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Sample records for action potential clamp

  1. Patch-Clamp Recording from Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes: Improving Action Potential Characteristics through Dynamic Clamp

    Science.gov (United States)

    Veerman, Christiaan C.; Zegers, Jan G.; Mengarelli, Isabella; Bezzina, Connie R.

    2017-01-01

    Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for studying inherited cardiac arrhythmias and developing drug therapies to treat such arrhythmias. Unfortunately, until now, action potential (AP) measurements in hiPSC-CMs have been hampered by the virtual absence of the inward rectifier potassium current (IK1) in hiPSC-CMs, resulting in spontaneous activity and altered function of various depolarising and repolarising membrane currents. We assessed whether AP measurements in “ventricular-like” and “atrial-like” hiPSC-CMs could be improved through a simple, highly reproducible dynamic clamp approach to provide these cells with a substantial IK1 (computed in real time according to the actual membrane potential and injected through the patch-clamp pipette). APs were measured at 1 Hz using perforated patch-clamp methodology, both in control cells and in cells treated with all-trans retinoic acid (RA) during the differentiation process to increase the number of cells with atrial-like APs. RA-treated hiPSC-CMs displayed shorter APs than control hiPSC-CMs and this phenotype became more prominent upon addition of synthetic IK1 through dynamic clamp. Furthermore, the variability of several AP parameters decreased upon IK1 injection. Computer simulations with models of ventricular-like and atrial-like hiPSC-CMs demonstrated the importance of selecting an appropriate synthetic IK1. In conclusion, the dynamic clamp-based approach of IK1 injection has broad applicability for detailed AP measurements in hiPSC-CMs. PMID:28867785

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Science.gov (United States)

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

    2013-06-15

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

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

    Science.gov (United States)

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

    2018-01-01

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

  6. Optical mapping of optogenetically shaped cardiac action potentials

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Molnar, Peter; Hickman, James J

    2014-01-01

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

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

    OpenAIRE

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

    1991-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

  10. Force-controlled patch clamp of beating cardiac cells.

    Science.gov (United States)

    Ossola, Dario; Amarouch, Mohamed-Yassine; Behr, Pascal; Vörös, János; Abriel, Hugues; Zambelli, Tomaso

    2015-03-11

    From its invention in the 1970s, the patch clamp technique is the gold standard in electrophysiology research and drug screening because it is the only tool enabling accurate investigation of voltage-gated ion channels, which are responsible for action potentials. Because of its key role in drug screening, innovation efforts are being made to reduce its complexity toward more automated systems. While some of these new approaches are being adopted in pharmaceutical companies, conventional patch-clamp remains unmatched in fundamental research due to its versatility. Here, we merged the patch clamp and atomic force microscope (AFM) techniques, thus equipping the patch-clamp with the sensitive AFM force control. This was possible using the FluidFM, a force-controlled nanopipette based on microchanneled AFM cantilevers. First, the compatibility of the system with patch-clamp electronics and its ability to record the activity of voltage-gated ion channels in whole-cell configuration was demonstrated with sodium (NaV1.5) channels. Second, we showed the feasibility of simultaneous recording of membrane current and force development during contraction of isolated cardiomyocytes. Force feedback allowed for a gentle and stable contact between AFM tip and cell membrane enabling serial patch clamping and injection without apparent cell damage.

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

    Science.gov (United States)

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

    2015-05-01

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

  12. Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.

    Science.gov (United States)

    Stoelzle, Sonja; Haythornthwaite, Alison; Kettenhofen, Ralf; Kolossov, Eugen; Bohlen, Heribert; George, Michael; Brüggemann, Andrea; Fertig, Niels

    2011-09-01

    Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.

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

    Science.gov (United States)

    Furong, Liu; Shengtian, L I

    2016-05-25

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

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

    Science.gov (United States)

    Li, S N; Zhang, K Y

    1992-11-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  18. Role of action potential configuration and the contribution of Ca2+ and K+ currents to isoprenaline-induced changes in canine ventricular cells

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, PP

    2012-01-01

    BACKGROUND AND PURPOSE Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca2+ current (ICa), slow delayed rectifier K+ current (IKs) and fast delayed rectifier K+ current (IKr) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. EXPERIMENTAL APPROACH Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. KEY RESULTS In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the IKr blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the IKs blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the ICa blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating ICa followed by a rise in IKs, both currents increased with increasing the cycle length. CONCLUSIONS AND IMPLICATIONS The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of IKs– but not IKr– may be responsible for the observed shortening of action potentials. PMID:22563726

  19. Use of the Satinsky clamp for hilar clamping during robotic partial nephrectomy: indications, technique, and multi-center outcomes.

    Science.gov (United States)

    Abdullah, Newaj; Rahbar, Haider; Barod, Ravi; Dalela, Deepansh; Larson, Jeff; Johnson, Michael; Mass, Alon; Zargar, Homayoun; Kaouk, Jihad; Allaf, Mohamad; Bhayani, Sam; Stifelman, Michael; Rogers, Craig

    2017-03-01

    A Satinsky clamp may be a backup option for hilar clamping during robotic partial nephrectomy (RPN) if there are challenges with application of bulldog clamps, but there are potential safety concerns. We evaluate outcomes of RPN using Satinsky vs. bulldog clamps, and provide tips for safe use of the Satinsky as a backup option. Using a multi-center database, we identified 1073 patients who underwent RPN between 2006 and 2013, and had information available about method of hilar clamping (bulldog clamp vs. Satinsky clamp). Patient baseline characteristics, tumor features, and perioperative outcomes were compared between the Satinsky and bulldog clamp groups. A Satinsky clamp was used for hilar clamping in 94 (8.8 %) RPN cases, and bulldog clamps were used in 979 (91.2 %) cases. The use of a Satinsky clamp was associated with greater operative time (198 vs. 175 min, p hilar clamping during challenging RPN cases, but requires careful technique, and was rarely necessary.

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

    DEFF Research Database (Denmark)

    Lewandowski, Rebecca; Procida, Kristina; Vaidyanathan, Ravi

    2008-01-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2014-08-25

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

  3. Role of action potential configuration and the contribution of C²⁺a and K⁺ currents to isoprenaline-induced changes in canine ventricular cells.

    Science.gov (United States)

    Szentandrássy, N; Farkas, V; Bárándi, L; Hegyi, B; Ruzsnavszky, F; Horváth, B; Bányász, T; Magyar, J; Márton, I; Nánási, P P

    2012-10-01

    Although isoprenaline (ISO) is known to activate several ion currents in mammalian myocardium, little is known about the role of action potential morphology in the ISO-induced changes in ion currents. Therefore, the effects of ISO on action potential configuration, L-type Ca²⁺ current (I(Ca)), slow delayed rectifier K⁺ current (I(Ks)) and fast delayed rectifier K⁺ current (I(Kr)) were studied and compared in a frequency-dependent manner using canine isolated ventricular myocytes from various transmural locations. Action potentials were recorded with conventional sharp microelectrodes; ion currents were measured using conventional and action potential voltage clamp techniques. In myocytes displaying a spike-and-dome action potential configuration (epicardial and midmyocardial cells), ISO caused reversible shortening of action potentials accompanied by elevation of the plateau. ISO-induced action potential shortening was absent in endocardial cells and in myocytes pretreated with 4-aminopyridine. Application of the I(Kr) blocker E-4031 failed to modify the ISO effect, while action potentials were lengthened by ISO in the presence of the I(Ks) blocker HMR-1556. Both action potential shortening and elevation of the plateau were prevented by pretreatment with the I(Ca) blocker nisoldipine. Action potential voltage clamp experiments revealed a prominent slowly inactivating I(Ca) followed by a rise in I(Ks) , both currents increased with increasing the cycle length. The effect of ISO in canine ventricular cells depends critically on action potential configuration, and the ISO-induced activation of I(Ks) - but not I(Kr) - may be responsible for the observed shortening of action potentials. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  4. Clamping characteristics study on different types of clamping unit

    Energy Technology Data Exchange (ETDEWEB)

    Jiao, Zhiwei; Liu, Haichao; Xie, Pengcheng [College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing China 100029 (China); Yang, Weimin [College of Mechanical and Electrical Engineering, Beijing University of Chemical Technology, Beijing China 100029 (China); State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing China 100029 (China)

    2015-05-22

    Plastic products are becoming more and more widely used in aerospace, IT, digital electronics and many other fields. With the development of technology, the requirement of product precision is getting higher and higher. However, type and working performance of clamping unit play a decisive role in product precision. Clamping characteristics of different types of clamping unit are discussed in this article, which use finite element numerical analysis method through the software ABAQUS to study the clamping uniformity, and detect the clamping force repeatability precision. The result shows that compared with toggled three-platen clamping unit, clamping characteristics of internal circulation two-platen clamping unit are better, for instance, its mold cavity deformation and force that bars and mold parting surface suffered are more uniform, and its clamping uniformity and repeatability precision is also better.

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

    Science.gov (United States)

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

    2015-08-01

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

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

    Science.gov (United States)

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

    2014-07-07

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2012-10-25

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

  9. Is early cord clamping, delayed cord clamping or cord milking best?

    Science.gov (United States)

    Vatansever, Binay; Demirel, Gamze; Ciler Eren, Elif; Erel, Ozcan; Neselioglu, Salim; Karavar, Hande Nur; Gundogdu, Semra; Ulfer, Gozde; Bahadir, Selcen; Tastekin, Ayhan

    2018-04-01

    To compare the antioxidant status of three cord clamping procedures (early clamping, delayed clamping and milking) by analyzing the thiol-disulfide balance. This randomized controlled study enrolled 189 term infants who were divided into three groups according to the cord clamping procedure: early clamping, delayed clamping and milking. Blood samples were collected from the umbilical arteries immediately after clamping, and the thiol/disulfide homeostasis was analyzed. The native and total thiol levels were significantly (p total thiol ratio was significantly (p = .026) lower in the delayed cord clamping and milking groups compared with the early clamping groups. Early cord clamping causes the production of more disulfide bonds and lower thiol levels, indicating that oxidation reactions are increased in the early cord clamping procedure compared with the delayed cord clamping and milking procedures. The oxidant capacity is greater with early cord clamping than with delayed clamping or cord milking. Delayed cord clamping or milking are beneficial in neonatal care, and we suggest that they be performed routinely in all deliveries.

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

    Science.gov (United States)

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

    2013-02-01

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

  11. Increased transient Na+ conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1-/y mouse.

    Science.gov (United States)

    Routh, Brandy N; Rathour, Rahul K; Baumgardner, Michael E; Kalmbach, Brian E; Johnston, Daniel; Brager, Darrin H

    2017-07-01

    Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 -/y mice. In fmr1 -/y L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na + conductance density is higher in fmr1 -/y L2/3 neurons. Measurements of three biophysically distinct K + currents revealed a depolarizing shift in the activation of a rapidly inactivating (A-type) K + conductance. Realistic neuronal simulations of the biophysical observations recapitulated the elevated action potential and repetitive firing phenotype. Fragile X syndrome is the most common form of inherited mental impairment and autism. The prefrontal cortex is responsible for higher order cognitive processing, and prefrontal dysfunction is believed to underlie many of the cognitive and behavioural phenotypes associated with fragile X syndrome. We recently demonstrated that somatic and dendritic excitability of layer (L) 5 pyramidal neurons in the prefrontal cortex of the fmr1 -/y mouse is significantly altered due to changes in several voltage-gated ion channels. In addition to L5 pyramidal neurons, L2/3 pyramidal neurons play an important role in prefrontal circuitry, integrating inputs from both lower brain regions and the contralateral cortex. Using whole-cell current clamp recording, we found that L2/3 pyramidal neurons in prefrontal cortex of fmr1 -/y mouse fired more action potentials for a given stimulus compared with wild-type neurons. In addition, action potentials in fmr1 -/y neurons were significantly larger, faster and narrower. Voltage clamp of outside-out patches from L2/3 neurons revealed that the transient Na + current was significantly larger in fmr1 -/y neurons. Furthermore, the activation curve of somatic A-type K + current was depolarized. Realistic conductance-based simulations revealed that these biophysical changes in Na

  12. Kv2 Channel Regulation of Action Potential Repolarization and Firing Patterns in Superior Cervical Ganglion Neurons and Hippocampal CA1 Pyramidal Neurons

    Science.gov (United States)

    Liu, Pin W.

    2014-01-01

    Kv2 family “delayed-rectifier” potassium channels are widely expressed in mammalian neurons. Kv2 channels activate relatively slowly and their contribution to action potential repolarization under physiological conditions has been unclear. We explored the function of Kv2 channels using a Kv2-selective blocker, Guangxitoxin-1E (GxTX-1E). Using acutely isolated neurons, mixed voltage-clamp and current-clamp experiments were done at 37°C to study the physiological kinetics of channel gating and action potentials. In both rat superior cervical ganglion (SCG) neurons and mouse hippocampal CA1 pyramidal neurons, 100 nm GxTX-1E produced near-saturating block of a component of current typically constituting ∼60–80% of the total delayed-rectifier current. GxTX-1E also reduced A-type potassium current (IA), but much more weakly. In SCG neurons, 100 nm GxTX-1E broadened spikes and voltage clamp experiments using action potential waveforms showed that Kv2 channels carry ∼55% of the total outward current during action potential repolarization despite activating relatively late in the spike. In CA1 neurons, 100 nm GxTX-1E broadened spikes evoked from −70 mV, but not −80 mV, likely reflecting a greater role of Kv2 when other potassium channels were partially inactivated at −70 mV. In both CA1 and SCG neurons, inhibition of Kv2 channels produced dramatic depolarization of interspike voltages during repetitive firing. In CA1 neurons and some SCG neurons, this was associated with increased initial firing frequency. In all neurons, inhibition of Kv2 channels depressed maintained firing because neurons entered depolarization block more readily. Therefore, Kv2 channels can either decrease or increase neuronal excitability depending on the time scale of excitation. PMID:24695716

  13. Modulatory action of acetylcholine on the Na+-dependent action potentials in Kenyon cells isolated from the mushroom body of the cricket brain.

    Science.gov (United States)

    Terazima, E; Yoshino, M

    2010-12-01

    Kenyon cells, intrinsic neurons of the insect mushroom body, have been assumed to be a site of conditioning stimulus (CS) and unconditioned stimulus (US) association in olfactory learning and memory. Acetylcholine (ACh) has been implicated to be a neurotransmitter mediating CS reception in Kenyon cells, causing rapid membrane depolarization via nicotinic ACh receptors. However, the long-term effects of ACh on the membrane excitability of Kenyon cells are not fully understood. In this study, we examined the effects of ACh on Na(+) dependent action potentials (Na(+) spikes) elicited by depolarizing current injection and on net membrane currents under the voltage clamp condition in Kenyon cells isolated from the mushroom body of the cricket Gryllus bimaculatus. Current-clamp studies using amphotericin B perforated-patch recordings showed that freshly dispersed cricket Kenyon cells could produce repetitive Na(+) spikes in response to prolonged depolarizing current injection. Bath application of ACh increased both the instantaneous frequency and the amplitudes of Na(+) spikes. This excitatory action of ACh on Kenyon cells is attenuated by the pre-treatment of the cells with the muscarinic receptor antagonists, atropine and scopolamine, but not by the nicotinic receptor antagonist mecamylamine. Voltage-clamp studies further showed that bath application of ACh caused an increase in net inward currents that are sensitive to TTX, whereas outward currents were decreased by this treatment. These results indicate that in order to mediate CS, ACh may modulate the firing properties of Na(+) spikes of Kenyon cells through muscarinic receptor activation, thus increasing Na conductance and decreasing K conductance. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2012-10-25

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

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

    Directory of Open Access Journals (Sweden)

    Alison R Taylor

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

  16. Photovoltaic panel clamp

    Science.gov (United States)

    Mittan, Margaret Birmingham [Oakland, CA; Miros, Robert H. J. [Fairfax, CA; Brown, Malcolm P [San Francisco, CA; Stancel, Robert [Loss Altos Hills, CA

    2012-06-05

    A photovoltaic panel clamp includes an upper and lower section. The interface between the assembled clamp halves and the module edge is filled by a flexible gasket material, such as EPDM rubber. The gasket preferably has small, finger like protrusions that allow for easy insertion onto the module edge while being reversed makes it more difficult to remove them from the module once installed. The clamp includes mounting posts or an integral axle to engage a bracket. The clamp also may include a locking tongue to secure the clamp to a bracket.

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

    Science.gov (United States)

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

    2017-04-01

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

  18. Selective Arterial Clamping Versus Hilar Clamping for Minimally Invasive Partial Nephrectomy.

    Science.gov (United States)

    Yezdani, Mona; Yu, Sue-Jean; Lee, David I

    2016-05-01

    Partial nephrectomy has become an accepted treatment of cT1 renal masses as it provides improved long-term renal function compared to radical nephrectomy (Campbell et al. J Urol. 182:1271-9, 2009). Hilar clamping is utilized to help reduce bleeding and improve visibility during tumor resection. However, concern over risk of kidney injury with hilar clamping has led to new techniques to reduce length of warm ischemia time (WIT) during partial nephrectomy. These techniques have progressed over the years starting with early hilar unclamping, controlled hypotension during tumor resection, selective arterial clamping, minimal margin techniques, and off-clamp procedures. Selective arterial clamping has progressed significantly over the years. The main question is what are the exact short- and long-term renal effects from increasing clamp time. Moreover, does it make sense to perform these more time-consuming or more complex procedures if there is no long-term preservation of kidney function? More recent studies have shown no difference in renal function 6 months from surgery when selective arterial clamping or even hilar clamping is employed, although there is short-term improved decline in estimated glomerular filtration rate (eGFR) with selective clamping and off-clamp techniques (Komninos et al. BJU Int. 115:921-8, 2015; Shah et al. 117:293-9, 2015; Kallingal et al. BJU Int. doi: 10.1111/bju.13192, 2015). This paper reviews the progression of total hilar clamping to selective arterial clamping (SAC) and the possible difference its use makes on long-term renal function. SAC may be attempted based on surgeon's decision-making, but may be best used for more complex, larger, more central or hilar tumors and in patients who have renal insufficiency at baseline or a solitary kidney.

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

    Science.gov (United States)

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

    2012-01-01

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

  20. Insulated pipe clamp design

    International Nuclear Information System (INIS)

    Anderson, M.J.; Hyde, L.L.; Wagner, S.E.; Severud, L.K.

    1980-01-01

    Thin wall large diameter piping for breeder reactor plants can be subjected to significant thermal shocks during reactor scrams and other upset events. On the Fast Flux Test Facility, the addition of thick clamps directly on the piping was undesired because the differential metal temperatures between the pipe wall and the clamp could have significantly reduced the pipe thermal fatigue life cycle capabilities. Accordingly, an insulated pipe clamp design concept was developed. The design considerations and methods along with the development tests are presented. Special considerations to guard against adverse cracking of the insulation material, to maintain the clamp-pipe stiffness desired during a seismic event, to minimize clamp restraint on the pipe during normal pipe heatup, and to resist clamp rotation or spinning on the pipe are emphasized

  1. The Anion Paradox in Sodium Taste Reception: Resolution by Voltage-Clamp Studies

    Science.gov (United States)

    Ye, Qing; Heck, Gerard L.; Desimone, John A.

    1991-11-01

    Sodium salts are potent taste stimuli, but their effectiveness is markedly dependent on the anion, with chloride yielding the greatest response. The cellular mechanisms that mediate this phenomenon are not known. This "anion paradox" has been resolved by considering the field potential that is generated by restricted electrodiffusion of the anion through paracellular shunts between taste-bud cells. Neural responses to sodium chloride, sodium acetate, and sodium gluconate were studied while the field potential was voltage-clamped. Clamping at electronegative values eliminated the anion effect, whereas clamping at electropositive potentials exaggerated it. Thus, field potentials across the lingual epithelium modulate taste reception, indicating that the functional unit of taste reception includes the taste cell and its paracellular microenvironment.

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

    Science.gov (United States)

    Yang, Li-Zhen; Zhu, Yi-Chun

    2015-07-05

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

  3. Radial wedge flange clamp

    Science.gov (United States)

    Smith, Karl H.

    2002-01-01

    A radial wedge flange clamp comprising a pair of flanges each comprising a plurality of peripheral flat wedge facets having flat wedge surfaces and opposed and mating flat surfaces attached to or otherwise engaged with two elements to be joined and including a series of generally U-shaped wedge clamps each having flat wedge interior surfaces and engaging one pair of said peripheral flat wedge facets. Each of said generally U-shaped wedge clamps has in its opposing extremities apertures for the tangential insertion of bolts to apply uniform radial force to said wedge clamps when assembled about said wedge segments.

  4. The plastic instability of clamped-clamped conical thin-walled pipe reducers

    International Nuclear Information System (INIS)

    Awad, Ibrahim; Saleh, Ch.A.R.; Ragab, A.R.

    2016-01-01

    The analytical study for plastic deformation of clamped–clamped conical reducer pipe under internal pressure does not deduce a closed form expression for the pressure at plastic instability. The presented study employs finite element analysis (FEA) to estimate the internal pressure at instability for conical reducers made of different materials and having different dimensional configurations. Forty dimensional configurations, classified as medium type, and five types of materials have been included in the analysis using ABAQUS package. A correlation expression is derived by nonlinear regression to predict the instability pressure. The proposed expression is verified for other dimensional configurations out of the above used forty models and for other materials. Experiments have been conducted by pressurizing conical clamped-clamped reducers until bursting in order to verify the finite element models. Comparison of instability pressures, strains and deflections at specific points along the conical surface shows satisfactory agreement between analysis and experiments. - Highlights: • This study offers a parametric study of the plastic instability pressure of clamped-clamped conical reducers. • A closed form analytical expression for the instability pressure is derived by using nonlinear regression. • The finite element analysis is validated by conducting bursting tests.

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

    Directory of Open Access Journals (Sweden)

    Hester M Den Ruijter

    2010-11-01

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

  6. Insulated pipe clamp design

    International Nuclear Information System (INIS)

    Anderson, M.J.; Hyde, L.L.; Wagner, S.E.; Severud, L.K.

    1980-01-01

    Thin wall large diameter piping for breeder reactor plants can be subjected to significant thermal shocks during reactor scrams and other upset events. On the Fast Flux Test Facility, the addition of thick clamps directly on the piping was undesired because the differential metal temperatures between the pipe wall and the clamp could have significantly reduced the pipe thermal fatigue life cycle capabilities. Accordingly, an insulated pipe clamp design concept was developed. 5 refs

  7. Theoretical and experimental nonlinear dynamics of a clamped-clamped beam MEMS resonator

    NARCIS (Netherlands)

    Mestrom, R.M.C.; Fey, R.H.B.; Nijmeijer, H.

    2008-01-01

    Microelectromechanical resonators feature nonlineardynamic responses. A first-principles based modeling approach is proposed for a clamped-clamped beam resonator. Starting from the partial differential equation for the beam including geometric and electrostatic nonlinear effects, a reduced-order

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

    Science.gov (United States)

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

    2018-04-27

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

  9. Loading dynamics of a sliding DNA clamp.

    KAUST Repository

    Cho, Won-Ki

    2014-05-22

    Sliding DNA clamps are loaded at a ss/dsDNA junction by a clamp loader that depends on ATP binding for clamp opening. Sequential ATP hydrolysis results in closure of the clamp so that it completely encircles and diffuses on dsDNA. We followed events during loading of an E. coli β clamp in real time by using single-molecule FRET (smFRET). Three successive FRET states were retained for 0.3 s, 0.7 s, and 9 min: Hydrolysis of the first ATP molecule by the γ clamp loader resulted in closure of the clamp in 0.3 s, and after 0.7 s in the closed conformation, the clamp was released to diffuse on the dsDNA for at least 9 min. An additional single-molecule polarization study revealed that the interfacial domain of the clamp rotated in plane by approximately 8° during clamp closure. The single-molecule polarization and FRET studies thus revealed the real-time dynamics of the ATP-hydrolysis-dependent 3D conformational change of the β clamp during loading at a ss/dsDNA junction.

  10. Planar patch clamp: advances in electrophysiology.

    Science.gov (United States)

    Brüggemann, Andrea; Farre, Cecilia; Haarmann, Claudia; Haythornthwaite, Ali; Kreir, Mohamed; Stoelzle, Sonja; George, Michael; Fertig, Niels

    2008-01-01

    Ion channels have gained increased interest as therapeutic targets over recent years, since a growing number of human and animal diseases have been attributed to defects in ion channel function. Potassium channels are the largest and most diverse family of ion channels. Pharmaceutical agents such as Glibenclamide, an inhibitor of K(ATP) channel activity which promotes insulin release, have been successfully sold on the market for many years. So far, only a small group of the known ion channels have been addressed as potential drug targets. The functional testing of drugs on these ion channels has always been the bottleneck in the development of these types of pharmaceutical compounds.New generations of automated patch clamp screening platforms allow a higher throughput for drug testing and widen this bottleneck. Due to their planar chip design not only is a higher throughput achieved, but new applications have also become possible. One of the advantages of planar patch clamp is the possibility of perfusing the intracellular side of the membrane during a patch clamp experiment in the whole-cell configuration. Furthermore, the extracellular membrane remains accessible for compound application during the experiment.Internal perfusion can be used not only for patch clamp experiments with cell membranes, but also for those with artificial lipid bilayers. In this chapter we describe how internal perfusion can be applied to potassium channels expressed in Jurkat cells, and to Gramicidin channels reconstituted in a lipid bilayer.

  11. Voltage clamp methods for the study of membrane currents and SR Ca2+ release in adult skeletal muscle fibres

    Science.gov (United States)

    Hernández-Ochoa, Erick O.; Schneider, Martin F.

    2012-01-01

    Skeletal muscle excitation-contraction (E-C)1 coupling is a process composed of multiple sequential stages, by which an action potential triggers sarcoplasmic reticulum (SR)2 Ca2+ release and subsequent contractile activation. The various steps in the E-C coupling process in skeletal muscle can be studied using different techniques. The simultaneous recordings of sarcolemmal electrical signals and the accompanying elevation in myoplasmic Ca2+, due to depolarization-initiated SR Ca2+ release in skeletal muscle fibres, have been useful to obtain a better understanding of muscle function. In studying the origin and mechanism of voltage dependency of E-C coupling a variety of different techniques have been used to control the voltage in adult skeletal fibres. Pioneering work in muscles isolated from amphibians or crustaceans used microelectrodes or ‘high resistance gap’ techniques to manipulate the voltage in the muscle fibres. The development of the patch clamp technique and its variant, the whole-cell clamp configuration that facilitates the manipulation of the intracellular environment, allowed the use of the voltage clamp techniques in different cell types, including skeletal muscle fibres. The aim of this article is to present an historical perspective of the voltage clamp methods used to study skeletal muscle E-C coupling as well as to describe the current status of using the whole-cell patch clamp technique in studies in which the electrical and Ca2+ signalling properties of mouse skeletal muscle membranes are being investigated. PMID:22306655

  12. Crystal structure of DNA polymerase III β sliding clamp from Mycobacterium tuberculosis.

    Science.gov (United States)

    Gui, Wen-Jun; Lin, Shi-Qiang; Chen, Yuan-Yuan; Zhang, Xian-En; Bi, Li-Jun; Jiang, Tao

    2011-02-11

    The sliding clamp is a key component of DNA polymerase III (Pol III) required for genome replication. It is known to function with diverse DNA repair proteins and cell cycle-control proteins, making it a potential drug target. To extend our understanding of the structure/function relationship of the sliding clamp, we solved the crystal structure of the sliding clamp from Mycobacterium tuberculosis (M. tuberculosis), a human pathogen that causes most cases of tuberculosis (TB). The sliding clamp from M. tuberculosis forms a ring-shaped head-to-tail dimer with three domains per subunit. Each domain contains two α helices in the inner ring that lie against two β sheets in the outer ring. Previous studies have indicated that many Escherichia coli clamp-binding proteins have a conserved LF sequence, which is critical for binding to the hydrophobic region of the sliding clamp. Here, we analyzed the binding affinities of the M. tuberculosis sliding clamp and peptides derived from the α and δ subunits of Pol III, which indicated that the LF motif also plays an important role in the binding of the α and δ subunits to the sliding clamp of M. tuberculosis. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Pipe clamp effects on thin-walled pipe design

    International Nuclear Information System (INIS)

    Lindquist, M.R.

    1980-01-01

    Clamp induced stresses in FFTF piping are sufficiently large to require structural assessment. The basic principles and procedures used in analyzing FFTF piping at clamp support locations for compliance with ASME Code rules are given. Typical results from a three-dimensional shell finite element pipe model with clamp loads applied over the clamp/pipe contact area are shown. Analyses performed to categorize clamp induced piping loads as primary or secondary in nature are described. The ELCLAMP Computer Code, which performs analyses at clamp locations combining clamp induced stresses with stresses from overall piping system loads, is discussed. Grouping and enveloping methods to reduce the number of individual clamp locations requiring analysis are described

  14. Multifrequency Excitation of a Clamped-Clamped Microbeam

    KAUST Repository

    Jaber, Nizar R.

    2016-01-20

    We present analytical and experimental investigation of an electrically actuated clamped-clamped microbeam under a twosource harmonic excitation. The first frequency is swept around the first mode of vibration where the second one is fixed. These microbeams are fabricated using polyimide as structural layer coated with nickel form top and chromium and gold layers from bottom. We demonstrate the excitation of additive and subtractive type resonance. We show that by properly tuning the frequency and the amplitude of the excitation force, the frequency bandwidth of the resonator is increased. Theoretically, we solved the eigenvalue problem for different axial forces to find the natural frequencies ratio that match the experimental values. Using Galerkin method, a reduced order model is derived to simulate the static and dynamic response of the device where using three symmetric mode shapes provided a good agreement with experimental data. © Copyright 2015 by ASME.

  15. COMPARISON OF EARLY AND DELAYED UMBILICAL CORD CLAMPING IN THE THIRD STAGE OF LABOUR

    Directory of Open Access Journals (Sweden)

    Tamara Serdinšek

    2015-09-01

    Full Text Available Background: Umbilical cord clamping in the third stage of labour is still controversial. Early cord clamping is defined as clamping at 10, 15, 30 or 60 seconds after delivery and delayed as clamping after 60 seconds or at 2-5 minutes after delivery, when the cord stops pulsating or when the placenta is visible within the birth canal. Early clamping is one of the three components of active management of the third stage of labour, which has been used widely in modern obstetrics during the last century. However, in some northern European countries, various parts of the USA and Canada and in developing countries physiological management is preferred.Conclusions: After publication of several trials describing advantages of delayed clamping, this has recently been progressively replacing early clamping. The most important advantages of delayed cord clamping are higher haemoglobin and ferritin levels, higher iron stores, lower incidence of iron deficiency anaemia, better cardiopulmonary adaptation, lower rate of respiratory distress syndrome, and longer duration of early breastfeeding in term neonates, while there is no increase in the incidence of postpartum haemorrhage. Delayed clamping seems to bring some advantages for preterm neonates as well. However, caution is still advised because of the potential adverse effects, especially polycythaemia with hyperviscosity, hyperbilirubinaemia and respiratory distress.

  16. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation.

    Science.gov (United States)

    Pashut, Tamar; Magidov, Dafna; Ben-Porat, Hana; Wolfus, Shuki; Friedman, Alex; Perel, Eli; Lavidor, Michal; Bar-Gad, Izhar; Yeshurun, Yosef; Korngreen, Alon

    2014-01-01

    Although transcranial magnetic stimulation (TMS) is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  17. Patch-clamp recordings of rat neurons from acute brain slices of the somatosensory cortex during magnetic stimulation

    Directory of Open Access Journals (Sweden)

    Tamar ePashut

    2014-06-01

    Full Text Available Although transcranial magnetic stimulation (TMS is a popular tool for both basic research and clinical applications, its actions on nerve cells are only partially understood. We have previously predicted, using compartmental modeling, that magnetic stimulation of central nervous system neurons depolarized the soma followed by initiation of an action potential in the initial segment of the axon. The simulations also predict that neurons with low current threshold are more susceptible to magnetic stimulation. Here we tested these theoretical predictions by combining in vitro patch-clamp recordings from rat brain slices with magnetic stimulation and compartmental modeling. In agreement with the modeling, our recordings demonstrate the dependence of magnetic stimulation-triggered action potentials on the type and state of the neuron and its orientation within the magnetic field. Our results suggest that the observed effects of TMS are deeply rooted in the biophysical properties of single neurons in the central nervous system and provide a framework both for interpreting existing TMS data and developing new simulation-based tools and therapies.

  18. Analysis list: Clamp [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Clamp Cell line + dm3 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Clamp.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Clam...p.5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/target/Clam...p.10.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Clamp.Cell_line.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/colo/Cell_line.gml ...

  19. Application of active electrode compensation to perform continuous voltage-clamp recordings with sharp microelectrodes.

    Science.gov (United States)

    Gómez-González, J F; Destexhe, A; Bal, T

    2014-10-01

    Electrophysiological recordings of single neurons in brain tissues are very common in neuroscience. Glass microelectrodes filled with an electrolyte are used to impale the cell membrane in order to record the membrane potential or to inject current. Their high resistance induces a high voltage drop when passing current and it is essential to correct the voltage measurements. In particular, for voltage clamping, the traditional alternatives are two-electrode voltage-clamp technique or discontinuous single electrode voltage-clamp (dSEVC). Nevertheless, it is generally difficult to impale two electrodes in a same neuron and the switching frequency is limited to low frequencies in the case of dSEVC. We present a novel fully computer-implemented alternative to perform continuous voltage-clamp recordings with a single sharp-electrode. To reach such voltage-clamp recordings, we combine an active electrode compensation algorithm (AEC) with a digital controller (AECVC). We applied two types of control-systems: a linear controller (proportional plus integrative controller) and a model-based controller (optimal control). We compared the performance of the two methods to dSEVC using a dynamic model cell and experiments in brain slices. The AECVC method provides an entirely digital method to perform continuous recording and smooth switching between voltage-clamp, current clamp or dynamic-clamp configurations without introducing artifacts.

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

    Science.gov (United States)

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

    2014-03-05

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

  1. Cell-Detection Technique for Automated Patch Clamping

    Science.gov (United States)

    McDowell, Mark; Gray, Elizabeth

    2008-01-01

    A unique and customizable machinevision and image-data-processing technique has been developed for use in automated identification of cells that are optimal for patch clamping. [Patch clamping (in which patch electrodes are pressed against cell membranes) is an electrophysiological technique widely applied for the study of ion channels, and of membrane proteins that regulate the flow of ions across the membranes. Patch clamping is used in many biological research fields such as neurobiology, pharmacology, and molecular biology.] While there exist several hardware techniques for automated patch clamping of cells, very few of those techniques incorporate machine vision for locating cells that are ideal subjects for patch clamping. In contrast, the present technique is embodied in a machine-vision algorithm that, in practical application, enables the user to identify good and bad cells for patch clamping in an image captured by a charge-coupled-device (CCD) camera attached to a microscope, within a processing time of one second. Hence, the present technique can save time, thereby increasing efficiency and reducing cost. The present technique involves the utilization of cell-feature metrics to accurately make decisions on the degree to which individual cells are "good" or "bad" candidates for patch clamping. These metrics include position coordinates (x,y) in the image plane, major-axis length, minor-axis length, area, elongation, roundness, smoothness, angle of orientation, and degree of inclusion in the field of view. The present technique does not require any special hardware beyond commercially available, off-the-shelf patch-clamping hardware: A standard patchclamping microscope system with an attached CCD camera, a personal computer with an imagedata- processing board, and some experience in utilizing imagedata- processing software are all that are needed. A cell image is first captured by the microscope CCD camera and image-data-processing board, then the image

  2. Multilevel-clamped multilevel converters (MLC2)

    DEFF Research Database (Denmark)

    Rodriguez, Pedro; Bellar, Maria Dias; Muñoz-Aguliar, Raúl Santiago

    2012-01-01

    clamping scheme is the ML clamping cell, which is composed of a pair of dc sources associated with one single-pole/triple-throw type of switch arrangement. The number of series-connected ML-clamping cells will set the number of levels of the synthesized waveform. By depending on the MCU arrangements......, different converter configurations can be derived, namely, the common clamping and the modular types. Both approaches can be accomplished by employing classical three-level neutral-point-clamped (NPC) technology. Thus, the overall structure of the resultant converter is kept simple, wherein the number...

  3. [Analysis of brain hemometabolism behavior during carotid endarterectomy with temporary clamping.].

    Science.gov (United States)

    Duval Neto, Gastão Fernandes; Niencheski, Augusto H

    2004-04-01

    Carotid endarterectomy with temporary clamping changes cerebral blood flow and cerebral metabolic oxygen demand ratio with consequent oligemic hypoxia or hemometabolic uncoupling. This study aimed at identifying changes in brain hemometabolism, evaluated through changes in oxyhemoglobin saturation in internal jugular vein bulb (SvjO2) during carotid endarterectomy with clamping, and at correlating these changes with potentially interfering factors, mainly end tidal CO2 pressure (P ET CO2) and cerebral perfusion pressure (CPP). Sixteen patients with unilateral carotid stenotic disease scheduled to carotid endarterectomy with carotid arterial clamping were enrolled in this study. Parameters including internal jugular bulb oxyhemoglobin saturation, stump pressure and end tidal CO2 pressure were measured at the following moments: M1 - pre-clamping; M2 - 3 minutes after clamping; M3 - pre-unclamping; M4 - post-unclamping). The comparison among SvjO2 (%, mean +/- SD) in all studied periods has shown differences between those recorded in moments M1 (52.25 +/- 7.87) and M2 (47.43 +/- 9.19). This initial decrease stabilized during temporary clamping, showing decrease in the comparison between M2 and M3 (46.56 +/- 9.25), without statistical significance (p = ns). At post-unclamping, M4 (47.68 +/- 9.12), SvjO2 was increased as compared to M2 and M3 clamping stages, however it was still lower than that of pre-clamping stage M1.(M4 x M1 - p brain hemometabolic uncoupling trend were correlated to P ET CO2. The comparison between CPP and SvjO2 showed weak correlation devoid of statistical significance. In the conditions of our study, SvjO2 measurement is a fast and effective way of clinically monitoring changes in CBF/CMRO2 ratio. Temporary carotid clamping implies in a trend towards brain hemometabolic uncoupling and, as a consequence, to oligemic ischemia; cerebral perfusion pressure does not assesses brain hemometabolic status (CBF and CMRO2 ratio); hypocapnia, may lead to

  4. Insulin action in human thighs after one-legged immobilization

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Mizuno, M.

    1989-01-01

    Insulin action was assessed in thighs of five healthy young males who had one knee immobilized for 7 days by a splint. The splint was not worn in bed. Subjects also used crutches to prevent weight bearing of the immobilized leg. Immobilization decreased the activity of citrate synthase and 3-OH......-acyl-CoA-dehydrogenase in the vastus lateralis muscle by 9 and 14%, respectively, and thigh volume by 5%. After 7 days of immobilization, a two-step euglycemic hyperinsulinemic clamp procedure combined with arterial and bilateral femoral venous catheterization was performed. Insulin action on glucose uptake and tyrosine release...... of the thighs at mean plasma insulin concentrations of 67 (clamp step I) and 447 microU/ml (clamp step II) was decreased by immobilization, whereas immobilization did not affect insulin action on thigh exchange of free fatty acids, glycerol, O2, or potassium. Before and during the clamp step I, lactate release...

  5. Analysis of the Pallet Clamping Conditions in Work Positioning

    Directory of Open Access Journals (Sweden)

    L. A. Kolesnikov

    2016-01-01

    Full Text Available Pallets of automatic transfer lines serve as the technological and work-transfer equipment. However, their design is based on the general principles of designing machine accessories. Calculation of the basic design parameters of work based on their functioning features is fairly relevant.In pallet transfer movement over work positioning there is a mismatch between axes of the basic bushing of a pallet and the clamping locks of positioning. The paper identifies the factors influencing it, and defines the conditions to ensure the trouble-free clamping lock. The circular and rhombic clamping of pallet is simultaneous. Further, a clamping load is calculated from the pallet mass (together with the work-piece and the geometric parameters of the pallet clamping.The paper reveals three movement stages of the clamping lock in a vertical plane when setting the pallet in work positioning:- a clamping lock free play till it encounters with the location bushing;- a clamping lock play length when the lead-in chamfer contacts the bushing chamfer;- a clamping lock play length over the circular surface of bushing.The study of this process has allowed us to calculate the time of pallet clamping and dynamic loads acting on the clamping lock. These calculations made it possible to calculate the required diameter of the clamping lock. The presented calculations allow a reasonable assigning the main design parameters of work positioning for the pallet automatic lines.

  6. Action Potential Broadening in Capsaicin-Sensitive DRG Neurons from Frequency-Dependent Reduction of Kv3 Current.

    Science.gov (United States)

    Liu, Pin W; Blair, Nathaniel T; Bean, Bruce P

    2017-10-04

    Action potential (AP) shape is a key determinant of cellular electrophysiological behavior. We found that in small-diameter, capsaicin-sensitive dorsal root ganglia neurons corresponding to nociceptors (from rats of either sex), stimulation at frequencies as low as 1 Hz produced progressive broadening of the APs. Stimulation at 10 Hz for 3 s resulted in an increase in AP width by an average of 76 ± 7% at 22°C and by 38 ± 3% at 35°C. AP clamp experiments showed that spike broadening results from frequency-dependent reduction of potassium current during spike repolarization. The major current responsible for frequency-dependent reduction of overall spike-repolarizing potassium current was identified as Kv3 current by its sensitivity to low concentrations of 4-aminopyridine (IC 50 action potentials of small-diameter rat DRG neurons showed spike broadening at frequencies as low as 1 Hz and that spike broadening resulted predominantly from frequency-dependent inactivation of Kv3 channels. Spike width helps to control transmitter release, conduction velocity, and firing patterns and understanding the role of particular potassium channels can help to guide new pharmacological strategies for targeting pain-sensing neurons selectively. Copyright © 2017 the authors 0270-6474/17/379705-10$15.00/0.

  7. Implementation of a fast 16-Bit dynamic clamp using LabVIEW-RT.

    Science.gov (United States)

    Kullmann, Paul H M; Wheeler, Diek W; Beacom, Joshua; Horn, John P

    2004-01-01

    The dynamic-clamp method provides a powerful electrophysiological tool for creating virtual ionic conductances in living cells and studying their influence on membrane potential. Here we describe G-clamp, a new way to implement a dynamic clamp using the real-time version of the Lab-VIEW programming environment together with a Windows host, an embedded microprocessor that runs a real-time operating system and a multifunction data-acquisition board. The software includes descriptions of a fast voltage-dependent sodium conductance, delayed rectifier, M-type and A-type potassium conductances, and a leak conductance. The system can also read synaptic conductance waveforms from preassembled data files. These virtual conductances can be reliably implemented at speeds < or =43 kHz while simultaneously saving two channels of data with 16-bit precision. G-clamp also includes utilities for measuring current-voltage relations, synaptic strength, and synaptic gain. Taking an approach built on a commercially available software/hardware platform has resulted in a system that is easy to assemble and upgrade. In addition, the graphical programming structure of LabVIEW should make it relatively easy for others to adapt G-clamp for new experimental applications.

  8. A Hybrid Model for Safety Pharmacology on an Automated Patch Clamp Platform: Using Dynamic Clamp to Join iPSC-Derived Cardiomyocytes and Simulations of Ik1 Ion Channels in Real-Time

    Directory of Open Access Journals (Sweden)

    Birgit Goversen

    2018-01-01

    Full Text Available An important aspect of the Comprehensive In Vitro Proarrhythmia Assay (CiPA proposal is the use of human stem cell-derived cardiomyocytes and the confirmation of their predictive power in drug safety assays. The benefits of this cell source are clear; drugs can be tested in vitro on human cardiomyocytes, with patient-specific genotypes if needed, and differentiation efficiencies are generally excellent, resulting in a virtually limitless supply of cardiomyocytes. There are, however, several challenges that will have to be surmounted before successful establishment of hSC-CMs as an all-round predictive model for drug safety assays. An important factor is the relative electrophysiological immaturity of hSC-CMs, which limits arrhythmic responses to unsafe drugs that are pro-arrhythmic in humans. Potentially, immaturity may be improved functionally by creation of hybrid models, in which the dynamic clamp technique joins simulations of lacking cardiac ion channels (e.g., IK1 with hSC-CMs in real-time during patch clamp experiments. This approach has been used successfully in manual patch clamp experiments, but throughput is low. In this study, we combined dynamic clamp with automated patch clamp of iPSC-CMs in current clamp mode, and demonstrate that IK1 conductance can be added to iPSC-CMs on an automated patch clamp platform, resulting in an improved electrophysiological maturity.

  9. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping improves systemic and cerebral oxygenation in preterm lambs.

