素CB1受体对大鼠视网膜神经节细胞诱发动作电位的作用%Activation of cannabinoid CB1 receptors modulates evoked action potentials in rat retinal ganglion cells

    蒋淑霞; 李倩; 王霄汉; 李芳; 王中峰

    2013-01-01

    Activation of cannabinoid CB1 receptors (CB 1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels.The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques.The results showed that under current-clamped condition perfusing WIN55212-2 (WIN,5 μmol/L),a CB1R agonist,did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs.In the presence of cocktail synaptic blockers,including excitatory postsynaptic receptor blockers CNQX and D-APV,and inhibitory receptor blockers bicuculline and strychnine,perfusion of WIN (5 μmol/L)hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA).Phaseplane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN.However,WIN significantly decreased +dV/dtmax and-dV/dtmax of action potentials,suggestive of reduced rising and descending velocities of action potentials.The effects of WIN were reversed by co-application of SR141716,a CB1R selective antagonist.Moreover,WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked.These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.%激活大麻素CB1受体(CB1Rs)通过调控多种离子通道,从而调节脊椎动物视网膜的功能.本文旨在利用膜片钳全细胞记录技术,在大鼠视网膜薄片上研究CB1Rs对神经节细胞兴奋性的作用.结果显示,在电流钳制状态下,灌流CB1R激动剂WIN55212-2 (WIN,5μmol/L)对神经节细胞的自发动作电位发放频率和静息膜电位均没有显著影响.在灌流液中加入CNQX,D-APV,bicuculline

  12. NIL-ANOSOV ACTIONS

    Barbot, Thierry; Maquera, Carlos

    2015-01-01

    We consider Anosov actions of a Lie group $G$ of dimension $k$ on a closed manifold of dimension $k+n.$We introduce the notion of Nil-Anosov action of $G$ (which includes the case where $G$ is nilpotent) and establishes the invariance by the entire group $G$of the associated stable and unstable foliations. We then prove a spectral decomposition Theoremfor such an action when the group $G$ is nilpotent. Finally, we focus on the case where $G$ is nilpotent andthe unstable bundle has codimension...

  13. Reasoning about Unreliable Actions

    White, Graham

    2012-01-01

    We analyse the philosopher Davidson's semantics of actions, using a strongly typed logic with contexts given by sets of partial equations between the outcomes of actions. This provides a perspicuous and elegant treatment of reasoning about action, analogous to Reiter's work on artificial intelligence. We define a sequent calculus for this logic, prove cut elimination, and give a semantics based on fibrations over partial cartesian categories: we give a structure theory for such fibrations. The existence of lax comma objects is necessary for the proof of cut elimination, and we give conditions on the domain fibration of a partial cartesian category for such comma objects to exist.

  14. Action Investment Energy Games

    Larsen, Kim Guldstrand; Laursen, Simon; Srba, Jiri

    2012-01-01

    We introduce the formalism of action investment energy games where we study the trade-off between investments limited by given budgets and resource constrained (energy) behavior of the underlying system. More specifically, we consider energy games extended with costs of enabling actions and fixed...... budgets for each player. We ask the question whether for any Player 2 investment there exists a Player 1 investment such that Player 1 wins the resulting energy game. We study the action investment energy game for energy intervals with both upper and lower bounds, and with a lower bound only, and give a...

  15. An Action Environment

    van den Brand, Mark; Iversen, Jørgen; Mosses, Peter David

    2004-01-01

    previous descriptions without change. This paper introduces a new formalism, ASDF, which has been designed specifically for giving reusable action semantic descriptions of individual language constructs. An initial case study in the use of ASDF has already provided reusable descriptions of all the basic...... constructs underlying Core ML. The paper also describes the Action Environment, a new environment supporting use and validation of ASDF descriptions. The Action Environment has been implemented on top of the ASF+SDF Meta-Environment, exploiting recent advances in techniques for integration of different...

  16. The Body in Action

    Grünbaum, Thor

    2008-01-01

    This article is about how to describe an agent's awareness of her bodily movements when she is aware of executing an action for a reason. Against current orthodoxy, I want to defend the claim that the agent's experience of moving has an epistemic place in the agent's awareness of her own...... intentional action. In "The problem," I describe why this should be thought to be problematic. In "Motives for denying epistemic role," I state some of the main motives for denying that bodily awareness has any epistemic role to play in the content of the agent's awareness of her own action. In "Kinaesthetic...

  17. Riverland expedited response action proposal

    The US Environmental Protection Agency (EPA) and Washington Department of Ecology (Ecology) recommended that the US Department of Energy (DOE) prepare an expedited response action (ERA) for the Riverland Railroad Car Wash Pit and the 600 Area Army Munitions Burial Site. A non-time-critical ERA proposal includes preparation of an engineering evaluation/cost analysis (EE/CA) section. The EE/CA is a rapid, focused evaluation of available technologies using specific screening factors to assess feasibility, appropriateness, and cost. The ERA proposal will undergo reviews by Westinghouse Hanford Company (WHC), DOE, EPA, Ecology, and the public. Ecology and EPA will issue an Action Agreement Memorandum after resolution of all review comments. The, memorandum will authorize remediation activities. The ERA goal is to reduce the potential for any contaminant migration to the soil column, groundwater, and Columbia River. The ERA may be the final remediation of the 100-IU-1 Operable Unit. A No Action Record of Decision may be issued after cleanup completion

  18. Normative Action Research

    Baboroglu, Oguz; Ravn, Ib

    1992-01-01

    /organizational research, the futures perspective implies that knowledge of the social/organizational world must be based upon images of desirable futures, so-called "futures theories", not causal descriptions of a problematic present. Futures theories identify ends and means for individual and organizational development......This paper presents an argument for an enrichment of action research methodology. To the current state of action research, we add a constructivist epistemological argument, as well as a crucial inspiration from some futures-oriented planning approaches. Within the domain of social....... They are generated jointly by the stakeholders of a system and the involved action researchers and are tested every time that the prescriptions for action contained in them are followed by a system's stakeholders....

  19. What is trammeling action?

    US Fish and Wildlife Service, Department of the Interior — The purpose of this short document is to provide guidelines and examples to clarify what is and is not a trammeling action. This document does not discuss how to...