    Directory of Open Access Journals (Sweden)

    Graeme R Polglase

    Full Text Available As measurement of arterial oxygen saturation (SpO2 is common in the delivery room, target SpO2 ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.We investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.Systemic and cerebral blood-flows, pressures and peripheral SpO2 and regional cerebral tissue oxygenation (SctO2 were measured continuously in apnoeic preterm lambs (126±1 day gestation. Positive pressure ventilation was initiated either 1 prior to umbilical cord clamping, or 2 after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.Clamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO2 and SctO2, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5-6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.The establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO2 nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.

  10. Piezoresistive cantilever force-clamp system

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung-Jin; Petzold, Bryan C.; Pruitt, Beth L. [Department of Mechanical Engineering, Stanford University, Stanford, California 94305 (United States); Goodman, Miriam B. [Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305 (United States)

    2011-04-15

    We present a microelectromechanical device-based tool, namely, a force-clamp system that sets or ''clamps'' the scaled force and can apply designed loading profiles (e.g., constant, sinusoidal) of a desired magnitude. The system implements a piezoresistive cantilever as a force sensor and the built-in capacitive sensor of a piezoelectric actuator as a displacement sensor, such that sample indentation depth can be directly calculated from the force and displacement signals. A programmable real-time controller operating at 100 kHz feedback calculates the driving voltage of the actuator. The system has two distinct modes: a force-clamp mode that controls the force applied to a sample and a displacement-clamp mode that controls the moving distance of the actuator. We demonstrate that the system has a large dynamic range (sub-nN up to tens of {mu}N force and nm up to tens of {mu}m displacement) in both air and water, and excellent dynamic response (fast response time, <2 ms and large bandwidth, 1 Hz up to 1 kHz). In addition, the system has been specifically designed to be integrated with other instruments such as a microscope with patch-clamp electronics. We demonstrate the capabilities of the system by using it to calibrate the stiffness and sensitivity of an electrostatic actuator and to measure the mechanics of a living, freely moving Caenorhabditis elegans nematode.

  11. The cardiovascular effects of aortic clamping and unclamping

    African Journals Online (AJOL)

    aortic clamping is that afterload and blood pressure increase, and ... individually, albeit they interact with each other. The degree of ... position of the aortic clamp, the greater the increase ... the increase in preload in response to aortic clamping.

  12. Simulation of action potential propagation in plants.

    Science.gov (United States)

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

    2011-12-21

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

  13. 21 CFR 882.4460 - Neurosurgical head holder (skull clamp).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Neurosurgical head holder (skull clamp). 882.4460... holder (skull clamp). (a) Identification. A neurosurgical head holder (skull clamp) is a device used to clamp the patient's skull to hold head and neck in a particular position during surgical procedures. (b...

  14. Early identification of hERG liability in drug discovery programs by automated patch clamp

    Directory of Open Access Journals (Sweden)

    Timm eDanker

    2014-09-01

    Full Text Available Blockade of the cardiac ion channel coded by hERG can lead to cardiac arrhythmia, which has become a major concern in drug discovery and development. Automated electrophysiological patch clamp allows assessment of hERG channel effects early in drug development to aid medicinal chemistry programs and has become routine in pharmaceutical companies. However, a number of potential sources of errors in setting up hERG channel assays by automated patch clamp can lead to misinterpretation of data or false effects being reported. This article describes protocols for automated electrophysiology screening of compound effects on the hERG channel current. Protocol details and the translation of criteria known from manual patch clamp experiments to automated patch clamp experiments to achieve good quality data are emphasized. Typical pitfalls and artifacts that may lead to misinterpretation of data are discussed. While this article focuses on hERG channel recordings using the QPatch (Sophion A/S, Copenhagen, Denmark technology, many of the assay and protocol details given in this article can be transferred for setting up different ion channel assays by automated patch clamp and are similar on other planar patch clamp platforms.

  15. Mechanics of wafer bonding: Effect of clamping

    Science.gov (United States)

    Turner, K. T.; Thouless, M. D.; Spearing, S. M.

    2004-01-01

    A mechanics-based model is developed to examine the effects of clamping during wafer bonding processes. The model provides closed-form expressions that relate the initial geometry and elastic properties of the wafers to the final shape of the bonded pair and the strain energy release rate at the interface for two different clamping configurations. The results demonstrate that the curvature of bonded pairs may be controlled through the use of specific clamping arrangements during the bonding process. Furthermore, it is demonstrated that the strain energy release rate depends on the clamping configuration and that using applied loads usually leads to an undesirable increase in the strain energy release rate. The results are discussed in detail and implications for process development and bonding tool design are highlighted.

  16. Evaluation of clamp effects on LMFBR piping systems

    International Nuclear Information System (INIS)

    Jones, G.L.

    1980-01-01

    Loop-type liquid metal breeder reactor plants utilize thin-wall piping to mitigate through-wall thermal gradients due to rapid thermal transients. These piping loops require a support system to carry the combined weight of the pipe, coolant and insulation and to provide attachments for seismic restraints. The support system examined here utilizes an insulated pipe clamp designed to minimize the stresses induced in the piping. To determine the effect of these clamps on the pipe wall a non-linear, two-dimensional, finite element model of the clamp, insulation and pipe wall was used to determine the clamp/pipe interface load distributions which were then applied to a three-dimensional, finite element model of the pipe. The two-dimensional interaction model was also utilized to estimate the combined clamp/pipe stiffness

  17. Load-deflection characteristics of small-bore insulated-pipe clamps

    International Nuclear Information System (INIS)

    Severud, L.K.; Clark, G.L.

    1981-12-01

    The special insulated clamps used on both FFTF and CRBR piping utilize a Belleville spring arrangement to compensate for pipe thermal expansion. Analysis indicates that this produces a non-linear, directionally sensitive clamp spring rate. Since these spring rates influence the seismic response of a supported piping system, it was deemed necessary to evaluate them further by test. This has been accomplished for the FFTF clamps. A more standard insulated pipe clamp, which does not incorporate Belleville springs to accommodate thermal expansion, was also tested. This type clamp is simple in design, and economically attractive. It may have wide application prospects for use in LMFBR small bore auxiliary piping operating at temperatures below 427 0 C. Load deflection tests were conducted on 2.54 CM and 7.62 CM diameter samples of these commercial clamps

  18. Load-deflection characteristics of small bore insulated pipe clamps

    International Nuclear Information System (INIS)

    Severud, L.K.; Clark, G.L.

    1982-01-01

    High temperature LMFBR piping is subject to rapid temperature changes during transient events. Typically, this pipe is supported by specially designed insulated pipe clamps to prevent excessive thermal stress from developing during these transients. The special insulated clamps used on both FFTF and CRBR piping utilize a Belleville spring arrangement to compensate for pipe thermal expansion. Analysis indicates that this produces a non-linear, directionally sensitive clamp spring rate. Since these spring rates influence the seismic response of a supported piping system, it was deemed necessary to evaluate them further by test. This has been accomplished for the FFTF clamps. A more standard insulated pipe clamp, which does not incorporate Belleville springs to accommodate thermal expansion, was also tested. This type clamp is simple in design, and economically attractive. It may have wide application prospects for use in LMFBR small bore auxiliary piping operating at temperatures below 427 0 C. Load deflection tests were conducted on 2.54 CM and 7.62 CM diameter samples of these commercial clamps

  19. In vivo patch-clamp analysis of response properties of rat primary somatosensory cortical neurons responding to noxious stimulation of the facial skin

    Directory of Open Access Journals (Sweden)

    Nasu Masanori

    2010-05-01

    Full Text Available Abstract Background Although it has been widely accepted that the primary somatosensory (SI cortex plays an important role in pain perception, it still remains unclear how the nociceptive mechanisms of synaptic transmission occur at the single neuron level. The aim of the present study was to examine whether noxious stimulation applied to the orofacial area evokes the synaptic response of SI neurons in urethane-anesthetized rats using an in vivo patch-clamp technique. Results In vivo whole-cell current-clamp recordings were performed in rat SI neurons (layers III-IV. Twenty-seven out of 63 neurons were identified in the mechanical receptive field of the orofacial area (36 neurons showed no receptive field and they were classified as non-nociceptive (low-threshold mechanoreceptive; 6/27, 22% and nociceptive neurons. Nociceptive neurons were further divided into wide-dynamic range neurons (3/27, 11% and nociceptive-specific neurons (18/27, 67%. In the majority of these neurons, a proportion of the excitatory postsynaptic potentials (EPSPs reached the threshold, and then generated random discharges of action potentials. Noxious mechanical stimuli applied to the receptive field elicited a discharge of action potentials on the barrage of EPSPs. In the case of noxious chemical stimulation applied as mustard oil to the orofacial area, the membrane potential shifted depolarization and the rate of spontaneous discharges gradually increased as did the noxious pinch-evoked discharge rates, which were usually associated with potentiated EPSP amplitudes. Conclusions The present study provides evidence that SI neurons in deep layers III-V respond to the temporal summation of EPSPs due to noxious mechanical and chemical stimulation applied to the orofacial area and that these neurons may contribute to the processing of nociceptive information, including hyperalgesia.

  20. Loading dynamics of a sliding DNA clamp.

    KAUST Repository

    Cho, Won-Ki; Jergic, Slobodan; Kim, Daehyung; Dixon, Nicholas E; Lee, Jong-Bong

    2014-01-01

    8° during clamp closure. The single-molecule polarization and FRET studies thus revealed the real-time dynamics of the ATP-hydrolysis-dependent 3D conformational change of the β clamp during loading at a ss/dsDNA junction.

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

    DEFF Research Database (Denmark)

    Thomsen, Morten B; Sosunov, Eugene A; Anyukhovsky, Evgeny P

    2008-01-01

    BACKGROUND: Four voltage-gated potassium currents, I(to,f) (K(V)4.2), I(to,s) (K(V)1.4), I(K,slow) (K(V)1.5+K(V)2.1), and I(SS) (TASK1), govern murine ventricular repolarization. Although the accessory subunit KChIP2 influences I(to,f) expression, in preliminary experiments we found that action...... 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...

  2. Acute alterations of somatodendritic action potential dynamics in hippocampal CA1 pyramidal cells after kainate-induced status epilepticus in mice.

    Directory of Open Access Journals (Sweden)

    Daniel Minge

    Full Text Available Pathophysiological remodeling processes at an early stage of an acquired epilepsy are critical but not well understood. Therefore, we examined acute changes in action potential (AP dynamics immediately following status epilepticus (SE in mice. SE was induced by intraperitoneal (i.p. injection of kainate, and behavioral manifestation of SE was monitored for 3-4 h. After this time interval CA1 pyramidal cells were studied ex vivo with whole-cell current-clamp and Ca(2+ imaging techniques in a hippocampal slice preparation. Following acute SE both resting potential and firing threshold were modestly depolarized (2-5 mV. No changes were seen in input resistance or membrane time constant, but AP latency was prolonged and AP upstroke velocity reduced following acute SE. All cells showed an increase in AP halfwidth and regular (rather than burst firing, and in a fraction of cells the notch, typically preceding spike afterdepolarization (ADP, was absent following acute SE. Notably, the typical attenuation of backpropagating action potential (b-AP-induced Ca(2+ signals along the apical dendrite was strengthened following acute SE. The effects of acute SE on the retrograde spread of excitation were mimicked by applying the Kv4 current potentiating drug NS5806. Our data unveil a reduced somatodendritic excitability in hippocampal CA1 pyramidal cells immediately after acute SE with a possible involvement of both Na(+ and K(+ current components.

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

    Science.gov (United States)

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

    2013-08-01

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

  4. Multiple Actions of Rotenone, an Inhibitor of Mitochondrial Respiratory Chain, on Ionic Currents and Miniature End-Plate Potential in Mouse Hippocampal (mHippoE-14 Neurons

    Directory of Open Access Journals (Sweden)

    Chin-Wei Huang

    2018-05-01

    Full Text Available Background/Aims: Rotenone (Rot is known to suppress the activity of complex I in the mitochondrial chain reaction; however, whether this compound has effects on ion currents in neurons remains largely unexplored. Methods: With the aid of patch-clamp technology and simulation modeling, the effects of Rot on membrane ion currents present in mHippoE-14 cells were investigated. Results: Addition of Rot produced an inhibitory action on the peak amplitude of INa with an IC50 value of 39.3 µM; however, neither activation nor inactivation kinetics of INa was changed during cell exposure to this compound. Addition of Rot produced little or no modifications in the steady-state inactivation curve of INa. Rot increased the amplitude of Ca2+-activated Cl- current in response to membrane depolarization with an EC50 value of 35.4 µM; further addition of niflumic acid reversed Rot-mediated stimulation of this current. Moreover, when these cells were exposed to 10 µM Rot, a specific population of ATP-sensitive K+ channels with a single-channel conductance of 18.1 pS was measured, despite its inability to alter single-channel conductance. Under current clamp condition, the frequency of miniature end-plate potentials in mHippoE-14 cells was significantly raised in the presence of Rot (10 µM with no changes in their amplitude and time course of rise and decay. In simulated model of hippocampal neurons incorporated with chemical autaptic connection, increased autaptic strength to mimic the action of Rot was noted to change the bursting pattern with emergence of subthreshold potentials. Conclusions: The Rot effects presented herein might exert a significant action on functional activities of hippocampal neurons occurring in vivo.

  5. Core clamping device for a nuclear reactor

    International Nuclear Information System (INIS)

    Guenther, R.W.

    1974-01-01

    The core clamping device for a fast neutron reactor includes clamps to support the fuel zone against the pressure vessel. The clamps are arranged around the circumference of the core. They consist of torsion bars arranged parallel at some distance around the core with lever arms attached to the ends whose force is directed in the opposite direction, pressing against the wall of the pressure vessel. The lever arms and pressure plates also actuated by the ends of the torsion bars transfer the stress, the pressure plates acting upon the fuel elements or fuel assemblies. Coupling between the ends of the torsion bars and the pressure plates is achieved by end carrier plates directly attached to the torsion bars and radially movable. This clamping device follows the thermal expansions of the core, allows specific elements to be disengaged in sections and saves space between the core and the neutron reflectors. (DG) [de

  6. Lotus birth, a holistic approach on physiological cord clamping.

    Science.gov (United States)

    Zinsser, Laura A

    2018-04-01

    The positive effects of delayed cord clamping (DCC) has been extensively researched. DCC means: waiting at least one minute after birth before clamping and cutting the cord or till the pulsation has stopped. With physiological clamping and cutting (PCC) the clamping and cutting can happen at the earliest after the pulsation has stopped. With a Lotus birth, no clamping and cutting of the cord is done. A woman called Clair Lotus Day imitated the holistic approach of PCC from an anthropoid ape in 1974. The chimpanzee did not separate the placenta from the newborn. The aim of this case report is to discuss and learn a different approach in the third stage of labour. Three cases of Lotus birth by human beings were observed. All three women gave birth in an out-of-hospital setting and had ambulant postnatal care. The placenta was washed, salted and herbs were put on 2-3h post partum. The placenta was wrapped in something that absorbs the moisture. The salting was repeated with a degreasing frequency depending on moistness of the placenta. On life day six all three Lotus babies experiences a natural separation of the cord. All three Lotus birth cases were unproblematic, no special incidence occurred. One should differentiate between early cord clamping (ECC), delayed cord clamping (DCC) and physiological cord clamping (PCC). Lotus birth might lead to an optimisation of the bonding and attachment. Research is needed in the areas of both PCC and Lotus birth. Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  7. π-Clamp-mediated cysteine conjugation

    Science.gov (United States)

    Zhang, Chi; Welborn, Matthew; Zhu, Tianyu; Yang, Nicole J.; Santos, Michael S.; van Voorhis, Troy; Pentelute, Bradley L.

    2016-02-01

    Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the ‘π-clamp’, that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody-drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.

  8. Axially Modulated Clamped-Guided Arch Resonator for Memory and Logic Applications

    KAUST Repository

    Hafiz, Md Abdullah Al; Tella, Sherif Adekunle; Alcheikh, Nouha; Fariborzi, Hossein; Younis, Mohammad I.

    2017-01-01

    We experimentally demonstrate memory and logic devices based on an axially modulated clamped-guided arch resonator. The device are electrostatically actuated and capacitively sensed, while the resonance frequency modulation is achieved through an axial electrostatic force from the guided side of the clamped-guided arch microbeam. We present two case studies: first, a dynamic memory based on the nonlinear frequency response of the resonator, and second, a reprogrammable two-input logic gate based on the linear frequency modulation of the resonator. These devices show energy cost per memory/logic operation in pJ, are fully compatible with CMOS fabrication processes, have the potential for on-chip system integration, and operate at room temperature.

  9. Axially Modulated Clamped-Guided Arch Resonator for Memory and Logic Applications

    KAUST Repository

    Hafiz, Md Abdullah Al

    2017-11-03

    We experimentally demonstrate memory and logic devices based on an axially modulated clamped-guided arch resonator. The device are electrostatically actuated and capacitively sensed, while the resonance frequency modulation is achieved through an axial electrostatic force from the guided side of the clamped-guided arch microbeam. We present two case studies: first, a dynamic memory based on the nonlinear frequency response of the resonator, and second, a reprogrammable two-input logic gate based on the linear frequency modulation of the resonator. These devices show energy cost per memory/logic operation in pJ, are fully compatible with CMOS fabrication processes, have the potential for on-chip system integration, and operate at room temperature.

  10. Applications of Dynamic Clamp to Cardiac Arrhythmia Research: Role in Drug Target Discovery and Safety Pharmacology Testing

    Directory of Open Access Journals (Sweden)

    Francis A. Ortega

    2018-01-01

    Full Text Available Dynamic clamp, a hybrid-computational-experimental technique that has been used to elucidate ionic mechanisms underlying cardiac electrophysiology, is emerging as a promising tool in the discovery of potential anti-arrhythmic targets and in pharmacological safety testing. Through the injection of computationally simulated conductances into isolated cardiomyocytes in a real-time continuous loop, dynamic clamp has greatly expanded the capabilities of patch clamp outside traditional static voltage and current protocols. Recent applications include fine manipulation of injected artificial conductances to identify promising drug targets in the prevention of arrhythmia and the direct testing of model-based hypotheses. Furthermore, dynamic clamp has been used to enhance existing experimental models by addressing their intrinsic limitations, which increased predictive power in identifying pro-arrhythmic pharmacological compounds. Here, we review the recent advances of the dynamic clamp technique in cardiac electrophysiology with a focus on its future role in the development of safety testing and discovery of anti-arrhythmic drugs.

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

    Science.gov (United States)

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

    2014-01-01

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

  12. A new clamp method for firing bricks | Obeng | Journal of Applied ...

    African Journals Online (AJOL)

    A new clamp method for firing bricks. ... Journal of Applied Science and Technology ... To overcome this operational deficiencies, a new method of firing bricks that uses brick clamp technique that incorporates a clamp wall of 60 cm thickness, a six tier approach of sealing the top of the clamp (by combination of green bricks) ...

  13. IMPORTANT: Fluke is recalling Digital Clamp Meters

    CERN Multimedia

    2013-01-01

    Fluke is voluntarily recalling four models of Digital Clamp Meters: Fluke 373, 374, 375 and 376. If you own one of these clamp meters, please stop using it and send it back to Fluke for repair even if you have not experienced problems.   Description of the problem: "The printed circuit assembly may not be properly fastened to the test lead input jack. This may result in inaccurate voltage readings, including a low or no-voltage reading on a circuit energised with a hazardous voltage, presenting a shock, electrocution or thermal burn hazard." To determine if your clamp meter is affected by this recall notice, and for more information, click here.

  14. Is "Delayed Umbilical Cord Clamping" Beneficial for Premature Newborns?

    Directory of Open Access Journals (Sweden)

    Amir-Mohammad Armanian

    2017-05-01

    Full Text Available Background: The appropriate moment for clamping the umbilical cord is controversial. Immediate cord clamping (ICC is an item of active management of the third stage of labor (AMTSL. Unclamped umbilical cord may cause inconvenience in preterm neonates because they commonly need some levels of emergent services. Some studies revealed delayed cord clamping (DCC of preterm neonates results in better health conditions like lower rates of respiratory distress syndrome (RDS, less morbidities in labor room and lower risk of postpartum hemorrhage. The aim of the present study was to determine the effect of delayed umbilical cord clamping on premature neonatal outcomes. Materials and Methods: In this single‑center randomized control trial study, sixty premature neonates (gestational age ≤ 34 weeks were randomly assigned to ICC (cord clamped at 5–10 seconds or DCC (30–45 seconds groups and followed up in neonatal intensive care unit (NICU. Primary outcomes were 1st and 5th minute Apgar score, average of level of hematocrit after birth, intra ventricle hemorrhage and need some levels of resuscitation. Results: Differences in demographic characteristics were not statistically significant. After birth, neonates who had delayed clamping had significantly higher mean hematocrit after at 4-hour of birth (49.58+5.15gr/dl vs. 46.58+5.40gr/dlin DCC vs. ICC groups, respectively (P=0.031. Delayed cord clamping reduced the duration of need to nasal continues positive airway pressure (NCPAP (86.7% and 60.0% in ICC and DCC groups, respectively, P= 0.039. Attractively, the results showed lower incidence of clinical sepsis in delayed cord clamping neonates (53.3% vs. 23.3% in ICC and DCC groups, respectively, P=0.033. Conclusion: Prematurity complications might decrease by delay umbilical cord clamping which improve the hematocrit, duration of need to NCPAP and incidence of clinical sepsis. Furthermore, DCC may have no negative impact on neonatal resuscitation.

  15. Diuretic response to acute hypertension is blunted during angiotensin II clamp

    DEFF Research Database (Denmark)

    Leong, Patrick K K; Zhang, Yibin; Yang, Li E

    2002-01-01

    and endogenous lithium clearance increased two- and threefold, respectively. We conclude that HOE-140, an inhibitor of the B(2) receptor, potentiates the sensitivity of arterial pressure to ANG II and that clamping systemic ANG II levels during acute hypertension blunts the magnitude of the pressure diuretic...

  16. A missing factor in chip-based patch clamp assay: gigaseal

    International Nuclear Information System (INIS)

    Ong, W-L; Yobas, L; Ong, W-Y

    2006-01-01

    The 'gold' standard in the study of ionic currents across biological membranes is the Patch Clamp method. However, this is a slow, labor and skill intensive process. High throughput patch clamp devices are mainly chip-based. A major challenge in these miniaturized devices is the low rate of 'Gigaseal' formation which is critical in the study of Single Channel effect. In a conventional patch clamp, a pipette moves and patches a fixed cell (cell-adhered patch) which is grown on the bottom of a Petri dish. In the chip-based case, the cells are in suspension and move towards the fixed patch clamp sites (cell-suspended patch). In this study, using the proven conventional patch clamp setup, we investigated the effect of the differences in the cell configurations between the convention patch clamp and cell-based patch clamp. It is shown that adhered cells (as used in the conventional setup) have a much higher rate of gigaseal formation as compared to the cells in suspension (as used in chip-based devices). We postulate that the arrangement of the cytoskeleton within the cell plays a major part in the formation of the gigaseal

  17. Screening action potentials: The power of light

    Directory of Open Access Journals (Sweden)

    Lars eKaestner

    2011-07-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  19. Overexpression of the Large-Conductance, Ca2+-Activated K+ (BK) Channel Shortens Action Potential Duration in HL-1 Cardiomyocytes.

    Science.gov (United States)

    Stimers, Joseph R; Song, Li; Rusch, Nancy J; Rhee, Sung W

    2015-01-01

    Long QT syndrome is characterized by a prolongation of the interval between the Q wave and the T wave on the electrocardiogram. This abnormality reflects a prolongation of the ventricular action potential caused by a number of genetic mutations or a variety of drugs. Since effective treatments are unavailable, we explored the possibility of using cardiac expression of the large-conductance, Ca2+-activated K+ (BK) channel to shorten action potential duration (APD). We hypothesized that expression of the pore-forming α subunit of human BK channels (hBKα) in HL-1 cells would shorten action potential duration in this mouse atrial cell line. Expression of hBKα had minimal effects on expression levels of other ion channels with the exception of a small but significant reduction in Kv11.1. Patch-clamped hBKα expressing HL-1 cells exhibited an outward voltage- and Ca2+-sensitive K+ current, which was inhibited by the BK channel blocker iberiotoxin (100 nM). This BK current phenotype was not detected in untransfected HL-1 cells or in HL-1 null cells sham-transfected with an empty vector. Importantly, APD in hBKα-expressing HL-1 cells averaged 14.3 ± 2.8 ms (n = 10), which represented a 53% reduction in APD compared to HL-1 null cells lacking BKα expression. APD in the latter cells averaged 31.0 ± 5.1 ms (n = 13). The shortened APD in hBKα-expressing cells was restored to normal duration by 100 nM iberiotoxin, suggesting that a repolarizing K+ current attributed to BK channels accounted for action potential shortening. These findings provide initial proof-of-concept that the introduction of hBKα channels into a cardiac cell line can shorten APD, and raise the possibility that gene-based interventions to increase hBKα channels in cardiac cells may hold promise as a therapeutic strategy for long QT syndrome.

  20. Reducing blood loss during laparoscopic myomectomy by temporary uterine artery clamping using bulldog clamp

    Directory of Open Access Journals (Sweden)

    Kai-Jo Chiang

    2014-01-01

    Full Text Available Uterine myoma is the most common benign gynecologic tumor worldwide. Mini-invasive surgery has become popular for myomectomy, with advantages over laparotomy. However, reducing blood loss during laparoscopic myomectomy is a major concern for the surgeon because of the limitation in making a quick control bleeding during the operation. Several methods have proved to decrease blood flow, but are not always effective or available. We present a case of uterine myoma with the uterine arteries clamped by bulldog clamps during laparoscopic myomectomy. The myoma was removed successfully with minimal blood loss (<50 ml during the operation. This is an effective, safe, and reliable method for reducing bleeding during laparoscopic myomectomy that does not require ligation of the uterine artery.

  1. Robotic multi-well planar patch-clamp for native and primary mammalian cells

    Science.gov (United States)

    Milligan, Carol J; Li, Jing; Sukumar, Piruthivi; Majeed, Yasser; Dallas, Mark L; English, Anne; Emery, Paul; Porter, Karen E; Smith, Andrew M; McFadzean, Ian; Beccano-Kelly, Dayne; Bahnasi, Yahya; Cheong, Alex; Naylor, Jacqueline; Zeng, Fanning; Liu, Xing; Gamper, Nikita; Jiang, Lin-Hua; Pearson, Hugh A; Peers, Chris; Robertson, Brian; Beech, David J

    2009-01-01

    Multi-well robotic planar patch-clamp has become common in drug development and safety programmes because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. It has not, however, been adopted significantly in other important areas of ion channel research, where conventional patch-clamp remains the favoured method. Here we show the wider potential of the multi-well approach with the capability for efficient intracellular solution exchange, describing protocols and success rates for recording from a range of native and primary mammalian cells derived from blood vessels, arthritic joints, and the immune and central nervous systems. The protocol involves preparing a suspension of single cells to be dispensed robotically into 4-8 microfluidic chambers each containing a glass chip with a small aperture. Under automated control, giga-seals and whole-cell access are achieved followed by pre-programmed routines of voltage paradigms and fast extracellular or intracellular solution exchange. Recording from 48 chambers usually takes 1-6 hr depending on the experimental design and yields 16-33 cell recordings. PMID:19197268

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

    Science.gov (United States)

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

    2015-01-01

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

  3. Analysis of the role of PCNA-DNA contacts during clamp loading

    Directory of Open Access Journals (Sweden)

    Goedken Eric R

    2010-01-01

    Full Text Available Abstract Background Sliding clamps, such as Proliferating Cell Nuclear Antigen (PCNA in eukaryotes, are ring-shaped protein complexes that encircle DNA and enable highly processive DNA replication by serving as docking sites for DNA polymerases. In an ATP-dependent reaction, clamp loader complexes, such as the Replication Factor-C (RFC complex in eukaryotes, open the clamp and load it around primer-template DNA. Results We built a model of RFC bound to PCNA and DNA based on existing crystal structures of clamp loaders. This model suggests that DNA would enter the clamp at an angle during clamp loading, thereby interacting with positively charged residues in the center of PCNA. We show that simultaneous mutation of Lys 20, Lys 77, Arg 80, and Arg 149, which interact with DNA in the RFC-PCNA-DNA model, compromises the ability of yeast PCNA to stimulate the DNA-dependent ATPase activity of RFC when the DNA is long enough to extend through the clamp. Fluorescence anisotropy binding experiments show that the inability of the mutant clamp proteins to stimulate RFC ATPase activity is likely caused by reduction in the affinity of the RFC-PCNA complex for DNA. We obtained several crystal forms of yeast PCNA-DNA complexes, measuring X-ray diffraction data to 3.0 Å resolution for one such complex. The resulting electron density maps show that DNA is bound in a tilted orientation relative to PCNA, but makes different contacts than those implicated in clamp loading. Because of apparent partial disorder in the DNA, we restricted refinement of the DNA to a rigid body model. This result contrasts with previous analysis of a bacterial clamp bound to DNA, where the DNA was well resolved. Conclusion Mutational analysis of PCNA suggests that positively charged residues in the center of the clamp create a binding surface that makes contact with DNA. Disruption of this positive surface, which had not previously been implicated in clamp loading function, reduces RFC

  4. File list: Oth.ALL.50.Clamp.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Clamp.AllCell dm3 TFs and others Clamp All cell types SRX159172,SRX15917...0,SRX159174,SRX159166,SRX159173 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.ALL.50.Clamp.AllCell.bed ...

  5. Is action potential threshold lowest in the axon?

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  7. Selective effects of an octopus toxin on action potentials

    Science.gov (United States)

    Dulhunty, Angela; Gage, Peter W.

    1971-01-01

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

  8. Meju, unsalted soybeans fermented with Bacillus subtilis and Aspergilus oryzae, potentiates insulinotropic actions and improves hepatic insulin sensitivity in diabetic rats.

    Science.gov (United States)

    Yang, Hye Jeong; Kwon, Dae Young; Kim, Min Jung; Kang, Suna; Park, Sunmin

    2012-05-02

    Although soybeans have the ability to attenuate insulin resistance, it is insufficient to alleviate type 2 diabetic symptoms and different types of fermented soybeans may have even better anti-diabetic effects. Meju, unsalted fermented soybeans exhibited better insulin sensitizing and insulinotropic actions than unfermented cooked soybeans (CSB). We investigated whether meju fermented in the traditional (TMS) manner for 60 days and meju fermented in the standardized (MMS) method inoculating Bacillus subtilis and Aspergillus oryzae for 6 days modulated insulin resistance, insulin secretion, and pancreatic β-cell growth and survival in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2 diabetic animal model. Diabetic rats were divided into 3 groups: 1) TMS (n = 20), 2) MMS (n = 20) or 3) casein (control; n = 20). Rats were provided with a high fat diet (40 energy % fat) containing assigned 10% meju for 8 weeks. At the end of experiment insulin resistance and insulin secretion capacity were measured by euglycemic hyperinsulinemic clamp and by hyperglycemic clamp, respectively. Additionally, β-cell mass and islet morphohometry were determined by immunohistochemistry and insulin signaling in the liver was measured by western blot. TMS and MMS increased isoflavonoid aglycones much more than CSB. CSB and TMS/MMS improved glucose tolerance in diabetic rats but the mechanism was different between treatments (P MMS enhanced only hepatic insulin sensitivity through activating insulin signaling in diabetic rats (P MMS, but not CSB, potentiated glucose-stimulated insulin secretion and β-cell mass (P MMS had better insulinotropic actions than the control (P MMS, especially when fermented with Bacillus subtilis and Aspergillus oryzae, was superior to CSB by increasing isoflavonoid aglycones and small peptides with regard to type 2 diabetic rats.

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

    Science.gov (United States)

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

    2016-10-01

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

  10. Modeling of SVM Diode Clamping Three-Level Inverter Connected to Grid

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Zhu, Jieqiong

    2011-01-01

    PLECS is used to model the diode clamping three-level inverter connected to grid and good results are obtained. First the output voltage SVM is described for diode clamping three-level inverter with loads connected to Y. Then the output voltage SVM of diode clamping three-level inverter is simply...... analyzed with loads connected to △. But it will be further researched in the future. Third, PLECS is briefly introduced. Fourth, the modeling of diode clamping three-level inverter is briefly presented with PLECS. Finally, a series of simulations are carried out. The simulation results tell us PLECS...... is very powerful tool to real power circuits and it is very easy to simulate them. They have also verified that SVM control strategy is feasible to control the diode clamping three-level inverter....

  11. Hypertrophic cardiomyopathy-linked mutation in troponin T causes myofibrillar disarray and pro-arrhythmic action potential changes in human iPSC cardiomyocytes.

    Science.gov (United States)

    Wang, Lili; Kim, Kyungsoo; Parikh, Shan; Cadar, Adrian Gabriel; Bersell, Kevin R; He, Huan; Pinto, Jose R; Kryshtal, Dmytro O; Knollmann, Bjorn C

    2018-01-01

    Mutations in cardiac troponin T (TnT) are linked to increased risk of ventricular arrhythmia and sudden death despite causing little to no cardiac hypertrophy. Studies in mice suggest that the hypertrophic cardiomyopathy (HCM)-associated TnT-I79N mutation increases myofilament Ca sensitivity and is arrhythmogenic, but whether findings from mice translate to human cardiomyocyte electrophysiology is not known. To study the effects of the TnT-I79N mutation in human cardiomyocytes. Using CRISPR/Cas9, the TnT-I79N mutation was introduced into human induced pluripotent stem cells (hiPSCs). We then used the matrigel mattress method to generate single rod-shaped cardiomyocytes (CMs) and studied contractility, Ca handling and electrophysiology. Compared to isogenic control hiPSC-CMs, TnT-I79N hiPSC-CMs exhibited sarcomere disorganization, increased systolic function and impaired relaxation. The Ca-dependence of contractility was leftward shifted in mutation containing cardiomyocytes, demonstrating increased myofilament Ca sensitivity. In voltage-clamped hiPSC-CMs, TnT-I79N reduced intracellular Ca transients by enhancing cytosolic Ca buffering. These changes in Ca handling resulted in beat-to-beat instability and triangulation of the cardiac action potential, which are predictors of arrhythmia risk. The myofilament Ca sensitizer EMD57033 produced similar action potential triangulation in control hiPSC-CMs. The TnT-I79N hiPSC-CM model not only reproduces key cellular features of TnT-linked HCM such as myofilament disarray, hypercontractility and diastolic dysfunction, but also suggests that this TnT mutation causes pro-arrhythmic changes of the human ventricular action potential. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Tuning permanent magnets with adjustable field clamps

    International Nuclear Information System (INIS)

    Schermer, R.I.

    1987-01-01

    The effective length of a permanent-magnet assembly can be varied by adjusting the geometrical parameters of a field clamp. This paper presents measurements on a representative dipole and quadrupole as the field clamp is withdrawn axially or radially. The detailed behavior depends upon the magnet multipolarity and geometry. As a rule-of-thumb, a 3-mm-thick iron plate placed at one end plane of the magnet will shorten the length by one-third of the magnet bore radius

  13. Analysis and Experiments on Sea Load and Fastened Mechanics on Pipe Clamps

    Directory of Open Access Journals (Sweden)

    Wang Zhuo

    2017-08-01

    Full Text Available When an offshore oil field completed and put into production, new subsea pipelines and the new cable need to be established. Cable protection pipe clamp is used to fix cable protection pipe on the jacket. In order to avoid the problem of traditional steel structure clamp splice, counterpoint, fastening difficulty when installed cable protection pipe under water, reduce the risk and workload of under water, This paper develop a new type of portable connecting riser clamp -“backpack clamp” which solve the riser cable protection pipe difficult underwater installation problem. The main structure of backpack clamp used three valves type structure. The load characteristic of a clamping device was determined by the Morison equation which was a classical theory. Clamp device underwater mechanics analysis model was established. The minimum tension pre-tightening force was determined. The results show that the strength of the base meets the requirements after strength analysis with finite element analysis method, stability and strength experiments, which means the clamp based on resin matrix composite is feasible.

  14. Action potential-based MEA platform for in vitro screening of drug-induced cardiotoxicity using human iPSCs and rat neonatal myocytes.

    Science.gov (United States)

    Jans, Danny; Callewaert, Geert; Krylychkina, Olga; Hoffman, Luis; Gullo, Francesco; Prodanov, Dimiter; Braeken, Dries

    2017-09-01

    Drug-induced cardiotoxicity poses a negative impact on public health and drug development. Cardiac safety pharmacology issues urged for the preclinical assessment of drug-induced ventricular arrhythmia leading to the design of several in vitro electrophysiological screening assays. In general, patch clamp systems allow for intracellular recordings, while multi-electrode array (MEA) technology detect extracellular activity. Here, we demonstrate a complementary metal oxide semiconductor (CMOS)-based MEA system as a reliable platform for non-invasive, long-term intracellular recording of cardiac action potentials at high resolution. Quinidine (8 concentrations from 10 -7 to 2.10 -5 M) and verapamil (7 concentrations from 10 -11 to 10 -5 M) were tested for dose-dependent responses in a network of cardiomyocytes. Electrophysiological parameters, such as the action potential duration (APD), rates of depolarization and repolarization and beating frequency were assessed. In hiPSC, quinidine prolonged APD with EC 50 of 2.2·10 -6 M. Further analysis indicated a multifactorial action potential prolongation by quinidine: (1) decreasing fast repolarization with IC 50 of 1.1·10 -6 M; (2) reducing maximum upstroke velocity with IC 50 of 2.6·10 -6 M; and (3) suppressing spontaneous activity with EC 50 of 3.8·10 -6 M. In rat neonatal cardiomyocytes, verapamil blocked spontaneous activity with EC 50 of 5.3·10 -8 M and prolonged the APD with EC 50 of 2.5·10 -8 M. Verapamil reduced rates of fast depolarization and repolarization with IC 50 s of 1.8 and 2.2·10 -7 M, respectively. In conclusion, the proposed action potential-based MEA platform offers high quality and stable long-term recordings with high information content allowing to characterize multi-ion channel blocking drugs. We anticipate application of the system as a screening platform to efficiently and cost-effectively test drugs for cardiac safety. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

    Science.gov (United States)

    Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

    2017-05-24

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

  16. Active energy recovery clamping circuit to improve the performance of power converters

    Science.gov (United States)

    Whitaker, Bret; Barkley, Adam

    2017-05-09

    A regenerative clamping circuit for a power converter using clamping diodes to transfer charge to a clamping capacitor and a regenerative converter to transfer charge out of the clamping capacitor back to the power supply input connection. The regenerative converter uses a switch connected to the midpoint of a series connected inductor and capacitor. The ends of the inductor and capacitor series are connected across the terminals of the power supply to be in parallel with the power supply.

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

    Science.gov (United States)

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

    2015-01-01

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

  18. File list: Oth.CeL.50.Clamp.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.50.Clamp.AllCell dm3 TFs and others Clamp Cell line SRX159172,SRX159170,SRX...159174,SRX159166,SRX159173 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.50.Clamp.AllCell.bed ...

  19. File list: Oth.CeL.05.Clamp.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.CeL.05.Clamp.AllCell dm3 TFs and others Clamp Cell line SRX159172,SRX159170,SRX...159174,SRX159166,SRX159173 http://dbarchive.biosciencedbc.jp/kyushu-u/dm3/assembled/Oth.CeL.05.Clamp.AllCell.bed ...

  20. An accurate online calibration system based on combined clamp-shape coil for high voltage electronic current transformers

    International Nuclear Information System (INIS)

    Li, Zhen-hua; Li, Hong-bin; Zhang, Zhi

    2013-01-01

    Electronic transformers are widely used in power systems because of their wide bandwidth and good transient performance. However, as an emerging technology, the failure rate of electronic transformers is higher than that of traditional transformers. As a result, the calibration period needs to be shortened. Traditional calibration methods require the power of transmission line be cut off, which results in complicated operation and power off loss. This paper proposes an online calibration system which can calibrate electronic current transformers without power off. In this work, the high accuracy standard current transformer and online operation method are the key techniques. Based on the clamp-shape iron-core coil and clamp-shape air-core coil, a combined clamp-shape coil is designed as the standard current transformer. By analyzing the output characteristics of the two coils, the combined clamp-shape coil can achieve verification of the accuracy. So the accuracy of the online calibration system can be guaranteed. Moreover, by employing the earth potential working method and using two insulating rods to connect the combined clamp-shape coil to the high voltage bus, the operation becomes simple and safe. Tests in China National Center for High Voltage Measurement and field experiments show that the proposed system has a high accuracy of up to 0.05 class

  1. An accurate online calibration system based on combined clamp-shape coil for high voltage electronic current transformers.

    Science.gov (United States)

    Li, Zhen-hua; Li, Hong-bin; Zhang, Zhi

    2013-07-01

    Electronic transformers are widely used in power systems because of their wide bandwidth and good transient performance. However, as an emerging technology, the failure rate of electronic transformers is higher than that of traditional transformers. As a result, the calibration period needs to be shortened. Traditional calibration methods require the power of transmission line be cut off, which results in complicated operation and power off loss. This paper proposes an online calibration system which can calibrate electronic current transformers without power off. In this work, the high accuracy standard current transformer and online operation method are the key techniques. Based on the clamp-shape iron-core coil and clamp-shape air-core coil, a combined clamp-shape coil is designed as the standard current transformer. By analyzing the output characteristics of the two coils, the combined clamp-shape coil can achieve verification of the accuracy. So the accuracy of the online calibration system can be guaranteed. Moreover, by employing the earth potential working method and using two insulating rods to connect the combined clamp-shape coil to the high voltage bus, the operation becomes simple and safe. Tests in China National Center for High Voltage Measurement and field experiments show that the proposed system has a high accuracy of up to 0.05 class.

  2. Glucoregulation after canine islet transplantation : Contribution of insulin secretory capacity, insulin action, and the entero-insular axis

    NARCIS (Netherlands)

    vanderBurg, MPM; van Suylichem, PTR; Guicherit, OR; Frolich, M; Lemkes, HHPJ; Gooszen, HG

    1997-01-01

    The physiological glucoregulatory mechanisms after islet transplantation have been incompletely investigated, We studied the insulin secretory capacity (ISC) by intravenous arginine stimulation during 35-mM glucose clamps, insulin action during hyperinsulinemic euglycemic clamps, and mixed-meal

  3. Computer Simulation Model to Train Medical Personnel on Glucose Clamp Procedures.

    Science.gov (United States)

    Maghoul, Pooya; Boulet, Benoit; Tardif, Annie; Haidar, Ahmad

    2017-10-01

    A glucose clamp procedure is the most reliable way to quantify insulin pharmacokinetics and pharmacodynamics, but skilled and trained research personnel are required to frequently adjust the glucose infusion rate. A computer environment that simulates glucose clamp experiments can be used for efficient personnel training and development and testing of algorithms for automated glucose clamps. We built 17 virtual healthy subjects (mean age, 25±6 years; mean body mass index, 22.2±3 kg/m 2 ), each comprising a mathematical model of glucose regulation and a unique set of parameters. Each virtual subject simulates plasma glucose and insulin concentrations in response to intravenous insulin and glucose infusions. Each virtual subject provides a unique response, and its parameters were estimated from combined intravenous glucose tolerance test-hyperinsulinemic-euglycemic clamp data using the Bayesian approach. The virtual subjects were validated by comparing their simulated predictions against data from 12 healthy individuals who underwent a hyperglycemic glucose clamp procedure. Plasma glucose and insulin concentrations were predicted by the virtual subjects in response to glucose infusions determined by a trained research staff performing a simulated hyperglycemic clamp experiment. The total amount of glucose infusion was indifferent between the simulated and the real subjects (85±18 g vs. 83±23 g; p=NS) as well as plasma insulin levels (63±20 mU/L vs. 58±16 mU/L; p=NS). The virtual subjects can reliably predict glucose needs and plasma insulin profiles during hyperglycemic glucose clamp conditions. These virtual subjects can be used to train personnel to make glucose infusion adjustments during clamp experiments. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  4. Structural consideration for hot and cold pipe clamps in LMFBR applications

    International Nuclear Information System (INIS)

    Anderson, M.J.; Huang, S.N.; Kappauf, H.; Wagner, S.E.; Wirtz, K.H.

    1983-01-01

    A series of analytical studies are described which evaluate stress levels induced in a 600 mm high temperature, thin-wall sodium pipeline by two alternate clamp designs. The first design consists of a band mounted directly on the pipe and is called the hot clamp. The second design consists of a band mounted using insulation standoffs and is called the cold clamp. Pipe stress levels induced by transient thermal dead weight and seismic loads are discussed. Pipe stress levels and system dynamic spring rates are presented. Procedures utilized to combine clamp induced pipe stress with other short and long term pipe system stresses are detailed. Recommendations for practical application in LMFBR pipe systems are made

  5. Structural considerations for hot and cold pipe clamps in LMFBR applications

    International Nuclear Information System (INIS)

    Anderson, M.J.; Huang, S.N.; Wagner, S.E.; Kappauf, H.; Wirtz, K.H.

    1983-01-01

    A series of analytical studies are described which evaluate stress levels induced in a 600 mm high temperature, thin-wall sodium pipeline by two alternate clamp designs. The first design consists of a band mounted directly on the pipe and is called the hot clamp. The second design consists of a band mounted using insulation standoffs and is called the cold clamp. Pipe stress levels induced by transient thermal dead weight and seismic loads are discussed. Pipe stress levels and system dynamic spring rates are presented. Procedures utilized to combine clamp induced pipe stress with other short and long term pipe system stresses are detailed. Recommendations for practical application in LMFBR pipe systems are made

  6. Investigation of the Dynamics of a Clamped-Clamped Microbeam Near the Third Mode Using a Partial Electrode

    KAUST Repository

    Masri, Karim M.

    2014-08-17

    We present an investigation of the dynamics of a clamped-clamped microbeam excited electrostatically near its third mode. To maximize the response at the third mode, a partial electrode configuration is utilized. A multi-mode Galerkin method is used to develop a reduced order model (ROM) of the beam. A shooting method to find the periodic motion is utilized to generate frequency response curves. The curves show hardenining behavior and dynamic pull-in. We show that the dynamic amplitude of the partial configuration is higher than that of a full electrode configuration. These results are promising for the use of higher-order modes for mass detection and for ultra sensitive resonant sensors.

  7. Investigation of the Dynamics of a Clamped-Clamped Microbeam Near the Third Mode Using a Partial Electrode

    KAUST Repository

    Masri, Karim M.; Younis, Mohammad I.

    2014-01-01

    We present an investigation of the dynamics of a clamped-clamped microbeam excited electrostatically near its third mode. To maximize the response at the third mode, a partial electrode configuration is utilized. A multi-mode Galerkin method is used to develop a reduced order model (ROM) of the beam. A shooting method to find the periodic motion is utilized to generate frequency response curves. The curves show hardenining behavior and dynamic pull-in. We show that the dynamic amplitude of the partial configuration is higher than that of a full electrode configuration. These results are promising for the use of higher-order modes for mass detection and for ultra sensitive resonant sensors.

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

    Science.gov (United States)

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

    2014-11-15

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

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

    Science.gov (United States)

    Berger, Klaus; Hocke, Thomas; Hessel, Horst

    2017-11-01

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

  10. Differential Regulation of Action Potential Shape and Burst-Frequency Firing by BK and Kv2 Channels in Substantia Nigra Dopaminergic Neurons.

    Science.gov (United States)

    Kimm, Tilia; Khaliq, Zayd M; Bean, Bruce P

    2015-12-16

    Little is known about the voltage-dependent potassium currents underlying spike repolarization in midbrain dopaminergic neurons. Studying mouse substantia nigra pars compacta dopaminergic neurons both in brain slice and after acute dissociation, we found that BK calcium-activated potassium channels and Kv2 channels both make major contributions to the depolarization-activated potassium current. Inhibiting Kv2 or BK channels had very different effects on spike shape and evoked firing. Inhibiting Kv2 channels increased spike width and decreased the afterhyperpolarization, as expected for loss of an action potential-activated potassium conductance. BK inhibition also increased spike width but paradoxically increased the afterhyperpolarization. Kv2 channel inhibition steeply increased the slope of the frequency-current (f-I) relationship, whereas BK channel inhibition had little effect on the f-I slope or decreased it, sometimes resulting in slowed firing. Action potential clamp experiments showed that both BK and Kv2 current flow during spike repolarization but with very different kinetics, with Kv2 current activating later and deactivating more slowly. Further experiments revealed that inhibiting either BK or Kv2 alone leads to recruitment of additional current through the other channel type during the action potential as a consequence of changes in spike shape. Enhancement of slowly deactivating Kv2 current can account for the increased afterhyperpolarization produced by BK inhibition and likely underlies the very different effects on the f-I relationship. The cross-regulation of BK and Kv2 activation illustrates that the functional role of a channel cannot be defined in isolation but depends critically on the context of the other conductances in the cell. This work shows that BK calcium-activated potassium channels and Kv2 voltage-activated potassium channels both regulate action potentials in dopamine neurons of the substantia nigra pars compacta. Although both

  11. Studies on the Action Potential From a Thermodynamic Perspective

    DEFF Research Database (Denmark)

    Wang, Tian

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

  12. Different methods of hilar clamping during partial nephrectomy: Impact on renal function.

    Science.gov (United States)

    Lee, Jeong Woo; Kim, Hwanik; Choo, Minsoo; Park, Yong Hyun; Ku, Ja Hyeon; Kim, Hyeon Hoe; Kwak, Cheol

    2014-03-01

    To evaluate the impact of different hilar clamping methods on changes in renal function after partial nephrectomy. We analyzed the clinical data of 369 patients who underwent partial nephrectomy for a single renal tumor of size ≤4.0 cm and a normal contralateral kidney. Patients were separated into three groups depending on hilar clamping method: non-clamping, cold ischemia and warm ischemia. Estimated glomerular filtration rate was examined at preoperative, nadir and 1 year postoperatively. Percent change in estimated glomerular filtration rate was used as the parameter to assess the renal functional outcome. Percent change in nadir estimated glomerular filtration rate in the non-clamping group was significantly less compared with the cold ischemia and warm ischemia groups (P hilar clamping (both warm ischemia and cold ischemia) were significantly associated with percent change in nadir estimated glomerular filtration rate, but not in 1-year estimated glomerular filtration rate. Non-clamping partial nephrectomy results in a lower percent change in nadir estimated glomerular filtration rate, whereas it carries an estimated glomerular filtration rate change at 1 year that is similar to partial nephrectomy with cold ischemia and warm ischemia. Cold ischemia and warm ischemia provide a similar effect on renal function. Therefore, when hilar clamping is required, minimization of ischemia time is necessary. © 2013 The Japanese Urological Association.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  14. The Investigation of the Corrosion Resistance of the Tension Clamps Skl14

    Directory of Open Access Journals (Sweden)

    Marek Pětioký

    2015-05-01

    Full Text Available At the level crossings it is possible to find the problems with the corrosion of the parts of the fastening system. These problems are especially at the rubber level crossings and in the tunnels. As a part of the thesis the problem of the corrosion of the tension clamp Skl14 of the producer Vossloh at the rubber level crossings is examined. For the purposes of the comparison the tension clamps without the corrosion protection and the tension clamps with the corrosion protection KTL were examined. As a first step the corrosion features of the tension clamps Skl14 were solved. The examination was divided into two parts. First part it was the examination according to ČSN EN ISO 9227. The samples of the tension clamps were putted into the corrosion chamber. After 1728 h the results of the corrosion impacts were not satisfied. It was decided for the second step of the examination. It was the immersion in an electrolyte solution. As a result of the paper the corrosion features of the tension clamps without the corrosion protection and with the corrosion protection are compared.

  15. Analysis of whole-cell currents by patch clamp of guinea-pig myenteric neurones in intact ganglia

    Science.gov (United States)

    Rugiero, François; Gola, Maurice; Kunze, Wolf A A; Reynaud, Jean-Claude; Furness, John B; Clerc, Nadine

    2002-01-01

    Whole-cell patch-clamp recordings taken from guinea-pig duodenal myenteric neurones within intact ganglia were used to determine the properties of S and AH neurones. Major currents that determine the states of AH neurones were identified and quantified. S neurones had resting potentials of −47 ± 6 mV and input resistances (Rin) of 713 ± 49 MΩ at voltages ranging from −90 to −40 mV. At more negative levels, activation of a time-independent, caesium-sensitive, inward-rectifier current (IKir) decreased Rin to 103 ± 10 MΩ. AH neurones had resting potentials of −57 ± 4 mV and Rin was 502 ± 27 MΩ. Rin fell to 194 ± 16 MΩ upon hyperpolarization. This decrease was attributable mainly to the activation of a cationic h current, Ih, and to IKir. Resting potential and Rin exhibited a low sensitivity to changes in [K+]o in both AH and S neurones. This indicates that both cells have a low background K+ permeability. The cationic current, Ih, contributed about 20 % to the resting conductance of AH neurones. It had a half-activation voltage of −72 ± 2 mV, and a voltage sensitivity of 8.2 ± 0.7 mV per e-fold change. Ih has relatively fast, voltage-dependent kinetics, with on and off time constants in the range of 50–350 ms. AH neurones had a previously undescribed, low threshold, slowly inactivating, sodium-dependent current that was poorly sensitive to TTX. In AH neurones, the post-action-potential slow hyperpolarizing current, IAHP, displayed large variation from cell to cell. IAHP appeared to be highly Ca2+ sensitive, since its activation with either membrane depolarization or caffeine (1 mm) was not prevented by perfusing the cell with 10 mm BAPTA. We determined the identity of the Ca2+ channels linked to IAHP. Action potentials of AH neurones that were elongated by TEA (10 mm) were similarly shortened and IAHP was suppressed with each of the three Ω-conotoxins GVIA, MVIIA and MVIIC (0.3–0.5 μm), but not with Ω-agatoxin IVA (0.2 μm). There was no

  16. RESULTS OF TESTS OF LIGHTNING-RODS WITH UNIVERSAL CLAMPS BY THE APERIODIC IMPULSES OF CURRENT OF ARTIFICIAL LIGHTNING WITH THE PEAK-TEMPORAL PARAMETERS RATIONED ON FOREIGN STANDARDS

    Directory of Open Access Journals (Sweden)

    M.I. Baranov

    2015-06-01

    Full Text Available Purpose. Test in obedience to the requirements of row of operating foreign standards of round metallic lightning-rods with the flat metallic universal clamps of the special type on firmness to direct action of аperiodic impulses of current of temporal form 10/350 μs by amplitude of 50 кА (N− class and 100 кА (H− class. Methodology. The order of leadthrough of these tests is certain the followings normative documents: International IEC 62305-1: 2010, Russian national GOST R IEC 62305-1-2010 and German national DIN EN 50164-1:2008 Standards. Results. Conducted on a powerful high-voltage pulsed current of artificial linear lightning with the peak-temporal parameters and admittances of test rationed on the indicated foreign standards rationed that all of the lightning-rods tested in collection with universal clamps, isolating holders and ceramic elements of roof of technical building were survive electrodynamics and electrothermal action of in-use single short blow of an artificial storm digit. Originality. First in domestic practice the similar model tests of lightning-rods are conducted with universal clamps, executed from different explorer materials, on firmness to flowing to on by it the indicated large impulsive currents of artificial lightning. Practical value. Real firmness to lightning of round copper and zincked steel lightning-rods is certain with the flat copper, zincked steel and non-rusting steel universal clamps of the special execution.

  17. Low-intensity repetitive magnetic stimulation lowers action potential threshold and increases spike firing in layer 5 pyramidal neurons in vitro.

    Science.gov (United States)

    Tang, Alexander D; Hong, Ivan; Boddington, Laura J; Garrett, Andrew R; Etherington, Sarah; Reynolds, John N J; Rodger, Jennifer

    2016-10-29

    Repetitive transcranial magnetic stimulation (rTMS) has become a popular method of modulating neural plasticity in humans. Clinically, rTMS is delivered at high intensities to modulate neuronal excitability. While the high-intensity magnetic field can be targeted to stimulate specific cortical regions, areas adjacent to the targeted area receive stimulation at a lower intensity and may contribute to the overall plasticity induced by rTMS. We have previously shown that low-intensity rTMS induces molecular and structural plasticity in vivo, but the effects on membrane properties and neural excitability have not been investigated. Here we investigated the acute effect of low-intensity repetitive magnetic stimulation (LI-rMS) on neuronal excitability and potential changes on the passive and active electrophysiological properties of layer 5 pyramidal neurons in vitro. Whole-cell current clamp recordings were made at baseline prior to subthreshold LI-rMS (600 pulses of iTBS, n=9 cells from 7 animals) or sham (n=10 cells from 9 animals), immediately after stimulation, as well as 10 and 20min post-stimulation. Our results show that LI-rMS does not alter passive membrane properties (resting membrane potential and input resistance) but hyperpolarises action potential threshold and increases evoked spike-firing frequency. Increases in spike firing frequency were present throughout the 20min post-stimulation whereas action potential (AP) threshold hyperpolarization was present immediately after stimulation and at 20min post-stimulation. These results provide evidence that LI-rMS alters neuronal excitability of excitatory neurons. We suggest that regions outside the targeted region of high-intensity rTMS are susceptible to neuromodulation and may contribute to rTMS-induced plasticity. Copyright © 2016 IBRO. All rights reserved.

  18. Four- year thyroidectomy procedures: Ligasure Vs. clamp & tie

    Directory of Open Access Journals (Sweden)

    Pazoki AR

    2010-01-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: The electrothermal bipolar vessel sealing system is an adjunct to the hemostatic technique, which has been successfully used in many abdominal operation, recently made available to thyroid surgery. The purpose of this was compare the outcomes of new hemostatic technique with traditional method of clamp and tie."n"nMethods: In this retrospective cross-sectional study has been done in surgery's wards of Milad & Rasul- Akram hospitals in Tehran, Iran. During three- year period between 2005-2008 all patients with different kind of pathology that need operation were assessed. Time duration of surgery and hospital stay and post surgery complication in two group, ligasure (n=45 and clamp & tie (n=145 were compared with each others."n"nResults: No difference was seen between two groups in time duration of surgery. Significant difference was seen in hospital stay and complications of surgery. Time of operation in Ligasure group was 132/22 minute and in clamp and tie group was 130/10 minute. There was found significant difference in duration of hospital stay and postoperative complication. Hypocalcemia were seen in two and 24 cases in Ligasure and Clamp & Tie group, respectively (p<0.05. Hospital stay was 2

  19. Numerical investigation of action potential transmission in plants

    Directory of Open Access Journals (Sweden)

    Mariusz Pietruszka

    2014-01-01

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

  20. Improved DNA clamps by stacking to adjacent nucleobases

    DEFF Research Database (Denmark)

    Fatthalla, M.I.; Pedersen, Erik Bjerregaard

    2012-01-01

    Three or four aromatic rings interconnected by acetylene bridges form a stiff conjugated system with sufficient conformational freedom to make it useful to link together the two strands of a DNA clamp. Upon targeting a ssDNA, the conformational flexibility allows better stacking of the linker...... to the underlying non-planar base triplet in the formed triplex. This type of triplexes has a substantially higher thermal melting temperature which can be further improved by inserting locked nucleic acids (LNAs) in the Hoogsteen part of the clamp. An extremely high sensitivity to mismatches is observed...

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

    KAUST Repository

    Keener, James P.; Newby, Jay M.

    2011-01-01

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

  2. Loss Distribution Analysis of Three-Level Active Neutral-Point-Clamped (3L-ANPC) Converter with Different PWM Strategies

    DEFF Research Database (Denmark)

    Zhang, Gang; Yang, Yongheng; Iannuzzo, Francesco

    2016-01-01

    The three-level (3L) Active Neutral-Point-Clamped (ANPC) topology has been introduced to resolve the uneven loss distribution issue in the classical 3L Neutral-Point-Clamped (NPC) topology. This Pulse-Width-Modulation (PWM) strategy is then an important means to fully explore the potential benefits...... are separated in order to improve the loss distribution among the power devices. A comparison between the proposed strategy and other major PWM strategies for the loss distribution is also carried out in this paper. Benchmarking results show that the proposed strategy has effective and superior performance...

  3. Formal Design Review Foot Clamp Modification

    International Nuclear Information System (INIS)

    OTEN, T.C.

    2000-01-01

    This report documents the Design Review performed for the foot clamp modification. The report documents the acceptability of the design, identifies the documents that were reviewed, the scope of the review and the members of the review team

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

    Science.gov (United States)

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

    2012-06-03

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

  5. The mode of inotropic action of ciguatoxin on guinea-pig cardiac muscle.

    Science.gov (United States)

    Seino, A.; Kobayashi, M.; Momose, K.; Yasumoto, T.; Ohizumi, Y.

    1988-01-01

    1. Ciguatoxin (CTX) caused a dose-dependent increase in the contractile force of the guinea-pig isolated left atria at concentrations ranging from 0.1 to 10 ng ml-1 with the ED50 value of 0.5 ng ml-1. 2. In the atria, tetrodotoxin (5 x 10(-7) M) inhibited markedly the inotropic action of CTX. The inotropic effect of CTX at low concentrations was abolished by practolol (10(-5) M) and reserpine (2 mg kg-1 daily, for 3 days), whereas that of CTX at high concentrations was partially inhibited by both drugs. 3. In single atrial cells, CTX (3 ng ml-1) produced a marked increase in the amplitude of longitudinal contractions. 4. CTX (3 ng ml-1) caused marked prolongation in the falling phase of action potentials of atrial strips without affecting the maximum rate of rise of action potentials and membrane resting potentials. The effect of CTX on action potentials was abolished by tetrodotoxin (10(-6) M). 5. The whole-cell patch-clamp experiments on myocytes revealed that CTX (20 ng ml-1) shifted the current-voltage curve of Na inward currents by 40 mV in the negative direction. CTX caused a small sustained Na inward current even at resting membrane potentials. 6. These results suggest that the inotropic action of lower concentrations of CTX is primarily due to an indirect action via noradrenaline release, whereas that of higher concentrations is caused not only by an indirect action but also by a direct action on voltage-dependent Na channels of cardiac muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3207997

  6. Molecular mechanism of DNA replication-coupled inactivation of the initiator protein in Escherichia coli: interaction of DnaA with the sliding clamp-loaded DNA and the sliding clamp-Hda complex.

    Science.gov (United States)

    Su'etsugu, Masayuki; Takata, Makoto; Kubota, Toshio; Matsuda, Yusaku; Katayama, Tsutomu

    2004-06-01

    In Escherichia coli, the ATP-DnaA protein initiates chromosomal replication. After the DNA polymerase III holoenzyme is loaded on to DNA, DnaA-bound ATP is hydrolysed in a manner depending on Hda protein and the DNA-loaded form of the DNA polymerase III sliding clamp subunit, which yields ADP-DnaA, an inactivated form for initiation. This regulatory DnaA-inactivation represses extra initiation events. In this study, in vitro replication intermediates and structured DNA mimicking replicational intermediates were first used to identify structural prerequisites in the process of DnaA-ATP hydrolysis. Unlike duplex DNA loaded with sliding clamps, primer RNA-DNA heteroduplexes loaded with clamps were not associated with DnaA-ATP hydrolysis, and duplex DNA provided in trans did not rescue this defect. At least 40-bp duplex DNA is competent for the DnaA-ATP hydrolysis when a single clamp was loaded. The DnaA-ATP hydrolysis was inhibited when ATP-DnaA was tightly bound to a DnaA box-bearing oligonucleotide. These results imply that the DnaA-ATP hydrolysis involves the direct interaction of ATP-DnaA with duplex DNA flanking the sliding clamp. Furthermore, Hda protein formed a stable complex with the sliding clamp. Based on these, we suggest a mechanical basis in the DnaA-inactivation that ATP-DnaA interacts with the Hda-clamp complex with the aid of DNA binding. Copyright Blackwell Publishing Limited

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

    Science.gov (United States)

    Casale, Amanda E.; McCormick, David A.

    2012-01-01

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

  8. The human dynamic clamp as a paradigm for social interaction.

    Science.gov (United States)

    Dumas, Guillaume; de Guzman, Gonzalo C; Tognoli, Emmanuelle; Kelso, J A Scott

    2014-09-02

    Social neuroscience has called for new experimental paradigms aimed toward real-time interactions. A distinctive feature of interactions is mutual information exchange: One member of a pair changes in response to the other while simultaneously producing actions that alter the other. Combining mathematical and neurophysiological methods, we introduce a paradigm called the human dynamic clamp (HDC), to directly manipulate the interaction or coupling between a human and a surrogate constructed to behave like a human. Inspired by the dynamic clamp used so productively in cellular neuroscience, the HDC allows a person to interact in real time with a virtual partner itself driven by well-established models of coordination dynamics. People coordinate hand movements with the visually observed movements of a virtual hand, the parameters of which depend on input from the subject's own movements. We demonstrate that HDC can be extended to cover a broad repertoire of human behavior, including rhythmic and discrete movements, adaptation to changes of pacing, and behavioral skill learning as specified by a virtual "teacher." We propose HDC as a general paradigm, best implemented when empirically verified theoretical or mathematical models have been developed in a particular scientific field. The HDC paradigm is powerful because it provides an opportunity to explore parameter ranges and perturbations that are not easily accessible in ordinary human interactions. The HDC not only enables to test the veracity of theoretical models, it also illuminates features that are not always apparent in real-time human social interactions and the brain correlates thereof.

  9. Clamp wins pipe repair prize

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    2001-04-01

    This paper describes the permanent pipeline repair system, developed by Tekmar, which is powered by seawater hydraulics and is easily installed and tested by any workclass remotely operated vehicle (rov). Details are given of the two main components of the system, namely, the diverless high pressure split repair clamp and the rov-operated tool to install it.

  10. Design and control of a novel gastroscope intervention mechanism with circumferentially pneumatic-driven clamping function.

    Science.gov (United States)

    Li, Yanmin; Liu, Hao; Hao, Siwen; Li, Hongyi; Han, Jianda; Yang, Yunsheng

    2017-03-01

    Robot-assisted manipulation is promising for solving problems such as understaffing and the risk of infection in gastro-intestinal endoscopy. However, the commonly used friction rollers in few existing systems have a potential risk of deforming flexible endoscopes for non-uniform clamping. This paper presents a robotic system for a standard flexible endoscope and focuses on a novel gastroscope intervention mechanism (GIM), which provides circumferentially uniform clamping with an airbag. The GIM works with a relay-on mechanism in a way similar to manual operation. The shear stiffness of airbag and the critical slipping force (CSF) were analysed to determine the parameters of the airbag. A fuzzy PID controller was employed to realize a fast response and high accuracy of pneumatic actuation. Experiments were performed to evaluate the accuracy, stiffness and CSF. In vitro and in vivo animal experiments were also carried out. The GIM realized an accuracy of 0.025 ± 0.2 mm and -0.03 ± 0.25° for push-pull and rotation without delivery resistance. Under polynomial could be used to describe the relationship between the CSF and pneumatic pressure. The novel GIM could effectively deliver gastroscopes. The pneumatic-driven clamping method proposed could protect the gastroscope by circumferentially uniform clamping force and the CSF could be properly controlled to guarantee operating safety. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  11. A High Step-Down Interleaved Buck Converter with Active-Clamp Circuits for Wind Turbines

    Directory of Open Access Journals (Sweden)

    Chih-Lung Shen

    2012-12-01

    Full Text Available In this paper, a high step-down interleaved buck coupled-inductor converter (IBCC with active-clamp circuits for wind energy conversion has been studied. In high step-down voltage applications, an IBCC can extend duty ratio and reduce voltage stresses on active switches. In order to reduce switching losses of active switches to improve conversion efficiency, a IBCC with soft-switching techniques is usually required. Compared with passive-clamp circuits, the IBCC with active-clamp circuits have lower switching losses and minimum ringing voltage of the active switches. Thus, the proposed IBCC with active-clamp circuits for wind energy conversion can significantly increase conversion efficiency. Finally, a 240 W prototype of the proposed IBCC with active-clamp circuits was built and implemented. Experimental results have shown that efficiency can reach as high as 91%. The proposed IBCC with active-clamp circuits is presented in high step-down voltage applications to verify the performance and the feasibility for energy conversion of wind turbines.

  12. Natural Vibration Analysis of Clamped Rectangular Orthotropic Plates

    Science.gov (United States)

    dalaei, m.; kerr, a. d.

    The natural vibrations of clamped rectangular orthotropic plates are analyzed using the extended Kantorovich method. The developed iterative scheme converges very rapidly to the final result. The obtained natural frequencies are evaluated for a square plate made of Kevlar 49 Epoxy and the obtained results are compared with those published by Kanazawa and Kawai, and by Leissa. The agreement was found to be very close. As there are no exact analytical solutions for clamped rectangular plates, the generated closed form expression for the natural modes, and the corresponding natural frequencies, are very suitable for use in engineering analyses.

  13. Effect of non-ideal clamping shape on the resonance frequencies of silicon nanocantilevers

    Energy Technology Data Exchange (ETDEWEB)

    Guillon, Samuel; Saya, Daisuke; Mazenq, Laurent; Nicu, Liviu [CNRS, LAAS, 7 Avenue du Colonel Roche, F-31077 Toulouse Cedex 4 (France); Perisanu, Sorin; Vincent, Pascal [LPMCN, Universite Claude Bernard Lyon 1 et CNRS, 43 boulevard du 11 novembre 1918, 69622 Villeurbanne Cedex (France); Lazarus, Arnaud; Thomas, Olivier, E-mail: sguillon@laas.fr [Structural Mechanics and Coupled Systems Laboratory, Conservatoire National des Arts et Metiers, 2 rue Conte, 75003 Paris (France)

    2011-06-17

    In this paper, we investigate the effects of non-ideal clamping shapes on the dynamic behavior of silicon nanocantilevers. We fabricated silicon nanocantilevers using silicon on insulator (SOI) wafers by employing stepper ultraviolet (UV) lithography, which permits a resolution of under 100 nm. The nanocantilevers were driven by electrostatic force inside a scanning electron microscope (SEM). Both lateral and out-of-plane resonance frequencies were visually detected with the SEM. Next, we discuss overhanging of the cantilever support and curvature at the clamping point in the silicon nanocantilevers, which generally arises in the fabrication process. We found that the fundamental out-of-plane frequency of a realistically clamped cantilever is always lower than that for a perfectly clamped cantilever, and depends on the cantilever width and the geometry of the clamping point structure. Using simulation with the finite-elements method, we demonstrate that this discrepancy is attributed to the particular geometry of the clamping point (non-zero joining curvatures and a flexible overhanging) that is obtained in the fabrication process. The influence of the material orthotropy is also investigated and is shown to be negligible.

  14. Clamped end conditions and cross section deformation in the finite element absolute nodal coordinate formulation

    International Nuclear Information System (INIS)

    Hussein, Bassam A.; Weed, David; Shabana, Ahmed A.

    2009-01-01

    In the finite element absolute nodal coordinate formulation (ANCF), the elimination of the relative translations and rotations at a point does not necessarily define a fully clamped joint, particularly in the case of fully parameterized ANCF finite elements that allow for the deformation of the cross section. In this investigation, the formulations and results of two different sets of clamped end conditions that define two different joints are compared. The first joint, called the partially clamped joint, eliminates only the translations and rotations at a point on the cross section. The second joint, called the fully clamped joint, eliminates all the translation, rotation and deformation degrees of freedom at a point on the cross section. The kinematic equations that define the partially and fully clamped joints are developed, and the dynamic equations used in the comparative numerical study presented in this paper are shown. As discussed in this investigation, the fully clamped joint does not allow for the deformation of the cross section at the joint node since the gradient vectors remain orthogonal unit vectors. The partially clamped joint, on the other hand, allows for the deformation of the cross section. Nanson's formula is used as a measure of the deformation of the cross section in the case of the partially clamped joint. A very flexible pendulum that has a rigid body attached to its free end is used to compare the results of the partially and fully clamped joints. The numerical results obtained using this very flexible pendulum example show that, while the type of joint (partially or fully clamped) does not significantly affect the gross reference motion of the system, there are fundamental differences between the two joints since the partially clamped joint allows for the cross section deformations at the joint node

  15. Role of the Checkpoint Clamp in DNA Damage Response

    Directory of Open Access Journals (Sweden)

    Mihoko Kai

    2013-01-01

    Full Text Available DNA damage occurs during DNA replication, spontaneous chemical reactions, and assaults by external or metabolism-derived agents. Therefore, all living cells must constantly contend with DNA damage. Cells protect themselves from these genotoxic stresses by activating the DNA damage checkpoint and DNA repair pathways. Coordination of these pathways requires tight regulation in order to prevent genomic instability. The checkpoint clamp complex consists of Rad9, Rad1 and Hus1 proteins, and is often called the 9-1-1 complex. This PCNA (proliferating cell nuclear antigen-like donut-shaped protein complex is a checkpoint sensor protein that is recruited to DNA damage sites during the early stage of the response, and is required for checkpoint activation. As PCNA is required for multiple pathways of DNA metabolism, the checkpoint clamp has also been implicated in direct roles in DNA repair, as well as in coordination of the pathways. Here we discuss roles of the checkpoint clamp in DNA damage response (DDR.

  16. Three-dimensional renal CT angiography for guiding segmental renal artery clamping during laparoscopic partial nephrectomy

    International Nuclear Information System (INIS)

    Xu, Yi; Shao, Pengfei; Zhu, Xiaomei; Lv, Qiang; Liu, Wangyan; Xu, Hai; Zhu, Yinsu; Yang, Guangyu; Tang, Lijun; Yin, Changjun

    2013-01-01

    Aim: To evaluate the effectiveness of three-dimensional (3D) renal computed tomography angiography (CTA) in guiding segmental renal artery clamping during laparoscopic partial nephrectomy (LPN). Materials and methods: Forty-three patients with renal tumours undergoing renal CTA before LPN were retrospectively enrolled in this study. 3D arteriogram reconstructed images were created to identify the renal tumour-supplying arteries. The number and location of these targeted vessels were annotated on 3D images preoperatively and compared with the clamped vessels during LPN. The consistency between target vessels annotated at CTA and clamped arteries at LPN was compared both using a patient-based analysis and vessel-based analysis. The χ 2 test was applied to analyse the influence of tumour size, location, and growth pattern on the number of clamped segmental renal branches. Results: On patient-based analysis, the number of targeted vessels was consistent with the clamped vessels during LPN in 33 of 43 patients. On vessel-based analysis, 56 of 65 target vessels annotated at CTA were clamped during LPN. More segmental renal branches (p = 0.04) were clamped in patients with tumours of larger size. Tumour location and growth pattern had no association with the number of clamped segmental branches during LPN. Conclusion: High-quality CTA images and 3D reconstruction images can detect detailed information of tumour-supplying arteries to renal tumours. 3D renal CTA is an effective way to guide segmental renal artery clamping during LPN

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

    Science.gov (United States)

    Muñoz, Fabián; Fuentealba, Pablo

    2012-01-01

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

  18. Locoregional Anesthesia for Carotid Endarterectomy: Identification of Patients with Intolerance to Cross-Clamping.

    Science.gov (United States)

    Dellaretti, Marcos; de Vasconcelos, Laura T; Dourado, Jules; de Souza, Renata F; Fontoura, Renato R; de Sousa, Atos A

    2016-03-01

    During carotid endarterectomy (CEA), carotid cross-clamping is performed to allow for artery incision and plaque removal. A small subgroup of patients can tolerate carotid occlusion for only a few seconds, if at all, without presenting neurologic deficit. These patients are described as having ''cross-clamp intolerance.'' The purpose of this study was to demonstrate the safety of locoregional anesthesia in identifying patients with cross-clamp intolerance and factors associated with this condition. From August 2008 to May 2010, 115 consecutive patients were submitted to CEA under locoregional anesthesia at the Santa Casa de Belo Horizonte; the procedure was performed by the main author. Patients who showed intolerance to internal carotid artery (ICA) occlusion for intolerance. Among the 115 participating patients, 9.6% (11 patients) showed intolerance to ICA occlusion and developed deficits in intolerance). The factor that was associated with cross-clamp intolerance was the mean degree of contralateral carotid stenosis, which was 57.5% for those who presented intolerance and 27.8% for those who tolerated ICA occlusion. Locoregional anesthesia is a safe method for identifying patients with cross-clamp intolerance. Patients with cross-clamp intolerance present contralateral stenosis that is greater on average than patients who readily tolerate carotid artery occlusion. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  20. Artifactual voltage response recorded from hair cells with patch-clamp amplifiers.

    Science.gov (United States)

    Masetto, S; Weng, T; Valli, P; Correia, M J

    1999-06-23

    Patch-clamp amplifiers (PCAs) are commonly used to characterize voltage- and current-clamp responses in the same cell. However, the cell membrane voltage response can be severely distorted by PCAs working in the current-clamp mode. Here we compare the voltage response of pigeon semicircular canal hair cells in situ, recorded with two different PCAs, and with a classic microelectrode bridge amplifier (BA). We found that the voltage response of hair cells recorded with PCAs differed significantly from that recorded with the BA. The true hair cell membrane voltage response to positive current steps was characterized by a strongly damped oscillation, whose frequency and duration depended on hair cell location in the sensory crista ampullaris.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  2. Dynamic assembly of Hda and the sliding clamp in the regulation of replication licensing.

    Science.gov (United States)

    Kim, Jin S; Nanfara, Michael T; Chodavarapu, Sundari; Jin, Kyeong S; Babu, Vignesh M P; Ghazy, Mohamed A; Chung, Scisung; Kaguni, Jon M; Sutton, Mark D; Cho, Yunje

    2017-04-20

    Regulatory inactivation of DnaA (RIDA) is one of the major regulatory mechanisms of prokaryotic replication licensing. In RIDA, the Hda-sliding clamp complex loaded onto DNA directly interacts with adenosine triphosphate (ATP)-bound DnaA and stimulates the hydrolysis of ATP to inactivate DnaA. A prediction is that the activity of Hda is tightly controlled to ensure that replication initiation occurs only once per cell cycle. Here, we determined the crystal structure of the Hda-β clamp complex. This complex contains two pairs of Hda dimers sandwiched between two β clamp rings to form an octamer that is stabilized by three discrete interfaces. Two separate surfaces of Hda make contact with the β clamp, which is essential for Hda function in RIDA. The third interface between Hda monomers occludes the active site arginine finger, blocking its access to DnaA. Taken together, our structural and mutational analyses of the Hda-β clamp complex indicate that the interaction of the β clamp with Hda controls the ability of Hda to interact with DnaA. In the octameric Hda-β clamp complex, the inability of Hda to interact with DnaA is a novel mechanism that may regulate Hda function. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    Science.gov (United States)

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

    2017-06-01

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

  4. The Effect of an Added Mass on the Frequency Shifts of a Clamped-Clamped Microbeam for Bio-Mass Detection

    KAUST Repository

    Bouchaala, Adam M.

    2016-12-05

    We present analytical formulations to calculate the induced resonance frequency shifts of electrically actuated clamped-clamped microbeams due to an added mass. Based on the Euler-Bernoulli beam theory, we investigate the linear dynamic responses of the beams added masses, which are modeled as discrete point masses. Analytical expressions based on perturbation techniques and a one-mode Galerkin approximation are developed to calculate accurately the frequency shifts under a DC voltage as a function of the added mass and position. The analytical results are compared to numerical solution of the eigenvalue problem. Results are shown for the fundamental as well as the higher-order modes of the beams. The results indicate a significant increase in the frequency shift, and hence the sensitivity of detection, when scaling down to nano scale and using higher-order modes.

  5. The Effect of an Added Mass on the Frequency Shifts of a Clamped-Clamped Microbeam for Bio-Mass Detection

    KAUST Repository

    Bouchaala, Adam M.; Nayfeh, Ali H.; Younis, Mohammad I.

    2016-01-01

    We present analytical formulations to calculate the induced resonance frequency shifts of electrically actuated clamped-clamped microbeams due to an added mass. Based on the Euler-Bernoulli beam theory, we investigate the linear dynamic responses of the beams added masses, which are modeled as discrete point masses. Analytical expressions based on perturbation techniques and a one-mode Galerkin approximation are developed to calculate accurately the frequency shifts under a DC voltage as a function of the added mass and position. The analytical results are compared to numerical solution of the eigenvalue problem. Results are shown for the fundamental as well as the higher-order modes of the beams. The results indicate a significant increase in the frequency shift, and hence the sensitivity of detection, when scaling down to nano scale and using higher-order modes.

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

    Directory of Open Access Journals (Sweden)

    János Brunner

    2014-03-01

    Full Text Available Backpropagating action potentials (bAPs and local calcium signals that they trigger are fundamental for dendritic functions. Here we addressed the question what extent the changes of local dendritic membrane properties can contribute to the shaping of the coupling between dendritic action potentials and the local calcium responses. Using a combination of in vitro electrophysiological and confocal imaging techniques we found that activation of dendritic GIRK channels via mGlu2 or GABAB receptors enhanced the bAP¬-triggered calcium signals in the dendrites of dentate gyrus granule cells (GCs. The enhancement of calcium signals was significant only in those dendritic regions, where these receptors are predominantly expressed. Similarly to GIRK channel activation, somatic hyperpolarization by DC current injection (from -64 mV to -77 mV, significantly increased bAP-associated calcium signals in the proximal dendrites. The hyperpolarization was associated with a decrease in the input resistance due to the rectification of the membrane potential of GCs. The effect of hyperpolarization on the calcium signals was maintained when T-type calcium currents were blocked but it decreased when GIRK channels were inhibited. Simultaneous dual somato-dendritic recordings from GCs showed that somatic hyperpolarization accelerated the repolarization phase of dendritic bAP in the proximal region whereas the rising phase and peak amplitude was not affected. We hypothesize that the larger driving force for calcium ions during the faster repolarization can contribute to the increasing in calcium signals. Employment of previously recorded dendritic bAP waveforms from hyperpolarized membrane potential as voltage command evoked larger calcium currents in nucleated patches compared to bAP waveform from the same recording at depolarized membrane potential. Furthermore, addition of native, high-voltage activated, inactivating potassium conductance by somatic dynamic clamp

  7. Effect of exercise on insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Richter, Erik; Mikines, K J; Galbo, Henrik

    1989-01-01

    The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

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

    Science.gov (United States)

    Lu, Siyuan; Madhukar, Anupam

    2013-02-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  10. Finite element analysis on factors influencing the clamping force in an electrostatic chuck

    International Nuclear Information System (INIS)

    Wang Xingkuo; Yang Yiyong; Cheng Jia; Wang Kesheng; Sun Yuchun; Cao Minglu; Ji Linhong

    2014-01-01

    As one of the core components of IC manufacturing equipment, the electrostatic chuck (ESC) has been widely applied in semiconductor processing such as etching, PVD and CVD. The clamping force of the ESC is one of the most important technical indicators. A multi-physics simulation software COMSOL is used to analyze the factors influencing the clamping force. The curves between the clamping force and the main parameters such as DC voltage, electrode thickness, electrode radius, dielectric thickness and helium gap are obtained. Moreover, the effects of these factors on the clamping force are investigated by means of orthogonal experiments. The results show that the factors can be ranked in order of voltage, electrode radius, helium gap and dielectric thickness according to their importance, which may offer certain reference for the design of ESCs. (semiconductor devices)

  11. Modelling the clamping force distribution among chips in press-pack IGBTs using the finite element method

    DEFF Research Database (Denmark)

    Hasmasan, Adrian Augustin; Busca, Christian; Teodorescu, Remus

    2012-01-01

    In this paper, a FEM (finite element method) based mechanical model for PP (press-pack) IGBTs (insulated gate bipolar transistors) is presented, which can be used to calculate the clamping force distribution among chips under various clamping conditions. The clamping force is an important parameter...... for the chip, because it influences contact electrical resistance, contact thermal resistance and power cycling capability. Ideally, the clamping force should be equally distributed among chips, in order to maximize the reliability of the PP IGBT. The model is built around a hypothetical PP IGBT with 9 chips......, and it has numerous simplifications in order to reduce the simulation time as much as possible. The developed model is used to analyze the clamping force distribution among chips, in various study cases, where uniform and non-uniform clamping pressures are applied on the studied PP IGBT....

  12. An isolated Hda-clamp complex is functional in the regulatory inactivation of DnaA and DNA replication.

    Science.gov (United States)

    Kawakami, Hironori; Su'etsugu, Masayuki; Katayama, Tsutomu

    2006-10-01

    In Escherichia coli, a complex consisting of Hda and the DNA-loaded clamp-subunit of the DNA polymerase III holoenzyme promotes hydrolysis of DnaA-ATP. The resultant ADP-DnaA is inactive for initiation of chromosomal DNA replication, thereby repressing excessive initiations. As the cellular content of the clamp is 10-100 times higher than that of Hda, most Hda molecules might be complexed with the clamp in vivo. Although Hda predominantly forms irregular aggregates when overexpressed, in the present study we found that co-overexpression of the clamp with Hda enhances Hda solubility dramatically and we efficiently isolated the Hda-clamp complex. A single molecule of the complex appears to consist of two Hda molecules and a single clamp. The complex is competent in DnaA-ATP hydrolysis and DNA replication in the presence of DNA and the clamp deficient subassembly of the DNA polymerase III holoenzyme (pol III*). These findings indicate that the clamp contained in the complex is loaded onto DNA through an interaction with the pol III* and that the Hda activity is preserved in these processes. The complex consisting of Hda and the DNA-unloaded clamp may play a specific role in a process proceeding to the DnaA-ATP hydrolysis in vivo.

  13. Patch Clamp: A Powerful Technique for Studying the Mechanism of Acupuncture

    Directory of Open Access Journals (Sweden)

    D. Zhang

    2012-01-01

    Full Text Available Cellular and molecular events can be investigated using electrophysiological techniques. In particular, the patch-clamp method provides detailed information. In addition, the patch-clamp technique has become a powerful method for investigating the mechanisms underlying the effects of acupuncture. In this paper, recent researches on how acupuncture might modulate electrophysiological responses in the central nervous system (CNS and affect peripheral structures are reviewed.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  15. Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index

    DEFF Research Database (Denmark)

    Tura, Andrea; Chemello, Gaetano; Szendroedi, Julia

    2018-01-01

    that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n = 359 and n = 154, respectively). After a stepwise selection approach, the best model for M value prediction was applied......AIMS/HYPOTHESIS: The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However......, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS). METHODS: We analysed datasets of people...

  16. Common voltage eliminating of SVM diode clamping three-level inverter connected to grid

    DEFF Research Database (Denmark)

    Guo, Yougui; Zeng, Ping; Zhu, Jieqiong

    2011-01-01

    A novel method of common voltage eliminating is put forward for SVM diode clamping three-level inverter connected to grid by calculation of common voltage of its various switching states. PLECS is used to model this three-level inverter connected to grid and good results are obtained. First...... analysis of common mode voltage for switching states of diode clamping 3-level inverter is given in detail. Second the common mode voltage eliminating control strategy of SVM is described for diode clamping three-level inverter. Third, PLECS is briefly introduced. Fourth, the modeling of diode clamping...... three-level inverter is presented with PLECS. Finally, a series of simulations are carried out. The simulation results tell us PLECS is a very powerful tool to real power circuits modeling. They have also verified that proposed common mode voltage eliminating control strategy of SVM is feasible...

  17. Investigation on the Behavior of the Jointing Clamps to the Simulated Environmental - LOCA

    International Nuclear Information System (INIS)

    Ivan, P.; Segarceanu, D.; Geambasu, C.

    2002-01-01

    The paper presents the main aspect concerning the electric parameter variation of jointing clamps operating under specific environmental conditions determinate by pressure, temperature and humidity. The testing of jointing clamps capability to meet and exceed the required performances all along its operating life implies the performing of LOCA simulation conditions while the jointing clamps is bright in a relatively short time under conditions equivalent to those at the end of its service life. The paper describes ageing and measurement techniques and the analyses of electric parameter behaviour in these environmental simulated conditions. (author)

  18. Meju, unsalted soybeans fermented with Bacillus subtilis and Aspergilus oryzae, potentiates insulinotropic actions and improves hepatic insulin sensitivity in diabetic rats

    Directory of Open Access Journals (Sweden)

    Yang Hye

    2012-05-01

    Full Text Available Abstract Background Although soybeans have the ability to attenuate insulin resistance, it is insufficient to alleviate type 2 diabetic symptoms and different types of fermented soybeans may have even better anti-diabetic effects. Meju, unsalted fermented soybeans exhibited better insulin sensitizing and insulinotropic actions than unfermented cooked soybeans (CSB. We investigated whether meju fermented in the traditional (TMS manner for 60 days and meju fermented in the standardized (MMS method inoculating Bacillus subtilis and Aspergillus oryzae for 6 days modulated insulin resistance, insulin secretion, and pancreatic β-cell growth and survival in 90% pancreatectomized (Px diabetic rats, a moderate and non-obese type 2 diabetic animal model. Methods Diabetic rats were divided into 3 groups: 1 TMS (n = 20, 2 MMS (n = 20 or 3 casein (control; n = 20. Rats were provided with a high fat diet (40 energy % fat containing assigned 10% meju for 8 weeks. At the end of experiment insulin resistance and insulin secretion capacity were measured by euglycemic hyperinsulinemic clamp and by hyperglycemic clamp, respectively. Additionally, β-cell mass and islet morphohometry were determined by immunohistochemistry and insulin signaling in the liver was measured by western blot. Results TMS and MMS increased isoflavonoid aglycones much more than CSB. CSB and TMS/MMS improved glucose tolerance in diabetic rats but the mechanism was different between treatments (P Conclusions The anti-diabetic action of MMS, especially when fermented with Bacillus subtilis and Aspergillus oryzae, was superior to CSB by increasing isoflavonoid aglycones and small peptides with regard to type 2 diabetic rats.