  20. NSP Action Plans

    Department of Housing and Urban Development — NSP Action Plans, also known as Substantial Amendments, contain a description of a grantee’s intended use for NSP funds. The plans contain information on the...

  1. Sustainability and Entrepreneurial Action

    Korsgaard, Steffen T.; Anderson, Alistair

    Abstract Objectives - This paper explores how entrepreneurial action can lead to environmental sustainability. It builds on the assumption that the creation of sustainble practices is one of the most important challenges facing the global society, and that entrepreneurial action is a vital......: resource oriented sustainable entrepreneurial action.  Approach - The paper uses a case study approach to build deeper theoretical knowledge of environmentally sustainable entrepreneurship.  Results - The paper identifies and analyses a distinct form of sustainable entrepreneurship -  resource oriented...... entrepreneurship - which uses bricolage in various ways to create sustainable solutions. Implications and value - The concept of resource oriented sustainable entrepreneurship contributes to the theoretical understanding of how entrepreneurial action can support sustainability, Furthermore the case study has...

  2. Asthma action plan

    Public Health Agency

    2014-01-01

    This action plans allow each child (or parent/carer) to record his or her asthma treatment to help manage their asthma when they are well, when their symptoms get worse and when they are suffering an asthma attack.

  3. Postpartum Depression Action Plan

    MENU Return to Web version Postpartum Depression | Postpartum Depression Action Plan Patient __________________________ Physician/NP/PA __________________ Clinic ____________________________ Phone Number ____________________ Choose one area and add other areas as you begin to feel ...

  4. 'Action 2016': AREVA's strategic action plan

    On December 13, 2011, Luc Oursel, CEO, and Pierre Aubouin, Chief Financial Officer presented the group's strategic plan for the period 2012-2016. The plan has been drawn up collectively and is based on a thorough-going analysis and a realistic assessment of perspectives for all group activities and associated resources. Development of nuclear and renewable energies: the fundamentals are unchanged. In this context, the German decision remains an isolated case and the great majority of nuclear programs around the world have been confirmed. More conservative in its projections than the International Energy Agency, the group expects growth of 2.2% annually, reaching 583 GW of installed nuclear capacity by 2030, against 378 GW today. However, the Fukushima accident will lead to delays in launching new programs. 'Action 2016' plan aims to consolidate AREVA's leadership in nuclear energy and become a leading player in renewable energy. The group's strategic action plan 'Action 2016' is based on the following strategic choices: - commercial priority given to value creation, - selectivity in investments, - strengthening of the financial structure. These demand an improvement in the group's performance by 2015. This plan makes nuclear safety a strategic priority for the industrial and commercial performance of the group. This ambitious performance plan for the period 2012-2016 will give the group the wherewithal to withstand a temporary slowdown in the market resulting from the Fukushima accident and to deliver safe and sustainable growth of the business. The plan sets out the strategic direction for the group's employees for the years ahead: taking advantage of the expected growth in nuclear and renewable energies, targeted investment programs, and return to self-financing as of 2014

  5. Commitment to action. Population Action International.

    Squires, S

    1994-01-01

    The national chair of Population Action International (formerly the Population Crisis Committee), Robin Chandler Duke, is a crusader for women's reproductive rights. She was in Bangladesh in 1971 during its civil war. Soldiers would rape young Muslim women, and their families would reject them when they became pregnant. The head of the exiled government agreed to let physicians from IPPF perform abortions on these women, which allowed families to take them back. Opposition to the abortions arose, however. This experience in Bangladesh sparked Ms. Duke's interest in population control. Her years as the wife of a US diplomat granted her access to powerful people worldwide. Her predecessor, retired US Army General Bill Draper, called Ms. Duke from his death bed in 1974 to ask her to be national chair of PAI. She served as a delegate in various international meetings, e.g., the 1980 UNESCO meetings in Belgrade. Spain and Luxembourg honored her for her work of campaigning for women's reproductive rights. She believes that rapid population growth is the most significant problem in the world today. It exacerbates poverty, environmental destruction, and political instability. She believes that universal availability of high quality, voluntary family planning services, including safe abortion, is needed to save humanity from the vicious cycle. Since family planning, sex education, and abortion are the most personal and sensitive parts of people's lives, Population Action frames family planning in the context of basic health care. AIDS complicates the issue, because contraception is no longer limited to birth control. Even though the organization realizes that sexual abstinence is the best way to avoid AIDS, it tries to educate female teenagers not to let boys coerce them to have sex. If they do, have sex Population Action advocates condom use. Ms. Duke cites the family planning successes of Indonesia, Zimbabwe, and Thailand. PMID:12319083

  6. Introducere in Action Learning

    Clausen, Søren Witzel

    In these years action learning has become an increasing aspect of qualifying in service training of teachers in Western European countries. In this article the model of action learning which has been developed by teachers at VIA University College and introduced to the teachers at the SCAN in...... service program will be described and the interaction and the learning aspects in the model will be analyzed....

  7. Reduced Poisson actions

    刘张炬; 杨奇林

    2000-01-01

    A sufficient and necessary condition is given for the action of the quotient of a Poisson-Lie group G on the quotient of a Poisson G-space P to be a Poisson action, where both the Poisson structures on the quotient group and the quotient manifold are induced by Dirac structures. The left invariant Dirac structure and the left invariant tensor descriptions of Poisson homogeneous spaces are proved to be equivalent.

  8. Institutional Logics in Action

    Lounsbury, Michael; Boxenbaum, Eva

    2013-01-01

    This double volume presents state-of-the-art research and thinking on the dynamics of actors and institutional logics. In the introduction, we briefly sketch the roots and branches of institutional logics scholarship before turning to the new buds of research on the topic of how actors engage ins...... prolific stream of research on institutional logics by deepening our insight into the active use of institutional logics in organizational action and interaction, including the institutional effects of such (inter)actions....

  9. Corrective Action Decision Document for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada, Rev. No. 0

    Robert Boehlecke

    2004-04-01

    The six bunkers included in CAU 204 were primarily used to monitor atmospheric testing or store munitions. The ''Corrective Action Investigation Plan (CAIP) for Corrective Action Unit 204: Storage Bunkers, Nevada Test Site, Nevada'' (NNSA/NV, 2002a) provides information relating to the history, planning, and scope of the investigation; therefore, it will not be repeated in this CADD. This CADD identifies potential corrective action alternatives and provides a rationale for the selection of a recommended corrective action alternative for each CAS within CAU 204. The evaluation of corrective action alternatives is based on process knowledge and the results of investigative activities conducted in accordance with the CAIP (NNSA/NV, 2002a) that was approved prior to the start of the Corrective Action Investigation (CAI). Record of Technical Change (ROTC) No. 1 to the CAIP (approval pending) documents changes to the preliminary action levels (PALs) agreed to by the Nevada Division of Environmental Protection (NDEP) and DOE, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This ROTC specifically discusses the radiological PALs and their application to the findings of the CAU 204 corrective action investigation. The scope of this CADD consists of the following: (1) Develop corrective action objectives; (2) Identify corrective action alternative screening criteria; (3) Develop corrective action alternatives; (4) Perform detailed and comparative evaluations of corrective action alternatives in relation to corrective action objectives and screening criteria; and (5) Recommend and justify a preferred corrective action alternative for each CAS within CAU 204.

  10. Action for twisted self-duality

    Bunster, Claudio; Henneaux, Marc

    2011-06-01

    One may write the Maxwell equations in terms of two gauge potentials, one electric and one magnetic, by demanding that their field strengths should be dual to each other. This requirement is the condition of twisted self-duality. It can be extended to p-forms in spacetime of D dimensions, and it survives the introduction of a variety of couplings among forms of different rank, and also to spinor and scalar fields, which emerge naturally from supergravity. In this paper we provide a systematic derivation of the action principle, whose equations of motion are the condition of twisted self-duality. The derivation starts from the standard Maxwell action, extended to include the aforementioned couplings, and proceeds via the Hamiltonian formalism through the resolution of Gauss’s law. In the pure Maxwell case we recover in this way an action that had been postulated by other authors, through an ansatz based on an action given earlier by us for untwisted self-duality. When Chern-Simons couplings are included, our action is, however, new. The derivation from the standard extended Maxwell action implies of course that the theory is Lorentz invariant and can be locally coupled to gravity. Nevertheless we include a direct compact Hamiltonian proof of these properties, which is based on the surface-deformation algebra. The symmetry in the dependence of the action on the electric and magnetic variables is manifest, since they appear as canonical conjugates. Spacetime covariance, although present, is not manifest.

  11. Identity and collective action among European Kurds.

    Ufkes, Elze G; Dovidio, John F; Tel, Gulizar

    2015-03-01

    This research investigated the role of group-based anger and efficacy in explaining the effects of subgroup (ethnic) and common (European) identity on collective action among Kurds in Europe responding to different types of disadvantage. Whereas stronger Kurdish identity positively predicted intentions for collective action (mediated by anger and efficacy), stronger common ingroup identity was negatively related to collective action intentions. This effect occurred primarily when structural disadvantage was salient, not when attention was drawn to a specific incident of disadvantage, and was mediated by anger but not efficacy. The findings complement recent work demonstrating that intergroup harmony can undermine social change, suggesting that stronger common-group identification reduces collective action by reducing minority-group members' sensitivity to potential bias against them. PMID:25257157

  12. A review of action estimation methods for galactic dynamics

    Sanders, Jason L

    2015-01-01

    We review the available methods for estimating actions, angles and frequencies of orbits in both axisymmetric and triaxial potentials. The methods are separated into two classes. Unless an orbit has been trapped by a resonance, convergent, or iterative, methods are able to recover the actions to arbitrarily high accuracy given sufficient computing time. Faster non-convergent methods rely on the potential being sufficiently close to a separable potential and the accuracy of the action estimate cannot be improved through further computation. We critically compare the accuracy of the methods and the required computation time for a range of orbits in an axisymmetric multi-component Galactic potential. We introduce a new method for estimating actions that builds on the adiabatic approximation of Sch\\"onich & Binney (2012) and discuss the accuracy required for the actions, angles and frequencies using suitable distribution functions for the thin and thick discs, the stellar halo and a star stream. We conclude t...

  13. Immigration Enforcement Actions - Annual Report

    Department of Homeland Security — Each year, the Department of Homeland Security (DHS) undertakes immigration enforcement actions involving hundreds of thousands of foreign nationals. These actions...

  14. Action research in inter-organisational networks

    Goduscheit, René Chester; Rasmussen, Erik Stavnsager; Jørgensen, Jacob Høj;

    2007-01-01

    Traditionally, the literature on action research has been aimed at intra-organisational issues. These studies have distinguished between two researcher roles: The problem-solver and the observer. This article addresses the distinct challenges of action research in inter-organisational projects....... In addition to the problem-solver and observer roles, the researcher in an inter-organisational setting can serve as a legitimiser of the project and manage to involve partners that in an ordinary business-to-business setting would not have participated. Based on an action research project in a Danish inter......-organisational network, this article discusses potential pitfalls in the legitimiser role. Lack of clarity in defining the researcher role and project ownership in relation to the funding organisation and the rest of the network can jeopardise the project and potentially the credibility of the researchers. The article...

  15. Effective action in general chiral superfield model

    Petrov, A. Yu.

    2000-01-01

    The effective action in general chiral superfield model with arbitrary k\\"{a}hlerian potential $K(\\bar{\\Phi},\\Phi)$ and chiral (holomorphic) potential $W(\\Phi)$ is considered. The one-loop and two-loop contributions to k\\"{a}hlerian effective potential and two-loop (first non-zero) contribution to chiral effective potential are found for arbitrary form of functions $K(\\bar{\\Phi},\\Phi)$ and $W(\\Phi)$. It is found that despite the theory is non-renormalizable in general case two-loop contributi...

  16. Action Research for Sustainability

    Egmose, Jonas

    to renew itself without eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming......How can action research further new research orientations towards sustainability? This book, empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating on urban sustainability, answers this question...... to provide local citizens with a greater say in the future of urban sustainability research, this book shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia...