  19. Research on micromanipulator’s clamping force sensing based on static wirerope tension of a surgical robot

    Directory of Open Access Journals (Sweden)

    Lingtao Yu

    2015-04-01

    Full Text Available The micromanipulator’s force feedback is one of the key research contents of minimally invasive surgical robotic system. Because the micromanipulator is a kind of compact construction which is suitable for valve installation with small space in surgery, especially for the influence of disinfection method, there are major difficulties and limitations to integrate compact sensors in the end of micromanipulator. This article focuses on the 3-degree-of-freedom micromanipulator’s clamping force sensing, and these three joints are actuated by wirerope driving. A clamping force sensing method is proposed based on static tension of wirerope driving, and a static model between the clamping force and wirerope’s static tension is established considering the influence of real friction resistance in the mechanical system. Finally, an equivalent experimental test platform for 3-degree-of-freedom micromanipulator’s clamping force sensing is set up, and then a series of experiments of the clamping force are studied. The frictional resistances of wirerope between the guide plate and guide pulley mechanism are tested, and a calibration and correction method of the experimental clamping force is proposed. The final experiment results show that the total average accuracy of experimental clamping force is about 78.3%, and it can be the basic measurement force to realize micromanipulator’s clamping force feedback of a minimally invasive surgical robot.

  20. Fiber Optic Detection of Action Potentials in Axons

    National Research Council Canada - National Science Library

    Smela, Elisabeth

    2006-01-01

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

  1. Clamp and Gas Nozzle for TIG Welding

    Science.gov (United States)

    Gue, G. B.; Goller, H. L.

    1982-01-01

    Tool that combines clamp with gas nozzle is aid to tungsten/inert-gas (TIG) welding in hard-to-reach spots. Tool holds work to be welded while directing a stream of argon gas at weld joint, providing an oxygen-free environment for tungsten-arc welding.

  2. Timing of umbilical cord-clamping and infant anaemia: the role of maternal anaemia.

    Science.gov (United States)

    Blouin, Brittany; Penny, Mary E; Maheu-Giroux, Mathieu; Casapía, Martín; Aguilar, Eder; Silva, Hermánn; Creed-Kanashiro, Hilary M; Joseph, Serene A; Gagnon, Anita; Rahme, Elham; Gyorkos, Theresa W

    2013-05-01

    Evidence from randomized controlled trials has shown that delayed cord-clamping is beneficial to infant iron status. The role of maternal anaemia in this relationship, however, has not been established. To determine the effect of maternal anaemia at delivery on the association between timing of umbilical cord-clamping and infant anaemia at 4 and 8 months of age. A cohort of pregnant women admitted to the labour room of Hospital Iquitos (Iquitos, Peru) and their newborns were recruited into the study during two time periods (18 May to 3 June and 6-20 July 2009). Between the two recruitment periods, the hospital's policy changed from early to delayed umbilical cord-clamping. Maternal haemoglobin levels were measured before delivery, and the time between delivery and cord-clamping was recorded at delivery for the entire cohort. Mother-infant pairs were followed-up at 4 (n = 207) and 8 months (n = 184) post partum. Infant haemoglobin levels were measured at follow-up visits. Data were analysed using logistic regression models. The prevalence of maternal anaemia (Hb anaemia was modified by the mother's anaemia status. Significant benefits of delayed cord-clamping in preventing anaemia were found in infants born to anaemic mothers at both 4 months (aOR = 0.59, 95% CI 0.36-0.99) and 8 months (aOR = 0.38, 95% CI 0.19-0.76) of age. The study contributes additional evidence in support of delayed cord-clamping. This intervention is likely to have most public health impact in areas with a high prevalence of anaemia during pregnancy.

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

    Science.gov (United States)

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

    1982-01-01

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

  4. Introducing the Action Potential to Psychology Students

    Science.gov (United States)

    Simon-Dack, Stephanie L.

    2014-01-01

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

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

    KAUST Repository

    Keener, James P.

    2011-07-01

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

  6. Enhancing endogenous stem cells in the newbornvia delayed umbilical cord clamping

    Institute of Scientific and Technical Information of China (English)

    Christopher Lawton; Sandra Acosta; Nate Watson; Chiara Gonzales-Portillo; hTeo Diamandis; Naoki Tajiri; Yuji Kaneko; Paul R. Sanberg; Cesar V. Borlongan

    2015-01-01

    There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal beneifts including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deifciency anemia in term infants. Human umbilical cord blood con-tains signiifcant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it en-hances blood lfow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant’s susceptibility to both neonatal and age-related diseases.

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

    Science.gov (United States)

    Eickenscheidt, Max; Zeck, Günther

    2014-06-01

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

  8. Clampe de Ganz no tratamento de urgência em lesões do anel pélvico Ganz clamps to treat emergencies in pelvic ring lesions

    Directory of Open Access Journals (Sweden)

    Gilberto José Cação Pereira

    2008-07-01

    Full Text Available OBJETIVO: Avaliar a eficiência do clampe de Ganz na estabilização e redução dos deslocamentos da pelve, quando utilizado no tratamento de urgência, além de aquilatar eventuais dificuldades e facilidades do método. MÉTODOS: O clampe de Ganz foi utilizado no tratamento de urgência em 31 pacientes com graves lesões do anel pélvico (Tile C associadas a importante instabilidade hemodinâmica. RESULTADO: Entre os pacientes, 27 (87,1% apresentaram evolução favorável, com estabilização, redução dos deslocamentos e compressão da região posterior do anel, além de estabilização hemodinâmica, e quatro (12,9% evoluíram para óbito. CONCLUSÃO: O clampe de Ganz mostrou-se eficiente ferramenta no tratamento de urgência das lesões do anel pélvico, por ser de concepção simples, de rápida colocação, não impedir ou dificultar procedimentos no abdome e, principalmente, por permitir a estabilização da pelve, redução dos deslocamentos e compressão na região posterior do anel, local onde ocorrem os maiores sangramentos, reduzindo-os ou eliminando-os.OBJECTIVE: To evaluate the effectiveness of Ganz clamp to stabilize and reduce pelvic dislocations in emergency situations, and to assess possible difficult and easy aspects of the method. METHOD: Ganz clamp was used in the emergency treatment of 31 patients with severe lesions of the pelvic ring (Tile C associated to major hemodynamic instability. RESULTS: Among the patients, 27 (87.1% presented a favorable evolution, with stabilization, reduction of dislocations, and compression of the posterior portion of the ring, and also hemodynamic stabilization, and 4 (12.9% died. CONCLUSION: The Ganz clamp was found to be an effective tool in the emergency treatment of pelvic ring lesions because it has an uncomplicated conception, allowing for a fast placement, because it does not prevent nor make it difficult for abdominal procedures, and most of all because it allows for the

  9. Evaluation of Introduction of a Delayed Cord Clamping Protocol for Premature Neonates in a High-Volume Maternity Center.

    Science.gov (United States)

    Liu, Lilly Y; Feinglass, Joe M; Khan, Janine Y; Gerber, Susan E; Grobman, William A; Yee, Lynn M

    2017-05-01

    To evaluate adherence to a delayed cord clamping protocol for preterm births in the first 2 years after its introduction, perform a quality improvement assessment, and determine neonatal outcomes associated with protocol implementation and adherence. This is a retrospective cohort study of women delivering singleton neonates at 23-32 weeks of gestation in the 2 years before (preprotocol) and 2 years after (postprotocol) introduction of a 30-second delayed cord clamping protocol at a large-volume academic center. This policy was communicated to obstetric and pediatric health care providers and nurses and reinforced with intermittent educational reviews. Barriers to receiving delayed cord clamping were assessed using χ tests and multivariable logistic regression. Neonatal outcomes then were compared between all neonates in the preprotocol period and all neonates in the postprotocol period and between all neonates in the preprotocol period and neonates receiving delayed cord clamping in the postprotocol period using multivariable linear and logistic regression analyses. Of the 427 eligible neonates, 187 were born postprotocol. Of these, 53.5% (n=100) neonates received delayed cord clamping according to the protocol. The rate of delayed cord clamping preprotocol was 0%. Protocol uptake and frequency of delayed cord clamping increased over the 2 years after its introduction. In the postprotocol period, cesarean delivery was the only factor independently associated with failing to receive delayed cord clamping (adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.25-0.96). In comparison with the preprotocol period, those who received delayed cord clamping in the postprotocol period had significantly higher birth hematocrit (β=2.46, P=.007) and fewer blood transfusions in the first week of life (adjusted OR 0.49, 95% CI 0.25-0.96). After introduction of an institutional delayed cord clamping protocol followed by continued health care provider education and

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

    Science.gov (United States)

    Crago, Patrick E; Makowski, Nathaniel S

    2014-10-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Higher order modes excitation of electrostatically actuated clamped–clamped microbeams: experimental and analytical investigation

    KAUST Repository

    Jaber, Nizar; Ramini, Abdallah; Carreno, Armando Arpys Arevalo; Younis, Mohammad I.

    2016-01-01

    © 2016 IOP Publishing Ltd. In this study, we demonstrate analytically and experimentally the excitations of the higher order modes of vibrations in electrostatically actuated clamped-clamped microbeam resonators. The concept is based on using

  13. 21 CFR 882.5175 - Carotid artery clamp.

    Science.gov (United States)

    2010-04-01

    ... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting mechanism that protrudes through the skin of the patient's neck. The clamp is used to occlude the patient's... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...

  14. Analysis and testing of the DIII-D ohmic heating coil lead repair clamp

    International Nuclear Information System (INIS)

    Reis, E.E.; Anderson, P.M.; Chin, E.; Robinson, J.I.

    1997-11-01

    DIII-D has been operating for the last year with limited volt-second capabilities due to structural failure of a conductor lead to one of the ohmic heating (OH) solenoids. The conductor failure was due to poor epoxy impregnation of the overwrap of the lead pack, resulting in copper fatigue and a water leak. A number of structural analyses were performed to assist in determining the failure scenario and to evaluate various repair options. A fatigue stress analysis of the leads with a failed epoxy overwrap indicated crack initiation after 1,000 cycles at the maximum operating conditions. The failure occurred in a very inaccessible area which restricted design repair options to concepts which could be implemented remotely. Several design options were considered for repairing the lead so that it can sustain the loads for 7.5 Vs conditions at full toroidal field. A clamp, along with preloaded banding straps and shim bags, provides a system that guarantees that the stress at the crack location is always compressive and prevents further crack growth in the conductor. Due to the limited space available for the repair, it was necessary to design the clamp system to operate at the material yield stress. The primary components of the clamp system were verified by load tests prior to installation. The main body of the clamp contains a load cell and potentiometer for monitoring the load-deflection characteristics of the clamp and conductors during plasma operation. Strain gages provides redundant instrumentation. If required, the preload on the conductors can be increased remotely by a special wrench attached to the clamp assembly

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

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf

    2013-04-01

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

  16. Ventilation before Umbilical Cord Clamping improves the physiological transition at birth.

    Directory of Open Access Journals (Sweden)

    Sasmira eBhatt

    2014-10-01

    Full Text Available The transition from a fetus to a neonate at birth represents a critical phase in our life. Most infants make this transition without complications, but preterm infants usually require some form of assistance due to immature cardiopulmonary systems that predispose them to lifelong sequelae. As the incidence of preterm birth is increasing, there is now an urgent need for the development of management strategies that facilitate this transition, which will likely include improved strategies for the management of the maternal third stage of labour. For instance, recent studies on the physiological transition at birth have led to the discovery that establishing ventilation in the infant before the umbilical cord is clamped greatly stabilizes the cardiovascular transition at birth. While most benefits of delayed clamping have previously been attributed to an increase in placenta to infant blood transfusion, clearly there are other significant benefits for the infant, which are not well understood. Nevertheless, if ventilation can be established before cord clamping in a preterm infant, the large adverse changes in cardiac function that normally accompanies umbilical cord clamping can be avoided. As preterm infants have an immature cerebral vascular bed, large swings in cardiovascular function places them at high risk of cerebral vascular rupture and the associated increased risk of mortality and morbidity. In view of the impact that cord clamping has on the cardiovascular transition at birth, it is also time to re-examine some of the strategies used in the management of the third stage of labour. These include the appropriate timing of uterotonic administration in relation to delivery of the infant and placenta. As there is a lack of evidence on the effects these individual practices have on the infant, there is a necessity to improve our understanding of their impact in order to develop strategies that facilitate the transition to newborn life.

  17. CLAMP - a toolkit for efficiently building customized clinical natural language processing pipelines.

    Science.gov (United States)

    Soysal, Ergin; Wang, Jingqi; Jiang, Min; Wu, Yonghui; Pakhomov, Serguei; Liu, Hongfang; Xu, Hua

    2017-11-24

    Existing general clinical natural language processing (NLP) systems such as MetaMap and Clinical Text Analysis and Knowledge Extraction System have been successfully applied to information extraction from clinical text. However, end users often have to customize existing systems for their individual tasks, which can require substantial NLP skills. Here we present CLAMP (Clinical Language Annotation, Modeling, and Processing), a newly developed clinical NLP toolkit that provides not only state-of-the-art NLP components, but also a user-friendly graphic user interface that can help users quickly build customized NLP pipelines for their individual applications. Our evaluation shows that the CLAMP default pipeline achieved good performance on named entity recognition and concept encoding. We also demonstrate the efficiency of the CLAMP graphic user interface in building customized, high-performance NLP pipelines with 2 use cases, extracting smoking status and lab test values. CLAMP is publicly available for research use, and we believe it is a unique asset for the clinical NLP community. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Effect of complete hilar versus only renal artery clamping on renal histomorphology following ischemia/reperfusion injury in an experimental model.

    Science.gov (United States)

    Umul, M; Cal, A C; Turna, B; Oktem, G; Aydın, H H

    2016-01-01

    To evaluate the effect of temporary complete hilar versus only renal artery clamping with different duration of warm ischemia on renal functions, and possibly identify a "safe" clamping type and duration of renal ischemia. Fifty male rabbits have been incorporated to study. Rabbits were subjected to ischemia/reperfusion injury by temporary vascular clamping. Reagents were randomized to 3 experimental groups (only renal artery clamping, complete hilar clamping, sham surgery) and sub-groups were determined according to different clamping times (30 and 60 minutes). Median laparotomy and left renal hilus dissection were performed to sham group. Only artery or complete hilar clamping was performed for 30 or 60 minutes by microvascular bulldog clamps to other reagents. Rabbits were sacrificed 10 days after primary surgery and left nephrectomy performed. Nephrectomy materials were evaluated for the level of nitric-oxide synthase (NOS) immunoreactivity, malondialdehyde (MDA) level and superoxide dismutase (SOD) activity and an electron microscopic examination was performed. NOS immunoreactivity was correlated with the temporary clamping time. We also observed that complete hilar vascular clamping entails an increase on NOS immunoreactivity. MDA levels were similar for all experimental surgery groups (p = 0.42). The SOD activity was decreased among all subgroups compared with sham surgery. But the significant decrease occurred in 30 minutes only artery and 30 minutes complete hilar clamping groups in proportion to sham surgery (p = 0.026 and p = 0.019, respectively). This current study suggested that only renal artery clamping under 30 minutes is more appropriate during renal surgical procedures requiring temporary vascular clamping.

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

    Science.gov (United States)

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

    2009-07-30

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

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

    Science.gov (United States)

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

    2015-11-01

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

  1. Three Level Diode Clamped Inverter Fed Induction Motor with Dtc-Svm

    OpenAIRE

    V. Ranjith Kumar

    2013-01-01

    This project presents a three-level diode-clamped inverter feeding an asynchronous motor drive with direct torque control (DTC). The control method is based on DTC operating principles. The stator voltage vector reference is computed from the stator flux and torque errors imposed by the flux and torque controllers. This voltage reference is then generated using a diode-clamped inverter, where each phase of the inverter can be implemented using a dc source, which would be available from fuel c...

  2. Suppression of Spiral Waves by Voltage Clamp Techniques in a Conductance-Based Cardiac Tissue Model

    International Nuclear Information System (INIS)

    Lian-Chun, Yu; Guo-Yong, Zhang; Yong, Chen; Jun, Ma

    2008-01-01

    A new control method is proposed to control the spatio-temporal dynamics in excitable media, which is described by the Morris–Lecar cells model. It is confirmed that successful suppression of spiral waves can be obtained by spatially clamping the membrane voltage of the excitable cells. The low voltage clamping induces breakup of spiral waves and the fragments are soon absorbed by low voltage obstacles, whereas the high voltage clamping generates travel waves that annihilate spiral waves through collision with them. However, each method has its shortcomings. Furthermore, a two-step method that combines both low and high voltage clamp techniques is then presented as a possible way of out this predicament. (cross-disciplinary physics and related areas of science and technology)

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

  5. Decoupling Action Potential Bias from Cortical Local Field Potentials

    Directory of Open Access Journals (Sweden)

    Stephen V. David

    2010-01-01

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

  6. Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yuguo Yu

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

  8. Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome.

    Science.gov (United States)

    Tyzio, Roman; Khalilov, Ilgam; Represa, Alfonso; Crepel, Valerie; Zilberter, Yuri; Rheims, Sylvain; Aniksztejn, Laurent; Cossart, Rosa; Nardou, Romain; Mukhtarov, Marat; Minlebaev, Marat; Epsztein, Jérôme; Milh, Mathieu; Becq, Helene; Jorquera, Isabel; Bulteau, Christine; Fohlen, Martine; Oliver, Viviana; Dulac, Olivier; Dorfmüller, Georg; Delalande, Olivier; Ben-Ari, Yehezkel; Khazipov, Roustem

    2009-08-01

    The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies. Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery. Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attached recordings of N-methyl-D-aspartate channels. Many cells spontaneously fired action potentials at a rate proportional to the level of neuronal depolarization. The reversal potential for GABA-activated currents, assessed by cell-attached single channel recordings, was close to the resting membrane potential. All spontaneously firing neurons recorded in cell-attached mode or imaged with biphoton microscopy were inhibited by GABA. Spontaneous epileptiform activity in the form of recurrent population bursts was suppressed by glutamate receptor antagonists, the GABA(A) receptor agonist isoguvacine, and the positive allosteric GABA(A) modulator diazepam. Blockade of GABA(A) receptors aggravated spontaneous epileptiform activity. The NKCC1 antagonist bumetanide had little effect on epileptiform activity. SWS cortical neurons have a relatively depolarized resting membrane potential and spontaneously fire action potentials that may contribute to increased network excitability. In contrast to previous data depicting excitatory and proconvulsive actions of GABA in certain pediatric and adult epilepsies, GABA plays mainly an inhibitory and anticonvulsive role in SWS pediatric cortex.

  9. Substrate clamping effects on irreversible domain wall dynamics in lead zirconate titanate thin films.

    Science.gov (United States)

    Griggio, F; Jesse, S; Kumar, A; Ovchinnikov, O; Kim, H; Jackson, T N; Damjanovic, D; Kalinin, S V; Trolier-McKinstry, S

    2012-04-13

    The role of long-range strain interactions on domain wall dynamics is explored through macroscopic and local measurements of nonlinear behavior in mechanically clamped and released polycrystalline lead zirconate-titanate (PZT) films. Released films show a dramatic change in the global dielectric nonlinearity and its frequency dependence as a function of mechanical clamping. Furthermore, we observe a transition from strong clustering of the nonlinear response for the clamped case to almost uniform nonlinearity for the released film. This behavior is ascribed to increased mobility of domain walls. These results suggest the dominant role of collective strain interactions mediated by the local and global mechanical boundary conditions on the domain wall dynamics. The work presented in this Letter demonstrates that measurements on clamped films may considerably underestimate the piezoelectric coefficients and coupling constants of released structures used in microelectromechanical systems, energy harvesting systems, and microrobots.

  10. Γ-source Neutral Point Clamped Inverter

    DEFF Research Database (Denmark)

    Mo, Wei; Loh, Poh Chiang; Blaabjerg, Frede

    Transformer based Z-source inverters are recently proposed to achieve promising buck-boost capability. They have improved higher buck-boost capability, smaller size and less components count over Z-source inverters. On the other hand, neutral point clamped inverters have less switching stress...... and better output performance comparing with traditional two-level inverters. Integrating these two types of configurations can help neutral point inverters achieve enhanced votlage buck-boost capability....

  11. Constant-frequency, clamped-mode resonant converters

    Science.gov (United States)

    Tsai, Fu-Sheng; Materu, Peter; Lee, Fred C.

    1987-01-01

    Two novel clamped-mode resonant converters are proposed which operate at a constant frequency while retaining many desired features of conventional series- and parallel-resonant converters. State-plane analysis techniques are used to identify all possible operating modes and define their mode boundaries. Control-to-output characteristics are derived that specify the regions for natural and forced commutation. The predicted operating modes are verified using a prototype circuit.

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

    Science.gov (United States)

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

    2012-01-01

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

  13. The optimal protocol to reduce blood loss and blood transfusion after unilateral total knee replacement: Low-dose IA-TXA plus 30-min drain clamping versus drainage clamping for the first 3 h without IA-TXA.

    Science.gov (United States)

    Park, Joo Hyun; Choi, Sung Wook; Shin, Eun Ho; Park, Myung Hoon; Kim, Myung Ku

    2017-01-01

    Although intraarticular tranexamic acid (IA-TXA) administration or drainage clamping are popular methods used to reduce blood loss after total knee replacement (TKR), the protocol remains controversial. We aimed (1) to establish new protocols through investigating whether two methods, that is, low-dose (500 mg) IA-TXA plus 30-min drain clamping and drainage clamping for the first 3 h without IA-TXA, can reduce blood loss and blood transfusion after unilateral TKR and (2) to make recommendations related to clinical application. This study, conducted from September 2014 to June 2016 related to enrolled 95 patients with primary osteoarthritis who were to have a unilateral cemented TKR, was nonrandomized and retrospective. In group A, the drain was released following tourniquet deflation. In group B, 500-mg TXA was injected into the knee joint via a drain tube after fascia closure and the drain was clamped for the first 30 min to prevent leakage. In group C, the drain was clamped for the first 3-h postoperation. Demographic characteristics and clinical data were collected, including the levels of hematocrit (Hct), the total blood loss (TBL), drained blood volume (BV), the amount of blood transfused, and any complications that developed. We found a significantly lower postoperative TBL, drained BV, decreasing Hct level, and less transfused BV in the IA-TXA injection group (group B) and the 3-h drainage clamping group (group C) compared to the conventional negative drainage group (group A; p optimal than drainage clamping in patients with high bleeding tendency or lateral retinacular release during TKR, who would be concerned about postoperative wound complication.

  14. [The Impact of Late Umbilical Cord Clamping on Neonatal Jaundice and Postpartum Hemorrhage: A Randomized Controlled Trail].

    Science.gov (United States)

    Chien, Pei-Chun; Yang, Cherng-Chia; Gau, Meei-Ling; Liu, Chieh-Yu; Lee, Tzu-Ying

    2015-08-01

    The current evidence supports the clinical benefits of late umbilical cord clamping. These benefits include increased blood volume and total body iron. Furthermore, delayed cord clamping facilitates the transplantation of stem cells, which helps the development of infant bodily systems. However, due to concerns related to postpartum hemorrhaging and neonate jaundice, most maternity units still clamp the cord immediately after a child is born. This study investigates the impact of delaying cord clamping on neonatal jaundice and postpartum hemorrhage. A randomized, controlled trial was conducted at a regional teaching hospital in northern Taiwan. One hundred and five healthy nulliparous women at 36 weeks of pregnancy were included and allocated randomly to the experiment group (n=44) and the control group (n=61). Participants in the experiment group received delayed cord clamping (DCC) at 3 minutes after delivery. Participants in the control group received early cord clamping (ECC) at around 1 minute after delivery. Clinical measures of the outcomes were measured by the infant transcutaneous bilirubin levels (TcB) and postpartum hemorrhage at birth. A structured questionnaire and biophysical measures were used to collect data on participant demographics, obstetrical information, maternal blood loss at birth, neonate weight and TcB level at hospitalization, and whether or not the infant received phototherapy at 4-7 days postpartum. Overall, there was no significant difference between the two groups in terms of neonatal jaundice, maternal hemorrhage at birth, and phototherapy rates at time of hospitalization and at 4-7 days postpartum. The findings of the present study support that late umbilical cord clamping does not increase the risk of maternal postpartum hemorrhaging or neonate jaundice. Thus, we suggest that clinicians inform clients during prenatal classes of the benefits of delayed cord clamping and also use current, evidence-based knowledge to dispel client

  15. Robotic Automation of In Vivo Two-Photon Targeted Whole-Cell Patch-Clamp Electrophysiology.

    Science.gov (United States)

    Annecchino, Luca A; Morris, Alexander R; Copeland, Caroline S; Agabi, Oshiorenoya E; Chadderton, Paul; Schultz, Simon R

    2017-08-30

    Whole-cell patch-clamp electrophysiological recording is a powerful technique for studying cellular function. While in vivo patch-clamp recording has recently benefited from automation, it is normally performed "blind," meaning that throughput for sampling some genetically or morphologically defined cell types is unacceptably low. One solution to this problem is to use two-photon microscopy to target fluorescently labeled neurons. Combining this with robotic automation is difficult, however, as micropipette penetration induces tissue deformation, moving target cells from their initial location. Here we describe a platform for automated two-photon targeted patch-clamp recording, which solves this problem by making use of a closed loop visual servo algorithm. Our system keeps the target cell in focus while iteratively adjusting the pipette approach trajectory to compensate for tissue motion. We demonstrate platform validation with patch-clamp recordings from a variety of cells in the mouse neocortex and cerebellum. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Equivalent circuit of frog atrial tissue as determined by voltage clamp-unclamp experiments.

    Science.gov (United States)

    Tarr, M; Trank, J

    1971-11-01

    The equivalent circuit that has been used in the analysis of nerve voltage-clamp data is that of the membrane capacity in parallel with the membrane resistance. Voltage-clamp experiments on frog atrial tissue indicate that this circuit will not suffice for this cardiac tissue. The change in membrane current associated with a step change in membrane potential does not show a rapid spike of capacitive current as would be expected for the simple parallel resistance-capacitance network. Rather, there is a step change in current followed by an exponential decay in current with a time constant of about 1 msec. This relatively slow capacitive charging current suggests that there is a resistance in series with the membrane capacity. A possible equivalent circuit is that of a series resistance external to the parallel resistance-capacitance network of the cell membranes. Another possible circuit assumes that the series resistance is an integral part of the cell membrane. The data presented in this paper demonstrate that the equivalent circuit of a bundle of frog atrial muscle is that of an external resistance in series with the cell membranes.

  17. From understanding cellular function to novel drug discovery: the role of planar patch-clamp array chip technology

    Directory of Open Access Journals (Sweden)

    Christophe ePy

    2011-10-01

    Full Text Available All excitable cell functions rely upon ion channels that are embedded in their plasma membrane. Perturbations of ion channel structure or function result in pathologies ranging from cardiac dysfunction to neurodegenerative disorders. Consequently, to understand the functions of excitable cells and to remedy their pathophysiology, it is important to understand the ion channel functions under various experimental conditions – including exposure to novel drug targets. Glass pipette patch-clamp is the state of the art technique to monitor the intrinsic and synaptic properties of neurons. However, this technique is labor-intensive and has low data throughput. Planar patch-clamp chips, integrated into automated systems, offer high throughputs but are limited to isolated cells from suspensions, resulting in questionable models of true physiological function, and are unsuitable for studies involving neuronal communication. Multi-electrode arrays (MEA, in contrast, have the ability to monitor network activity by measuring local field potentials from multiple extracellular sites, but specific ion channel activity is challenging to extract from these multiplexed signals. Here we describe a novel planar patch-clamp chip technology that enables the simultaneous high resolution electrophysiological interrogation of individual neurons at multiple sites in synaptically connected neuronal networks, thereby combining the advantages of MEA and patch-clamp techniques. Each neuron can be probed through an aperture that connects to a dedicated subterranean microfluidic channel. Neurons growing in networks are aligned to the apertures by physisorbed or chemisorbed chemical cues. In this review, we describe the design and fabrication process of these chips, the approach to the chemical patterning for cell placement, and present physiological data from cultured neuronal cells.

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

    Science.gov (United States)

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

    2018-01-01

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

  19. Design and experimental research of a novel inchworm type piezo-driven rotary actuator with the changeable clamping radius.

    Science.gov (United States)

    Zhao, Hongwei; Fu, Lu; Ren, Luquan; Huang, Hu; Fan, Zunqiang; Li, Jianping; Qu, Han

    2013-01-01

    In this paper, a novel piezo-driven rotary actuator with the changeable clamping radius is developed based on the inchworm principle. This actuator mainly utilizes three piezoelectric actuators, a flexible gripper, a clamping block, and a rotor to achieve large stroke rotation with high resolution. The design process of the flexible gripper consisting of the driving unit and the clamping unit is described. Lever-type mechanisms were used to amplify the micro clamping displacements. The amplifying factor and parasitic displacement of the lever-type mechanism in the clamping unit was analyzed theoretically and experimentally. In order to investigate the rotation characteristics of the actuator, a series of experiments was carried out. Experimental results indicate that the actuator can rotate at a speed of 77,488 μrad/s with a driving frequency of 167 Hz. The rotation resolution and maximum load torque of the actuator are 0.25 μrad and 37 N mm, respectively. The gripper is movable along the z direction based on an elevating platform, and the clamping radius can change from 10.6 mm to 25 mm. Experimental results confirm that the actuator can achieve different rotation speeds by changing the clamping radius.

  20. Experimental determination of optimal clamping torque for AB-PEM Fuel cell

    Directory of Open Access Journals (Sweden)

    Noor Ul Hassan

    2016-04-01

    Full Text Available Polymer electrolyte Membrane (PEM fuel cell is an electrochemical device producing electricity by the reaction of hydrogen and oxygen without combustion. PEM fuel cell stack is provided with an appropriate clamping torque to prevent leakage of reactant gases and to minimize the contact resistance between gas diffusion media (GDL and bipolar plates. GDL porous structure and gas permeability is directly affected by the compaction pressure which, consequently, drastically change the fuel cell performance. Various efforts were made to determine the optimal compaction pressure and pressure distributions through simulations and experimentation. Lower compaction pressure results in increase of contact resistance and also chances of leakage. On the other hand, higher compaction pressure decreases the contact resistance but also narrows down the diffusion path for mass transfer from gas channels to the catalyst layers, consequently, lowering cell performance. The optimal cell performance is related to the gasket thickness and compression pressure on GDL. Every stack has a unique assembly pressure due to differences in fuel cell components material and stack design. Therefore, there is still need to determine the optimal torque value for getting the optimal cell performance. This study has been carried out in continuation of deve­lopment of Air breathing PEM fuel cell for small Unmanned Aerial Vehicle (UAV application. Compaction pressure at minimum contact resistance was determined and clamping torque value was calcu­la­ted accordingly. Single cell performance tests were performed at five different clamping torque values i.e 0.5, 1.0, 1.5, 2.0 and 2.5 N m, for achieving optimal cell per­formance. Clamping pressure distribution tests were also performed at these torque values to verify uniform pressure distribution at optimal torque value. Experimental and theoretical results were compared for making inferences about optimal cell perfor­man­ce. A

  1. Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and proinflammatory responses in the kidney.

    Science.gov (United States)

    Mariappan, Meenalakshmi M; DeSilva, Kristin; Sorice, Gian Pio; Muscogiuri, Giovanna; Jimenez, Fabio; Ahuja, Seema; Barnes, Jefferey L; Choudhury, Goutam Ghosh; Musi, Nicolas; DeFronzo, Ralph; Kasinath, Balakuntalam S

    2014-02-01

    Increase in matrix protein content in the kidney is a cardinal feature of diabetic kidney disease. While renal matrix protein content is increased by chronic hyperglycemia, whether it is regulated by acute elevation of glucose and insulin has not been addressed. In this study, we aimed to evaluate whether short duration of combined hyperglycemia and hyperinsulinemia, mimicking the metabolic environment of prediabetes and early type 2 diabetes, induces kidney injury. Normal rats were subjected to either saline infusion (control, n = 4) or 7 h of combined hyperglycemic-hyperinsulinemic clamp (HG+HI clamp; n = 6). During the clamp, plasma glucose and plasma insulin were maintained at about 350 mg/dl and 16 ng/ml, respectively. HG+HI clamp increased the expression of renal cortical transforming growth factor-β (TGF-β) and renal matrix proteins, laminin and fibronectin. This was associated with the activation of SMAD3, Akt, mammalian target of rapamycin (mTOR) complexes, and ERK signaling pathways and their downstream target events in the initiation and elongation phases of mRNA translation, an important step in protein synthesis. Additionally, HG+HI clamp provoked renal inflammation as shown by the activation of Toll-like receptor 4 (TLR4) and infiltration of CD68-positive monocytes. Urinary F2t isoprostane excretion, an index of renal oxidant stress, was increased in the HG+HI clamp rats. We conclude that even a short duration of hyperglycemia and hyperinsulinemia contributes to activation of pathways that regulate matrix protein synthesis, inflammation, and oxidative stress in the kidney. This finding could have implications for the control of short-term rises in blood glucose in diabetic individuals at risk of developing kidney disease.

  2. Protein associations in DnaA-ATP hydrolysis mediated by the Hda-replicase clamp complex.

    Science.gov (United States)

    Su'etsugu, Masayuki; Shimuta, Toh-Ru; Ishida, Takuma; Kawakami, Hironori; Katayama, Tsutomu

    2005-02-25

    In Escherichia coli, the activity of ATP-bound DnaA protein in initiating chromosomal replication is negatively controlled in a replication-coordinated manner. The RIDA (regulatory inactivation of DnaA) system promotes DnaA-ATP hydrolysis to produce the inactivated form DnaA-ADP in a manner depending on the Hda protein and the DNA-loaded form of the beta-sliding clamp, a subunit of the replicase holoenzyme. A highly functional form of Hda was purified and shown to form a homodimer in solution, and two Hda dimers were found to associate with a single clamp molecule. Purified mutant Hda proteins were used in a staged in vitro RIDA system followed by a pull-down assay to show that Hda-clamp binding is a prerequisite for DnaA-ATP hydrolysis and that binding is mediated by an Hda N-terminal motif. Arg(168) in the AAA(+) Box VII motif of Hda plays a role in stable homodimer formation and in DnaA-ATP hydrolysis, but not in clamp binding. Furthermore, the DnaA N-terminal domain is required for the functional interaction of DnaA with the Hda-clamp complex. Single cells contain approximately 50 Hda dimers, consistent with the results of in vitro experiments. These findings and the features of AAA(+) proteins, including DnaA, suggest the following model. DnaA-ATP is hydrolyzed at a binding interface between the AAA(+) domains of DnaA and Hda; the DnaA N-terminal domain supports this interaction; and the interaction of DnaA-ATP with the Hda-clamp complex occurs in a catalytic mode.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. MEMS-based clamp with a passive hold function for precision position retaining of micro manipulators

    International Nuclear Information System (INIS)

    Brouwer, D M; Van Dijk, J; Soemers, H M J R; De Jong, B R; De Boer, M J; Jansen, H V; Krijnen, G J M

    2009-01-01

    In this paper the design, modeling and fabrication of a precision MEMS-based clamp with a relatively large clamping force are presented. The purpose of the clamp is to mechanically fix a six-degree-of-freedom (DOF) MEMS-based sample manipulator (Brouwer et al J. Int. Soc. Precis. Eng. Nanotechnol. submitted) once the sample has been positioned in all DOFs. The clamping force is generated by a rotational electrostatic comb-drive actuator and can be latched passively by a parallel plate type electrostatically driven locking device. The clamp design is based on the principles of exact constraint design, resulting in a high actuation compliance (flexibility) combined with a high suspension stiffness. Therefore, a relatively large blocking force of 1.4 mN in relation to the used area of 1.8 mm 2 is obtained. The fabrication is based on silicon bulk micromachining technology and combines a high-aspect-ratio deep reactive ion etching (DRIE), conformal deposition of low-pressure chemical vapor deposition (LPCVD) silicon nitride and an anisotropic potassium hydroxide (KOH) backside etching technology. Special attention is given to void reduction of Si x N y trench isolation and reduction of heating phenomena during front-side release etching. Guidelines are given for the applied process. Measurements showed that the clamp was able to fix, hold and release a test actuator. The dynamic behavior was in good agreement with the modal analysis

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

    Science.gov (United States)

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

    2018-03-28

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

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

    Science.gov (United States)

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

    2015-11-25

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

  7. Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping

    Directory of Open Access Journals (Sweden)

    Christopher Lawton

    2015-01-01

    Full Text Available There is currently no consensus among clinicians and scientists over the appropriate or optimal timing for umbilical cord clamping. However, many clinical studies have suggested that delayed cord clamping is associated with various neonatal benefits including increased blood volume, reduced need for blood transfusion, increased cerebral oxygenation in pre-term infants, and decreased frequency of iron deficiency anemia in term infants. Human umbilical cord blood contains significant amounts of stem and progenitor cells and is currently used in the treatment of several life-threatening diseases. We propose that delayed cord clamping be encouraged as it enhances blood flow from the placenta to the neonate, which is accompanied by an increase supply of valuable stem and progenitor cells, as well as may improve blood oxygenation and increase blood volume, altogether reducing the infant′s susceptibility to both neonatal and age-related diseases.

  8. The evaluation on clamping force of high strength bolts by length parameter

    International Nuclear Information System (INIS)

    Kim, Kang-Seok; Nah, Hwan-Seon; Lee, Hyeon-Ju; Lee, Kang-Min

    2009-01-01

    It has been reported that the length parameter of high strength bolts results in the variance in tension loads. The required turn for each length is specified in AISC RCSC specification. This study was focused on evaluating any influence on the clamping torque subjected to length parameter of high strength bolts. The two kinds of high strength bolts of specimen are as follows; High Strength Hexagon bolt defined on ASTM A490 and Torque Shear Bolt on KS B 2819. The length parameter ranged from 60mm(3d) to 140mm(7d). The torque, turn of nut and the clamping force were analyzed to review whether length parameter can be affected on the required tension load. To test whether the length parameter has an impact on the torque and turn of nut for the required strength and clamping force, statistical analysis is carried out. (author)

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

    Directory of Open Access Journals (Sweden)

    Mary Jane Beilby

    2017-04-01

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

  10. Thermodynamic basis for engineering high-affinity, high-specificity binding-induced DNA clamp nanoswitches.

    Science.gov (United States)

    Idili, Andrea; Plaxco, Kevin W; Vallée-Bélisle, Alexis; Ricci, Francesco

    2013-12-23

    Naturally occurring chemoreceptors almost invariably employ structure-switching mechanisms, an observation that has inspired the use of biomolecular switches in a wide range of artificial technologies in the areas of diagnostics, imaging, and synthetic biology. In one mechanism for generating such behavior, clamp-based switching, binding occurs via the clamplike embrace of two recognition elements onto a single target molecule. In addition to coupling recognition with a large conformational change, this mechanism offers a second advantage: it improves both affinity and specificity simultaneously. To explore the physics of such switches we have dissected here the thermodynamics of a clamp-switch that recognizes a target DNA sequence through both Watson-Crick base pairing and triplex-forming Hoogsteen interactions. When compared to the equivalent linear DNA probe (which relies solely on Watson-Crick interactions), the extra Hoogsteen interactions in the DNA clamp-switch increase the probe's affinity for its target by ∼0.29 ± 0.02 kcal/mol/base. The Hoogsteen interactions of the clamp-switch likewise provide an additional specificity check that increases the discrimination efficiency toward a single-base mismatch by 1.2 ± 0.2 kcal/mol. This, in turn, leads to a 10-fold improvement in the width of the "specificity window" of this probe relative to that of the equivalent linear probe. Given these attributes, clamp-switches should be of utility not only for sensing applications but also, in the specific field of DNA nanotechnology, for applications calling for a better control over the building of nanostructures and nanomachines.

  11. Andrographolide inhibits arrhythmias and is cardioprotective in rabbits

    OpenAIRE

    Zeng, Mengliu; Jiang, Wanzhen; Tian, Youjia; Hao, Jie; Cao, Zhenzhen; Liu, Zhipei; Fu, Chen; Zhang, Peihua; Ma, Jihua

    2017-01-01

    Andrographolide has a protective effect on the cardiovascular system. To study its cardic-electrophysiological effects, action potentials and voltage-gated Na+ (INa), Ca2+ (ICaL), and K+ (IK1, IKr, Ito and IKur) currents were recorded using whole-cell patch clamp and current clamp techniques. Additionally, the effects of andrographolide on aconitine-induced arrhythmias were assessed on electrocardiograms in vivo. We found that andrographolide shortened action potential duration and reduced ma...

  12. Reversible fastener clamp load monitor with continuous visual or remote readout

    Science.gov (United States)

    Hodge, Malcolm H.; Kausel, Theodore C., Jr.; Begley, Matthew R.

    1998-03-01

    SIMS has developed a simple means for detecting and monitoring both absolute and relative clamp load, or bolt tension, in fastener systems. More than twenty-five percent of automotive failures are known to be due to undetected loss of fastener clamp load. While the equivalent aerospace maintenance statistics are not known, the average automobile has 3,500 fasteners while a Boeing 747 has closer to one million. It is therefore anticipated that the new SensaBolt clamp load tracking system could find wide applications in the aerospace arena. We describe a visually-evident and retrofitted clamp load monitoring design which is based on the differential joint substrate compression at, and immediately adjacent to, the fastener location. This intrinsically-accurate indicator does not necessarily require alteration in either the bolt or nut geometries, thereby facilitating product introduction and retrofit in aging aircraft applications. In addition, SensaBolt's sole reliance on substrate compression renders it more accurate then torque wrench or turn-of-nut techniques. Readout may be accomplished by any of three principal methods: for those applications with ease of access to the sensor, loss of tension can be determined by direct visual inspection. Application of a standard wrench can then be made to restore the fastener's proper tightness, per the SensaBolt indicators. In those instances where line-of-sight is unimpeded and more formal inspection is desired, the SensaBolt may be interrogated by a laser scanner bar code reader. Finally, SensaBolt may be addressed by the SIMS fiber optic harness for those instances where full-time remote interrogation is desired.

  13. A simple technique to measure regional cerebral blood flow during intravascular ballon clamping

    International Nuclear Information System (INIS)

    Furuhata, Shigeru; Kubo, Atsushi; Kawase, Takeshi; Ibata, Yukio; Toya, Shigeo

    1988-01-01

    A case of giant internal carotid ophthalmic aneurysm was presented. In order to clarify whether the patient could tolerate carotid occlusion, a ballon clamping test was performed before surgery. The cerebral blood flow was measured using early imaging by single photon emission computed tomography (SPECT) with N-isopropyl-(iodine-123)-p-iodoamphetamine ( 123 I-IMP). When the ballon clamping test was performed the tracer was injected, and scanning was performed 35 minutes after removing the catheter. This tracer enabled a 'memory of blood flow' during temporary ischemia to determine the character of quick diffusion and slow wash out, that could not be performed by other methods of cerebral blood flow measurement. SPECT with 123 I-IMP can simplify the measurement of cerebral blood flow during the balloon clamping test. (author)

  14. Interactions Between SNAP-25 and Synaptotagmin-1 Are Involved in Vesicle Priming, Clamping Spontaneous and Stimulating Evoked Neurotransmission

    DEFF Research Database (Denmark)

    Schupp, Melanie; Malsam, Jörg; Ruiter, Marvin

    2016-01-01

    between region I (vesicle priming) and region II (evoked release). Spontaneous release was disinhibited by region I mutations and found to correlate with defective complexin (Cpx) clamping in an in vitro fusion assay, pointing to an interdependent role of synaptotagmin and Cpx in release clamping...... triggering, depend on direct SNARE complex interaction. SIGNIFICANCE STATEMENT: The function of synaptotagmin-1 (syt-1):soluble NSF attachment protein receptor (SNARE) interactions during neurotransmission remains unclear. We mutated SNAP-25 within the recently identified region I and region II...... was disinhibited by region I mutation and found to correlate with defective complexin (Cpx) clamping in vitro, pointing to an interdependent role of synaptotagmin and Cpx in release clamping. Therefore, vesicle priming, clamping spontaneous release, and eliciting evoked release are three different functions of syt...

  15. Antinociceptive action of oxytocin involves inhibition of potassium channel currents in lamina II neurons of the rat spinal cord

    Directory of Open Access Journals (Sweden)

    Darbon Pascal

    2009-11-01

    Full Text Available Abstract Background Growing evidence in the literature shows that oxytocin (OT has a strong spinal anti-nociceptive action. Oxytocinergic axons originating from a subpopulation of paraventricular hypothalamic neurons establish synaptic contacts with lamina II interneurons but little is known about the functional role of OT with respect to neuronal firing and excitability. Results Using the patch-clamp technique, we have recorded lamina II interneurons in acute transverse lumbar spinal cord slices of rats (15 to 30 days old and analyzed the OT effects on action potential firing ability. In the current clamp mode, we found that bath application of a selective OT-receptor agonist (TGOT reduced firing in the majority of lamina II interneurons exhibiting a bursting firing profile, but never in those exhibiting a single spike discharge upon depolarization. Interestingly, OT-induced reduction in spike frequency and increase of firing threshold were often observed, leading to a conversion of the firing profile from repetitive and delayed profiles into phasic ones and sometimes further into single spike profile. The observed effects following OT-receptor activation were completely abolished when the OT-receptor agonist was co-applied with a selective OT-receptor antagonist. In current and voltage clamp modes, we show that these changes in firing are strongly controlled by voltage-gated potassium currents. More precisely, transient IA currents and delayed-rectifier currents were reduced in amplitude and transient IA current was predominantly inactivated after OT bath application. Conclusion This effect of OT on the firing profile of lamina II neurons is in good agreement with the antinociceptive and analgesic properties of OT described in vivo.