  17. Action Research for Sustainability

    Egmose, Jonas

    eroding its own foundation of existence, it argues that since sustainability cannot be invented but only supported (or eroded) by science, we need to reframe science in the role of sustaining sustain-ability. Through analyses of a three year action research programme, aiming to provide local citizens......Analysing processes of social learning this work addresses how action research can further new research orientations towards sustainability. Empirically situated in the field of upstream public engagement, involving local residents, researchers and practitioners in bottom-up processes deliberating...... with a greater say in the future of urban sustainability research, the work shows how action research can make important methodological contributions to processes of social learning between citizens and scientists by enabling free spaces in peoples everyday life and within academia, where aspects...

  18. Improving Learning and Teaching through Action Learning and Action Research.

    Zuber-Skeriit, Ortrun

    1993-01-01

    A theoretical framework for action learning and action research is presented, as a basis for better understanding college instruction and learning. Action research is viewed as a philosophy, theory of learning, research methodology, and teaching technique. It is argued that action research both increases knowledge and improves teaching.…

  19. A Self-Study of the Teaching of Action Research in a University Context

    Choi, Jung-ah

    2011-01-01

    Despite the potential benefits of action research, teaching action research in a university setting can present challenges. Analyzing my own experiences of teaching a university-based course on action research, this self-study investigates what my students (all classroom teachers) did and did not understand about action research and what hindered…

  20. Mining Login Data for Actionable Student Insight

    Agnihotri, Lalitha; Aghababyan, Ani; Mojarad, Shirin; Riedesel, Mark; Essa, Alfred

    2015-01-01

    Student login data is a key resource for gaining insight into their learning experience. However, the scale and the complexity of this data necessitate a thorough exploration to identify potential actionable insights, thus rendering it less valuable compared to student achievement data. To compensate for the underestimation of login data…

  1. Class actions in Portugal

    Raimundo, Maria Carlos Miranda

    2013-01-01

    Even eighteen years after the implementation of Law 83/95, of August 31, about the rights of participation in class action litigation in Portugal, there is no sufficient evidence of its applicability. Contrarily to what is observed in other countries as the United States and Brazil it seems that in Portugal, there is no interest of the several parties that would be involved in a class action litigation to obtain information or inform other parties relatively to the main procedures on it and t...

  2. Collective Action under Globalization

    Scheuer, Steen

    organizations deliberating collective action. Institutional factors are especially important for understanding still persisting inter-country variance, and they point to a novel industrial conflict calculus for employees. This calculus seems to entail a more restricted use, but not the withering away of the......Collective action in the form of industrial conflict has declined dramatically since the high tide in the 1970s in Europe. This article argues that this decline is the result of significant changes in both economic and institutional factors, influencing the calculations of employees and of their...

  3. Improvisation in Action

    Bansler, Jørgen P.; Havn, Erling C.

    2003-01-01

    The paper discusses the role of extemporaneous action and bricolage in designing and implementing information systems in organizations. We report a longitudinal field study of design and implementation of a Web-based groupware application in a multinational corporation. We adopt a sensemaking...... perspective to analyze the dynamics of this process and show that improvisational action and bricolage (making do with the materials at hand) played a vital role in the development of the application. Finally, we suggest that this case study provides an occasion to reconsider how we conceptualize information...

  4. Genre as Fictional Action

    Auken, Sune

    2014-01-01

    The arcticle is an interdisciplinary study between literary and rhetorical genre research. Its starting point is the well-deserved leading position held by Rhetorical Genre Studies (RGS). The article proposes a scholarly collaboration between Literary Studies and RGS and posits one possible start...... starting point for this collaboration by utilizing Carolyn Miller´s central concept of "Genre as Social Action" as a way to analyze literary characters´ social actions within narratives through an interpretation of their uses of genre....

  5. Action Programming Languages

    Thielscher, Michael

    2008-01-01

    Artificial systems that think and behave intelligently are one of the most exciting and challenging goals of Artificial Intelligence. Action Programming is the art and science of devising high-level control strategies for autonomous systems which employ a mental model of their environment and which reason about their actions as a means to achieve their goals. Applications of this programming paradigm include autonomous software agents, mobile robots with high-level reasoning capabilities, and General Game Playing. These lecture notes give an in-depth introduction to the current state-of-the-ar

  6. Ação de potenciais hidrogeniônicos no crescimento e produtividade de sálvia (Salvia officinalis L. Action of potentials of hydrogen on growth and productivity of sage (Salvia officinalis L.

    L.H Ilkiu-Vidal

    2010-03-01

    Full Text Available O potencial hidrogeniônico (pH do solo é um parâmetro que indica o nível de acidez ou alcalinidade do mesmo. Sabe-se que as plantas respondem de diferentes maneiras às mudanças no pH dos solos. Poucos artigos relacionam o crescimento e produtividade de plantas medicinais à variação do pH dos solos. O objetivo deste experimento foi avaliar o efeito de diferentes potenciais hidrogeniônicos, em solo Latossolo Vermelho Distroférrico, no crescimento e produção de sálvia. Com o auxílio de curva de neutralização da acidez do solo foram aplicadas diferentes doses de CaCO3 para atingir pH de 4,5; 5,0; 5,5; 6,0 e 6,5. O experimento foi conduzido em casa de vegetação durante 18 meses, perfazendo as fases de semeadura, transplantio e três cortes. Os parâmetros avaliados foram altura de plantas, massa seca de folhas, raízes e da parte aérea (soma das massas secas das folhas, ramos e caule, área foliar e volume das raízes. O crescimento e produção das plantas de sálvia foram diretamente afetados com a variação do pH do solo. A manutenção de pH > 5,0 foi suficiente para aumentar significativamente a área foliar, a massa seca das folhas e da parte área das plantas de sálvia em 52,2%, 60,5% e 42,4%, respectivamente, e não afetou o desenvolvimento das raízes de sálvia cultivadas em solos com diferentes pHs.The soil potential of hydrogen (pH is a parameter that indicates the acidity or alkalinity level. Plants are known to react differently to changes in the soil pH. Few studies have related growth and productivity of medicinal plants to the soil pH variation. The aim of this experiment was to evaluate the effect of different potentials of hydrogen in Oxisol on sage growth and productivity. With the aid of a soil acidity neutralization curve, different CaCO3 levels were applied to reach pH values of 4.5, 5.0, 5.5, 6.0 and 6.5. The experiment was carried out in a greenhouse during 18 months, covering sowing, transplanting and

  7. Action Learning and its Applications

    Dilworth, Dr Robert

    2010-01-01

    This second volume of two discusses the employment of action learning in different contexts, including healthcare, education, government, military and the business world. Use of action learning in delivery of Future Search Conferences is addressed, as well as action learning in community and civil society and the future of action learning.

  8. From Awareness to Action

    Micklos, John, Jr.

    2012-01-01

    What inspires young people to become activists? Events such as wars or regime changes obviously raise high emotions. But some choose to get involved because they saw a need and felt compelled to take action. Young Americans have a long track record as activists. Among other things, they played a key role in the civil rights movement of the 1950s…

  9. Sustainability as Moral Action

    Dunn, Merrily S.; Hart-Steffes, Jeanne S.

    2012-01-01

    When one considers sustainability as a moral action, there are equally complex realities at hand--climate change, resource depletion, water and land rights. One author describes this broad sense of sustainability as "the connection of specific social and environmental problems to the functioning of human and ecological systems" (Jenkins, 2011).…

  10. Theater and action research

    Tofteng, Ditte Maria Børglum; Husted, Mia

    2011-01-01

    difficulties reaching the public agenda or influencing structures of power. In this article we follow the creation of a play and of scenes that address the life, sufferings, and wishes of unemployed people. The skills of actors, writers, and producers are worked into a critical utopian action research project...

  11. Immunomodulatory actions of antibiotics

    Minić Svetlana

    2009-01-01

    Full Text Available Introduction. Antimicrob drugs and immune system interaction has been studied since the pioneer works of Metchnikoff. After the introduction of antibiotics in clinical practice this area has attracted little attention of investigators, because of the lack of standards. This is the reason that the studying of the influence of antibiotics on immune system is still at its beginning. Aim: To point out the immunomodulatory action of some antibiotics on certain components of immune system. Methods and results. The literaure findings show that antibiotics exspress immunomodulatory action on some components of immune system such as fagocytes (polymorphonucleary, macrophages, monocytes, cytokines, immunoglobulines, and on cellular immunity. The principles of antibiotics action on phagocyte are the inhibition of chemotaxis and oxidants production. Macrolides applied for a short time enchance the phagocytic functions while their long use leads to immunosupression. Some cephalosporines and rifampicin in therapeutic doses inhibit the oxydative metabolism of macrophages. Tetracyclines, clindamycines, chloramphenicol and tobramycin inhibit the synthesis of superoxyd anione. The action of some antibiotics on cytokine and specific antibodies is also important. Cellular immunity can be affected as well. After administration of certain antibiotics it takes 1-2 weeks to reestablish normal cellular immunity, and for other even more. Conclusion. There is still no clear standing on real effects of antibiotics on the immune system. Clinicians should search for more information from this new-old field of investigation in order to give more adequate therapy to patients.

  12. The action of France

    After a favorable period for the weapons mastership, the disarmament and the non-proliferation, the conditions of international safety and the strategical context revealed recently worrying developments. The France is decided to continue its action in favor of the disarmament and the non-proliferation in the continuity of its political engagements. (A.L.B.)

  13. Jump into Action

    Ball, Stephen; Cohen, Ann; Meyer, Margaret

    2012-01-01

    Jump Into Action (JIA) is a school-based team-taught program to help fifth-grade students make healthy food choices and be more active. The JIA team (physical education teacher, classroom teacher, school nurse, and parent) work together to provide a supportive environment as students set goals to improve food choices and increase activity.…

  14. Justifying Action Research

    Helskog, Guro Hansen

    2014-01-01

    In this paper I use a general philosophy of science perspective in looking at the problem of justifying action research. First I try to clarify the concept of justification, by contrasting it with the concept of validity, which seems to be used almost as a synonym in some parts of the literature. I discuss the need for taking a stand in relation…

  15. Class Actions in Denmark

    Werlauff, Erik

    2009-01-01

    The article deals with the relatively new Danish Act on Class Action (Danish: gruppesøgsmål) which was suggested by The Permanent Council on Civil procedure (Retsplejerådet) of which the article's author is a member. The operability of the new provisions is illustrated through some wellknown Danish...

  16. RPII Action Plan

    This document outlines RPII's committments under the Public Service Action Plan 2010 to 2014, otherwise known as the Croke Park Agreement. The document describes the proposed changes to the workplan, the benefits arising from the changes and the timeframe for implementing the committments

  17. China’s Actions

    2010-01-01

    China’s National Development and Reform Commission publicized the country’s policies and actions for addressing climate change in a report released on November 26,2009.The report highlighted China’s efforts in cutting greenhouse gas emissions in 2009 by

  18. Reconnecting Actions and Consequences

    Petersen, Marianne Graves; Ludvigsen, Martin; Krogh, Peter

    2009-01-01

    In this paper we present a brief critique of the current approach to the design of pervasive computing artifacts; claiming that this in itself promotes solutions that prevent end-users from accessing and understanding the consequences of their actions in terms of energy sustainability, specifically...

  19. Hope for Environmental Action

    Fleischer, Barbara J.; DeMoor, Emily

    2015-01-01

    Environmental consciousness-raising programs tend to emphasize the magnitude of imminent ecological disasters, if humans continue on their current trajectory. While these environmental literacy programs also call for action to avoid cataclysmic ecological changes, psychological research on "learned helplessness" suggests that information…

  20. Joint action: Current perspectives

    Galantucci, B.; Sebanz, N.

    2009-01-01

    In recent years researchers have begun to investigate how the perceptual, motor and cognitive activities of two or more individuals become organized into coordinated action. In the first part of this introduction we identify three common threads among the ten papers of this special issue that exempl

  1. Partial Actions and Power Sets

    Jesús Ávila

    2013-01-01

    Full Text Available We consider a partial action (X,α with enveloping action (T,β. In this work we extend α to a partial action on the ring (P(X,Δ,∩ and find its enveloping action (E,β. Finally, we introduce the concept of partial action of finite type to investigate the relationship between (E,β and (P(T,β.