  16. Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

    Science.gov (United States)

    Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.

    2015-01-01

    Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

  17. Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

    Science.gov (United States)

    Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-05-01

    Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.

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

    Science.gov (United States)

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

    2015-01-01

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

  19. 7 CFR 1945.19 - Reporting potential natural disasters and initial actions.

    Science.gov (United States)

    2010-01-01

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

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

    Science.gov (United States)

    Rodriguez-Falces, Javier

    2015-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  2. Estimating the Cost of Early Infant Male Circumcision in Zimbabwe: Results From a Randomized Noninferiority Trial of AccuCirc Device Versus Mogen Clamp

    Science.gov (United States)

    Mavhu, Webster; Hatzold, Karin; Biddle, Andrea K.; Madidi, Ngonidzashe; Ncube, Getrude; Mugurungi, Owen; Ticklay, Ismail; Cowan, Frances M.; Thirumurthy, Harsha

    2015-01-01

    Background: Safe and cost-effective programs for implementing early infant male circumcision (EIMC) in Africa need to be piloted. We present results on a relative cost analysis within a randomized noninferiority trial of EIMC comparing the AccuCirc device with Mogen clamp in Zimbabwe. Methods: Between January and June 2013, male infants who met inclusion criteria were randomized to EIMC through either AccuCirc or Mogen clamp conducted by a doctor, using a 2:1 allocation ratio. We evaluated the overall unit cost plus the key cost drivers of EIMC using both AccuCirc and Mogen clamp. Direct costs included consumable and nonconsumable supplies, device, personnel, associated staff training, and environmental costs. Indirect costs comprised capital and support personnel costs. In 1-way sensitivity analyses, we assessed potential changes in unit costs due to variations in main parameters, one at a time, holding all other values constant. Results: The unit costs of EIMC using AccuCirc and Mogen clamp were $49.53 and $55.93, respectively. Key cost drivers were consumable supplies, capacity utilization, personnel costs, and device price. Unit prices are likely to be lowest at full capacity utilization and increase as capacity utilization decreases. Unit prices also fall with lower personnel salaries and increase with higher device prices. Conclusions: EIMC has a lower unit cost when using AccuCirc compared with Mogen clamp. To minimize unit costs, countries planning to scale-up EIMC using AccuCirc need to control costs of consumables and personnel. There is also need to negotiate a reasonable device price and maximize capacity utilization. PMID:26017658

  3. Estimating the Cost of Early Infant Male Circumcision in Zimbabwe: Results From a Randomized Noninferiority Trial of AccuCirc Device Versus Mogen Clamp.

    Science.gov (United States)

    Mangenah, Collin; Mavhu, Webster; Hatzold, Karin; Biddle, Andrea K; Madidi, Ngonidzashe; Ncube, Getrude; Mugurungi, Owen; Ticklay, Ismail; Cowan, Frances M; Thirumurthy, Harsha

    2015-08-15

    Safe and cost-effective programs for implementing early infant male circumcision (EIMC) in Africa need to be piloted. We present results on a relative cost analysis within a randomized noninferiority trial of EIMC comparing the AccuCirc device with Mogen clamp in Zimbabwe. Between January and June 2013, male infants who met inclusion criteria were randomized to EIMC through either AccuCirc or Mogen clamp conducted by a doctor, using a 2:1 allocation ratio. We evaluated the overall unit cost plus the key cost drivers of EIMC using both AccuCirc and Mogen clamp. Direct costs included consumable and nonconsumable supplies, device, personnel, associated staff training, and environmental costs. Indirect costs comprised capital and support personnel costs. In 1-way sensitivity analyses, we assessed potential changes in unit costs due to variations in main parameters, one at a time, holding all other values constant. The unit costs of EIMC using AccuCirc and Mogen clamp were $49.53 and $55.93, respectively. Key cost drivers were consumable supplies, capacity utilization, personnel costs, and device price. Unit prices are likely to be lowest at full capacity utilization and increase as capacity utilization decreases. Unit prices also fall with lower personnel salaries and increase with higher device prices. EIMC has a lower unit cost when using AccuCirc compared with Mogen clamp. To minimize unit costs, countries planning to scale-up EIMC using AccuCirc need to control costs of consumables and personnel. There is also need to negotiate a reasonable device price and maximize capacity utilization.

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

    Science.gov (United States)

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

    1986-11-01

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

  5. Clamped seismic metamaterials: ultra-low frequency stop bands

    International Nuclear Information System (INIS)

    Achaoui, Y; Enoch, S; Guenneau, S; Antonakakis, T; Brûlé, S; Craster, R V

    2017-01-01

    The regularity of earthquakes, their destructive power, and the nuisance of ground vibration in urban environments, all motivate designs of defence structures to lessen the impact of seismic and ground vibration waves on buildings. Low frequency waves, in the range 1–10 Hz for earthquakes and up to a few tens of Hz for vibrations generated by human activities, cause a large amount of damage, or inconvenience; depending on the geological conditions they can travel considerable distances and may match the resonant fundamental frequency of buildings. The ultimate aim of any seismic metamaterial, or any other seismic shield, is to protect over this entire range of frequencies; the long wavelengths involved, and low frequency, have meant this has been unachievable to date. Notably this is scalable and the effects also hold for smaller devices in ultrasonics. There are three approaches to obtaining shielding effects: bragg scattering, locally resonant sub-wavelength inclusions and zero-frequency stop-band media. The former two have been explored, but the latter has not and is examined here. Elastic flexural waves, applicable in the mechanical vibrations of thin elastic plates, can be designed to have a broad zero-frequency stop-band using a periodic array of very small clamped circles. Inspired by this experimental and theoretical observation, all be it in a situation far removed from seismic waves, we demonstrate that it is possible to achieve elastic surface (Rayleigh) wave reflectors at very large wavelengths in structured soils modelled as a fully elastic layer periodically clamped to bedrock. We identify zero frequency stop-bands that only exist in the limit of columns of concrete clamped at their base to the bedrock. In a realistic configuration of a sedimentary basin 15 m deep we observe a zero frequency stop-band covering a broad frequency range of 0–30 Hz. (paper)

  6. A self-strain feedback tuning-fork-shaped ionic polymer metal composite clamping actuator with soft matter elasticity-detecting capability for biomedical applications.

    Science.gov (United States)

    Feng, Guo-Hua; Huang, Wei-Lun

    2014-12-01

    This paper presents a smart tuning-fork-shaped ionic polymer metal composite (IPMC) clamping actuator for biomedical applications. The two fingers of the actuator, which perform the clamping motion, can be electrically controlled through a unique electrode design on the IPMC material. The generated displacement or strain of the fingers can be sensed using an integrated soft strain-gage sensor. The IPMC actuator and associated soft strain gage were fabricated using a micromachining technique. A 13.5×4×2 mm(3) actuator was shaped from Nafion solution and a selectively grown metal electrode formed the active region. The strain gage consisted of patterned copper foil and polyethylene as a substrate. The relationship between the strain gage voltage output and the displacement at the front end of the actuator's fingers was characterized. The equivalent Young's modulus, 13.65 MPa, of the soft-strain-gage-integrated IPMC finger was analyzed. The produced clamping force exhibited a linear increasing rate of 1.07 mN/s, based on a dc driving voltage of 7 V. Using the developed actuator to clamp soft matter and simultaneously acquire its Young's modulus was achieved. This demonstrated the feasibility of the palpation function and the potential use of the actuator in minimally invasive surgery. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2015-03-10

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

  9. Small Molecules for Early Endosome-Specific Patch Clamping.

    Science.gov (United States)

    Chen, Cheng-Chang; Butz, Elisabeth S; Chao, Yu-Kai; Grishchuk, Yulia; Becker, Lars; Heller, Stefan; Slaugenhaupt, Susan A; Biel, Martin; Wahl-Schott, Christian; Grimm, Christian

    2017-07-20

    To resolve the subcellular distribution of endolysosomal ion channels, we have established a novel experimental approach to selectively patch clamp Rab5 positive early endosomes (EE) versus Rab7/LAMP1-positive late endosomes/lysosomes (LE/LY). To functionally characterize ion channels in endolysosomal membranes with the patch-clamp technique, it is important to develop techniques to selectively enlarge the respective organelles. We found here that two small molecules, wortmannin and latrunculin B, enlarge Rab5-positive EE when combined but not Rab7-, LAMP1-, or Rab11 (RE)-positive vesicles. The two compounds act rapidly, specifically, and are readily applicable in contrast to genetic approaches or previously used compounds such as vacuolin, which enlarges EE, RE, and LE/LY. We apply this approach here to measure currents mediated by TRPML channels, in particular TRPML3, which we found to be functionally active in both EE and LE/LY in overexpressing cells as well as in endogenously expressing CD11b+ lung-tissue macrophages. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Meeks, Julian P; Mennerick, Steven

    2004-01-07

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

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

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

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

  12. Long-Time Choledochal Clamping in Wistar Rats Causes Biliary Obstruction Progressing to Hepatic Fibrosis.

    Science.gov (United States)

    Jorge, G D L; Tártaro, R R; Escanhoela, C A F; Boin, I D F S F

    2016-09-01

    Biliary complications are important causes of morbidity and mortality in patients undergoing hepatic surgery. The aim of the study was to evaluate late liver alterations after a long period of choledochal clamping in Wistar rats. Ten male Wistar rats, weighing 304 grams, anesthetized with sodium thiopental (25 mg/kg) and xylazine (10 mg/kg) intravenously, were distributed into 2 groups: the choledochal clamping group (CCG) and the operation sham group (OSG), with 5 animals each submitted to an abdominal incision. In the CCG, the choledochal was isolated, dissected, and clamped with a microvascular clamp for 40 minutes. After this occlusion time, the clamp was removed and the incision was closed. In the OSG the animals, under normal conditions, were submitted only to anesthesia and laparotomy for choledochal manipulation. In all animals, after the 31st day, a hepatic biopsy was carried out for histology and blood biochemical tests: total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase. The animals were euthanized under anesthesia. This research was approved by the Ethics Committee on Animal Use (CEUA, Unicamp, No. 2511-1). In the CCG, 100% of the animals showed bile duct dilatation, ductular proliferation, and portal inflammatory infiltrate; 60% showed regenerative nodule formation; and 80% had porta-porta septa and foci of necrosis, all of which were not found in the OSG. All CCG group biochemical tests had significant increases (P Wistar rats caused hepatic dysfunction and biochemical and histological injuries with degrees of distortion to the hepatic architecture. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. [Time of cord clamping and neonatal complications, a prospective study].

    Science.gov (United States)

    Rincón, D; Foguet, A; Rojas, M; Segarra, E; Sacristán, E; Teixidor, R; Ortega, A

    2014-09-01

    To assess the effects of early or late clamping of the umbilical cord in term newborns, assessing the levels of hemoglobin, hematocrit, and ferritin, and their correlation with some of the complications. A prospective study of healthy newborns at term or born by dystotic or eutocic delivery in our hospital between May 2009 until May 2010. Patients were assigned according to the time of clamping, group 1 (<60 seconds), group 2 (1 to<2 minutes), and group 3 (2 to 3 minutes). Laboratory tests were performed at birth and at 48 hours of life, assessing the levels of hemoglobin, hematocrit, ferritin, and bilirubin. The risk of polycythemia, respiratory distress syndrome, neonatal phototherapy or admission to the Intensive Care Unit and the hospital stay, were evaluated. A total of 242 patients were included: group 1 (g1=80), group 2 (g2=31) y group 3 (g3=131). The background maternal and neonatal characteristics were similar in all sets. The first test showed significant differences in ferritin levels in those infants with delayed clamping (g1: 111 mg/dl, g2: 125 mg/dl, g3: 173 mg/dl; p<0.01). In the second analysis the values of hemoglobin (g1: 17.3 g/dl, g2: 18.9 g/dl, g3: 19.2 g/dl; p<0.01), hematocrit (g1: 53.4%, g2: 58%, g3: 59%; p<0.01) and ferritin (g1: 254 mg/dl, g2: 254.7 mg/dl, g3: 313 mg/dl; p = 0.008) were statistically higher in this group. As regards complications, a significant increase was observed in the number of cases of polycythemia symptoms in group 3. The late cord clamping is associated with an increase in hematocrit, hemoglobin and ferritin at 48 hours of life, as well as an increased risk of polycythemia present with symptoms. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Changes in the action potential and transient outward potassium current in cardiomyocytes during acute cardiac rejection in rats.

    Science.gov (United States)

    Luo, Wenqi; Jia, Yixin; Zheng, Shuai; Li, Yan; Han, Jie; Meng, Xu

    2017-01-01

    Acute cardiac rejection contributes to the changes in the electrophysiological properties of grafted hearts. However, the electrophysiological changes of cardiomyocytes during acute cardiac rejection are still unknown. An understanding of the electrophysiological mechanisms of cardiomyocytes could improve the diagnosis and treatment of acute cardiac rejection. So it is important to characterize the changes in the action potential ( AP ) and the transient outward potassium current ( I to ) in cardiomyocytes during acute cardiac rejection. Heterotopic heart transplantation was performed in allogeneic [Brown Norway (BN)-to-Lewis] and isogeneic (BN-to-BN) rats. Twenty models were established in each group. Ten recipients were sacrificed at the 2nd day and the other ten recipients were sacrificed at the 4 th day after the operation in each group. Histopathological examinations of the grafted hearts were performed in half of the recipients in each group randomly. The other half of the grafted hearts were excised rapidly and enzymatically dissociated to obtain single cardiomyocytes. The AP and I to current were recorded using the whole cell patch-clamp technique. Forty grafted hearts were successfully harvested and used in experiments. Histologic examination showed mild rejection at the 2 nd day and moderate rejection at the 4 th day in the allogeneic group after cardiac transplantation, while no evidence of histologic lesions of rejection were observed in the isogeneic group. Compared with the isogeneic group, the action potential duration ( APD ) of cardiomyocytes in the allogeneic group was significantly prolonged ( APD 90 was 49.28±5.621 mV in the isogeneic group and 88.08±6.445 mV in the allogeneic group at the 2 nd day, P=0.0016; APD 90 was 59.34±5.183 mV in the isogeneic group and 104.0±9.523 mV in the allogeneic group at the 4 th day, P=0.0064). The current density of I to was significantly decreased at the 4 th day after cardiac transplantation. The APD of

  15. The free vibration of free-clamped fluid-coupled coaxial cylindrical shells

    International Nuclear Information System (INIS)

    Tani, Junji; Haiji, Hirohisa

    1986-01-01

    The linear free vibration of free-clamped coaxial cylinders partially filled with incompressible, inviscid liquid in the annular gap is investigated theoretically on the basis of the Donnell-type equations for cylinders and the velocity potential theory for liquid motion. The problem is solved by the modified Galerkin method. The initial axisymmetric deformation of the shell due to the static liquid pressure as well as the boundary condition on the free liquid surface are fully taken into consideration. It is found that the static liquid pressure and the liquid surface condition have a significant effect on the natural frequency, and that the interactive effect of the coaxial cylinders becomes small and the mode shape changes with an increase in the wave number and the annular gap. (author)

  16. Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps

    International Nuclear Information System (INIS)

    Finegood, D.T.; Bergman, R.N.; Vranic, M.

    1988-01-01

    We previously demonstrated that conventional tracer methods applied to euglycemic-hyperinsulinemic glucose clamps result in substantially negative estimates for the rate of endogenous glucose production, particularly during the first half of 180-min clamps. We also showed that addition of tracer to the exogenous glucose infusate resulted in nonnegative endogenous glucose production (Ra) estimates. In this study, we investigated the underlying cause of negative estimates of Ra from conventional clamp/tracer methods and the reason for the difference in estimates when tracer is added to the exogenous glucose infusate. We performed euglycemic-hyperinsulinemic (300-microU/ml) clamps in normal dogs without (cold GINF protocol, n = 6) or with (hot GINF protocol, n = 6) tracer (D-[3-3H]glucose) added to the exogenous glucose infusate. In the hot GINF protocol, sufficient tracer was added to the exogenous glucose infusate such that arterial plasma specific activity (SAa) did not change from basal through the clamp period (P greater than .05). In the cold GINF studies, plasma SAa fell 81 +/- 2% from the basal level by the 3rd h of clamping. We observed a significant, transient, positive venous-arterial difference in specific activity (SAv-SAa difference) during the cold GINF studies. The SAv-SAa difference reached a peak of 27 +/- 6% at 30 min and diminished to a plateau of 7 +/- 1% between 70 and 180 min. We also observed a positive but constant SAv-SAa difference (4.6 +/- 0.2% between 10 and 180 min) during the hot GINF studies

  17. Inertial piezoelectric linear motor driven by a single-phase harmonic wave with automatic clamping mechanism

    Science.gov (United States)

    He, Liangguo; Chu, Yuheng; Hao, Sai; Zhao, Xiaoyong; Dong, Yuge; Wang, Yong

    2018-05-01

    A novel, single-phase, harmonic-driven, inertial piezoelectric linear motor using an automatic clamping mechanism was designed, fabricated, and tested to reduce the sliding friction and simplify the drive mechanism and power supply control of the inertial motor. A piezoelectric bimorph and a flexible hinge were connected in series to form the automatic clamping mechanism. The automatic clamping mechanism was used as the driving and clamping elements. A dynamic simulation by Simulink was performed to prove the feasibility of the motor. The finite element method software COMSOL was used to design the structure of the motor. An experimental setup was built to validate the working principle and evaluate the performance of the motor. The prototype motor outputted a no-load velocity of 3.178 mm/s at a voltage of 220 Vp-p and a maximum traction force of 4.25 N under a preload force of 8 N. The minimum resolution of 1.14 μm was achieved at a driving frequency of 74 Hz, a driving voltage of 50 Vp-p, and a preload force of 0 N.

  18. Safety of minimally invasive mitral valve surgery without aortic cross-clamp.

    Science.gov (United States)

    Umakanthan, Ramanan; Leacche, Marzia; Petracek, Michael R; Kumar, Sathappan; Solenkova, Nataliya V; Kaiser, Clayton A; Greelish, James P; Balaguer, Jorge M; Ahmad, Rashid M; Ball, Stephen K; Hoff, Steven J; Absi, Tarek S; Kim, Betty S; Byrne, John G

    2008-05-01

    We developed a technique for open heart surgery through a small (5 cm) right-anterolateral thoracotomy without aortic cross-clamp. One hundred and ninety-five consecutive patients (103 male and 92 female), age 69 +/- 8 years, underwent surgery between January 2006 and July 2007. Mean preoperative New York Heart Association function class was 2.2 +/- 0.7. Thirty-five patients (18%) had an ejection fraction 0.35 or less. Cardiopulmonary bypass was instituted through femoral (176 of 195, 90%), axillary (18 of 195, 9%), or direct aortic (1 of 195, 0.5%) cannulation. Under cold fibrillatory arrest (mean temperature 28.2 degrees C) without aortic cross-clamp, mitral valve repair (72 of 195, 37%), mitral valve replacement (117 of 195, 60%), or other (6 of 195, 3%) procedures were performed. Concomitant procedures included maze (45 of 195, 23%), patent foramen ovale closure (42 of 195, 22%) and tricuspid valve repair (16 of 195, 8%), or replacement (4 of 195, 2%). Thirty-day mortality was 3% (6 of 195). Duration of fibrillatory arrest, cardiopulmonary bypass, and "skin to skin" surgery were 88 +/- 32, 118 +/- 52, and 280 +/- 78 minutes, respectively. Ten patients (5%) underwent reexploration for bleeding and 44% did not receive any blood transfusions. Six patients (3%) sustained a postoperative stroke, eight (4%) developed low cardiac output syndrome, and two (1%) developed renal failure requiring hemodialysis. Mean length of hospital stay was 7 +/- 4.8 days. This simplified technique of minimally invasive open heart surgery is safe and easily reproducible. Fibrillatory arrest without aortic cross-clamping, with coronary perfusion against an intact aortic valve, does not increase the risk of stroke or low cardiac output. It may be particularly useful in higher risk patients in whom sternotomy with aortic clamping is less desirable.

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

    Science.gov (United States)

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

    2017-06-01

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

  20. Integral transform solution of bending problem of clamped orthotropic rectangular plates

    International Nuclear Information System (INIS)

    An, C.; Gu, J.-J.; Su, J.

    2011-01-01

    The generalized integral transform technique (GITT) is employed to obtain an exact solution for the bending problem of fully clamped orthotropic rectangular plates. The use of the GITT approach in the analysis of the transverse deflection equation leads to a coupled system of fourth order differential equations in the dimensionless longitudinal spatial variable. The resulting transformed ODE system is then numerically solved by making use of the subroutine DBVPFD from IMSL Library. Numerical results with automatic global accuracy control are produced for different values of aspect ratio. Critical comparisons with previously reported numerical results are performed with excellent agreement. Several sets of reference results for clamped orthotropic rectangular plates are also provided for future covalidation purposes. (author)

  1. Gigaseal formation in patch clamping with applications of nanotechnology

    CERN Document Server

    Malboubi, Majid

    2014-01-01

    This book presents an investigation of gigaseal formation using micro/nanotechnology. The aims of the book are twofold. First, it explains the mechanisms of gigaseal formation using the latest discoveries. Second, it provides practical techniques for frequent formation of high resistance seals. The formation of a high-resistance electrical seal, also known as a gigaseal, between a cell membrane and a glass micropipette tip is essential in patch-clamp experiments. Even though four decades have passed since the introduction of the patch-clamping technique by Neher and Sakmann, gigaseal formation remains an obstacle in developing the high-throughput ion channel screening systems required by the pharmaceutical industry. Here the authors share their latest methods for achieving gigaseal formation and describe techniques that are highly desirable at both research and industrial levels. Nanotechnology has been found to be a powerful tool for studying and modifying glass micropipettes and in tackling the problem of g...

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

  4. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men

    DEFF Research Database (Denmark)

    Pilgaard, K; Jensen, C; Schou, J

    2009-01-01

    h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic...... and peripheral insulin action. RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p ...-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p

  5. Flange joint system for SRF cavities utilizing high force spring clamps for low particle generation

    Science.gov (United States)

    None

    2017-09-05

    A flange joint system for SRF cavities. The flange joint system includes a set of high force spring clamps that produce high force on the simple flanges of Superconducting Radio Frequency (SRF) cavities to squeeze conventional metallic seals. The system establishes the required vacuum and RF-tight seal with minimum particle contamination to the inside of the cavity assembly. The spring clamps are designed to stay within their elastic range while being forced open enough to mount over the flange pair. Upon release, the clamps have enough force to plastically deform metallic seal surfaces and continue to a new equilibrium sprung dimension where the flanges remain held against one another with enough preload such that normal handling will not break the seal.

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

    Directory of Open Access Journals (Sweden)

    Gabija Jarašiūnaitė

    2015-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-03-10

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

  8. Direct Effect of Remifentanil and Glycine Contained in Ultiva® on Nociceptive Transmission in the Spinal Cord: In Vivo and Slice Patch Clamp Analyses.

    Directory of Open Access Journals (Sweden)

    Makoto Sumie

    Full Text Available Ultiva® is commonly administered intravenously for analgesia during general anaesthesia and its main constituent remifentanil is an ultra-short-acting μ-opioid receptor agonist. Ultiva® is not approved for epidural or intrathecal use in clinical practice. Previous studies have reported that Ultiva® provokes opioid-induced hyperalgesia by interacting with spinal dorsal horn neurons. Ultiva® contains glycine, an inhibitory neurotransmitter but also an N-methyl-D-aspartate receptor co-activator. The presence of glycine in the formulation of Ultiva® potentially complicates its effects. We examined how Ultiva® directly affects nociceptive transmission in the spinal cord.We made patch-clamp recordings from substantia gelatinosa (SG neurons in the adult rat spinal dorsal horn in vivo and in spinal cord slices. We perfused Ultiva® onto the SG neurons and analysed its effects on the membrane potentials and synaptic responses activated by noxious mechanical stimuli.Bath application of Ultiva® hyperpolarized membrane potentials under current-clamp conditions and produced an outward current under voltage-clamp conditions. A barrage of excitatory postsynaptic currents (EPSCs evoked by the stimuli was suppressed by Ultiva®. Miniature EPSCs (mEPSCs were depressed in frequency but not amplitude. Ultiva®-induced outward currents and suppression of mEPSCs were not inhibited by the μ-opioid receptor antagonist naloxone, but were inhibited by the glycine receptor antagonist strychnine. The Ultiva®-induced currents demonstrated a specific equilibrium potential similar to glycine.We found that intrathecal administration of Ultiva® to SG neurons hyperpolarized membrane potentials and depressed presynaptic glutamate release predominantly through the activation of glycine receptors. No Ultiva®-induced excitatory effects were observed in SG neurons. Our results suggest different analgesic mechanisms of Ultiva® between intrathecal and intravenous

  9. NIMBY, CLAMP, and the location of new nuclear-related facilities: U.S. national and 11 site-specific surveys.

    Science.gov (United States)

    Greenberg, Michael R

    2009-09-01

    Public and political opposition have made finding locations for new nuclear power plants, waste management, and nuclear research and development facilities a challenge for the U.S. government and the nuclear industry. U.S. government-owned properties that already have nuclear-related activities and commercial nuclear power generating stations are logical locations. Several studies and utility applications to the Nuclear Regulatory Commission suggest that concentrating locations at major plants (CLAMP) has become an implicit siting policy. We surveyed 2,101 people who lived within 50 miles of 11 existing major nuclear sites and 600 who lived elsewhere in the United States. Thirty-four percent favored CLAMP for new nuclear power plants, 52% for waste management facilities, and 50% for new nuclear laboratories. College educated, relatively affluent male whites were the strongest CLAMP supporters. They disproportionately trusted those responsible for the facilities and were not worried about existing nuclear facilities or other local environmental issues. Notably, they were concerned about continuing coal use. Not surprisingly, CLAMP proponents tended to be familiar with their existing local nuclear site. In short, likely CLAMP sites have a large and politically powerful core group to support a CLAMP policy. The challenge to proponents of nuclear technologies will be to sustain this support and expand the base among those who clearly are less connected and receptive to new nearby sites.

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  11. Comparison between symmetrical and asymmetrical single phase multilevel inverter with diode-clamped topology

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Nami, A.; Zare, F.

    2008-01-01

    In this paper, a different configuration based on different DC bus voltage for a diode-clamped multilevel inverter has been presented. Two different symmetrical and asymmetrical arrangements of a four-level diode clamped inverters have been compared, in order to find an optimum arrangement...... compared with the conventional four-level inverter and this will lead to the reduction of harmonic content of output voltage. A predictive current control technique has been carried out to verify the viability of new configuration. The advantages of this control method are simplicity and applicability...

  12. Effects of mixing technologies on continuous methyl ester production: Comparison of using plug flow, static mixer, and ultrasound clamp

    International Nuclear Information System (INIS)

    Somnuk, Krit; Prasit, Tanongsak; Prateepchaikul, Gumpon

    2017-01-01

    Highlights: • Four types of continuous reactors were compared with methyl ester conversion. • Plug flow, static mixer, ultrasound clamp, SM with ultrasound reactors were tested. • The 16 × 400 W ultrasound clamps were operated at 20 kHz frequency for US reactor. • The US reactor was clearly superior over the other types of continuous reactor. • The US reactor was the most effective alternative with short reactor length. - Abstract: Four types of continuous reactors, namely plug flow reactor (PF), static mixer reactor (SM), ultrasound clamp on tubular reactor (US), and static mixer combined with ultrasound (SM/US) were compared for their purities of methyl ester in biodiesel production from refined palm oil (RPO). The reactor conditions were: KOH 4, 6, 8, 10, and 12 g L −1 , methanol content 20 vol.%, and under 20 L h −1 RPO flow rate at 60 °C temperature. The highest purity of methyl esters: 81.99 wt.% for PF, 95.70 wt.% for SM, 98.98 wt.% for US, and 97.67 wt.% for SM/US, were achieved with 900 mm, 900 mm, 700 mm, and 900 mm reactor lengths respectively, and 12 g L −1 of KOH was used in all cases. The 16 × 400 W ultrasound clamp was operated at 20 kHz frequency, and among short length reactors the US case was more effective than PF, SM, or SM/US. Moreover, ester purity from the US reactor was slightly decreased by the lowest 4 g L −1 KOH. The US reactor was clearly superior over the other types of continuous reactor, and had the potential to reduce KOH consumption by sonochemical effects on the base-catalyzed transesterification reaction.

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

    Science.gov (United States)

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

    2017-01-01

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

  14. Applicability of fiber model in seismic response analysis for center-clamp type bushings on transformers

    International Nuclear Information System (INIS)

    Miyagawa, Yoshinori; Sato, Hiroaki

    2015-01-01

    A bushing is a device for insulation and support of a conductor. Especially it is called center-clamp type when it is connected with a metal holder through clamping force. As a consequence of damage of center-clamp type bushings in Tohoku Earthquake in 2011, refinement of the response analysis method and review of the seismic design procedure became necessary. In the present report, the fiber model, which can evaluate non-linear behavior in the section subjected to axial force and bending moment, was implemented to the CRIEPI's finite element analysis program 'Mastrd' considering following characteristics of center-clamp type bushings. a) The gasket section between a porcelain tube and a metal holder has a torus shape. b) Springs around the top of the bushing give clamping force, but they lock in excessive base rotation. c) The gasket does not resist against tension. d) Local resistance against compression due to bending increases in use of very thin gaskets. The developed program was verified through comparison with the shaking table test result for real bushings whose voltage classes were 154 kV and 275 kV. Deformation indices as rotation angle and base opening due to bending were influenced by damping conditions. Though there was not the condition which brought about remarkable underestimation, reduction of damping for a fiber model element was preferable for safety. On the other hand, bending moment was consistent with experimental results because it tended not to fluctuate in the non-linear region. (author)

  15. Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure

    DEFF Research Database (Denmark)

    Petrie, John R; Malik, Muhammad Omar; Balkau, Beverley

    2013-01-01

    and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex...

  16. Estimates for lower order eigenvalues of a clamped plate problem

    OpenAIRE

    Cheng, Qing-Ming; Huang, Guangyue; Wei, Guoxin

    2009-01-01

    For a bounded domain $\\Omega$ in a complete Riemannian manifold $M^n$, we study estimates for lower order eigenvalues of a clamped plate problem. We obtain universal inequalities for lower order eigenvalues. We would like to remark that our results are sharp.

  17. Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

    Directory of Open Access Journals (Sweden)

    Guan-Ling Lu

    2009-09-01

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

  18. Two unique ligand-binding clamps of Rhizopus oryzae starch binding domain for helical structure disruption of amylose.

    Directory of Open Access Journals (Sweden)

    Ting-Ying Jiang

    Full Text Available The N-terminal starch binding domain of Rhizopus oryzae glucoamylase (RoSBD has a high binding affinity for raw starch. RoSBD has two ligand-binding sites, each containing a ligand-binding clamp: a polyN clamp residing near binding site I is unique in that it is expressed in only three members of carbohydrate binding module family 21 (CBM21 members, and a Y32/F58 clamp located at binding site II is conserved in several CBMs. Here we characterized different roles of these sites in the binding of insoluble and soluble starches using an amylose-iodine complex assay, atomic force microscopy, isothermal titration calorimetry, site-directed mutagenesis, and structural bioinformatics. RoSBD induced the release of iodine from the amylose helical cavity and disrupted the helical structure of amylose type III, thereby significantly diminishing the thickness and length of the amylose type III fibrils. A point mutation in the critical ligand-binding residues of sites I and II, however, reduced both the binding affinity and amylose helix disruption. This is the first molecular model for structure disruption of the amylose helix by a non-hydrolytic CBM21 member. RoSBD apparently twists the helical amylose strands apart to expose more ligand surface for further SBD binding. Repeating the process triggers the relaxation and unwinding of amylose helices to generate thinner and shorter amylose fibrils, which are more susceptible to hydrolysis by glucoamylase. This model aids in understanding the natural roles of CBMs in protein-glycan interactions and contributes to potential molecular engineering of CBMs.

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

    Science.gov (United States)

    Saung, Wint Thu; Foskett, J. Kevin

    2017-01-01

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

  20. 33 CFR 183.532 - Clips, straps, and hose clamps.

    Science.gov (United States)

    2010-07-01

    ... resistant material; and (2) Not cut or abrade the fuel line. (b) If tested in accordance with the fire test under § 183.590, a hose clamp installed on a fuel line system requiring metallic fuel lines or “USCG... (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Equipment Standards § 183.532 Clips...

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

    Directory of Open Access Journals (Sweden)

    Philip Gemmell

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

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

    Science.gov (United States)

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

    2014-01-01

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

  3. Role of clamping tube thoracostomy prior to removal in non-cardiac thoracic trauma

    International Nuclear Information System (INIS)

    Rasheed, M.A.; Majeed, F.A.; Naz, A.

    2016-01-01

    The frequently encountered thoracic trauma in surgical emergencies is a major cause of mortality and morbidity. Eighty percent of thoracic trauma can be managed by simple insertion of tube thoracostomy. Though guidelines for insertion are comprehensively explained in literature, an ideal algorithm for discontinuation is not available. A standard and safe defined protocol would eliminate hesitancy in confident removal among general surgeons. The objective of this study was to determine role of clamping trial prior to removal in terms of frequency of recurrent pneumothorax. Methods: This study was conducted in department of Surgery Combined military hospital/Military Hospital Rawalpindi from April 2013 to March 2014. Total 180 patients with blunt or penetrating thoracic trauma were included in the study. Chest tube (28-36 Fr) was inserted in Trauma centre under strict asepsis. Tubes were then connected to under water seal for minimum six hours. Patients were randomly divided in two equal groups (90 in each). In Group A, Clamping trial was given before attempting removal while in Group B, tube was removed immediately without clamping trial. Patients of both groups were observed two hourly for development of recurrent pneumothorax. Data was analysed using SPSS-18. Results: The comparison of frequency of recurrent pneumothorax in Group A (9 patients, 10%) and in Group B (4 patients, 4.5%) was not found to be statistically significant. (p-value 2.073). Conclusion: Clamping trial is unnecessary prior to removal of tube thoracostomy in blunt and penetrating non-cardiac thoracic trauma in terms of recurrent pneumothorax. (author)

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  6. Mycobacterium tuberculosis class II apurinic/apyrimidinic-endonuclease/3'-5' exonuclease III exhibits DNA regulated modes of interaction with the sliding DNA β-clamp.

    Science.gov (United States)

    Khanam, Taran; Rai, Niyati; Ramachandran, Ravishankar

    2015-10-01

    The class-II AP-endonuclease (XthA) acts on abasic sites of damaged DNA in bacterial base excision repair. We identified that the sliding DNA β-clamp forms in vivo and in vitro complexes with XthA in Mycobacterium tuberculosis. A novel 239 QLRFPKK245 motif in the DNA-binding domain of XthA was found to be important for the interactions. Likewise, the peptide binding-groove (PBG) and the C-terminal of β-clamp located on different domains interact with XthA. The β-clamp-XthA complex can be disrupted by clamp binding peptides and also by a specific bacterial clamp inhibitor that binds at the PBG. We also identified that β-clamp stimulates the activities of XthA primarily by increasing its affinity for the substrate and its processivity. Additionally, loading of the β-clamp onto DNA is required for activity stimulation. A reduction in XthA activity stimulation was observed in the presence of β-clamp binding peptides supporting that direct interactions between the proteins are necessary to cause stimulation. Finally, we found that in the absence of DNA, the PBG located on the second domain of the β-clamp is important for interactions with XthA, while the C-terminal domain predominantly mediates functional interactions in the substrate's presence. © 2015 John Wiley & Sons Ltd.

  7. The Effect of PRGF on Healing of Clamp-Induced Tendinopathy in Animals

    Directory of Open Access Journals (Sweden)

    Uğur Diliçıkık

    2018-04-01

    Material and Methods: A preliminary study was designed to obtain more apparent tendinopathy changes in the subculture. Histopathologically, second level compression with a clamp for 1 minute followed by releasing for 3 minutes applying the same mechanical stimulus procedure for four times, was defined as the optimal compression mode for the most optimal damage in terms of tendinopathy. Thirty-four female Sprague Downey type rats were divided into five separate groups and clamped tendon damage was formed on unilateral (left Acchilles tendons. The first group was a control group (Kontrol: CN; in the second group tissue specimens were taken from the rats immediately after being clamped (K-0; from the group 3, tissue samples were taken 1 week after clamping (K-7. Immediately after the tendinopathy model was applied to the animals in the fourth group (PRGF, the PRGF injection was performed to the subjects from the blood that was obtained from the control group, while an isotonic saline solution was injected into the subjects in the fifth group (SF, and tissue samples from both groups were obtained 1 week after. Results: The samples were examined by means of a transmission electron microscope. In the K-0 group among the collagenous fibers, vacuoles are observed in the cytoplasm of the edematous areas and fibrocytes, and in comparison, with K-7 and SF group there was a significant increase in fibroblast and collagen fiber synthesis in the PRGF-treated group. Furthermore, fibroblast and new collagen synthesis were observed to be increased in K-7 and SF groups. An intense increase in organelle levels was observed in PRGF group fibroblasts. Conclusion: This data suggests that PRGF may provide a better healing response in tendons with limited healing and circulation, which enhances the activation in the cells at the beginning of the healing process.

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

    Science.gov (United States)

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

    1986-01-01

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

  9. Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: a patch clamp analysis in gene-targeted mice.

    Science.gov (United States)

    Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M; Ma, Minghong

    2006-02-07

    A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendritic knobs of mouse OSNs that express the odorant receptor MOR23 along with the green fluorescent protein. All of the 53 cells examined responded to lyral, a known ligand for MOR23. There were profound differences in response kinetics, particularly in the deactivation phase. The cells were very sensitive to lyral, with some cells responding to as little as 10 nM. The dynamic range was unexpectedly broad, with threshold and saturation in individual cells often covering three log units of lyral concentration. The potential causes and biological significance of this cellular heterogeneity are discussed. Patch clamp recording from OSNs that express a defined OR provides a powerful approach to investigate the sensory inputs to individual glomeruli.

  10. Outside-out "sniffer-patch" clamp technique for in situ measures of neurotransmitter release.

    Science.gov (United States)

    Muller-Chrétien, Emilie

    2014-01-01

    The mechanism underlying neurotransmitter release is a critical research domain for the understanding of neuronal network function; however, few techniques are available for the direct detection and measurement of neurotransmitter release. To date, the sniffer-patch clamp technique is mainly used to investigate these mechanisms from individual cultured cells. In this study, we propose to adapt the sniffer-patch clamp technique to in situ detection of neurosecretion. Using outside-out patches from donor cells as specific biosensors plunged in acute cerebral slices, this technique allows for proper detection and quantification of neurotransmitter release at the level of the neuronal network.

  11. Scanning electron microscope/energy dispersive x ray analysis of impact residues on LDEF tray clamps

    Science.gov (United States)

    Bernhard, Ronald P.; Durin, Christian; Zolensky, Michael E.

    1992-01-01

    To better understand the nature of particulates in low-Earth orbit (LEO), and their effects on spacecraft hardware, we are analyzing residues found in impacts on the Long Duration Exposure Facility (LDEF) tray clamps. LDEF experiment trays were held in place by 6 to 8 chromic-anodized aluminum (6061-T6) clamps that were fastened to the spacecraft frame using three stainless steel hex bolts. Each clamp exposed an area of approximately 58 sq cm (4.8 cm x 12.7 cm x .45 cm, minus the bolt coverage). Some 337 out of 774 LDEF tray clamps were archived at JSC and are available through the Meteoroid & Debris Special Investigation Group (M&D SIG). Optical scanning of clamps, starting with Bay/Row A01 and working toward H25, is being conducted at JSC to locate and document impacts as small as 40 microns. These impacts are then inspected by Scanning Electron Microscopy/Energy Dispersive X-ray Analysis (SEM/EDXA) to select those features which contain appreciable impact residue material. Based upon the composition of projectile remnants, and using criteria developed at JSC, we have made a preliminary discrimination between micrometeoroid and space debris residue-containing impact features. Presently, 13 impacts containing significant amounts of unmelted and semi-melted micrometeoritic residues were forwarded to Centre National d'Etudes Spatiales (CNES) in France. At the CNES facilities, the upgraded impacts were analyzed using a JEOL T330A SEM equipped with a NORAN Instruments, Voyager X-ray Analyzer. All residues were quantitatively characterized by composition (including oxygen and carbon) to help understand interplanetary dust as possibly being derived from comets and asteroids.

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

    NARCIS (Netherlands)

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

    2009-01-01

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

  13. Neutral-point current modeling and control for Neutral-Point Clamped three-level converter drive with small DC-link capacitors

    DEFF Research Database (Denmark)

    Maheshwari, Ram Krishan; Munk-Nielsen, Stig; Busquets-Monge, Sergio

    2011-01-01

    A Neutral-Point-Clamped (NPC) three-level inverter with small DC-link capacitors is presented in this paper. This inverter requires zero average neutral-point current for stable neutral-point potential. A simple carrier based modulation strategy is proposed for achieving zero average neutral...... drive with only 14 μF DC-link capacitors. A fast and stable performance of the neutral-point voltage controller is achieved and verified by experiments....

  14. Biological cell controllable patch-clamp microchip

    Science.gov (United States)

    Penmetsa, Siva; Nagrajan, Krithika; Gong, Zhongcheng; Mills, David; Que, Long

    2010-12-01

    A patch-clamp (PC) microchip with cell sorting and positioning functions is reported, which can avoid drawbacks of random cell selection or positioning for a PC microchip. The cell sorting and positioning are enabled by air bubble (AB) actuators. AB actuators are pneumatic actuators, in which air pressure is generated by microheaters within sealed microchambers. The sorting, positioning, and capturing of 3T3 cells by this type of microchip have been demonstrated. Using human breast cancer cells MDA-MB-231 as the model, experiments have been demonstrated by this microchip as a label-free technical platform for real-time monitoring of the cell viability.

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

    Science.gov (United States)

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

    2017-11-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Analysis of failed and nickel-coated 3093 beam clamp components at the East Tennessee Technology Park (ETTP).

    Energy Technology Data Exchange (ETDEWEB)

    Singh, D.; Pappacena, K.; Gaviria, J.; Burtsteva, T.; Nuclear Engineering Division

    2010-10-11

    The U.S. Department of Energy and its contractor, Bechtel Jacobs Company (BJC), are undertaking a major effort to clean up the former gaseous diffusion facility (K-25) located in Oak Ridge, TN. The decontamination and decommissioning activities require systematic removal of contaminated equipment and machinery followed by demolition of the buildings. As part of the cleanup activities, a beam clamp, used for horizontal life lines (HLLs) for fall protection, was discovered to be fractured during routine inspection. The beam clamp (yoke and D-ring) was a component in the HLL system purchased from Reliance Industries LLC. Specifically, the U-shaped stainless steel yoke of the beam clamp failed in a brittle mode at under less than 10% of the rated design capacity of 14,500 lb. The beam clamp had been in service for approximately 16 months. Bechtel Jacobs approached Argonne National Laboratory to assist in identifying the root cause of the failure of the beam clamp. The objectives of this study were to (1) review the prior reports and documents on the subject, (2) understand the possible failure mechanism(s) that resulted in the failed beam clamp components, (3) recommend approaches to mitigate the failure mechanism(s), and (4) evaluate the modified beam clamp assemblies. Energy dispersive x-ray analysis and chemical analysis of the corrosion products on the failed yoke and white residue on an in-service yoke indicated the presence of zinc, sulfur, and calcium. Analysis of rainwater in the complex, as conducted by BJC, indicated the presence of sulfur and calcium. It was concluded that, as a result of galvanic corrosion, zinc from the galvanized components of the beam clamp assembly (D-ring) migrated to the corroded region in the presence of the rainwater. Under mechanical stress, the corrosion process would have accelerated, resulting in the catastrophic failure of the yoke. As suggested by Bechtel Jacobs personnel, hydrogen embrittlement as a consequence of corrosion

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

    OpenAIRE

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

    2004-01-01

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

  19. space vector pulse width modulation of a multi-level diode clamped

    African Journals Online (AJOL)

    ES Obe

    step by step development of MATLAB /SIMULINK modeling of the space vector ..... Pulse Width Mod. of Multi-Level Diode Clamped Converter 119 powergui. Discrete, .... Load. Figure 22: Block diagram of the three level DCC design. 3 LEVEL ...