  2. The Role of natural gas and biomethane in the fuel mix of the future in Germany. Required action and potential solutions to accelerate adoption in transport applications; Erdgas und Biomethan im kuenftigen Kraftstoffmix. Handlungsbedarf und Loesungsansaetze fuer eine beschleunigte Etablierung im Verkehr

    NONE

    2011-09-15

    The contribution under consideration reports on the need of action and on solution attempts for an accelerated establishment of natural gas and bio methane in the future fuel mix. The authors come to the following conclusions: The energy situation and climatic situation require a stronger diversification of fuels and drives. The targets for the amount of natural gas and bio methane as a fuel are not reached yet. The characteristics of natural gas speak for an accelerated establishment in the traffic sector. The admixture of bio methane can increase the climatic, environmental and resources advantages. In order to penetrate the market all participants involved must commit themselves to a concrete 'roadmap'. The contribution shows which measures must be converted by the participants involved in order to be able to utilize fully the potentials of the employment of natural gas and bio methane in the traffic sector.

  3. 不同浓度瑞芬太尼对兔心室肌单相动作电位的电生理特性影响%Effects of different concentrations of remifentanil on ventricular monophasic action potential electrophysiological properties in isolated rabbit heart

    刘艳秋; 高鸿; 龙娟; 李惠; 张凯强

    2015-01-01

    Objective To study the effects of different concentrations of remifentanil on monophasic action potentials ( MAP ) of myocardium in isolated rabbit hearts.Methods Twenty -four prepared isolated heart perfusion model by Langendorff.The hearts were randomly divided into four groups after perfusion with K-H 15 minutes ( n=6 ): it continue perfusion 60 min in control group.The heart model in test groups were treated perfused with 12 ,25 and 50 ng・ mL-1 of remifentanil with K-H solution 60 min.The heart rate( HR) , the 0 phase of the maximum rate of rise( Vmax ) , the monophasic action potential amplitude ( MAPA) and monophasic action potential duration of repolarization at 50% and 90%( MAPD50 , MAPD90 ) were recorded after balanced infusion 15 min (T0), continued perfusion 15,30,60 min (T1 -T3).Results The HR, prolonger MAPD50 and MAPD90 at T1 -T3 in test groups were slower than T0 and control group ( P <0.05 ) .Both the Vmax and MAPA at T1 -T3 in the middle and high concentrations groups was slower was lower than T0 , control group and low concentration of test group (P<0.05).Conclusion Remifentanil slows the heart rate and prolong the action potential duration when the process was not concentration dependent.Effect of middle and high concentrations of remifentanil on depolarization may be one of the mechanisms that cause heart block.%目的:观察不同浓度瑞芬太尼对心室肌单相动作电位的影响。方法制备Langendorff离体兔心脏模型24个,K-H液灌注15 min后,随机分为4组,每组均6只,对照组继续灌注 K -H 液60 min;实验组分别灌注含12,25,50 ng・ mL-1瑞芬太尼的K-H液60 min。平衡灌注15 min (T0)、继续灌注15,30,60 min ( T1~T3)时,记录心率、0相最大上升速率( Vmax )、单相动作电位振幅( MAPA)及单相动作电位复极50%,90%的时程( MAPD50,MAPD90)。结果与T0和对照组比较,3个浓度瑞芬太尼组在T1~T3时

  4. Numerical path integration with Coulomb potential

    Myrheim, Jan

    2003-01-01

    A simple and efficient method for quantum Monte Carlo simulation is presented, based on discretization of the action in the path integral, and a Gaussian averaging of the potential, which works well e.g. with the Coulomb potential.

  5. Mode of action of etoxazole.

    Nauen, Ralf; Smagghe, Guy

    2006-05-01

    The mode of action of the 2,4-diphenyl-1,3-oxazoline acaricide/insecticide etoxazole has been argued to be moulting inhibition, but experimental results supporting this hypothesis are lacking. This study investigated the effect of etoxazole on chitin biosynthesis in the fall armyworm, Spodoptera frugiperda (Smith) (Lepidoptera: Noctuidae). Etoxazole induced moulting defects in fall armyworm larvae similar, if not identical, to those caused by benzoylphenylureas, a well-known class of insecticidal chitin biosynthesis inhibitors. Furthermore, in contrast to untreated larvae, the chitin content in the integuments of larvae several days after treatment did not differ from that in freshly ecdysed individuals, thus suggesting strong chitin biosynthesis inhibition in vivo. A more detailed investigation of the inhibitory potential by incubating cultured integument pieces from larvae of S. frugiperda with [14C]N-acetyl-D-glucosamine, a radiolabelled chitin precursor, revealed I50 values of 2.95 and 0.071 microM for etoxazole and triflumuron respectively. The incorporation of radiolabel into potassium hydroxide-resistant material was inhibited by etoxazole in a dose-dependent manner. Based on these results, it is concluded that the acaricidal and insecticidal mode of action of etoxazole is chitin biosynthesis inhibition. PMID:16555232

  6. Corrective Action Investigation Plan for Corrective Action Unit 137: Waste Disposal Sites, Nevada Test Site, Nevada

    This Corrective Action Investigation Plan (CAIP) contains project-specific information including facility descriptions, environmental sample collection objectives, and criteria for conducting site investigation activities at Corrective Action Unit (CAU) 137: Waste Disposal Sites. This CAIP has been developed in accordance with the ''Federal Facility Agreement and Consent Order'' (FFACO) (1996) that was agreed to by the State of Nevada, the U.S. Department of Energy (DOE), and the U.S. Department of Defense. Corrective Action Unit 137 contains sites that are located in Areas 1, 3, 7, 9, and 12 of the Nevada Test Site (NTS), which is approximately 65 miles (mi) northwest of Las Vegas, Nevada (Figure 1-1). Corrective Action Unit 137 is comprised of the eight corrective action sites (CASs) shown on Figure 1-1 and listed below: (1) CAS 01-08-01, Waste Disposal Site; (2) CAS 03-23-01, Waste Disposal Site; (3) CAS 03-23-07, Radioactive Waste Disposal Site; (4) CAS 03-99-15, Waste Disposal Site; (5) CAS 07-23-02, Radioactive Waste Disposal Site; (6) CAS 09-23-07, Radioactive Waste Disposal Site; (7) CAS 12-08-01, Waste Disposal Site; and (8) CAS 12-23-07, Waste Disposal Site. The Corrective Action Investigation (CAI) will include field inspections, radiological surveys, geophysical surveys, sampling of environmental media, analysis of samples, and assessment of investigation results, where appropriate. Data will be obtained to support corrective action alternative evaluations and waste management decisions. The CASs in CAU 137 are being investigated because hazardous and/or radioactive constituents may be present in concentrations that could potentially pose a threat to human health and the environment. Existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives for the CASs. Additional information will be generated by conducting a CAI before evaluating and selecting corrective action