  20. Voltage Balancing Control of Diode-Clamped Multilevel Inverter

    Directory of Open Access Journals (Sweden)

    ŞCHIOP Adrian

    2013-10-01

    Full Text Available In this paper is developed a control scheme for mono-phase diode clamped inverter to achieve balancing voltages on inverter capacitors. First, it develops a control scheme without taking into account the need to balance voltage on two capacitors. It examines the effects on the output voltage inverter, and then it realizes two control schemes that will balance the voltages. The simulations of control schemes were performed in OrCAD Pspice.

  1. Five-level Z-source diode-clamped inverter

    DEFF Research Database (Denmark)

    Gao, F.; Loh, Poh Chiang; Blaabjerg, Frede

    2010-01-01

    This study proposes a five-level Z-source diode-clamped inverter designed with two intermediate Z-source networks connected between the dc input sources and rear-end inverter circuitry. By partially shorting the Z-source networks, new operating states not previously reported for two-level Z......-source inverter are introduced here for operating the proposed inverter with voltage buck–boost energy conversion ability and five-level phase voltage switching. These characteristic features are in fact always ensured at the inverter terminal output by simply adopting a properly designed carrier modulation...

  2. Bingham Sealing and Application in Vacuum Clamping

    Science.gov (United States)

    Yao, S. M.; Teo, Wee Kin; Geng, Zunmin; Turner, Sam; Ridgway, Keith

    2011-12-01

    Vacuum clamping is extensively used in shell machining. In this paper a Bingham Sealing (BS) is presented and formulized based on Bingham plastic performance. The sealing capability of BS is evaluated in various cases. A new Bingham plastic is developed and the yield stress is measured. The performances of "O"ring sealing and BS with the developed Bingham plastic are compared to the static experiment. In this experiment the same vacuum is achieved and the distortion of the blade with BS is better than that with "O" ring sealing.

  3. Bingham Sealing and Application in Vacuum Clamping

    International Nuclear Information System (INIS)

    Yao, S M; Teo, Wee Kin; Geng Zunmin; Turner, Sam; Ridgway, Keith

    2011-01-01

    Vacuum clamping is extensively used in shell machining. In this paper a Bingham Sealing (BS) is presented and formulized based on Bingham plastic performance. The sealing capability of BS is evaluated in various cases. A new Bingham plastic is developed and the yield stress is measured. The performances of Or ing sealing and BS with the developed Bingham plastic are compared to the static experiment. In this experiment the same vacuum is achieved and the distortion of the blade with BS is better than that with 'O' ring sealing.

  4. Surface deformation during an action potential in pearled cells

    Science.gov (United States)

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

    2017-11-01

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

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

    OpenAIRE

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

    2008-01-01

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

  6. The hypertriglyceridemic clamp technique. Studies using long-chain and structured triglyceride emulsions in healthy subjects.

    Science.gov (United States)

    Nordenström, Jörgen; Thörne, Anders; Aberg, Wiveca; Carneheim, Claes; Olivecrona, Thomas

    2006-11-01

    In a randomized crossover study, plasma kinetics of 2 different types of fat emulsions were studied in 8 healthy volunteers by using a hypertriglyceridemic clamp technique. The method involves the stabilization of serum triglyceride (TG) concentration during 180 minutes at a predetermined level (4 mmol/L) by adjustment of TG infusion rate by repeated online measurements of serum TG concentration. The fat emulsions under study were a long-chain fatty acid triglyceride (LCT) emulsion (Intralipid 20%, Fresenius Kabi, Sweden) and a structured triglyceride (STG) emulsion (Structolipid 20%, Fresenius Kabi) where medium- and long-chain fatty acids have been interesterified within a TG molecule. The hypertriglyceridemic clamp was found to have acceptable reproducibility when tested in 3 healthy individuals on 2 different occasions, as similar steady-state TG levels were obtained by infusing similar amounts of fat. The average (+/-SEM) TG concentration during the 180-minute clamp was similar for STGs and LCTs (4.0 +/- 0.1 vs 3.9 +/- 0.1 mmol/L; not significant), but the amount of fat that had to be infused was significantly higher during STG than during LCT clamping (0.31 +/- 0.04 vs 0.21 +/- 0.02 g TG per minute; P < .05). Higher serum levels of free fatty acids (1.80 +/- 0.13 vs 0.96 +/- 0.09 mmol/L; P < .05), free glycerol (1.30 +/- 0.07 vs 0.76 +/- 0.08 mmol/L; P < .001), and beta-OH butyrate (1.61 +/- 0.44 vs 1.17 +/- 0.23 mmol/L; not significant) were obtained at the end of the clamp during infusion of STGs compared with LCTs. During infusion of STGs the medium-chain fatty acids octanoic (C:8) and decanoic acid (C:10) constituted approximately half of circulating fatty acids that correspond to the compositional ratio of the emulsion. Plasma lipoprotein lipase (LPL) concentration was higher during STG than during LCT clamping (6.06 +/- 0.62 vs 3.15 +/- 0.40 mU/mL; P < .05), and there was a positive correlation between the mean LPL concentration and the amount of

  7. Simple hardware implementation of voltage balancing in capacitor-clamped inverter

    Czech Academy of Sciences Publication Activity Database

    Kokeš, Petr; Semerád, Radko

    2009-01-01

    Roč. 54, č. 4 (2009), s. 325-341 ISSN 0001-7043 R&D Projects: GA MPO FT-TA4/077 Institutional research plan: CEZ:AV0Z20570509 Keywords : capacitor -clamped multilevel inverter * flying capacitor voltage balancing * pulse width modulation (PWM) Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering

  8. Block of voltage-gated potassium channels by Pacific ciguatoxin-1 contributes to increased neuronal excitability in rat sensory neurons

    International Nuclear Information System (INIS)

    Birinyi-Strachan, Liesl C.; Gunning, Simon J.; Lewis, Richard J.; Nicholson, Graham M.

    2005-01-01

    The present study investigated the actions of the polyether marine toxin Pacific ciguatoxin-1 (P-CTX-1) on neuronal excitability in rat dorsal root ganglion (DRG) neurons using patch-clamp recording techniques. Under current-clamp conditions, bath application of 2-20 nM P-CTX-1 caused a rapid, concentration-dependent depolarization of the resting membrane potential in neurons expressing tetrodotoxin (TTX)-sensitive voltage-gated sodium (Na v ) channels. This action was completely suppressed by the addition of 200 nM TTX to the external solution, indicating that this effect was mediated through TTX-sensitive Na v channels. In addition, P-CTX-1 also prolonged action potential and afterhyperpolarization (AHP) duration. In a subpopulation of neurons, P-CTX-1 also produced tonic action potential firing, an effect that was not accompanied by significant oscillation of the resting membrane potential. Conversely, in neurons expressing TTX-resistant Na v currents, P-CTX-1 failed to alter any parameter of neuronal excitability examined in this study. Under voltage-clamp conditions in rat DRG neurons, P-CTX-1 inhibited both delayed-rectifier and 'A-type' potassium currents in a dose-dependent manner, actions that occurred in the absence of alterations to the voltage dependence of activation. These actions appear to underlie the prolongation of the action potential and AHP, and contribute to repetitive firing. These data indicate that a block of potassium channels contributes to the increase in neuronal excitability, associated with a modulation of Na v channel gating, observed clinically in response to ciguatera poisoning

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

    International Nuclear Information System (INIS)

    Montvay, I.; Gutbrod, F.

    1983-11-01

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

  10. Effects of clamping force on the water transport and performance of a PEM (proton electrolyte membrane) fuel cell with relative humidity and current density

    International Nuclear Information System (INIS)

    Cha, Dowon; Ahn, Jae Hwan; Kim, Hyung Soon; Kim, Yongchan

    2015-01-01

    The clamping force should be applied to a proton electrolyte membrane (PEM) fuel cell due to its structural characteristics. The clamping force affects the ohmic and mass transport resistances in the PEM fuel cell. In this study, the effects of the clamping force on the water transport and performance characteristics of a PEM fuel cell are experimentally investigated with variations in the relative humidity and current density. The water transport characteristics were analyzed by calculating the net drag coefficient. The ohmic resistance decreased with the increase in the clamping force due to the reduced contact resistance and more even membrane hydration. However, the mass transport resistance increased with the increase in the clamping force due to the gas diffusion layer compression. The net drag coefficient decreased with the increase in the clamping force due to high water back-diffusion. Additionally, the relationship between the total resistance and the net drag coefficient was investigated. - Highlights: • Effects of clamping force on the performance of a PEM fuel cell are investigated. • Water transport characteristics are analyzed using net drag coefficient. • Ohmic resistance decreased with clamping force, but mass transport resistance increased. • Net drag coefficient decreased with the increase in clamping force. • Total resistance was significantly degraded for a net drag coefficient below 0.2.

  11. External mean flow influence on sound transmission through finite clamped double-wall sandwich panels

    Science.gov (United States)

    Liu, Yu; Catalan, Jean-Cédric

    2017-09-01

    This paper studies the influence of an external mean flow on the sound transmission through finite clamped double-wall sandwich panels lined with poroelastic materials. Biot's theory is employed to describe wave propagation in poroelastic materials and various configurations of coupling the poroelastic layer to the facing plates are considered. The clamped boundary of finite panels are dealt with by the modal superposition theory and the weighted residual (Garlekin) method, leading to a matrix equation solution for the sound transmission loss (STL) through the structure. The theoretical model is validated against existing theories of infinite sandwich panels with and without an external flow. The numerical results of a single incident wave show that the external mean flow has significant effects on the STL which are coupled with the clamped boundary effect dominating in the low-frequency range. The external mean flow also influences considerably the limiting incidence angle of the panel system and the effect of the incidence angle on the STL. However, the influences of the azimuthal angle and the external flow orientation are negligible.

  12. Isolated PWM DC-AC SICAM with an active capacitive voltage clamp[Pulse Density Modulated; Pulse Width Modulation

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.

    2004-03-15

    In this report an isolated PWM DC-AC SICAM with an active capacitive voltage clamp is presented. AC-DC power supply is implemented in its simplest form: diode rectifier followed by a medium-size charge-storage capacitors and possibly with an EMC filter on the mains entrance. Isolation from the AC mains is achieved using a high frequency (HF) transformer, whose voltages are not audio-modulated. The latter simplifies the design and is expected to have many advantages over the approach where the transformer voltages are modulated in regards to the audio signal reference. Input stage is built as a DC-AC inverter (push-pull, half-bridge or a full-bridge) and operated with 50% duty cycle, with all the challenges to avoid transformer saturation and obtain symmetrical operation. On the secondary side the output section is implemented as rectifier+inverter AC-AC stage, i.e. a true bidirectional bridge, which operation is aimed towards amplification of the audio signal. In order to solve the problem with the commutation of the load current, a dead time between the incoming and outgoing bidirectional switch is implemented, while a capacitive voltage clamp is used to keep the induced overvoltage to reasonable levels. The energy stored in the clamping capacitor is not wasted as in the dissipative clamps, but is rather transferred back to the primary side for further processing using an auxiliary isolated single-switch converter, i.e. an active clamping technique is used. (au)

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

    Science.gov (United States)

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

    2014-09-01

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

  14. Early differential defects of insulin secretion and action in 19-year-old caucasian men who had low birth weight

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Dela, Flemming

    2002-01-01

    Several studies have linked low birth weight (LBW) and type 2 diabetes. We investigated hepatic and peripheral insulin action including intracellular glucose metabolism in 40 19-year-old men (20 LBW, 20 matched control subjects), using the hyperinsulinemic-euglycemic clamp technique at two...

  15. Insulin action in vivo: studies in control and exercise trained rats

    Energy Technology Data Exchange (ETDEWEB)

    James, D.E.

    1984-01-01

    This thesis is primarily concerned with in vivo insulin action and how this is modified by exercise training. The aims are; to define differential insulin action within the major insulin sensitive tissues; to characterize the relationship between these individual responses and whole body insulin action; and to examine the effect of exercise training on whole body and differential tissue insulin action. A technique, based on the euglycaemic clamp, is described for examining in vivo insulin action on glucose utilization and storage in individual tissues in the conscious, unrestrained rat. Tissue glucose metabolic rate (Rg') was estimated using (/sup 3/H)-2-deoxyglucose and glucose disposal was examined by measuring glycogen content and /sup 14/C-glucose incorporation into tissue glycogen or lipids. Elevating plasma insulin to 150 mU/l resulted in significant increases of glucose utilization in skeletal muscle and adipose tissue. Oxidative skeletal muscle could account for up to 70% of total glucose disposal whereas adipose tissue and liver could account for less than 3%. The following conclusions have been drawn from these studies. The whole body insulin response curve for glucose utilization closely reflects muscle glucose metabolism; mild elevations in plasma insulin will markedly elevate the glucose utilization rate in oxidative but not glycolytic skeletal muscle fibers; the increased whole body insulin sensitivity which is observed following exercise training is due to increased insulin sensitivity in skeletal muscle. These results indicate that exercise training will undoubtedly result in improved glucose disposal in the prandial state. This emphasises the potential benefit of exercise in obesity and Type II diabetes.

  16. Analytical and experimental investigation on transmission loss of clamped double panels: implication of boundary effects.

    Science.gov (United States)

    Xin, F X; Lu, T J

    2009-03-01

    The air-borne sound insulation performance of a rectangular double-panel partition clamp mounted on an infinite acoustic rigid baffle is investigated both analytically and experimentally and compared with that of a simply supported one. With the clamped (or simply supported) boundary accounted for by using the method of modal function, a double series solution for the sound transmission loss (STL) of the structure is obtained by employing the weighted residual (Galerkin) method. Experimental measurements with Al double-panel partitions having air cavity are subsequently carried out to validate the theoretical model for both types of the boundary condition, and good overall agreement is achieved. A consistency check of the two different models (based separately on clamped modal function and simply supported modal function) is performed by extending the panel dimensions to infinite where no boundaries exist. The significant discrepancies between the two different boundary conditions are demonstrated in terms of the STL versus frequency plots as well as the panel deflection mode shapes.

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

    NARCIS (Netherlands)

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

    1985-01-01

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

  18. Robust Clamping Force Control of an Electro-Mechanical Brake System for Application to Commercial City Buses

    Directory of Open Access Journals (Sweden)

    Sangjune Eum

    2017-02-01

    Full Text Available This paper proposes a sensor-less robust force control method for improving the control performance of an electro-mechanical brake (EMB which is applicable to commercial city buses. The EMB generates the accurate clamping force commanded by a driver through an independent motor control at each wheel instead of using existing mechanical components. In general, an EMB undergoes parameter variation and a backdrivability problem. For this reason, the cascade control strategy (e.g., force-position cascade control structure is proposed and the disturbance observer is employed to enhance control robustness against model variations. Additionally, this paper proposed the clamping force estimation method for a sensor-less control, i.e., the clamping force observer (CFO. Finally, in order to confirm the performance and effectiveness of a proposed robust control method, several experiments are performed and analyzed.

  19. Feasibility, safety and image quality of cardiac FDG studies during hyperinsulinaemic-euglycaemic clamping

    International Nuclear Information System (INIS)

    Bax, Jeroen J.; Visser, Frans C.; Lingen, Arthur van; Visser, Cees A.; Poldermans, Don; Elhendy, Abdou; Boersma, Eric

    2002-01-01

    Fluorine-18 fluorodeoxyglucose (FDG) imaging for the assessment of myocardial viability has become an integral part of the diagnostic and prognostic work-up of patients with ischaemic cardiomyopathy. To ensure good image quality, in particular in patients with diabetes mellitus, hyperinsulinaemic-euglycaemic clamping has been proposed. In this study we evaluated the safety and the image quality of cardiac FDG imaging during clamping in a large group of patients, including a subgroup with diabetes mellitus. The incidence of viability (on both a segment and a patient basis) was also determined for patients with and without diabetes mellitus. The safety and image quality of cardiac FDG studies during clamping were evaluated in 131 patients, including 19 with diabetes mellitus. Image quality was assessed visually and quantitatively using heart-to-lung (H/L), heart-to-liver (H/Li) and myocardium-to-background (M/B) ratios. Blood samples were drawn at baseline and at the time of FDG injection to determine levels of glucose, free fatty acids and insulin. The metabolic circumstances were optimal for FDG imaging: high insulin levels, low free fatty acid levels and glucose levels in the normal range (levels of substrates were comparable between patients with and patients without diabetes mellitus). No serious side-effects occurred in any patient. Image quality (assessed visually) was good in all patients. The quantitative parameters of image quality (H/L, H/Li and M/B) were comparable between patients with and patients without diabetes mellitus. The incidence of viability was high: 38% of patients without and 58% of patients with diabetes mellitus had substantial viability despite contractile dysfunction. It is concluded that cardiac FDG imaging during clamping is safe and provides excellent image quality, including in patients with diabetes mellitus. The incidence of viability is high, in particular in patients with diabetes mellitus. (orig.)

  20. Influence of non-steady state during isoglycemic hyperinsulinemic clamp in hypertension. A LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, M H; Andersen, U B; Wachtell, K

    1999-01-01

    We wanted to investigate whether time to steady state was reached within 2 h of insulin infusion during isoglycemic hyperinsulinemic clamp, comparing the glucose uptake index (M/IG) with Bergman's insulin sensitivity index (Sip). We performed a 2-h oral glucose tolerance test and a 3-h isoglycemic....... Because the 2-h M/IG correlated strongly with the 3-h Sip with relatively narrow limits of agreement, it is a good measure of insulin sensitivity. However, a 2-h clamp results in lower insulin sensitivity values in elderly, hypertensive patients due to the fact that steady state is not reached...

  1. The Potential of Deweyan-Inspired Action Research

    Science.gov (United States)

    Stark, Jody L.

    2014-01-01

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

  2. Dynamic characteristics of rotating pretwisted clamped-clamped beam under thermal stress

    International Nuclear Information System (INIS)

    Zhang, Bo; Li, Yueming; Lu, Wei Zhen

    2016-01-01

    Effects of thermal stress on the vibration characteristics, buckling limit and critical speed of a rotating pretwisted beam clamped to rigid hub at a stagger angle were investigated. By considering the work done by thermal stress, the thermal influence on stiffness matrix was introduced in the dynamic model. The motion equations were derived based on Lagrange equation by employing three pure Cartesian deformation variables combined with nonlinear von Karman strain formula. Numerical investigations studied the modal characteristics of the beam. Numerical results calculated from a commercial finite element code and obtained with the present modeling method were in good agreement with the previous results reported in the literature. The combined softening effects due to the thermal stress and the rotation motion were observed. Furthermore, it is shown that the inclusion of thermal stress is necessary for blades operating under a high temperature field. Buckling thermal loads and the critical rotating speed were calculated through solving the corresponding nonlinear equations numerically, and some pertinent conclusions are outlined. It is also found that the peak value position of the first mode shape approaches to the tip of blade with the increment of rotating speed and hub radius. However, the variation in the environment temperature causes only a slight alteration in the mode shape

  3. Dynamic characteristics of rotating pretwisted clamped-clamped beam under thermal stress

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bo; Li, Yueming [State Key Laboratory for Strength and Vibration of Mechanical Structures, Shaanxi Key Laboratory of Environment and Control for Flight Vehicle, School of Aerospace, Xi' an Jiaotong UniversityXi' an (China); Lu, Wei Zhen [Dept. of Civil and Architectural Engineering, City University of Hong Kong, Hong Kong (China)

    2016-09-15

    Effects of thermal stress on the vibration characteristics, buckling limit and critical speed of a rotating pretwisted beam clamped to rigid hub at a stagger angle were investigated. By considering the work done by thermal stress, the thermal influence on stiffness matrix was introduced in the dynamic model. The motion equations were derived based on Lagrange equation by employing three pure Cartesian deformation variables combined with nonlinear von Karman strain formula. Numerical investigations studied the modal characteristics of the beam. Numerical results calculated from a commercial finite element code and obtained with the present modeling method were in good agreement with the previous results reported in the literature. The combined softening effects due to the thermal stress and the rotation motion were observed. Furthermore, it is shown that the inclusion of thermal stress is necessary for blades operating under a high temperature field. Buckling thermal loads and the critical rotating speed were calculated through solving the corresponding nonlinear equations numerically, and some pertinent conclusions are outlined. It is also found that the peak value position of the first mode shape approaches to the tip of blade with the increment of rotating speed and hub radius. However, the variation in the environment temperature causes only a slight alteration in the mode shape.

  4. Eccentric exercise decreases maximal insulin action in humans

    DEFF Research Database (Denmark)

    Asp, Svend; Daugaard, J R; Kristiansen, S

    1996-01-01

    subjects participated in two euglycaemic clamps, performed in random order. One clamp was preceded 2 days earlier by one-legged eccentric exercise (post-eccentric exercise clamp (PEC)) and one was without the prior exercise (control clamp (CC)). 2. During PEC the maximal insulin-stimulated glucose uptake...... for all three clamp steps used (P maximal activity of glycogen synthase was identical in the two thighs for all clamp steps. 3. The glucose infusion rate (GIR......) necessary to maintain euglycaemia during maximal insulin stimulation was lower during PEC compared with CC (15.7%, 81.3 +/- 3.2 vs. 96.4 +/- 8.8 mumol kg-1 min-1, P maximal...

  5. Trans-Z-source and Γ-Z-source neutral-point-clamped inverters

    DEFF Research Database (Denmark)

    Wei, Mo; Loh, Poh Chiang; Blaabjerg, Frede

    2015-01-01

    Z-source neutral-point-clamped (NPC) inverters are earlier proposed for obtaining voltage buck-boost and three-level switching simultaneously. Their performances are, however, constrained by a trade-off between their input-to-output gain and modulation ratio. This trade-off can lead to high...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-04-26

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

  7. Evaluation of diel patterns of relative changes in cell turgor of tomato plants using leaf patch clamp pressure probes

    NARCIS (Netherlands)

    Lee, K.M.; Driever, S.M.; Heuvelink, E.; Rüger, S.; Zimmermann, U.; Gelder, de A.; Marcelis, L.F.M.

    2012-01-01

    Relative changes in cell turgor of leaves of well-watered tomato plants were evaluated using the leaf patch clamp pressure probe (LPCP) under dynamic greenhouse climate conditions. Leaf patch clamp pressure changes, a measure for relative changes in cell turgor, were monitored at three different

  8. Targeted Endovascular Temporary Vessel Occlusion with a Reverse Thermosensitive Polymer for Near-Bloodless Partial Nephrectomy: Comparison to Standard Surgical Clamping Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Flacke, Sebastian, E-mail: Sebastian.Flacke@lahey.org [Lahey Clinic, Tuft University Medical School, Department of Radiology (United States); Harty, Niall J.; Laskey, Daniel H.; Moinzadeh, Alireza [Lahey Clinic, Tuft University Medical School, Department of Urology (United States); Benn, James A. [Pluromed Inc (United States); Villani, Rosanna [DaVinci Biomedical Research Products (United States); Kalra, Aarti [Lahey Clinic, Tuft University Medical School, Department of Pathology (United States); Libertino, John A.; Madras, Peter N. [Lahey Clinic, Tuft University Medical School, Department of Urology (United States)

    2012-10-15

    Purpose: To determine whether reversible blood flow interruption to a randomly chosen target region of the kidney may be achieved with the injection of a reverse thermoplastic polymer through an angiographic catheter, thereby facilitating partial nephrectomy without compromising blood flow to the remaining kidney or adding risks beyond those encountered by the use of hilar clamping. Methods: Fifteen pigs underwent partial nephrectomy after blood flow interruption by vascular cross-clamping or injection of polymer (Lumagel Trade-Mark-Sign ) into a segmental artery. Five animals were euthanized after surgery (three open and two laparoscopic resection, cross-clamping n = 2), and 10 (open resection, cross-clamping n = 4) were euthanized after 6 weeks' survival. Blood specimens were obtained periodically, and angiogram and necropsy were performed at 6 weeks. Results: Selective renal ischemia was achieved in all cases. Surgical resection time averaged 9 and 24.5 min in the open and laparoscopic groups, respectively. Estimated blood loss was negligible with the exception of one case where an accessory renal artery was originally overlooked. Reversal of the polymer to a liquid state was consistent angiographically and visually in all cases. Time to complete flow return averaged 7.4 and 2 min for polymer and clamping, respectively. Angiography at 6 weeks revealed no evidence of vascular injury. Laboratory data and necropsies revealed no differences between animals undergoing vascular clamping or polymer injection. Conclusion: Lumagel was as effective as vascular clamping in producing a near bloodless operative field for partial nephrectomy while maintaining flow to the uninvolved portion of the affected kidney.

  9. Solution study of the Escherichia coli DNA polymerase III clamp loader reveals the location of the dynamic ψχ heterodimer

    Directory of Open Access Journals (Sweden)

    Farzaneh Tondnevis

    2015-09-01

    Full Text Available Several X-ray crystal structures of the E. coli core clamp loader containing the five core (δ′, δ, and three truncated γ subunits have been determined, but they lack the ψ and χ subunits. We report the first solution structure of the complete seven-subunit clamp loader complex using small angle X-ray scattering. This structure not only provides information about the location of the χ and ψ subunits but also provides a model of the dynamic nature of the clamp loader complex.

  10. Odorant responses of olfactory sensory neurons expressing the odorant receptor MOR23: A patch clamp analysis in gene-targeted mice

    OpenAIRE

    Grosmaitre, Xavier; Vassalli, Anne; Mombaerts, Peter; Shepherd, Gordon M.; Ma, Minghong

    2006-01-01

    A glomerulus in the mammalian olfactory bulb receives axonal inputs from olfactory sensory neurons (OSNs) that express the same odorant receptor (OR). Glomeruli are generally thought to represent functional units of olfactory coding, but there are no data on the electrophysiological properties of OSNs that express the same endogenous OR. Here, using patch clamp recordings in an intact epithelial preparation, we directly measured the transduction currents and receptor potentials from the dendr...

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

    Science.gov (United States)

    Bahar, Entaz; Kim, Hyongsuk; Yoon, Hyonok

    2016-09-15

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

  12. A Hybrid Cascade Converter Topology With Series-Connected Symmetrical and Asymmetrical Diode-Clamped H-Bridge Cells

    DEFF Research Database (Denmark)

    Nami, Alireza; Zare, Firuz; Ghosh, Arindam

    2011-01-01

    to approach a very low total harmonic distortion of voltage and current, which leads to the possible elimination of the output filter. Regarding the proposed configuration, a new cascade inverter is verified by cascading an asymmetrical diode-clamped inverter, in which 19 levels can be synthesized in output......A novel H-bridge multilevel pulsewidth modulation converter topology based on a series connection of a high-voltage diode-clamped inverter and a low-voltage conventional inverter is proposed in this paper. A dc link voltage arrangement for the new hybrid and asymmetric solution is presented to have...... voltage with the same number of components. To balance the dc link capacitor voltages for the maximum output voltage resolution as well as synthesize asymmetrical dc link combination, a new multi-output boost converter is utilized at the dc link voltage of a seven-level H-bridge diode-clamped inverter...

  13. Impedance spectra of patch clamp scenarios for single cells immobilized on a lab-on-a-chip

    DEFF Research Database (Denmark)

    Alberti, Massimo; Snakenborg, Detlef; Lopacinska, Joanna M.

    2014-01-01

    and simulated impedance spectra proved that the presented method could distinguish between a cell-attached mode and a whole-cell mode even with low-quality seals. In physiological conditions, the capacitance of HeLa cells was measured to *38 pF. The first gigaseal was recorded and maintained for 40 min. Once...... membrane. After incubating the chip for 24 h, HeLa cells adhered and grew on the chip surface but did not survive when trapped on the microapertures. The microfluidic system proved to work as a micro electrophysiological analysis system, and the IS-based method can be used for further studies on the post......A simple method based on impedance spectroscopy (IS) was developed to distinguish between different patch clamp modes for single cells trapped on microapertures in a patch clamp microchannel array designed for patch clamping on cultured cells. The method allows detecting via impedance analysis...

  14. Laser microsurgery of higher plant cell walls permits patch-clamp access

    International Nuclear Information System (INIS)

    Henriksen, G.H.; Taylor, A.R.; Brownlee, C.; Assmann, S.M.

    1996-01-01

    Plasma membranes of guard cells in epidermal peels of Vicia faba and Commelina communis can be made accessible to a patch-clamp pipet by removing a small portion (1-3 micrometer in diameter) of the guard cell wall using a microbeam of ultraviolet light generated by a nitrogen laser. Using this laser microsurgical technique, we have measured channel activity across plasma membranes of V. faba guard cells in both cell-attached and isolated patch configurations. Measurements made in the inside-out patch configuration revealed two distinct K+-selective channels. Major advantages of the laser microsurgical technique include the avoidance of enzymatic protoplast isolation, the ability to study cell types that have been difficult to isolate as protoplasts or for which enzymatic isolation protocols result in protoplasts not amenable to patch-clamp studies, the maintenance of positional information in single-channel measurements, reduced disruption of cell-wall-mediated signaling pathways, and the ability to investigate intercellular signaling through studies of cells remaining situated within tissue

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

    Science.gov (United States)

    Desbois, Andrew P; Smith, Valerie J

    2010-02-01

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

  16. A Novel Neutral Point Clamped Full-Bridge Topology for Transformerless Photovoltaic Grid-Connected Inverters

    Directory of Open Access Journals (Sweden)

    M. Pakdel

    2017-04-01

    Full Text Available This paper presents a novel neutral point clamped full-bridge topology for transformerless photovoltaic grid-tied inverters. Transformerless grid-connected inverters have been used widely in recent years since they offer higher efficiency and lower costs. Ground leakage current suppression is the main issue which should be considered carefully in transformerless photovoltaic grid-connected inverters. Among different methods used to decline ground leakage current, neutral point clamped (NPC topologies are considered more useful and effective. In NPC topologies, the short-circuited output voltage at the freewheeling period is clamped to the middle of the DC bus voltage. Therefore, the common-mode voltage (CM will be constant at the whole switching period. Various NPC topologies such as H6 [1], HB-ZVR [2], oH5 [3], and PN-NPC [4] have been proposed. In this paper, a novel NPC topology is proposed which has lower power losses and higher efficiency over previous topologies. Furthermore, the proposed NPC topology exhibits a similar ground leakage current with the PN-NPC topology. The proposed NPC topology is analyzed theoretically using simulation studies and an experimental prototype is provided to verify theoretical analysis and simulation studies.

  17. Ion channel electrophysiology via integrated planar patch-clamp chip with on-demand drug exchange.

    Science.gov (United States)

    Chen, Chang-Yu; Tu, Ting-Yuan; Jong, De-Shien; Wo, Andrew M

    2011-06-01

    Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays. Copyright © 2011 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    International Nuclear Information System (INIS)

    Rivacoba, A.

    1984-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  2. Humanin: a novel central regulator of peripheral insulin action.

    Directory of Open Access Journals (Sweden)

    Radhika H Muzumdar

    2009-07-01

    Full Text Available Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM and Alzheimer's disease (AD. A novel mitochondria-associated peptide, Humanin (HN, has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity.Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice.We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  4. Neuroprotective effect of interleukin-6 regulation of voltage-gated Na+ channels of cortical neurons is time- and dose-dependent

    Directory of Open Access Journals (Sweden)

    Wei Xia

    2015-01-01

    Full Text Available Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours by studying voltage-gated Na + channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na + currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na + channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.

  5. A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

    Science.gov (United States)

    Saad, M F; Anderson, R L; Laws, A; Watanabe, R M; Kades, W W; Chen, Y D; Sands, R E; Pei, D; Savage, P J; Bergman, R N

    1994-09-01

    An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

  6. Screening of E. coli β-clamp Inhibitors Revealed that Few Inhibit Helicobacter pylori More Effectively: Structural and Functional Characterization

    Directory of Open Access Journals (Sweden)

    Preeti Pandey

    2018-01-01

    Full Text Available The characteristic of interaction with various enzymes and processivity-promoting nature during DNA replication makes β-clamp an important drug target. Helicobacter pylori (H. pylori have several unique features in DNA replication machinery that makes it different from other microorganisms. To find out whether difference in DNA replication proteins behavior accounts for any difference in drug response when compared to E. coli, in the present study, we have tested E. coli β-clamp inhibitor molecules against H. pylori β-clamp. Various approaches were used to test the binding of inhibitors to H. pylori β-clamp including docking, surface competition assay, complex structure determination, as well as antimicrobial assay. Out of five shortlisted inhibitor molecules on the basis of docking score, three molecules, 5-chloroisatin, carprofen, and 3,4-difluorobenzamide were co-crystallized with H. pylori β-clamp and the structures show that they bind at the protein-protein interaction site as expected. In vivo studies showed only two molecules, 5-chloroisatin, and 3,4-difluorobenzamide inhibited the growth of the pylori with MIC values in micro molar range, which is better than the inhibitory effect of the same drugs on E. coli. Therefore, the evaluation of such drugs against H. pylori may explore the possibility to use to generate species-specific pharmacophore for development of new drugs against H. pylori.

  7. Screening of E. coli β-clamp Inhibitors Revealed that Few Inhibit Helicobacter pylori More Effectively: Structural and Functional Characterization.

    Science.gov (United States)

    Pandey, Preeti; Verma, Vijay; Dhar, Suman Kumar; Gourinath, Samudrala

    2018-01-11

    The characteristic of interaction with various enzymes and processivity-promoting nature during DNA replication makes β-clamp an important drug target. Helicobacter pylori ( H. pylori ) have several unique features in DNA replication machinery that makes it different from other microorganisms. To find out whether difference in DNA replication proteins behavior accounts for any difference in drug response when compared to E. coli , in the present study, we have tested E. coli β-clamp inhibitor molecules against H. pylori β-clamp. Various approaches were used to test the binding of inhibitors to H. pylori β-clamp including docking, surface competition assay, complex structure determination, as well as antimicrobial assay. Out of five shortlisted inhibitor molecules on the basis of docking score, three molecules, 5-chloroisatin, carprofen, and 3,4-difluorobenzamide were co-crystallized with H. pylori β-clamp and the structures show that they bind at the protein-protein interaction site as expected. In vivo studies showed only two molecules, 5-chloroisatin, and 3,4-difluorobenzamide inhibited the growth of the pylori with MIC values in micro molar range, which is better than the inhibitory effect of the same drugs on E. coli . Therefore, the evaluation of such drugs against H. pylori may explore the possibility to use to generate species-specific pharmacophore for development of new drugs against H. pylori .

  8. Investigating the effect of clamping force on the fatigue life of bolted plates using volumetric approach

    International Nuclear Information System (INIS)

    Esmaeili, F.; Chakherlou, T. N.; Zehsaz, M.; Hasanifard, S.

    2013-01-01

    In this paper, the effects of bolt clamping force on the fatigue life for bolted plates made from Al7075-T6 have been studied on the values of notch strength reduction factor obtained by volumetric approach. To attain stress distribution around the notch (hole) which is required for volumetric approach, nonlinear finite element simulations were carried out. To estimate the fatigue life, the available smooth S-N curve of Al7075-T6 and the notch strength reduction factor obtained from volumetric method were used. The estimated fatigue life was compared with the available experimental test results. The investigation shows that there is a good agreement between the life predicted by the volumetric approach and the experimental results for various specimens with different amount of clamping forces. Volumetric approach and experimental results showed that the fatigue life of bolted plates improves because of the compressive stresses created around the plate hole due to clamping force.

  9. Characterization of a patch-clamp microchannel array towards neuronal networks analysis

    DEFF Research Database (Denmark)

    Alberti, Massimo; Snakenborg, Detlef; Lopacinska, Joanna M.

    2010-01-01

    for simultaneous patch clamping of cultured cells or neurons in the same network. A disposable silicon/silicon dioxide (Si/SiO2) chip with a microhole array was integrated in a microfluidic system for cell handling, perfusion and electrical recording. Fluidic characterization showed that our PC mu CA can work...

  10. Negligible substrate clamping effect on piezoelectric response in (111)-epitaxial tetragonal Pb(Zr, Ti)O3 films

    International Nuclear Information System (INIS)

    Yamada, Tomoaki; Yasumoto, Jun; Ito, Daisuke; Yoshino, Masahito; Nagasaki, Takanori; Sakata, Osami; Imai, Yasuhiko; Kiguchi, Takanori; Shiraishi, Takahisa; Shimizu, Takao; Funakubo, Hiroshi

    2015-01-01

    The converse piezoelectric responses of (111)- and (001)-epitaxial tetragonal Pb(Zr 0.35 Ti 0.65 )O 3 [PZT] films were compared to investigate the orientation dependence of the substrate clamping effect. Synchrotron X-ray diffraction (XRD) and piezoelectric force microscopy revealed that the as-grown (111)-PZT film has a polydomain structure with normal twin boundaries that are changed by the poling process to inclined boundaries, as predicted by Romanov et al. [Phys. Status Solidi A 172, 225 (1999)]. Time-resolved synchrotron XRD under bias voltage showed the negligible impact of substrate clamping on the piezoelectric response in the (111)-PZT film, unlike the case for (001)-PZT film. The origin of the negligible clamping effect in the (111)-PZT film is discussed from the viewpoint of the elastic properties and the compensation of lattice distortion between neighboring domains

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

    Science.gov (United States)

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

    2017-05-06

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

  12. Characterization of heterologously expressed transporter genes by patch- and voltage-clamp methods: Application to cyclic nucleotide-dependent responses

    KAUST Repository

    Lemtiri-Chlieh, Fouad

    2013-09-03

    The application of patch- and voltage-clamp methods to study ion transport can be limited by many hurdles: the size of the cells to be patched and/or stabbed, the subcellular localization of the molecule of interest, and its density of expression that could be too low even in their own native environment. Functional expression of genes using recombinant DNA technology not only overcomes those hurdles but also affords additional and elegant investigations such as single-point mutation studies and subunit associations/regulations. In this chapter, we give a step-by-step description of two electrophysiological methods, patch clamp and two-electrode voltage clamp (TEVC), that are routinely used in combination with heterologous gene expression to assist researchers interested in the identification and characterization of ion transporters. We describe how to (1) obtain and maintain the cells suitable for the use with each of the above-mentioned methods (i.e., HEK-293 cells and yeast spheroplasts to use with the patch-clamp methodology and Xenopus laevis oocytes with TEVC), (2) transfect/inject them with the gene of interest, and (3) record ion transport activities. © Springer Science+Business Media New York 2013.

  13. Characterization of heterologously expressed transporter genes by patch- and voltage-clamp methods: Application to cyclic nucleotide-dependent responses

    KAUST Repository

    Lemtiri-Chlieh, Fouad; Ali, Rashid Ayesha

    2013-01-01

    The application of patch- and voltage-clamp methods to study ion transport can be limited by many hurdles: the size of the cells to be patched and/or stabbed, the subcellular localization of the molecule of interest, and its density of expression that could be too low even in their own native environment. Functional expression of genes using recombinant DNA technology not only overcomes those hurdles but also affords additional and elegant investigations such as single-point mutation studies and subunit associations/regulations. In this chapter, we give a step-by-step description of two electrophysiological methods, patch clamp and two-electrode voltage clamp (TEVC), that are routinely used in combination with heterologous gene expression to assist researchers interested in the identification and characterization of ion transporters. We describe how to (1) obtain and maintain the cells suitable for the use with each of the above-mentioned methods (i.e., HEK-293 cells and yeast spheroplasts to use with the patch-clamp methodology and Xenopus laevis oocytes with TEVC), (2) transfect/inject them with the gene of interest, and (3) record ion transport activities. © Springer Science+Business Media New York 2013.

  14. Gain-clamping techniques in two-stage double-pass L-band EDFA

    Indian Academy of Sciences (India)

    Two designs of long-wavelength band erbium-doped fiber amplifier (L-band. EDFA) for gain clamping in double-pass systems are demonstrated and compared. The first design is based on ring laser technique where a backward amplified spontaneous emis- sion (ASE) from the second stage is routed into the feedback loop ...

  15. Analysis of the Pallet Clamping Conditions in Work Positioning

    OpenAIRE

    L. A. Kolesnikov

    2016-01-01

    Pallets of automatic transfer lines serve as the technological and work-transfer equipment. However, their design is based on the general principles of designing machine accessories. Calculation of the basic design parameters of work based on their functioning features is fairly relevant.In pallet transfer movement over work positioning there is a mismatch between axes of the basic bushing of a pallet and the clamping locks of positioning. The paper identifies the factors influencing it, and ...

  16. The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy.

    Science.gov (United States)

    Kamiyama, Yoshihiro; Yamashita, Shinichi; Nakagawa, Atsuhiro; Fujii, Shinji; Mitsuzuka, Koji; Kaiho, Yasuhiro; Ito, Akihiro; Abe, Takaaki; Tominaga, Teiji; Arai, Yoichi

    2017-09-01

    In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.

  17. 2D and 3D assessment of sustentaculum tali screw fixation with or without Screw Targeting Clamp.

    Science.gov (United States)

    De Boer, A Siebe; Van Lieshout, Esther M M; Vellekoop, Leonie; Knops, Simon P; Kleinrensink, Gert-Jan; Verhofstad, Michael H J

    2017-12-01

    Precise placement of sustentaculum tali screw(s) is essential for restoring anatomy and biomechanical stability of the calcaneus. This can be challenging due to the small target area and presence of neurovascular structures on the medial side. The aim was to evaluate the precision of positioning of the subchondral posterior facet screw and processus anterior calcanei screw with or without a Screw Targeting Clamp. The secondary aim was to evaluate the added value of peroperative 3D imaging over 2D radiographs alone. Twenty Anubifix™ embalmed, human anatomic lower limb specimens were used. A subchondral posterior facet screw and a processus anterior calcanei screw were placed using an extended lateral approach. A senior orthopedic trauma surgeon experienced in calcaneal fracture surgery and a senior resident with limited experience in calcaneal surgery performed screw fixation in five specimens with and in five specimens without the clamp. 2D lateral and axial radiographs and a 3D recording were obtained postoperatively. Anatomical dissection was performed postoperatively as a diagnostic golden standard in order to obtain the factual screw positions. Blinded assessment of quality of fixation was performed by two surgeons. In 2D, eight screws were considered malpositioned when placed with the targeting device versus nine placed freehand. In 3D recordings, two additional screws were malpositioned in each group as compared to the golden standard. As opposed to the senior surgeon, the senior resident seemed to get the best results using the Screw Targeting Clamp (number of malpositioned screws using freehand was eight, and using the targeting clamp five). In nine out of 20 specimens 3D images provided additional information concerning target area and intra-articular placement. Based on the 3D assessment, five additional screws would have required repositioning. Except for one, all screw positions were rated equally after dissection when compared with 3D examinations

  18. A New Class III Antiarrhythmic Drug Niferidil Prolongs Action Potentials in Guinea Pig Atrial Myocardium via Inhibition of Rapid Delayed Rectifier.

    Science.gov (United States)

    Abramochkin, Denis V; Kuzmin, Vladislav S; Rosenshtraukh, Leonid V

    2017-12-01

    A new class III antiarrhythmic drug niferidil (RG-2) has been introduced as a highly effective therapy for cases of persistent atrial fibrillation, but ionic mechanisms of its action are poorly understood. In the present study, the effects of niferidil on action potential (AP) waveform and potassium currents responsible for AP repolarization were investigated in guinea pig atrial myocardium. APs were recorded with sharp glass microelectrodes in multicellular atrial preparations. Whole-cell patch-clamp technique was used to measure K + currents in isolated myocytes. In multicellular atrial preparations, 10 -8  M niferidil effectively prolonged APs by 15.2 ± 2.8% at 90% repolarization level. However, even the highest tested concentrations, 10 -6  M and 10 -5  M failed to prolong APs more than 32.5% of control duration. The estimated concentration of niferedil for half-maximal AP prolongation was 1.13 × 10 -8  M. Among the potassium currents responsible for AP repolarization phase, I K1 was found to be almost insensitive to niferidil. However, another inward rectifier, I KACh , was effectively suppressed by micromolar concentrations of niferidil with IC 50  = 9.2 × 10 -6  M. I KATP was much less sensitive to the drug with IC 50  = 2.26 × 10 -4  M. The slow component of delayed rectifier, I Ks , also demonstrated low sensitivity to niferidil-the highest used concentration, 10 -4  M, decreased peak I Ks density to 46.2 ± 5.5% of control. Unlike I Ks , the rapid component of delayed rectifier, I Kr , appeared to be extremely sensitive to niferidil. The IC 50 was 1.26 × 10 -9  M. I Kr measured in ventricular myocytes was found to be less sensitive to niferidil with IC 50  = 3.82 × 10 -8  M. Niferidil prolongs APs in guinea pig atrial myocardium via inhibition of I Kr .