  7. Defining actionable mutations for oncology therapeutic development.

    Carr, T Hedley; McEwen, Robert; Dougherty, Brian; Johnson, Justin H; Dry, Jonathan R; Lai, Zhongwu; Ghazoui, Zara; Laing, Naomi M; Hodgson, Darren R; Cruzalegui, Francisco; Hollingsworth, Simon J; Barrett, J Carl

    2016-04-26

    Genomic profiling of tumours in patients in clinical trials enables rapid testing of multiple hypotheses to confirm which genomic events determine likely responder groups for targeted agents. A key challenge of this new capability is defining which specific genomic events should be classified as 'actionable' (that is, potentially responsive to a targeted therapy), especially when looking for early indications of patient subgroups likely to be responsive to new drugs. This Opinion article discusses some of the different approaches being taken in early clinical development to define actionable mutations, and describes our strategy to address this challenge in early-stage exploratory clinical trials. PMID:27112209

  8. Action without frontiers. SADC meeting.

    Klouda, T

    1997-02-01

    The factors which affect AIDS and the transmission of HIV transcend national, racial, cultural, religious, political, and programmatic boundaries. The European Union and the Southern African Development Community (SADC) jointly held a conference in Lilongwe, Malawi, during December 4-6 to bring together senior officials from a wide range of development sectors in the 12 countries of the SADC region to examine the potential for regional, comprehensive action on relevant issues. Conference outcomes will be reviewed and agreed upon at a future regional ministerial meeting. Origins of the conference, innovative aspects of the conference, and regional and sectoral involvement are discussed. Employment, mining, medical drugs, education, and tourism were discussed extensively at the conference as separate sectors. PMID:12292059

  9. Action Research-the Way to Enhancing Teacher Professional Development

    刘颖

    2013-01-01

      This paper introduces the notion of action research in its international academic context. Action research is potentially beneficial to both pre-service teachers and in-service teachers in their professional development and it should play an important role in the curriculum renewal of English teaching methodology in China.

  10. New fixed point action for SU(3) lattice gauge theory

    Blatter, Marc; Niedermayer, Ferenc

    1996-01-01

    We present a new fixed point action for SU(3) lattice gauge theory, which has --- compared to earlier published fixed point actions --- shorter interaction range and smaller violations of rotational symmetry in the static $q\\bar{q}$-potential even at shortest distances.

  11. New fixed point action for SU(3) lattice gauge theory

    We present a new fixed point action for SU(3) lattice gauge theory, which has - compared to earlier published fixed point actions - shorter interaction range and smaller violations of rotational symmetry in the static qq potential even at shortest distances. (orig.)

  12. Deliberation, Capability and Action Research: Knowledge and Becoming

    Gibbs, Paul

    2014-01-01

    In this short paper I examine whether obtaining the capability to change practice can be solely achieved through reflective action research, and how. I take as our framework of analysis that offered by Aristotelian thought, especially in the discussion of powers and potential. I conclude that action research as a way of changing practice cannot be…

  13. Agroecology Education: Action-Oriented Learning and Research

    Lieblein, Geir; Breland, Tor Arvid; Francis, Charles; Ostergaard, Edvin

    2012-01-01

    Purpose: This article examines and evaluates the potential contributions from action learning and action research with stakeholders to higher education in agriculture and food systems. Design/Methodology/Approach: The research is based on our experiences over the past two decades of running PhD courses and an MSc degree programme in Agroecology in…

  14. Corrective Action Investigation Plan for Corrective Action Unit 139: Waste Disposal Sites, Nevada Test Site, Nevada

    Corrective Action Unit (CAU) 139 is located in Areas 3, 4, 6, and 9 of the Nevada Test Site, which is 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 139 is comprised of the seven corrective action sites (CASs) listed below: (1) 03-35-01, Burn Pit; (2) 04-08-02, Waste Disposal Site; (3) 04-99-01, Contaminated Surface Debris; (4) 06-19-02, Waste Disposal Site/Burn Pit; (5) 06-19-03, Waste Disposal Trenches; (6) 09-23-01, Area 9 Gravel Gertie; and (7) 09-34-01, Underground Detection Station. These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives with the exception of CASs 09-23-01 and 09-34-01. Regarding these two CASs, CAS 09-23-01 is a gravel gertie where a zero-yield test was conducted with all contamination confined to below ground within the area of the structure, and CAS 09-34-01 is an underground detection station where no contaminants are present. Additional information will be obtained by conducting a corrective action investigation (CAI) before evaluating corrective action alternatives and selecting the appropriate corrective action for the other five CASs where information is insufficient. The results of the field investigation will support a defensible evaluation of viable corrective action alternatives that will be presented in the Corrective Action Decision Document. The sites will be investigated based on the data quality objectives (DQOs) developed on January 4, 2006, by representatives of the Nevada Division of Environmental Protection; U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office; Stoller-Navarro Joint Venture; and Bechtel Nevada. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective actions for CAU 139

  15. Perfect Actions and Operators for Lattice QCD

    Wiese, Uwe-Jens

    1996-05-01

    Wilson's renormalization group implies that lattice actions located on a renormalized trajectory emanating from a fixed point represent perfect discretizations of continuum physics. With a perfect action the spectrum of a lattice theory is identical with the one of the continuum theory even at finite lattice spacing. Similarly, perfect operators yield cut-off independent matrix elements. Hence, continuum QCD can in principle be reconstructed from a lattice with finite spacing. In practice it is difficult to construct perfect actions and perfect operators explicitly. Here perturbation theory is used to derive perfect actions for quarks and gluons by performing a block renormalization group transformation directly from the continuum. The renormalized trajectory for free massive quarks is identified and a parameter in the renormalization group transformation is tuned such that for 1-d configurations the perfect action reduces to the nearest neighbor Wilson fermion action. Then the 4-d perfect action turns out to be extremely local as well, which is vital for numerical simulations. The fixed point action for free gluons is also obtained by blocking from the continuum. For 2-d configurations it reduces to the standard plaquette action, and for 4-d configurations it is still very local. With interactions between quarks and gluons switched on the perfect quark-gluon and 3-gluon vertex functions are computed analytically. In particular, a perfect clover term can be extracted from the quark-gluon vertex. The perturbatively perfect action is directly applicable to heavy quark physics. The construction of a perfect QCD action for light quarks should include nonperturbative effects, which is possible using numerical methods. Classically perfect quark and gluon fields are constructed as well. They allow to interpolate the continuum fields from the lattice data. In this way one can obtain information about space-time regions between lattice points. The classically perfect fields

  16. Regulatory actions post - Fukushima

    The paper presents the results of the safety reviews performed in Romania after the Fukushima accident and the resulting actions for improving the safety. The actions taken by the National Commission for Nuclear Activities Control (CNCAN) to improve the regulatory framework include the development of new regulations and the enhancement of inspection practices, taking account of the lessons learned from the Fukushima accident. A regulation on the response to transients, accidents and emergency situations at nuclear power plants has been developed, which includes requirements on transient and accident scenarios that have to be covered by the Emergency Operating Procedures (EOPs), accident scenarios to be covered by the Severe Accident Management Guidelines (SAMGs), emergency situations to be covered by the on-site emergency response plan and emergency response procedures. (authors)

  17. Action against Kruemmel rejected

    In its verdict dated September 2nd, 1976 - 10 A 211/74 -, the administrative court of Schleswig-Holstein at Schleswig has rejected with costs the action of a plaintiff resident in Hessen concerning the contestation of the 2nd partial licence for the erection of a nuclear power station at Kruemmel near Hamburg. The verdict is not subject to appeal. Furthermore, the administrative court of Schleswig-Holstein at Schleswig, in its verdict dated September 2nd, 1976 - 10 A 214/74 - has rejected with costs the actions of eight plaintiffs living in Hamburg and surroundings, concerning the contestation of the 1st, 2nd and 3rd partial licence for the erection of a nuclear power station at Kruemmel near Hamburg. An appeal against this verdict has been lodged at the higher administrative court at Lueneburg. The main gounds for the two judgments are given in full text. (orig./HP)

  18. The Prose of Action

    Christiansen, Ulrik; Thrane, Sof

    2014-01-01

    In this paper we study how risk management systems are applied to make organizational actors interested in responding to emerging risks. The empirical domain of the paper is the Defense Procurement Unit in a Scandinavian country. The paper is based on detailed data from monthly risk update meetings......, interviews with both military and civilian managers, and 1 year's worth of monthly risk reports. Our study illustrates how Frontline Managers – to make General Management at the Procurement Unit interested in responding to emerging risks – use the content of the risk reports. The translation of emerging...... risks changes over time in response to a lack of action on reported risks. In these processes Frontline Managers take on new responsibilities to make General Managers take action on reported risk. The reporting practice changes from the mere identification of risk to risk assessment and, finally, to...

  19. INFORM'ACTION

    STAFF ASSOCIATION

    2010-01-01

    INFORM’ACTION Commission ! It’s all in the title ! At a time when one of the keywords is COMMUNICATE, the Staff Association has a duty to take it seriously. This is why, among other reasons, the youngest of the Staff Association internal commissions was created in 20005. As its name indicates, this commission is responsible for INFORMING, TRAINING (FORMER) and organizing ACTIONs. INFORMING : The members of this commission endeavour to work using all imaginable and known channels of information: articles, emails, alerts, posters, web site, organizing meetings, distributing flyers, banners, videos, etc. In 2009 a new web site (http://cern.ch/association) was put on line.   Since then this site has been continually updated to provide information regarding the latest news in the social domain (Pension Fund, CHIS, 5YR), and also special offers for our members, club news, and social and cultural activities. In 2009 and 2010, the Staff Association notice boards were ...

  20. Finding minimal action sequences with a simple evaluation of actions

    Ashvin eShah

    2014-11-01

    Full Text Available Animals are able to discover the minimal number of actions that achieves an outcome (the minimal action sequence. In most accounts of this, actions are associated with a measure of behavior that is higher for actions that lead to the outcome with a shorter action sequence, and learning mechanisms find the actions associated with the highest measure. In this sense, previous accounts focus on more than the simple binary signal of ``was the outcome achieved?''; they focus on ``how well was the outcome achieved?'' However, such mechanisms may not govern all types of behavioral development. In particular, in the process of action discovery (Redgrave and Gurney, 2006, actions are reinforced if they simply lead to a salient outcome because biological reinforcement signals occur too quickly to evaluate the consequences of an action beyond an indication of the outcome's occurrence. Thus, action discovery mechanisms focus on the simple evaluation of ``was the outcome achieved?'' and not ``how well was the outcome achieved?'' Notwithstanding this impoverishment of information, can the process of action discovery find the minimal action sequence? We address this question by implementing computational mechanisms, referred to in this paper as no-cost learning rules, in which each action that leads to the outcome is associated with the same measure of behavior. No-cost rules focus on ``was the outcome achieved?'' and are consistent with action discovery. No-cost rules discover the minimal action sequence in simulated tasks and execute it for a substantial amount of time. Extensive training, however, results in extraneous actions, suggesting that a separate process (which has been proposed in action discovery must attenuate learning if no-cost rules participate in behavioral development. We describe how no-cost rules develop behavior, what happens when attenuation is disrupted, and relate the new mechanisms to wider computational and biological context.