  19. Investigating ion channel conformational changes using voltage clamp fluorometry.

    Science.gov (United States)

    Talwar, Sahil; Lynch, Joseph W

    2015-11-01

    Ion channels are membrane proteins whose functions are governed by conformational changes. The widespread distribution of ion channels, coupled with their involvement in most physiological and pathological processes and their importance as therapeutic targets, renders the elucidation of these conformational mechanisms highly compelling from a drug discovery perspective. Thanks to recent advances in structural biology techniques, we now have high-resolution static molecular structures for members of the major ion channel families. However, major questions remain to be resolved about the conformational states that ion channels adopt during activation, drug modulation and desensitization. Patch-clamp electrophysiology has long been used to define ion channel conformational states based on functional criteria. It achieves this by monitoring conformational changes at the channel gate and cannot detect conformational changes occurring in regions distant from the gate. Voltage clamp fluorometry involves labelling cysteines introduced into domains of interest with environmentally sensitive fluorophores and inferring structural rearrangements from voltage or ligand-induced fluorescence changes. Ion channel currents are monitored simultaneously to verify the conformational status. By defining real time conformational changes in domains distant from the gate, this technique provides unexpected new insights into ion channel structure and function. This review aims to summarise the methodology and highlight recent innovative applications of this powerful technique. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Meningeal norepinephrine produces headache behaviors in rats via actions both on dural afferents and fibroblasts.

    Science.gov (United States)

    Wei, Xiaomei; Yan, Jin; Tillu, Dipti; Asiedu, Marina; Weinstein, Nicole; Melemedjian, Ohannes; Price, Theodore; Dussor, Gregory

    2015-10-01

    Stress is commonly reported to contribute to migraine although mechanisms by which this may occur are not fully known. The purpose of these studies was to examine whether norepinephrine (NE), the primary sympathetic efferent transmitter, acts on processes in the meninges that may contribute to the pain of migraine. NE was applied to rat dura using a behavioral model of headache. Primary cultures of rat trigeminal ganglia retrogradely labeled from the dura mater and of rat dural fibroblasts were prepared. Patch-clamp electrophysiology, Western blot, and ELISA were performed to examine the effects of NE. Conditioned media from NE-treated fibroblast cultures was applied to the dura using the behavioral headache model. Dural injection both of NE and media from NE-stimulated fibroblasts caused cutaneous facial and hindpaw allodynia in awake rats. NE application to cultured dural afferents increased action potential firing in response to current injections. Application of NE to dural fibroblasts increased phosphorylation of ERK and caused the release of interleukin-6 (IL-6). These data demonstrate that NE can contribute to pro-nociceptive signaling from the meninges via actions on dural afferents and dural fibroblasts. Together, these actions of NE may contribute to the headache phase of migraine. © International Headache Society 2015.

  1. 76 FR 21938 - Potential Environmental Impacts of the Proposed Runway 13 Extension and Associated Actions for...

    Science.gov (United States)

    2011-04-19

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

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

    Science.gov (United States)

    Un, M Kerem; Kaghazchi, Hamed

    2018-01-01

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

  3. del Nido versus St. Thomas Cardioplegia Solutions: A Single-Center Retrospective Analysis of Post Cross-Clamp Defibrillation Rates.

    Science.gov (United States)

    Buel, Shane T; Striker, Carrie Whittaker; O'Brien, James E

    2016-06-01

    There are many cardioplegia solutions currently in use for pediatric cardiopulmonary bypass (CPB). The most common being del Nido solution. Another common cardioplegia solution used for pediatric CPB is St. Thomas. In October 2014, Children's Mercy Kansas City changed from the use of modified St. Thomas to del Nido. This study compared rates of post cross-clamp fibrillation requiring defibrillation between del Nido solution and modified St. Thomas solution stratified by weight at Children's Mercy Kansas City. This retrospective study consisted of 394 patients who underwent cardiac surgery requiring cardioplegia between January 1, 2014 and July 31, 2015. The outcome measured was defibrillation upon cross-clamp removal. Statistical significance was determined using Fishers exact test with a two-sided significance level of .05. Incidence of defibrillation post cross-clamp removal was 4.4% in the del Nido group and 26.8% in the St. Thomas group (p Thomas group (p Thomas group (p Thomas group (p 60-kg category had an incidence of defibrillation of 16.7% in the del Nido group and 63% in the St. Thomas group (p Thomas and del Nido cardioplegia solutions. Analyses of weight stratifications demonstrate a decrease in the rate of defibrillation post cross-clamp removal in all categories within the del Nido group.

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

    NARCIS (Netherlands)

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

    1989-01-01

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

  5. Fabrication of Si-based planar type patch clamp biosensor using silicon on insulator substrate

    International Nuclear Information System (INIS)

    Zhang, Z.L.; Asano, T.; Uno, H.; Tero, R.; Suzui, M.; Nakao, S.; Kaito, T.; Shibasaki, K.; Tominaga, M.; Utsumi, Y.; Gao, Y.L.; Urisu, T.

    2008-01-01

    The aim of this paper is to fabricate the planar type patch clamp ion-channel biosensor, which is suitable for the high throughput screening, using silicon-on-insulator (SOI) substrate. The micropore with 1.2 μm diameter is formed through the top Si layer and the SiO 2 box layer of the SOI substrate by focused ion beam (FIB). Then the substrate is assembled into the microfluidic circuit. The human embryonic kidney 293 (HEK-293) cell transfected with transient receptor potential vanilloid type 1 (TRPV1) is positioned on the micropore and the whole-cell configuration is formed by the suction. Capsaicin is added to the extracellular solution as a ligand molecule, and the channel current showing the desensitization unique to TRPV1 is measured successfully

  6. Fabrication of Si-based planar type patch clamp biosensor using silicon on insulator substrate

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Z.L.; Asano, T. [Graduate University for Advanced Studies, Myodaiji, Okazaki, 444-8585 (Japan); Uno, H. [Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan); Tero, R. [Graduate University for Advanced Studies, Myodaiji, Okazaki, 444-8585 (Japan); Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan); Suzui, M.; Nakao, S. [Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan); Kaito, T. [SII NanoTechnology Inc., 36-1, Takenoshita, Oyama-cho, Sunto-gun, Shizuoka, 410-1393 (Japan); Shibasaki, K.; Tominaga, M. [Okazaki Institute for Integrative Bioscience, 5-1, Higashiyama, Myodaiji, Okazaki, 444-8787 (Japan); Utsumi, Y. [Laboratory of Advanced Science and Technology for Industry, University of Hyogo, 3-1-2, Koto, Kamigori, Ako-gun, Hyogo, 678-1205 (Japan); Gao, Y.L. [Department of Physics and Astronomy, Rochester University, Rochester, New York 14627 (United States); Urisu, T. [Graduate University for Advanced Studies, Myodaiji, Okazaki, 444-8585 (Japan); Institute for Molecular Science, Myodaiji, Okazaki, 444-8585 (Japan)], E-mail: urisu@ims.ac.jp

    2008-03-03

    The aim of this paper is to fabricate the planar type patch clamp ion-channel biosensor, which is suitable for the high throughput screening, using silicon-on-insulator (SOI) substrate. The micropore with 1.2 {mu}m diameter is formed through the top Si layer and the SiO{sub 2} box layer of the SOI substrate by focused ion beam (FIB). Then the substrate is assembled into the microfluidic circuit. The human embryonic kidney 293 (HEK-293) cell transfected with transient receptor potential vanilloid type 1 (TRPV1) is positioned on the micropore and the whole-cell configuration is formed by the suction. Capsaicin is added to the extracellular solution as a ligand molecule, and the channel current showing the desensitization unique to TRPV1 is measured successfully.

  7. Acute phase response in lactating dairy cows during hyperinsulinemic hypoglycaemic and hyperinsulinemic euglycaemic clamps and after intramammary LPS challenge.

    Science.gov (United States)

    De Matteis, L; Bertoni, G; Lombardelli, R; Wellnitz, O; Van Dorland, H A; Vernay, M C M B; Bruckmaier, R M; Trevisi, E

    2017-06-01

    The link between energy availability, turnover of energy substrates and the onset of inflammation in dairy cows is complex and poorly investigated. To clarify this, plasma inflammatory variables were measured in mid-lactating dairy cows allocated to three groups: hyperinsulinemic hypoglycaemic clamp, induced by insulin infusion (HypoG, n = 5); hyperinsulinemic euglycaemic clamp, induced by insulin and glucose infusion (EuG; n = 6); control, receiving a saline solution infusion (NaCl; n = 6). At 48 h after the start of i.v. infusions, two udder quarters per cow were challenged with 200 μg of E. coli lipopolysaccharide (LPS). Individual blood samples were taken before clamps, before LPS challenge (i.e. 48 h after clamps) and 6.5 h after. At 48 h, positive acute phase proteins (posAPP) did not differ among groups, whereas albumin and cholesterol (index of lipoproteins), negative APP (negAPP), were lower (p insulin at the tissue-level makes dairy cows more susceptible to inflammatory events. In contrast, HypoG seems to attenuate the inflammatory response. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  8. Impact of delayed umbilical cord clamping on public cord blood donations: can we help future patients and benefit infant donors?

    Science.gov (United States)

    Ciubotariu, Rodica; Scaradavou, Andromachi; Ciubotariu, Ilinca; Tarnawski, Michal; Lloyd, Sara; Albano, Maria; Dobrila, Ludy; Rubinstein, Pablo; Grunebaum, Amos

    2018-03-25

    Cord blood (CB) is a widely accepted stem cell source and its clinical utilization depends, to a great extent, on its cell content. Birth-to-clamping (BTC) time of umbilical cord determines placental transfusion to the newborn, and the remaining blood that can be collected and banked. The 2017 Committee Opinion of the American College of Obstetrics and Gynecologists (ACOG) recommends a delay of "at least 30-60 seconds" before clamping the cord for all newborns to ensure adequate iron stores. The impact of delayed cord clamping (DCC) on public CB banking can be substantial. Cord blood units (CBUs) collected from 1210 mothers at one hospital were evaluated for total nucleated cells (TNCs) and weight/volume based on time to clamping. Bank staff recorded BTC time in seconds as reported by obstetricians; collections were performed ex utero. Immediate clamping was defined as BTC of less than 30 seconds, whereas DCC was defined as BTC of 30 seconds or more. Cord clamping was immediate in 903 (75%) and delayed in 307 (25%) deliveries. Successful recovery (% clinical CBUs) decreased 10-fold with DCC of more than 60 seconds (22% vs. 2.4%, p < 0.001). CBUs collected after DCC of more than 60 seconds had significantly lower TNC counts than those after DCC of less than 60 seconds (p < 0.0001). Furthermore, 38% to 46% of CBUs after DCC of more than 60 seconds had volume of less than 40 mL. Our study indicates that DCC of 30 to 60 seconds has a small negative impact on collection of high-TNC-count CBUs. However, increasing BTC to more than 60 seconds decreases significantly both TNC content and volume, reducing drastically the chances of obtaining clinically useful CBUs. © 2018 AABB.

  9. Correlation of open cell-attached and excised patch clamp techniques.

    Science.gov (United States)

    Filipovic, D; Hayslett, J P

    1995-11-01

    The excised patch clamp configuration provides a unique technique for some types of single channel analyses, but maintenance of stable, long-lasting preparations may be confounded by rundown and/or rapid loss of seal. Studies were performed on the amiloride-sensitive Na+ channel, located on the apical surface of A6 cells, to determine whether the nystatin-induced open cell-attached patch could serve as an alternative configuration. Compared to excised inside-out patches, stable preparations were achieved more readily with the open cell-attached patch (9% vs. 56% of attempts). In both preparations, the current voltage (I-V) relation was linear, current amplitudes were equal at opposite equivalent clamped voltages, and Erev was zero in symmetrical Na+ solutions, indicating similar Na+ activities on the cytosolic and external surfaces of the patch. Moreover, there was no evidence that nystatin altered channel activity in the patch because slope conductance (3-4pS) and Erev (75 mV), when the bath was perfused with a high K:low Na solution (ENa = 80 mV), were nearly equal in both patch configurations. Our results therefore indicate that the nystatin-induced open cell-attached patch can serve as an alternative approach to the excised inside-out patch when experiments require modulation of univalent ions in the cytosol.

  10. Dual patch voltage clamp study of low membrane resistance astrocytes in situ.

    Science.gov (United States)

    Ma, Baofeng; Xu, Guangjin; Wang, Wei; Enyeart, John J; Zhou, Min

    2014-03-17

    Whole-cell patch clamp recording has been successfully used in identifying the voltage-dependent gating and conductance properties of ion channels in a variety of cells. However, this powerful technique is of limited value in studying low membrane resistance cells, such as astrocytes in situ, because of the inability to control or accurately measure the real amplitude of command voltages. To facilitate the study of ionic conductances of astrocytes, we have developed a dual patch recording method which permits membrane current and membrane potential to be simultaneously recorded from astrocytes in spite of their extraordinarily low membrane resistance. The utility of this technique is demonstrated by measuring the voltage-dependent activation of the inwardly rectifying K+ current abundantly expressed in astrocytes and multiple ionic events associated with astrocytic GABAA receptor activation. This protocol can be performed routinely in the study of astrocytes. This method will be valuable for identifying and characterizing the individual ion channels that orchestrate the electrical activity of low membrane resistance cells.

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

    Science.gov (United States)

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

    2014-11-01

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

  12. Negligible substrate clamping effect on piezoelectric response in (111)-epitaxial tetragonal Pb(Zr, Ti)O{sub 3} films

    Energy Technology Data Exchange (ETDEWEB)

    Yamada, Tomoaki, E-mail: t-yamada@nucl.nagoya-u.ac.jp [Department of Materials, Physics and Energy Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012 (Japan); Yasumoto, Jun; Ito, Daisuke; Yoshino, Masahito; Nagasaki, Takanori [Department of Materials, Physics and Energy Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603 (Japan); Sakata, Osami [Synchrotron X-ray Station at SPring-8 and Synchrotron X-ray Group, National Institute for Materials Science, Sayo-cho, Sayo-gun, Hyogo 679-5148 (Japan); Department of Innovative and Engineered Material, Tokyo Institute of Technology, Yokohama 226-8503 (Japan); Imai, Yasuhiko [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Kiguchi, Takanori [Institute for Materials Research, Tohoku University, Sendai, Miyagi 980-8577 (Japan); Shiraishi, Takahisa; Shimizu, Takao; Funakubo, Hiroshi [Department of Innovative and Engineered Material, Tokyo Institute of Technology, Yokohama 226-8503 (Japan)

    2015-08-21

    The converse piezoelectric responses of (111)- and (001)-epitaxial tetragonal Pb(Zr{sub 0.35}Ti{sub 0.65})O{sub 3} [PZT] films were compared to investigate the orientation dependence of the substrate clamping effect. Synchrotron X-ray diffraction (XRD) and piezoelectric force microscopy revealed that the as-grown (111)-PZT film has a polydomain structure with normal twin boundaries that are changed by the poling process to inclined boundaries, as predicted by Romanov et al. [Phys. Status Solidi A 172, 225 (1999)]. Time-resolved synchrotron XRD under bias voltage showed the negligible impact of substrate clamping on the piezoelectric response in the (111)-PZT film, unlike the case for (001)-PZT film. The origin of the negligible clamping effect in the (111)-PZT film is discussed from the viewpoint of the elastic properties and the compensation of lattice distortion between neighboring domains.

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

    Science.gov (United States)

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

    2018-04-11

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

  14. Quantitative analysis of dual whole-cell voltage-clamp determination of gap junctional conductance

    NARCIS (Netherlands)

    van Rijen, H. V.; Wilders, R.; van Ginneken, A. C.; Jongsma, H. J.

    1998-01-01

    The dual whole-cell voltage-clamp technique is used widely for determination of kinetics and conductance of gap junctions. The use of this technique may, however, occasion to considerable errors. We have analysed the errors in steady state junctional conductance measurements under different

  15. J-integral analysis of heterogeneous mismatched girth welds in clamped single-edge notched tension specimens

    International Nuclear Information System (INIS)

    Hertelé, Stijn; De Waele, Wim; Verstraete, Matthias; Denys, Rudi; O'Dowd, Noel

    2014-01-01

    Flaw assessment procedures require a quantification of crack driving force, and such procedures are generally based on the assumption of weld homogeneity. However, welds generally have a heterogeneous microstructure, which will influence the crack driving force. This paper describes a stress-based methodology to assess complex heterogeneous welds using a J-based approach. Clamped single-edge notched tension specimens, representative of girth weld flaws, are analyzed and the influence of weld heterogeneity on crack driving force has been determined. The use of a modified limit load for heterogeneous welds is proposed, suitable for implementation in a ‘homogenized’ J-integral estimation scheme. It follows from an explicit modification of an existing solution for centre cracked tension specimens. The proposed solution provides a good estimate of crack driving force and any errors in the approximation may be accounted for by means of a small safety factor on load bearing capacity. - Highlights: • We present a crack driving force estimation procedure for heterogeneous welds. • The procedure is based on a ‘homogenized’ version of the EPRI equation. • Complex welds are translated into equivalent idealized mismatched welds. • The procedure is validated for clamped SE(T) specimens. • A mismatch limit load for clamped SE(T) specimens is developed

  16. Five-Level Z-Source Neutral Point-Clamped Inverter

    DEFF Research Database (Denmark)

    Gao, F.; Loh, P.C.; Blaabjerg, Frede

    2007-01-01

    This paper proposes a five-level Z-source neutralpoint- clamped (NPC) inverter with two Z-source networks functioning as intermediate energy storages coupled between dc sources and NPC inverter circuitry. Analyzing the operational principles of Z-source network with partial dclink shoot......-through scheme reveals the hidden theories in the five-level Z-source NPC inverter unlike the operational principle appeared in the general two-level Z-source inverter, so that the five-level Z-source NPC inverter can be designed with the modulation of carrier-based phase disposition (PD) or alternative phase...

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

    Science.gov (United States)

    Gray, Richard A; Pathmanathan, Pras

    2016-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Dimitrios Zikos

    2013-04-01

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

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

    Science.gov (United States)

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

    2011-04-04

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

  20. Analysis of electrically evoked compound action potential of the auditory nerve in children with bilateral cochlear implants.

    Science.gov (United States)

    Caldas, Fernanda Ferreira; Cardoso, Carolina Costa; Barreto, Monique Antunes de Souza Chelminski; Teixeira, Marina Santos; Hilgenberg, Anacléia Melo da Silva; Serra, Lucieny Silva Martins; Bahmad Junior, Fayez

    2016-01-01

    The cochlear implant device has the capacity to measure the electrically evoked compound action potential of the auditory nerve. The neural response telemetry is used in order to measure the electrically evoked compound action potential of the auditory nerve. To analyze the electrically evoked compound action potential, through the neural response telemetry, in children with bilateral cochlear implants. This is an analytical, prospective, longitudinal, historical cohort study. Six children, aged 1-4 years, with bilateral cochlear implant were assessed at five different intervals during their first year of cochlear implant use. There were significant differences in follow-up time (p=0.0082) and electrode position (p=0.0019) in the T-NRT measure. There was a significant difference in the interaction between time of follow-up and electrode position (p=0.0143) when measuring the N1-P1 wave amplitude between the three electrodes at each time of follow-up. The electrically evoked compound action potential measurement using neural response telemetry in children with bilateral cochlear implants during the first year of follow-up was effective in demonstrating the synchronized bilateral development of the peripheral auditory pathways in the studied population. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  1. Gasket-holder to put in place gaskets for connection of pipes with clamp fittings

    International Nuclear Information System (INIS)

    Fiori, R.

    1989-01-01

    Gasket-holder comprising 2 arms with tongues holding the gasket and fixing devices on a pipe clamp fitting and centering means. Application is made to fit circular gaskets on pipe with conic end in adverse environment [fr

  2. Contamination of current-clamp measurement of neuron capacitance by voltage-dependent phenomena

    Science.gov (United States)

    White, William E.

    2013-01-01

    Measuring neuron capacitance is important for morphological description, conductance characterization, and neuron modeling. One method to estimate capacitance is to inject current pulses into a neuron and fit the resulting changes in membrane potential with multiple exponentials; if the neuron is purely passive, the amplitude and time constant of the slowest exponential give neuron capacitance (Major G, Evans JD, Jack JJ. Biophys J 65: 423–449, 1993). Golowasch et al. (Golowasch J, Thomas G, Taylor AL, Patel A, Pineda A, Khalil C, Nadim F. J Neurophysiol 102: 2161–2175, 2009) have shown that this is the best method for measuring the capacitance of nonisopotential (i.e., most) neurons. However, prior work has not tested for, or examined how much error would be introduced by, slow voltage-dependent phenomena possibly present at the membrane potentials typically used in such work. We investigated this issue in lobster (Panulirus interruptus) stomatogastric neurons by performing current clamp-based capacitance measurements at multiple membrane potentials. A slow, voltage-dependent phenomenon consistent with residual voltage-dependent conductances was present at all tested membrane potentials (−95 to −35 mV). This phenomenon was the slowest component of the neuron's voltage response, and failure to recognize and exclude it would lead to capacitance overestimates of several hundredfold. Most methods of estimating capacitance depend on the absence of voltage-dependent phenomena. Our demonstration that such phenomena make nonnegligible contributions to neuron responses even at well-hyperpolarized membrane potentials highlights the critical importance of checking for such phenomena in all work measuring neuron capacitance. We show here how to identify such phenomena and minimize their contaminating influence. PMID:23576698

  3. Action Learning: Avoiding Conflict or Enabling Action

    Science.gov (United States)

    Corley, Aileen; Thorne, Ann

    2006-01-01

    Action learning is based on the premise that action and learning are inextricably entwined and it is this potential, to enable action, which has contributed to the growth of action learning within education and management development programmes. However has this growth in action learning lead to an evolution or a dilution of Revan's classical…

  4. Modulation Methods for Neutral-Point-Clamped Wind Power Converter Achieving Loss and Thermal Redistribution Under Low-Voltage Ride-Through

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2014-01-01

    The three-level neutral-point (NP)-clamped (3L-NPC) converter is a promising multilevel topology in the application of megawatt wind power generation systems. However, the growing requirements by grid codes may impose high stress and even give reliability problem to this converter topology......, with the proposed modulation methods, the thermal distribution in the 3L-NPC wind power inverter undergoing LVRT becomes more equal, and the junction temperature of the most stressed devices can be also relieved. Also, the control ability of the dc-bus NP potential, which is one of the crucial considerations...

  5. Timing of umbilical cord clamping among infants born at 22 through 27 weeks' gestation.

    Science.gov (United States)

    Backes, C H; Huang, H; Iams, J D; Bauer, J A; Giannone, P J

    2016-01-01

    To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation. This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s). Forty mother-infant pairs were randomized. Infants in the ICC and DCC groups had mean gestational ages (GA) of 24.6 and 24.4 weeks, respectively. No differences were observed between the groups across all available safety measures, although infants in the DCC group had higher admission temperatures than infants in the ICC group (97.4 vs. 96.2 °F, P=0.04). During the first 24 h of life, blood pressures were lower in the ICC group than in the DCC group (P<0.05), despite a threefold greater incidence of treatment for hypotension (45% vs. 12%, P<0.01). Infants in the ICC group had increased numbers of red blood transfusions (in first 28 days of life) than infants in DCC group (4.1±3.9 vs. 2.8±2.2, P=0.04). Among infants born at an average GA of 24 weeks', DCC appears safe, logistically feasible, and offers hematological and circulatory advantages compared with ICC. A more comprehensive appraisal of this practice is needed.

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

    Science.gov (United States)

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

    2017-10-01

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

  7. Pituitary-gonadal and pituitary-thyroid axis hormone concentrations before and during a hypoglycemic clamp after sleep deprivation in healthy men.

    Directory of Open Access Journals (Sweden)

    Kamila Jauch-Chara

    Full Text Available Total sleep deprivation (TSD exerts strong modulatory effects on the secretory activity of endocrine systems that might be related to TSD-induced challenges of cerebral glucose metabolism. Here, we investigate whether TSD affects the course of male pituitary-gonadal and pituitary-thyroid axis related hormones during a subsequent 240-min hypoglycemic clamp. Ten healthy men were tested on 2 different conditions, TSD and 7-hour regular sleep. Circulating concentrations of total testosterone, prolactin (PRL, thyroid stimulating hormone (TSH, free triiodothyronine (fT3, and free thyroxin (fT4 were measured during baseline and a subsequent hypoglycemic clamp taking place in the morning. Basal, i.e. at 07:00 am measured, concentrations of total testosterone (P = 0.05 and PRL (P<0.01 were lower while the values of TSH (P = 0.02, fT3 (P = 0.08, and fT4 (P = 0.04 were higher after TSD as compared to regular sleep. During the subsequent hypoglycemic clamp (all measurements from baseline to the end of the clamp analyzed total testosterone concentrations in the regular sleep (P<0.01 but not in the TSD condition (P = 0.61 decreased, while PRL levels increased (P = 0.05 irrespectively of the experimental condition (P = 0.31. TSH concentrations decreased during hypoglycemia (P<0.01, with this decrease being more pronounced after TSD (P = 0.04. However, at the end of the hypoglycemic clamp concentrations all of the above mentioned hormones did not differ between the two sleep conditions. Our data indicate a profound influence of TSD on male pituitary-gonadal and pituitary-thyroid axis hormones characterized by reduced basal testosterone and PRL levels and increased TSH levels. However, since concentrations of these hormones measured at the end of the 240-min hypoglycemic clamp were not affected by TSD it can be speculated that the influence of TSD on the two endocrine axes is rather short lived or does not interact in an additive

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

    DEFF Research Database (Denmark)

    Krarup, Christian

    2004-01-01

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

  9. Battery charger with a capacitor-diode clamped LLC resonant converter

    OpenAIRE

    Tsang, C.; Bingham, C.; Foster, M. P.; Stone, D.; Leech, J.

    2016-01-01

    The paper proposes a novel battery charger through use of\\ud two serially-connected LLC resonant converters. The first\\ud stage utilises a capacitor-diode clamped LLC resonant\\ud converter which allows operation in both constant voltage\\ud (CV) and constant current (CC) modes, as found in most\\ud battery chargers, to be realised, whilst the second stage\\ud provides the necessary gain and line and load regulation. A\\ud design example is included that demonstrates the resulting\\ud converter top...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  12. Pathological prolongation of action potential duration as a cause of the reduced alpha-adrenoceptor-mediated negative inotropy in streptozotocin-induced diabetic mice myocardium.

    Science.gov (United States)

    Kanae, Haruna; Hamaguchi, Shogo; Wakasugi, Yumi; Kusakabe, Taichi; Kato, Keisuke; Namekata, Iyuki; Tanaka, Hikaru

    2017-11-01

    Effect of pathological prolongation of action potential duration on the α-adrenoceptor-mediated negative inotropy was studied in streptozotocin-induced diabetic mice myocardium. In streptozotocin-treated mouse ventricular myocardium, which had longer duration of action potential than that in control mice, the negative inotropic response induced by phenylephrine was smaller than that in control mice. 4-Aminopyridine prolonged the action potential duration and decreased the negative inotropy in control mice. Cromakalim shortened the action potential duration and increased the negative inotropy in streptozotocin-treated mice. These results suggest that the reduced α-adrenoceptor-mediated inotropy in the diabetic mouse myocardium is partly due to its prolonged action potential. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  13. Balance control strategy of two-amplitude actively clamped resonant DC-Link inverter clamping voltage%双幅有源箝位谐振直流环节逆变器箝位电压平衡控制策略

    Institute of Scientific and Technical Information of China (English)

    陈沁野; 张德华; 侯尧杰

    2012-01-01

    Aiming at the big loss of the traditional clamping voltage balance control strategies, in two-amplitude actively clamped resonant DC-LINK inverter, the work process of DC link was analyzed. In order to keep the clamp capacitor voltage balance the value set in DC-link work, no short-circuit control was proposed.The DC-link of inverter was calculated by Mathcad. The loss of two modes of short-circuit control and no short-circuit control were compared.Under the no short-circuit control and voltage ripple is not be greater than twenty percent, the parameters of the clamp capacitor were calculated. The results indicate that, the micro-power ACRDCLI clamping voltage balance use no short-circuit control,that can reduce the loss of the DC link and can use thin-film capacitor as a clamp capacitor to achieve the micro-power ACRDCLI low loss and iong life requirements.%针对微型功率双幅有源箝位谐振直流环节逆变器在正常工作过程中,传统箝位电压平衡母线短路控制策略带来损耗大的问题,开展了直流环节工作过程的分析,针对直流环节正常工作的情况下,箝位电容电压必须能平衡在设定值,提出了箝位电压平衡母线无短路控制策略,根据给出的损耗估算方法,通过Mathcad计算,对比了母线短路控制和无短路控制两种方式下的损耗,同时计算出了母线无短路控制箝位电容电压纹波不大于20%下的箝位电容参数.研究结果表明:微型功率ACRDCLI箝位电压平衡采用母线无短线控制,不但可以减少双幅有源箝位谐振直流环节逆变器的损耗,并且可以使用薄膜电容作为箝位电容,以达到微型功率ACRDCLI损耗低、寿命长的要求.

  14. Teachers in Action Research: Assumptions and Potentials

    Science.gov (United States)

    Li, Yuen-Ling

    2008-01-01

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

  15. Hda monomerization by ADP binding promotes replicase clamp-mediated DnaA-ATP hydrolysis.

    Science.gov (United States)

    Su'etsugu, Masayuki; Nakamura, Kenta; Keyamura, Kenji; Kudo, Yuka; Katayama, Tsutomu

    2008-12-26

    ATP-DnaA is the initiator of chromosomal replication in Escherichia coli, and the activity of DnaA is regulated by the regulatory inactivation of the DnaA (RIDA) system. In this system, the Hda protein promotes DnaA-ATP hydrolysis to produce inactive ADP-DnaA in a mechanism that is mediated by the DNA-loaded form of the replicase sliding clamp. In this study, we first revealed that hda translation uses an unusual initiation codon, CUG, located downstream of the annotated initiation codon. The CUG initiation codon could be used for restricting the Hda level, as this initiation codon has a low translation efficiency, and the cellular Hda level is only approximately 100 molecules per cell. Hda translated using the correct reading frame was purified and found to have a high RIDA activity in vitro. Moreover, we found that Hda has a high affinity for ADP but not for other nucleotides, including ATP. ADP-Hda was active in the RIDA system in vitro and stable in a monomeric state, whereas apo-Hda formed inactive homomultimers. Both ADP-Hda and apo-Hda could form complexes with the DNA-loaded clamp; however, only ADP-Hda-DNA-clamp complexes were highly functional in the following interaction with DnaA. Formation of ADP-Hda was also observed in vivo, and mutant analysis suggested that ADP binding is crucial for cellular Hda activity. Thus, we propose that ADP is a crucial Hda ligand that promotes the activated conformation of the protein. ADP-dependent monomerization might enable the arginine finger of the Hda AAA+ domain to be accessible to ATP bound to the DnaA AAA+ domain.

  16. Potassium Chloride Versus Voltage Clamp Contractures in Ventricular Muscle

    Science.gov (United States)

    Morad, M.; Reeck, S.; Rao, M.

    1981-01-01

    In frog ventricle, developed tension was markedly larger in response to depolarization caused by a voltage clamp step than to depolarization induced by high concentrations of potassium chloride. Measurement of extracellular potassium activity at the surface and at the depth of muscle during the development of contractures showed that the diffusion of potassium is much slower than the spread of depolarization through the cross section of muscle. These two observations suggest that competition between the depolarizing and the negative inotropic effects of an increase in the extracellular potassium ion concentration may determine the time course and magnitude of contractile tension in heart muscle.

  17. Overmodulation of n-level three-leg DC-AC diode-clamped converters with comprehensive capacitor voltage balance

    DEFF Research Database (Denmark)

    Busquets-Monge, S.; Maheshwari, Ram Krishan; Munk-Nielsen, Stig

    2013-01-01

    This paper presents a novel PWM strategy for nlevel three-leg semiconductor-clamped dc-ac converters in the overmodulation region, with dc-link capacitor voltage balance in every switching cycle. The strategy is based on the virtual-vector concept. Suitable reference vector trajectories are selec......This paper presents a novel PWM strategy for nlevel three-leg semiconductor-clamped dc-ac converters in the overmodulation region, with dc-link capacitor voltage balance in every switching cycle. The strategy is based on the virtual-vector concept. Suitable reference vector trajectories...

  18. Enhanced static ground power unit based on flying capacitor based h-bridge hybrid active-neutral-point-clamped converter

    DEFF Research Database (Denmark)

    Abarzadeh, Mostafa; Madadi Kojabadi, Hossein; Deng, Fujin

    2016-01-01

    Static power converters have various applications, such as static ground power units (GPUs) for airplanes. This study proposes a new configuration of a static GPU based on a novel nine-level flying capacitor h-bridge active-neutral-point-clamped (FCHB_ANPC) converter. The main advantages of the p......Static power converters have various applications, such as static ground power units (GPUs) for airplanes. This study proposes a new configuration of a static GPU based on a novel nine-level flying capacitor h-bridge active-neutral-point-clamped (FCHB_ANPC) converter. The main advantages...

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

    Science.gov (United States)

    Pearman, Charles M.

    2014-01-01

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

  20. Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

    Directory of Open Access Journals (Sweden)

    Morgan Kristen

    2011-01-01

    Full Text Available Abstract Background We and others have demonstrated previously that ghrelin receptor (GhrR knock out (KO mice fed a high fat diet (HFD have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG and hyperinsulinemic-euglycemic (HI-E clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd, and decreased hepatic glucose production (HGP. HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is

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

    Science.gov (United States)

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

    2003-01-01

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

  2. The activity of spontaneous action potentials in developing hair cells is regulated by Ca(2+-dependence of a transient K+ current.

    Directory of Open Access Journals (Sweden)

    Snezana Levic

    Full Text Available Spontaneous action potentials have been described in developing sensory systems. These rhythmic activities may have instructional roles for the functional development of synaptic connections. The importance of spontaneous action potentials in the developing auditory system is underpinned by the stark correlation between the time of auditory system functional maturity, and the cessation of spontaneous action potentials. A prominent K(+ current that regulates patterning of action potentials is I(A. This current undergoes marked changes in expression during chicken hair cell development. Although the properties of I(A are not normally classified as Ca(2+-dependent, we demonstrate that throughout the development of chicken hair cells, I(A is greatly reduced by acute alterations of intracellular Ca(2+. As determinants of spike timing and firing frequency, intracellular Ca(2+ buffers shift the activation and inactivation properties of the current to more positive potentials. Our findings provide evidence to demonstrate that the kinetics and functional expression of I(A are tightly regulated by intracellular Ca(2+. Such feedback mechanism between the functional expression of I(A and intracellular Ca(2+ may shape the activity of spontaneous action potentials, thus potentially sculpting synaptic connections in an activity-dependent manner in the developing cochlea.

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

    Directory of Open Access Journals (Sweden)

    Anne-Kathrin Theis

    2018-04-01

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

  4. Significance of Shrinkage Induced Clamping Pressure in Fiber-Matrix Bonding in Cementitious Composite Materials

    DEFF Research Database (Denmark)

    Stang, Henrik

    1996-01-01

    used in high performance cementitious composite materials.Assuming a Coulomb type of friction on the fiber/matrix interface andusing typical values for the frictional coefficient it is shownthat the shrinkage induced clamping pressure could be one of the mostimportant factors determining the frictional...

  5. Trans-Z-source Neutral Point Clamped inverter

    DEFF Research Database (Denmark)

    Mo, W.; Loh, P. C.; Li, D.

    2012-01-01

    Transformer based Z-source (trans-Z-source) inverters are recently proposed by extending the traditional Z-source inverter with higher buck-boost capability as well as reducing the passive components at the same time. Multi-Level Z-source inverters are single-stage topological solutions used...... for buck-boost energy conversion with all the favourable advantages of multi-level switching retained. This paper presents three-level trans-Z-source Neutral Point Clamped (NPC) inverter topology, which achieves both the advantages of trans-Z-source and three-level NPC inverter configuration. With proper...... modulation scheme, the three-level trans-Z-source inverter can function with minimum of six device commutations per half carrier cycle (same as the traditional buck NPC inverter), while maintaining to produce the designed volt-sec average and inductive voltage boosting at ac output terminals. The designed...

  6. Characterization of the mandible Atta laevigata and the bioinspiration for the development of a biomimetic surgical clamp

    Energy Technology Data Exchange (ETDEWEB)

    Brito, Thays Obando; Elzubair, Amal; Araújo, Leonardo Sales; Camargo, Sergio Alvaro de Souza; Almeida, Luiz Henrique, E-mail: thaysdesigner@hotmail.com [Coordenacao de Pos-Graduacao e Pesquisa de Engenharia (PEMM/COPPE/UFRJ), Rio de Janeiro, RJ (Brazil). Programa de Engenharia Metalúrgica e de Materiais; Souza, Jorge Luiz Pereira [Instituto Nacional de Pesquisas da Amazônia, Manaus, AM (Brazil)

    2017-11-15

    Approximately thousand years ago it was reported the use of mandibles of ants for suture. In this sense, bioinspired components, as absorbable surgical clamps, can be designed. This study is aimed to characterize the mandible of the ant Atta laevigata in order to help the selection of candidate biomaterials for application as surgical clamps. Three pairs of mandibles were used and ten nanoindenations were performed in each pair. The average hardness for the samples in the internal and external regions were 0.36 ± 0.06 GPa and 0.19 ± 0.04 GPa, respectively and the average elastic modulus for the internal and external regions were 6.16 ± 0.23 GPa and 2.74 ± 0.44 GPa, respectively. The morphology of the mandible was observed in detail by scanning electron microscopy, as well as Energy-dispersive X-ray spectroscopy. The average roughnesses on the internal and external regions, measured by atomic force microscopy, were 6.73 ± 0.90 nm and 11.87 ± 1.42 nm, respectively. From these results, it was possible to identify biomaterials that mimic the mandible behaviour for surgical clamp. (author)

  7. Loss and thermal redistributed modulation methods for three-level neutral-point-clamped wind power inverter undergoing Low Voltage Ride Through

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2012-01-01

    The three-level neutral-point-clamped (3L-NPC) converter is a promising multilevel topology in the application of mega-watts wind power generation system. However, the growing requirements by grid codes may impose high stress and even give reliability problem to this converter topology. This paper...... modulation methods, the thermal distribution in the 3L-NPC wind power inverter undergoing LVRT becomes more equal, and the junction temperature of the most stressed devices can be also relieved. Also the control ability of DC-bus neutral point potential, which is one of the crucial considerations for the 3L...

  8. Shape of a clamped stiff harpsichord wire driven at a resonant frequency

    Science.gov (United States)

    Hanson, Roger J.; Macomber, Hilliard Kent; Boucher, Mathew A.

    2002-05-01

    A wire transversely driven by a sinusoidal force at the resonant frequency of a vibrational mode vibrates at the driving frequency and at harmonics generated by nonlinear processes in the wire. If the amplitude of a harmonic is measured as a function of position along the wire, its shape is revealed. It differs significantly from a sinusoid in the vicinity of either end of the wire because the ends are clamped and the wire has significant stiffness. The shapes of various harmonics have been determined for a brass harpsichord wire, 70 cm long, from optical detector measurements made at different distances from a clamped end. Knowledge of shape facilitates the determination of antinode amplitudes of harmonics when the gross motion of the wire is so large that the detectors must be positioned near an end of the wire because of their very limited dynamic range. Some observations of harmonics and related phenomena were reported previously [Hanson et al., J. Acoust Soc. Am. 108, 2592 (2000); 106, 2141 (1999)]. The shape information is also needed to help separate nonlinear effects possibly occurring in the detectors from those of interest, occurring in the wire itself.

  9. Underlying mechanism of regulatory actions of diclofenac, a nonsteroidal anti-inflammatory agent, on neuronal potassium channels and firing: an experimental and theoretical study.

    Science.gov (United States)

    Huang, C W; Hung, T Y; Liao, Y K; Hsu, M C; Wu, S N

    2013-06-01

    Diclofenac (DIC), a nonsteroidal anti-inflammatory drug, is known to exert anti-nociceptive and anti-convulsant actions; however, its effects on ion currents, in neurons remain debatable. We aimed to investigate (1) potential effects of diclofenac on membrane potential and potassium currents in differentiated NSC-34 neuronal cells and dorsal root ganglion (DRG) neurons with whole-cell patch-clamp technology, and (2) firing of action potentials (APs), using a simulation model from hippocampal CA1 pyramidal neurons based on diclofenac's effects on potassium currents. In the NSC-34 cells, diclofenac exerted an inhibitory effect on delayed-rectifier K⁺ current (I(KDR)) with an IC₅₀ value of 73 μM. Diclofenac not merely inhibited the I(KDR) amplitude in response to membrane depolarization, but also accelerated the process of current inactivation. The inhibition by diclofenac of IK(DR) was not reversed by subsequent application of either naloxone. Importantly, diclofenac (300 μM) increased the amplitude of M-type K⁺ current (I)(KM)), while flupirtine (10 μM) or meclofenamic acid (10 μM) enhanced it effectively. Consistently, diclofenac (100 μM) increased the amplitude of I(KM) and diminished the I(KDR) amplitude, with a shortening of inactivation time constant in DRG neurons. Furthermore, by using the simulation modeling, we demonstrated the potential electrophysiological mechanisms underlying changes in AP firing caused by diclofenac. During the exposure to diclofenac, the actions on both I(KM) and I(KDR) could be potential mechanism through which it influences the excitability of fast-spiking neurons. Caution needs to be made in attributing the effects of diclofenac primarily to those produced by the activation of I(KM).

  10. A new configuration for multilevel converters with diode clamped topology

    DEFF Research Database (Denmark)

    Nami, A.; Zare, F.; Ledwich, G.

    2008-01-01

    Due to the increased use of renewable energy and power elctronic applications, more multilevel converters (MLC) are developed. A Neutral Point Clamped (NPC) inverter is one of the most used multilevel topologies for wind turbine (WT) and photovoltaic (PV) applications. One of the most crucial...... of load changes which can avoid neutral point balancing problem in such converters. In addition, the presented topology is suitable for renewable energy systems to boost the low rectified output-voltage. In order to verify the proposed topology, steady state analysis, modelling and simulations are carried...

  11. Model Predictive Control of Z-source Neutral Point Clamped Inverter

    DEFF Research Database (Denmark)

    Mo, Wei; Loh, Poh Chiang; Blaabjerg, Frede

    2011-01-01

    This paper presents Model Predictive Control (MPC) of Z-source Neutral Point Clamped (NPC) inverter. For illustration, current control of Z-source NPC grid-connected inverter is analyzed and simulated. With MPC’s advantage of easily including system constraints, load current, impedance network...... response are obtained at the same time with a formulated Z-source NPC inverter network model. Operation steady state and transient state simulation results of MPC are going to be presented, which shows good reference tracking ability of this method. It provides new control method for Z-source NPC inverter...

  12. Contributions of a unique β-clamp to substrate recognition illuminates the molecular basis of exolysis in ferulic acid esterases.

    Science.gov (United States)

    Gruninger, Robert J; Cote, Chris; McAllister, Tim A; Abbott, D Wade

    2016-04-01

    Lignocellulosic biomass is a promising renewable resource; however, deconstruction of this material is still the rate-limiting step. Major obstacles in the biocatalytic turnover of lignocellulose are ester-linked decorations that prevent access to primary structural polysaccharides. Enzymes targeting these esters represent promising biotools for increasing bioconversion efficiency. Ruminant livestock are unique in their ability to degrade lignocellulose through the action of their gut microbiome. The anaerobic fungi (phylum Neocallimastigomycota) are key members of this ecosystem that express a large repertoire of carbohydrate-active enzymes (CAZymes) with little sequence identity with characterized CAZymes [Lombard, Golaconda, Drula, Coutinho and Henrissat (2014) Nucleic Acids Res. 42: , D490-D495]. We have identified a carbohydrate esterase family 1 (CE1) ferulic acid esterase (FAE) belonging to Anaeromyces mucronatus(AmCE1/Fae1a), and determined its X-ray structure in both the presence [1.55 Å (1 Å=0.1 nm)] and absence (1.60 Å) of ferulic acid. AmCE1 adopts an α/β-hydrolase fold that is structurally conserved with bacterial FAEs, and possesses a unique loop, termed the β-clamp, that encloses the ligand. Isothermal titration calorimetry reveals that substrate binding is driven by enthalpic contributions, which overcomes a large entropic penalty. A comparative analysis of AmCE1 with related enzymes has uncovered the apparent structural basis for differential FAE activities targeting cross-linking ferulic acid conjugates compared with terminal decorations. Based on comparisons to structurally characterized FAEs, we propose that the β-clamp may define the structural basis of exolytic activities in FAEs. This provides a structure-based tool for predicting exolysis and endolysis in CE1. These insights hold promise for rationally identifying enzymes tailored for bioconversion of biomass with variations in cell wall composition. © 2016 Authors; published by

  13. Super agonist actions of clothianidin and related compounds on the SAD beta 2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes.

    Science.gov (United States)

    Ihara, Makoto; Matsuda, Kazuhiko; Shimomura, Masaru; Sattelle, David B; Komai, Koichiro

    2004-03-01

    To compare the actions of clothianidin, a neonicotinoid acting on insect nicotinic acetylcholine receptors, and related compounds with that of imidacloprid, the compounds were tested on the Drosophila SAD-chicken beta2 nicotinic acetylcholine receptor expressed in Xenopus laevis oocytes using two-electrode voltage-clamp electrophysiology. The maximum response of the SAD beta 2 nicotinic receptor to clothianidin was larger than that observed for acetylcholine. Ring breakage of the imidazolidine ring of imidacloprid resulting in the generation of a guanidine group was critical for this super agonist action.

  14. A low-voltage sense amplifier with two-stage operational amplifier clamping for flash memory

    Science.gov (United States)

    Guo, Jiarong

    2017-04-01

    A low-voltage sense amplifier with reference current generator utilizing two-stage operational amplifier clamp structure for flash memory is presented in this paper, capable of operating with minimum supply voltage at 1 V. A new reference current generation circuit composed of a reference cell and a two-stage operational amplifier clamping the drain pole of the reference cell is used to generate the reference current, which avoids the threshold limitation caused by current mirror transistor in the traditional sense amplifier. A novel reference voltage generation circuit using dummy bit-line structure without pull-down current is also adopted, which not only improves the sense window enhancing read precision but also saves power consumption. The sense amplifier was implemented in a flash realized in 90 nm flash technology. Experimental results show the access time is 14.7 ns with power supply of 1.2 V and slow corner at 125 °C. Project supported by the National Natural Science Fundation of China (No. 61376028).

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

    Science.gov (United States)

    Pearman, Charles M

    2014-12-01

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

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

    Science.gov (United States)

    Belz, Regina G

    2016-01-01

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

  17. Intra-articular injection of tranexamic acid via a drain plus drain-clamping to reduce blood loss in cementless total knee arthroplasty

    Directory of Open Access Journals (Sweden)

    Mutsuzaki Hirotaka

    2012-09-01

    Full Text Available Abstract Background Patients undergoing cementless total knee arthroplasty (TKA sometimes suffer large blood loss. In a retrospective study, we explored whether postoperative intra-articular retrograde injection of tranexamic acid (TA and leaving a drain clamp in place for 1 h reduced blood loss. Patients and methods Patients (n = 140 treated with unilateral primary cementless TKA (posterior cruciate ligament retained were divided into two groups: those who had an intra-articular injection of TA (1000 mg and drain clamping for 1 h postoperatively (study group, n = 70 and those who were not given TA and did not undergo clamping of their drains (control group, n = 70. Postoperative total blood loss, volume of drainage, hemoglobin level, transfusion amounts and rates, D-dimer level at postoperative day (POD 7, and complications were recorded. Results Total blood loss, total drainage, mean transfusion volume, and transfusion rates were lower in the study group than in controls (P P P  Conclusions Immediately postoperative intra-articular retrograde injection of TA and 1 h of drain-clamping effectively reduced blood loss and blood transfusion after cementless TKA. We believe that this method is simple, easy, and suitable for these patients.

  18. Hda Monomerization by ADP Binding Promotes Replicase Clamp-mediated DnaA-ATP Hydrolysis*S⃞

    Science.gov (United States)

    Su'etsugu, Masayuki; Nakamura, Kenta; Keyamura, Kenji; Kudo, Yuka; Katayama, Tsutomu

    2008-01-01

    ATP-DnaA is the initiator of chromosomal replication in Escherichia coli, and the activity of DnaA is regulated by the regulatory inactivation of the DnaA (RIDA) system. In this system, the Hda protein promotes DnaA-ATP hydrolysis to produce inactive ADP-DnaA in a mechanism that is mediated by the DNA-loaded form of the replicase sliding clamp. In this study, we first revealed that hda translation uses an unusual initiation codon, CUG, located downstream of the annotated initiation codon. The CUG initiation codon could be used for restricting the Hda level, as this initiation codon has a low translation efficiency, and the cellular Hda level is only ∼100 molecules per cell. Hda translated using the correct reading frame was purified and found to have a high RIDA activity in vitro. Moreover, we found that Hda has a high affinity for ADP but not for other nucleotides, including ATP. ADP-Hda was active in the RIDA system in vitro and stable in a monomeric state, whereas apo-Hda formed inactive homomultimers. Both ADP-Hda and apo-Hda could form complexes with the DNA-loaded clamp; however, only ADP-Hda-DNA-clamp complexes were highly functional in the following interaction with DnaA. Formation of ADP-Hda was also observed in vivo, and mutant analysis suggested that ADP binding is crucial for cellular Hda activity. Thus, we propose that ADP is a crucial Hda ligand that promotes the activated conformation of the protein. ADP-dependent monomerization might enable the arginine finger of the Hda AAA+ domain to be accessible to ATP bound to the DnaA AAA+ domain. PMID:18977760

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

    Science.gov (United States)

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

    2016-02-03

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

  20. Closed-form solution for static pull-in voltage of electrostatically actuated clamped-clamped micro/nano beams under the effect of fringing field and van der Waals force

    Science.gov (United States)

    Bhojawala, V. M.; Vakharia, D. P.

    2017-12-01

    This investigation provides an accurate prediction of static pull-in voltage for clamped-clamped micro/nano beams based on distributed model. The Euler-Bernoulli beam theory is used adapting geometric non-linearity of beam, internal (residual) stress, van der Waals force, distributed electrostatic force and fringing field effects for deriving governing differential equation. The Galerkin discretisation method is used to make reduced-order model of the governing differential equation. A regime plot is presented in the current work for determining the number of modes required in reduced-order model to obtain completely converged pull-in voltage for micro/nano beams. A closed-form relation is developed based on the relationship obtained from curve fitting of pull-in instability plots and subsequent non-linear regression for the proposed relation. The output of regression analysis provides Chi-square (χ 2) tolerance value equals to 1  ×  10-9, adjusted R-square value equals to 0.999 29 and P-value equals to zero, these statistical parameters indicate the convergence of non-linear fit, accuracy of fitted data and significance of the proposed model respectively. The closed-form equation is validated using available data of experimental and numerical results. The relative maximum error of 4.08% in comparison to several available experimental and numerical data proves the reliability of the proposed closed-form equation.

  1. Percutaneous clamping of spiral and oblique fractures of the tibial shaft: a safe and effective reduction aid during intramedullary nailing.

    Science.gov (United States)

    Collinge, Cory A; Beltran, Michael J; Dollahite, Henry A; Huber, Florian G

    2015-06-01

    The reduction of tibial shaft fractures during intramedullary nailing is important if limb alignment is to be restored and successful clinical outcomes are expected. We have used a percutaneously applied (or open) clamp or clamps to achieve and maintain reduction during nailing of all amendable tibial shaft fractures. In this article, we describe the technique and preliminary results comparing closed, simple spiral and oblique tibial shaft fractures (OTA 42-A1 and A2) managed with percutaneous clamp-assisted nailing (CAN) versus nailing using manual reduction (MRN) held by the surgical team. In the MRN group, there were an increased fracture gap (P = 0.04) and trends toward malalignment (P = 0.07) and healing time (P = 0.06) compared with the CAN group. There were also trends in clinical; no wound complications occurred in either group. We have found that percutaneous CAN of closed, simple spiral and oblique tibial shaft fractures seems safe and allows for early predictable union with reproducible alignment compared with nailing using MRN.

  2. Pulsewidth-modulated 2-source neutral-point-clamped inverter

    DEFF Research Database (Denmark)

    Blaabjerg, Frede; Loh, Poh Chang; Gao, Feng

    2007-01-01

    This paper presents the careful integration of a newly proposed Z-source topological concept to the basic neutral-point-clamped (NPC) inverter topology for designing a three-level inverter with both voltage-buck and voltage-boost capabilities. The designed Z-source NPC inverter uses two unique X......-shaped inductance-capacitance (LC) impedance networks that are connected between two isolated dc input power sources and its inverter circuitry for boosting its AC output voltage. Through the design of an appropriate pulsewidth-modulation (PWM) algorithm, the two impedance networks can be short......-circuited sequentially (without shooting through the inverter full DC link) for implementing the ldquonearest-three-vectorrdquo modulation principle with minimized harmonic distortion and device commutations per half carrier cycle while performing voltage boosting. With only a slight modification to the inverter PWM...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

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

    NARCIS (Netherlands)

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

    1996-01-01

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

  6. Map-based model of the cardiac action potential

    International Nuclear Information System (INIS)

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

    2011-01-01

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

  7. Map-based model of the cardiac action potential

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-07-25

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

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

    Science.gov (United States)

    Abouelela, Ahmed; Wieraszko, Andrzej

    2016-01-01

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

  9. Harmonic elimination in diode-clamped multilevel inverter using evolutionary algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Barkati, Said [Laboratoire d' analyse des Signaux et Systemes (LASS), Universite de M' sila, BP. 166, rue Ichbilia 28000 M' sila (Algeria); Baghli, Lotfi [Groupe de Recherche en Electrotechnique et Electronique de Nancy (GREEN), CNRS UMR 7030, Universite Henri Poincare Nancy 1, BP. 239, 54506 Vandoeuvre-les-Nancy (France); Berkouk, El Madjid; Boucherit, Mohamed-Seghir [Laboratoire de Commande des Processus (LCP), Ecole Nationale Polytechnique, BP. 182, 10 Avenue Hassen Badi, 16200 El Harrach, Alger (Algeria)

    2008-10-15

    This paper describes two evolutionary algorithms for the optimized harmonic stepped-waveform technique. Genetic algorithms and particle swarm optimization are applied to compute the switching angles in a three-phase seven-level inverter to produce the required fundamental voltage while, at the same time, specified harmonics are eliminated. Furthermore, these algorithms are also used to solve the starting point problem of the Newton-Raphson conventional method. This combination provides a very effective method for the harmonic elimination technique. This strategy is useful for different structures of seven-level inverters. The diode-clamped topology is considered in this study. (author)

  10. Electrothermally actuated tunable clamped-guided resonant microbeams

    Science.gov (United States)

    Alcheikh, N.; Hajjaj, A. Z.; Jaber, N.; Younis, M. I.

    2018-01-01

    We present simulation and experimental investigation demonstrating active alteration of the resonant and frequency response behavior of resonators by controlling the electrothermal actuation method on their anchors. In-plane clamped-guided arch and straight microbeams resonators are designed and fabricated with V-shaped electrothermal actuators on their anchors. These anchors not only offer various electrothermal actuation options, but also serve as various mechanical stiffness elements that affect the operating resonance frequency of the structures. We have shown that for an arch, the first mode resonance frequency can be increased up to 50% of its initial value. For a straight beam, we have shown that before buckling, the resonance frequency decreases to very low values and after buckling, it increases up to twice of its initial value. These results can be promising for the realization of different wide-range tunable microresonator. The experimental results have been compared to multi-physics finite-element simulations showing good agreement among them.

  11. Electrothermally actuated tunable clamped-guided resonant microbeams

    KAUST Repository

    Alcheikh, Nouha

    2017-06-11

    We present simulation and experimental investigation demonstrating active alteration of the resonant and frequency response behavior of resonators by controlling the electrothermal actuation method on their anchors. In-plane clamped-guided arch and straight microbeams resonators are designed and fabricated with V-shaped electrothermal actuators on their anchors. These anchors not only offer various electrothermal actuation options, but also serve as various mechanical stiffness elements that affect the operating resonance frequency of the structures. We have shown that for an arch, the first mode resonance frequency can be increased up to 50% of its initial value. For a straight beam, we have shown that before buckling, the resonance frequency decreases to very low values and after buckling, it increases up to twice of its initial value. These results can be promising for the realization of different wide–range tunable microresonator. The experimental results have been compared to multi-physics finite-element simulations showing good agreement among them.

  12. Evaluation influence of machining parameters on shape form errors in turning of machine parts clamped in the chuck with adaptive jaws

    Directory of Open Access Journals (Sweden)

    I.V. Lutsiv

    2017-12-01

    Full Text Available The paper deals with the derivation problem of the dependence of machine part geometric form deviation in cross section area on clamping diameter as well as cutting speed, feed and cutting depth in semi finish machining. The analysis of single factor circular deviation dependences on machining conditions values is performed. Using the special software application package the laboratory conditions experiment results are analyzed. The dispersion analysis including options for main linear and quadratic effects evaluation is given and the simplification model of experiment results is obtained. It presents the evaluation empiric dependence of cutting conditions and clamping diameter influence on shape error forming (dynamic error. It is found that to obtain the necessary form accuracy in machining with lathe chuck equipped with the adaptive clamping jaws it is desirable to control the most statistically significant factors that actually are the cutting depth and feed.

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

    Science.gov (United States)

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

    2015-07-01

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

  14. Effects of penicillin on procaine-elicited bursts of potential in central neuron of snail, Achatina fulica.

    Science.gov (United States)

    Chen, Yi-Hung; Lu, Kuan-Ling; Hsiao, Ru-Wan; Lee, Ya-Ling; Tsai, Hong-Chieh; Lin, Chia Hsien; Tsai, Ming-Cheng

    2008-08-01

    Effects of penicillin on changes in procaine-elicited bursts of potential (BoP) were studied in a central neuron (RP4) of snail, Achatina fulica Ferussac. Procaine elicited BoP in the RP4 neuron while penicillin elicited depolarization of the neuron. Penicillin decreased the BoP elicited by procaine in a concentration-dependent manner. The effect of penicillin on the procaine-elicited BoP was not altered in the preparations treated with ascorbate or L-NAME (N-nitro-L-arginine methyl ester). However, the inhibitory effect of penicillin on the procaine-elicited BoP was enhanced with a decrease in extracellular sodium ion. Sodium ion was one of the important ions contributing to the action potential of the neuron. Two-electrode voltage-clamp studies revealed that penicillin decreased the fast sodium inward current of the neuron. It is concluded that penicillin inhibited the BoP elicited by procaine and sodium ion altered the effect of penicillin on procaine-elicited BoP.

  15. Combined Triplex/Duplex Invasion of Double-Stranded DNA by "Tail-Clamp" Peptide Nucleic Acid

    DEFF Research Database (Denmark)

    Bentin, Thomas; Larsen, H. J.; Nielsen, Peter E.

    2003-01-01

    as determined by T-m measurements. Binding to double-stranded (ds) DNA occurred by combined triplex and duplex invasion as analyzed by permanganate probing. Furthermore, C-50 measurements revealed that tail-clamp PNAs consistently bound the dsDNA target more efficiently, and kinetics experiments revealed...

  16. A novel, "double-clamp" binding mode for human heme oxygenase-1 inhibition.

    Directory of Open Access Journals (Sweden)

    Mona N Rahman

    Full Text Available The development of heme oxygenase (HO inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl-4,4-diphenyl-2-butanone (QC-308. Using a carbon monoxide (CO formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC(50 = 0.27±0.07 µM than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC(50 = 4.0±1.8 µM. The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This "double-clamp" binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.

  17. A novel, "double-clamp" binding mode for human heme oxygenase-1 inhibition.

    Science.gov (United States)

    Rahman, Mona N; Vlahakis, Jason Z; Vukomanovic, Dragic; Lee, Wallace; Szarek, Walter A; Nakatsu, Kanji; Jia, Zongchao

    2012-01-01

    The development of heme oxygenase (HO) inhibitors is critical in dissecting and understanding the HO system and for potential therapeutic applications. We have established a program to design and optimize HO inhibitors using structure-activity relationships in conjunction with X-ray crystallographic analyses. One of our previous complex crystal structures revealed a putative secondary hydrophobic binding pocket which could be exploited for a new design strategy by introducing a functional group that would fit into this potential site. To test this hypothesis and gain further insights into the structural basis of inhibitor binding, we have synthesized and characterized 1-(1H-imidazol-1-yl)-4,4-diphenyl-2-butanone (QC-308). Using a carbon monoxide (CO) formation assay on rat spleen microsomes, the compound was found to be ∼15 times more potent (IC(50) = 0.27±0.07 µM) than its monophenyl analogue, which is already a potent compound in its own right (QC-65; IC(50) = 4.0±1.8 µM). The crystal structure of hHO-1 with QC-308 revealed that the second phenyl group in the western region of the compound is indeed accommodated by a definitive secondary proximal hydrophobic pocket. Thus, the two phenyl moieties are each stabilized by distinct hydrophobic pockets. This "double-clamp" binding offers additional inhibitor stabilization and provides a new route for improvement of human heme oxygenase inhibitors.

  18. PWM Regulation of Grid-Tied PV System on the Base of Photovoltaic-Fed Diode-Clamped Inverters

    Directory of Open Access Journals (Sweden)

    Oleschuk V.I.

    2015-12-01

    Full Text Available Investigation of grid-tied photovoltaic system on the base of two diode-clamped inverters, controlled by specific algorithms of pulse-width modulation (PWM, has been done. This system includes two strings of photovoltaic panels feeding two diode-clamped inverters. The outputs of inverters are connected with the corresponding windings on the primary side of three-phase transformer, connected with a grid. In order to reduce phase voltage distortion and to increase efficiency of operation of the system, special scheme of control and modulation of inverters has been used, providing minimization of common-mode voltages and voltage waveforms symmetries under different operating conditions. Detailed simulation of processes in this photovoltaic-fed power conversion system has been executed. The results of simulations verify good performance of photovoltaic system regulated in accordance with specific strategy of control and modulation.

  19. The Circuit-Level Decoupling Modulation Strategy for Three-Level Neutral-Point-Clamped (TL-NPC) Inverter

    DEFF Research Database (Denmark)

    Zhang, Zhe; Thomsen, Ole Cornelius; Andersen, Michael A. E.

    2011-01-01

    In this paper, a circuit-level decoupling modulation strategy is proposed for the three-level (TL) neutral-point-clamped (NPC) inverters. With the proposed modulation scheme, the TL-NPC inverter can be decoupled into two three-level Buck converters in each defined operating section, which makes...

  20. Higher order modes excitation of electrostatically actuated clamped–clamped microbeams: experimental and analytical investigation

    KAUST Repository

    Jaber, Nizar

    2016-01-06

    © 2016 IOP Publishing Ltd. In this study, we demonstrate analytically and experimentally the excitations of the higher order modes of vibrations in electrostatically actuated clamped-clamped microbeam resonators. The concept is based on using partial electrodes with shapes that induce strong excitation of the mode of interest. The devices are fabricated using polyimide as a structural layer coated with nickel from the top and chrome and gold layers from the bottom. Experimentally, frequency sweeps with different electro-dynamical loading conditions are shown to demonstrate the excitation of the higher order modes of vibration. Using a half electrode, the second mode is excited with high amplitude of vibration compared with almost zero response using the full electrode. Also, using a two-third electrode configuration is shown to amplify the third mode resonance amplitude compared with the full electrode under the same electrical loading conditions. An analytical model is developed based on the Euler-Bernollui beam model and the Galerkin method to simulate the device response. Good agreement between the simulation results and the experimental data is reported.

  1. A direct proofreader-clamp interaction stabilizes the Pol III replicase in the polymerization mode

    KAUST Repository

    Jergic, Slobodan; Horan, Nicholas P.; Elshenawy, Mohamed; Mason, Claire E.; Urathamakul, Thitima; Ozawa, Kiyoshi; Robinson, Andrew J.; Goudsmits, Joris M H; Wang, Yao; Pan, Xuefeng; Beck, Jennifer L.; Van Oijen, Antoine M.; Huber, Thomas L.; Hamdan, Samir; Dixon, Nicholas E.

    2013-01-01

    Processive DNA synthesis by the αÉ"θ core of the Escherichia coli Pol III replicase requires it to be bound to the β 2 clamp via a site in the α polymerase subunit. How the É" proofreading exonuclease subunit influences DNA synthesis by α was not previously understood. In this work, bulk assays of DNA replication were used to uncover a non-proofreading activity of É". Combination of mutagenesis with biophysical studies and single-molecule leading-strand replication assays traced this activity to a novel β-binding site in É" that, in conjunction with the site in α, maintains a closed state of the αÉ"θ-β 2 replicase in the polymerization mode of DNA synthesis. The É"-β interaction, selected during evolution to be weak and thus suited for transient disruption to enable access of alternate polymerases and other clamp binding proteins, therefore makes an important contribution to the network of protein-protein interactions that finely tune stability of the replicase on the DNA template in its various conformational states. © 2013 European Molecular Biology Organization.

  2. A direct proofreader-clamp interaction stabilizes the Pol III replicase in the polymerization mode

    KAUST Repository

    Jergic, Slobodan

    2013-02-22

    Processive DNA synthesis by the αÉ"θ core of the Escherichia coli Pol III replicase requires it to be bound to the β 2 clamp via a site in the α polymerase subunit. How the É" proofreading exonuclease subunit influences DNA synthesis by α was not previously understood. In this work, bulk assays of DNA replication were used to uncover a non-proofreading activity of É". Combination of mutagenesis with biophysical studies and single-molecule leading-strand replication assays traced this activity to a novel β-binding site in É" that, in conjunction with the site in α, maintains a closed state of the αÉ"θ-β 2 replicase in the polymerization mode of DNA synthesis. The É"-β interaction, selected during evolution to be weak and thus suited for transient disruption to enable access of alternate polymerases and other clamp binding proteins, therefore makes an important contribution to the network of protein-protein interactions that finely tune stability of the replicase on the DNA template in its various conformational states. © 2013 European Molecular Biology Organization.

  3. High Performance ZVT with Bus Clamping Modulation Technique for Single Phase Full Bridge Inverters

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Yinglai; Ayyanar, Raja

    2016-03-20

    This paper proposes a topology based on bus clamping modulation and zero-voltage-transition (ZVT) technique to realize zero-voltage-switching (ZVS) for all the main switches of the full bridge inverters, and inherent ZVS and/or ZCS for the auxiliary switches. The advantages of the strategy include significant reduction in the turn-on loss of the ZVT auxiliary switches which typically account for a major part of the total loss in other ZVT circuits, and reduction in the voltage ratings of auxiliary switches. The modulation scheme and the commutation stages are analyzed in detail. Finally, a 1kW, 500 kHz switching frequency inverter of the proposed topology using SiC MOSFETs has been built to validate the theoretical analysis. The ZVT with bus clamping modulation technique of fixed timing and adaptive timing schemes are implemented in DSP TMS320F28335 resulting in full ZVS for the main switches in the full bridge inverter. The proposed scheme can save up to 33 % of the switching loss compared with no ZVT case.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

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

    DEFF Research Database (Denmark)

    Henneberg, Kaj-åge; R., Plonsey

    1994-01-01

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

  6. Physiologic Responses to Infrarenal Aortic Cross-Clamping during Laparoscopic or Conventional Vascular Surgery in Experimental Animal Model: Comparative Study

    Directory of Open Access Journals (Sweden)

    María F. Martín-Cancho

    2008-01-01

    Full Text Available The aim of this study was to compare the hemodynamic and ventilatory effects of prolonged infrarenal aortic cross-clamping in pigs undergoing either laparotomy or laparoscopy. 18 pigs were used for this study. Infrarenal aortic crossclamping was performed for 60 minutes in groups I (laparotomy, n=6 and II (laparoscopy, n=6. Group III (laparoscopy, n=6 underwent a 120-minute long pneumoperitoneum in absence of aortic clamping (sham group. Ventilatory and hemodynamic parameters and renal function were serially determined in all groups. A significant decrease in pH and significant increase in PaCO2 were observed in group II, whereas no changes in these parameters were seen in group I and III. All variables returned to values similar to baseline in groups I and II 60 minutes after declamping. A significant increase in renal resistive index was evidenced during laparoscopy, with significantly higher values seen in Group II. Thus a synergic effect of pneumoperitoneum and aortic cross-clamping was seen in this study. These two factors together cause decreased renal perfusion and acidosis, thus negatively affecting the patient's general state during this type of surgery.

  7. The actions of mdivi-1, an inhibitor of mitochondrial fission, on rapidly activating delayed-rectifier K⁺ current and membrane potential in HL-1 murine atrial cardiomyocytes.

    Science.gov (United States)

    So, Edmund Cheung; Hsing, Chung-Hsi; Liang, Chia-Hua; Wu, Sheng-Nan

    2012-05-15

    Mdivi-1 is an inhibitor of dynamin related protein 1- (drp1)-mediated mitochondrial fission. However, the mechanisms through which this compound interacts directly with ion currents in heart cells remain unknown. In this study, its effects on ion currents and membrane potential in murine HL-1 cardiomyocytes were investigated. In whole-cell recordings, the addition of mdivi-1 decreased the amplitude of tail current (I(tail)) for the rapidly activating delayed-rectifier K⁺ current (I(Kr)) in a concentration-dependent manner with an IC₅₀ value at 11.6 μM, a value that resembles the inhibition requirement for mitochondrial division. It shifted the activation curve of I(tail) to depolarized voltages with no change in the gating charge. However, mdivi-1 did not alter the rate of recovery from current inactivation. In cell-attached configuration, mdivi-1 inside the pipette suppressed the activity of acetylcholine-activated K⁺ channels without modifying the single-channel conductance. Mdivi-1 (30 μM) slightly depressed the peak amplitude of Na⁺ current with no change in the overall current-voltage relationship. Under current-clamp recordings, addition of mdivi-1 resulted in prolongation for the duration of action potentials (APs) and to increase the firing of spontaneous APs in HL-1 cells. Similarly, in pituitary GH₃ cells, mdivi-1 was effective in directly suppressing the amplitude of ether-à-go-go-related gene-mediated K⁺ current. Therefore, the lengthening of AP duration and increased firing of APs caused by mdivi-1 can be primarily explained by its inhibition of these K⁺ channels enriched in heart cells. The observed effects of mdivi-1 on ion currents were direct and not associated with its inhibition of mitochondrial division. Copyright © 2012 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Wang Shihong; Xie Yuanfang; Qu Zhilin

    2008-01-01

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

  9. Multi-mode excitation of a clamped–clamped microbeam resonator

    KAUST Repository

    Younis, Mohammad I.

    2015-02-18

    We present modeling and simulation of the nonlinear dynamics of a microresonator subjected to two-source electrostatic excitation. The resonator is composed of a clamped–clamped beam excited by a DC voltage load superimposed to two AC voltage loads of different frequencies. One frequency is tuned close to the first natural frequency of the beam and the other is close to the third (second symmetric) natural frequency. A multi-mode Galerkin procedure is applied to extract a reduced-order model, which forms the basis of the numerical simulations. Time history response, Poincare’ sections, Fast Fourier Transforms FFT, and bifurcation diagrams are used to reveal the dynamics of the system. The results indicate complex nonlinear phenomena, which include quasiperiodic motion, torus bifurcations, and modulated chaotic attractors.

  10. Enhanced Buck-Boost Three-Level Neutral-Point-Clamped Inverters

    DEFF Research Database (Denmark)

    Tan, K. K.; Gao, F.; Chiang Loh, Poh

    2009-01-01

    In traditional three-level neutral-point-clamped (NPC) inverters, a major issue is capacitor voltage imbalance, which results in low order harmonics. The compensation of the capacitor voltages often require additional control complexity, which cannot be conveniently implemented. The "alternative...... phase opposition disposition" (APOD) modulation method used in traditional NPC topologies also has lower harmonics performance as compared to the "phase disposition" (PD) modulation method.In this paper, we introduce a new three-level NPC topology that utilises the harmonically superior PD modulation...... method, with the ability to easily adjust for capacitor voltage imbalances. To further improve the boost capability of the three-level NPC inverters, another new topology introduces 2 additional diodes,achieving higher boost performance while totally eliminating thepossibility of capacitor voltage...

  11. Surface analysis of anodized aluminum clamps from NASA-LDEF satellite

    Science.gov (United States)

    Grammer, H. L.; Wightman, J. P.; Young, Philip R.

    1992-01-01

    Surface analysis results of selected anodized aluminum clamps containing black (Z306) and white (A276) paints which received nearly six years of Low Earth Orbit (LEO) exposure on the Long Duration Exposure Facility are reported. Surface analytical techniques, including x-ray photoelectron spectroscopy (XPS), Auger electron spectroscopy (AES), and scanning electron microscopy/energy dispersive analysis by x-ray (SEM/EDAX), showed significant differences in the surface composition of these materials depending upon the position on the LDEF. Differences in the surface composition are attributed to varying amounts of atomic oxygen and vacuum ultraviolet radiation (VUV). Silicon containing compounds were the primary contaminant detected on the materials.

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

    Science.gov (United States)

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

    2011-01-01

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

  13. Morphological Characterization of the Action Potential Initiation Segment in GnRH Neuron Dendrites and Axons of Male Mice.

    Science.gov (United States)

    Herde, Michel K; Herbison, Allan E

    2015-11-01

    GnRH neurons are the final output neurons of the hypothalamic network controlling fertility in mammals. In the present study, we used ankyrin G immunohistochemistry and neurobiotin filling of live GnRH neurons in brain slices from GnRH-green fluorescent protein transgenic male mice to examine in detail the location of action potential initiation in GnRH neurons with somata residing at different locations in the basal forebrain. We found that the vast majority of GnRH neurons are bipolar in morphology, elaborating a thick (primary) and thinner (secondary) dendrite from opposite poles of the soma. In addition, an axon-like process arising predominantly from a proximal dendrite was observed in a subpopulation of GnRH neurons. Ankyrin G immunohistochemistry revealed the presence of a single action potential initiation zone ∼27 μm in length primarily in the secondary dendrite of GnRH neurons and located 30 to 140 μm distant from the cell soma, depending on the type of process and location of the cell body. In addition to dendrites, the GnRH neurons with cell bodies located close to hypothalamic circumventricular organs often elaborated ankyrin G-positive axon-like structures. Almost all GnRH neurons (>90%) had their action potential initiation site in a process that initially, or ultimately after a hairpin loop, was coursing in the direction of the median eminence. These studies indicate that action potentials are initiated in different dendritic and axonal compartments of the GnRH neuron in a manner that is dependent partly on the neuroanatomical location of the cell body.

  14. Piezoelectric constants for ZnO calculated using classical polarizable core-shell potentials

    International Nuclear Information System (INIS)

    Dai Shuangxing; Dunn, Martin L; Park, Harold S

    2010-01-01

    We demonstrate the feasibility of using classical atomistic simulations, i.e. molecular dynamics and molecular statics, to study the piezoelectric properties of ZnO using core-shell interatomic potentials. We accomplish this by reporting the piezoelectric constants for ZnO as calculated using two different classical interatomic core-shell potentials: that originally proposed by Binks and Grimes (1994 Solid State Commun. 89 921-4), and that proposed by Nyberg et al (1996 J. Phys. Chem. 100 9054-63). We demonstrate that the classical core-shell potentials are able to qualitatively reproduce the piezoelectric constants as compared to benchmark ab initio calculations. We further demonstrate that while the presence of the shell is required to capture the electron polarization effects that control the clamped ion part of the piezoelectric constant, the major shortcoming of the classical potentials is a significant underprediction of the clamped ion term as compared to previous ab initio results. However, the present results suggest that overall, these classical core-shell potentials are sufficiently accurate to be utilized for large scale atomistic simulations of the piezoelectric response of ZnO nanostructures.

  15. Glucose consumption by various tissues in pregnant rats : effects of a 6-day euglycaemic hyperinsulinaemic clamp

    NARCIS (Netherlands)

    Nieuwenhuizen, AG; Schuiling, GA; Bonen, A; Paans, AMJ; Vaalburg, W; Koiter, TR

    In the course of pregnancy maternal tissues become increasingly more insensitive to insulin. As 6 days of euglycaemic hyperinsulinaemic clamping, from day 8 until 14 of gestation, ameliorates total glucose consumption, we analysed the contribution of individual tissues in this phenomenon. We

  16. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    Energy Technology Data Exchange (ETDEWEB)

    Ljusev, P.; Andersen, Michael A.E.

    2005-07-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify design, increase efficiency and integration level, reduce product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented. (au)

  17. Direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp

    DEFF Research Database (Denmark)

    Ljusev, Petar; Andersen, Michael Andreas E.

    2005-01-01

    This paper discusses the advantages and problems when implementing direct energy conversion switching-mode audio power amplifiers. It is shown that the total integration of the power supply and Class D audio power amplifier into one compact direct converter can simplify the design, increase...... efficiency, reduce the product volume and lower its cost. As an example, the principle of operation and the measurements made on a direct-conversion switching-mode audio power amplifier with active capacitive voltage clamp are presented....

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wing-Chiu Tong

    2011-04-01

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

  20. Dynamics of T-Junction Solution Switching Aimed at Patch Clamp Experiments.

    Science.gov (United States)

    Auzmendi, Jerónimo A; Smoler, Mariano; Moffatt, Luciano

    2015-01-01

    Solutions exchange systems are responsible for the timing of drug application on patch clamp experiments. There are two basic strategies for generating a solution exchange. When slow exchanges are bearable, it is easier to perform the exchange inside the tubing system upstream of the exit port. On the other hand, fast, reproducible, exchanges are usually performed downstream of the exit port. As both strategies are combinable, increasing the performance of upstream exchanges is desirable. We designed a simple method for manufacturing T-junctions (300 μm I.D.) and we measured the time profile of exchange of two saline solutions using a patch pipette with an open tip. Three factors were found to determine the timing of the solution switching: pressure, travelled distance and off-center distance. A linear relationship between the time delay and the travelled distance was found for each tested pressure, showing its dependence to the fluid velocity, which increased with pressure. The exchange time was found to increase quadratically with the delay, although a sizeable variability remains unexplained by this relationship. The delay and exchange times increased as the recording pipette moved away from the center of the stream. Those increases became dramatic as the pipette was moved close to the stream borders. Mass transport along the travelled distance between the slow fluid at the border and the fast fluid at the center seems to contribute to the time course of the solution exchange. This effect would be present in all tubing based devices. Present results might be of fundamental importance for the adequate design of serial compound exchangers which would be instrumental in the discovery of drugs that modulate the action of the physiological agonists of ion channels with the purpose of fine tuning their physiology.

  1. Retained Intra-Abdominal Surgical Clamp Complicating Emergency Laparotomy: Incidental Finding on Hysterosalpingogram for Evaluation of Tubal Infertility

    Directory of Open Access Journals (Sweden)

    Adebiyi Gbadebo Adesiyun

    2014-01-01

    Full Text Available The finding of intraperitoneal foreign body complicating surgical intervention broadly remains as an issue of safety in the operative room, a source of emotive concern for the patient, and an upsetting but equally embarrassing situation to the surgeon and the team. However, in the media world, it is a source of sumptuous and captivating headline on the newspaper and to the legal profession, an attractive case to prosecute. A middle age teacher presented with secondary infertility. She had emergency laparotomy fifteen years ago for ruptured tubal ectopic pregnancy in a private hospital and postoperative period was uneventful. Amongst other investigations to find out the cause of infertility, she had hysterosalpingography and a radio-opaque clamp was visualized on the films. She was counselled and had laparotomy. A pair of surgical Kocher clamps was retrieved buried in the mesentery.

  2. New aspects of HERG K⁺ channel function depending upon cardiac spatial heterogeneity.

    Directory of Open Access Journals (Sweden)

    Pen Zhang

    Full Text Available HERG K(+ channel, the genetic counterpart of rapid delayed rectifier K(+ current in cardiac cells, is responsible for many cases of inherited and drug-induced long QT syndromes. HERG has unusual biophysical properties distinct from those of other K(+ channels. While the conventional pulse protocols in patch-clamp studies have helped us elucidate these properties, their limitations in assessing HERG function have also been progressively noticed. We employed AP-clamp techniques using physiological action potential waveforms recorded from various regions of canine heart to study HERG function in HEK293 cells and identified several novel aspects of HERG function. We showed that under AP-clamp IHERG increased gradually with membrane repolarization, peaked at potentials around 20-30 mV more negative than revealed by pulse protocols and at action potential duration (APD to 60%-70% full repolarization, and fell rapidly at the terminal phase of repolarization. We found that the rising phase of IHERG was conferred by removal of inactivation and the decaying phase resulted from a fall in driving force, which were all determined by the rate of membrane repolarization. We identified regional heterogeneity and transmural gradient of IHERG when quantified with the area covered by IHERG trace. In addition, we observed regional and transmural differences of IHERG in response to dofetilide blockade. Finally, we characterized the influence of HERG function by selective inhibition of other ion currents. Based on our results, we conclude that the distinct biophysical properties of HERG reported by AP-clamp confer its unique function in cardiac repolarization thereby in antiarrhythmia and arrhythmogenesis.

  3. A complete dc characterization of a constant-frequency, clamped-mode, series-resonant converter

    Science.gov (United States)

    Tsai, Fu-Sheng; Lee, Fred C.

    1988-01-01

    The dc behavior of a clamped-mode series-resonant converter is characterized systematically. Given a circuit operating condition, the converter's mode of operation is determined and various circuit parameters are calculated, such as average inductor current (load current), rms inductor current, peak capacitor voltage, rms switch currents, average diode currents, switch turn-on currents, and switch turn-off currents. Regions of operation are defined, and various circuit characteristics are derived to facilitate the converter design.

  4. Evaluation of the clamping force in high tension bolt by using the ultrasonic nonlinearity

    International Nuclear Information System (INIS)

    Jang, Kyung Young; Cheon, Hae Wha; Ha, Hob; Park, Man Sick; Kim, No You

    2005-01-01

    High tension bolts have been used widely for the clamping of many kinds of large structure. Therefore, its estimation has been regarded as main issue in the maintenance of high tension bolts. This paper proposes a novel method using the ultrasonic nonlinearity, which is based on the dependency of sound speed on the stress. For this we introduce nonlinear elastic constants in the stress-strain relationship, and derive the sound speed as a linear function of stress. In order to verify the usefulness of the proposed method, two kinds of experiments are carried out: The first one is to measure the sound speed when the bolt is stressed by the tension tester. The result showed good agreement with the expected linear relationship between the sound speed and the axial stress. The second one is to measure the sound speed when the bolt is stressed by the torque wrench. The results showed that the sound speed was decreased when the torque was increased. From these results we can say that the proposed method is enough useful to evaluate the clamping force in the high tension bolt.

  5. Limitations of the dual voltage clamp method in assaying conductance and kinetics of gap junction channels

    NARCIS (Netherlands)

    Wilders, R.; Jongsma, H. J.

    1992-01-01

    The electrical properties of gap junctions in cell pairs are usually studied by means of the dual voltage clamp method. The voltage across the junctional channels, however, cannot be controlled adequately due to an artificial resistance and a natural resistance, both connected in series with the gap

  6. High performance control strategy for single-phase three-level neutral-point-clamped traction four-quadrant converters

    DEFF Research Database (Denmark)

    Kejian, Song; Konstantinou, Georgios; Jing, Li

    2017-01-01

    Operational data from Chinese railways indicate a number of challenges for traction four-quadrant converter (4QC) control including low-order voltage and current harmonics and reference tracking. A control strategy for a single-phase three-level neutral-point-clamped 4QC employed in the electric...

  7. Experimental background of pain treatment by heat application - rapid heating and cooling in patch clamp experiments

    Czech Academy of Sciences Publication Activity Database

    Dittert, Ivan; Slovák, P.; Jíra, J.

    2005-01-01

    Roč. 8, Suppl.2 (2005), s. 32-32 ISSN 1212-0634. [Česko-Slovenské dialógy o bolesti /7./. 13.10.2005 - 15.10.2005, Bojnice] Institutional research plan: CEZ:AV0Z50110509 Keywords : patch clamp * channels Subject RIV: CF - Physical ; Theoretical Chemistry

  8. [Effects of 2-(p-dimethylaminostyryl) pyridine methycholide (DSPM-Ci) on ECG, left atrium contractivity and on papillary muscle action potentials].

    Science.gov (United States)

    Jiang, X Y; Zhou, C M; Li, D M; Zhang, K J

    1996-01-01

    The effects of DSPM-Cl on ECG in rats, on the dose-effect curve in guinea pig left atria and on the fast action potential (AP), high-K+ depolarized slow action potential (SAP) in guinea pigs papillary muscle were examined electrophysiologically. DSPM-Cl (2 mg.kg-1) showed significant nagative frequency, negative conductivity effect, and prolonged the PP and PR interval. DSPM-CI (30-50 mumol.L-1) was shown to inhibit left atria contractility and shift the concentration-response curve of Iso and CaCl2 to the right with PD2' values of 4.60 and 4.13, respectively. In addition, DSPM-Cl was found to prolong the duration of action potential 90 (APD90) and effective refractory period (ERP), and decrease the maximal upstroke velocity (Vmax) in K(+)-depolarized guinea pigs papillary muscles. The results suggest that, like verpamil, DSPM-Cl might be a calcium antagonist.

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

    Science.gov (United States)

    Farren, Margaret; Crotty, Yvonne; Kilboy, Laura

    2015-01-01

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

  10. A simulation of T-wave alternans vectocardiographic representation performed by changing the ventricular heart cells action potential duration.

    Science.gov (United States)

    Janusek, D; Kania, M; Zaczek, R; Zavala-Fernandez, H; Maniewski, R

    2014-04-01

    The presence of T wave alternans (TWA) in the surface ECG signals has been recognized as a marker of electrical instability, and is hypothesized to be related to patients at increased risk for ventricular arrhythmias. In this paper we present a TWA simulation study. The TWA phenomenon was simulated by changing the duration of the ventricular heart cells action potential. The magnitude was calculated in the surface ECG with the use of the time domain method. The spatially concordant TWA, where during one heart beat all ventricular cells display a short-duration action potential and during the next beat they exhibit a long-duration action potential, as well as the discordant TWA, where at least one region is out of phase, was simulated. The vectocardiographic representation was employed. The obtained results showed a high level of T-loop pattern and location disturbances connected to the discordant TWA simulation in contrast to the concordant one. This result may be explained by the spatial heterogeneity of the ventricular repolarization process, which could be higher for the discordant TWA than for the concordant TWA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Yu-Wei Wu

    2012-05-01

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

  12. Control of local intracellular calcium concentration with dynamic-clamp controlled 2-photon uncaging.

    Directory of Open Access Journals (Sweden)

    Erwin Idoux

    Full Text Available The variations of the intracellular concentration of calcium ion ([Ca(2+](i are at the heart of intracellular signaling, and their imaging is therefore of enormous interest. However, passive [Ca(2+](i imaging provides no control over these variations, meaning that a full exploration of the functional consequences of [Ca(2+](i changes is difficult to attain. The tools designed so far to modify [Ca(2+](i, even qualitatively, suffer drawbacks that undermine their widespread use. Here, we describe an electro-optical technique to quantitatively set [Ca(2+](i, in real time and with sub-cellular resolution, using two-photon Ca(2+ uncaging and dynamic-clamp. We experimentally demonstrate, on neurons from acute olfactory bulb slices of Long Evans rats, various capabilities of this technique previously difficult to achieve, such as the independent control of the membrane potential and [Ca(2+](i variations, the functional knocking-in of user-defined virtual voltage-dependent Ca(2+ channels, and the standardization of [Ca(2+](i patterns across different cells. Our goal is to lay the groundwork for this technique and establish it as a new and versatile tool for the study of cell signaling.

  13. Single aortic clamping in coronary artery bypass surgery reduces cerebral embolism and improves neurocognitive outcomes.

    Science.gov (United States)

    Gasparovic, Hrvoje; Borojevic, Marko; Malojcic, Branko; Gasparovic, Kristina; Biocina, Bojan

    2013-10-01

    Aortic manipulation releases embolic material, thereby enhancing the probability of adverse neurologic outcomes following coronary artery bypass grafting (CABG). We prospectively evaluated 59 patients undergoing CABG. Patients in the single (SC, n = 37) and multiple clamp (MC, n = 22) groups were comparable in relation to age and operative risk (p > 0.05). Neurocognitive evaluation consisted of the Auditory Verbal Learning Test (AVLT), Color Trails Test A, the Grooved Pegboard test and the Mini-Mental State Examination. Data acquisition was performed preoperatively, early postoperatively and at the 4-month follow-up. Intraoperative transcranial Doppler (TCD) monitoring was used to quantify the embolic load in relation to different aortic clamping strategies. Preoperative neurocognitive results were similar between the groups (p > 0.05). The incidence of postoperative delirium was greater in the MC group but this failed to reach statistical significance (23% vs 8%, p = 0.14). SC patients had fewer embolization signals (270 ± 181 vs 465 ± 160, p cognitive depression was greater in the MC group (p cognition deficits and superior late restoration of function.

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

    Science.gov (United States)

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

    2007-12-01

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

  15. A clamping force measurement system for monitoring the condition of bolted joints on railway track joints and points

    International Nuclear Information System (INIS)

    Tesfa, B; Horler, G; Thobiani, F Al; Gu, F; Ball, A D

    2012-01-01

    Many industrial structures associated with railway infrastructures rely on a large number of bolted joint connections to ensure safe and reliable operation of the track and trackside furniture. Significant sums of money are spent annually to repair the damage caused by bolt failures and to maintain the integrity of bolted structures. In the UK, Network Rail (the organization responsible for rail network maintenance and safety) conducts corrective and preventive maintenance manually on 26,000 sets of points (each having approximately 30 bolted joints per set), in order to ensure operational success and safety for the travelling public. Such manual maintenance is costly, disruptive, unreliable and prone to human error. The aim of this work is to provide a means of automatically measuring the clamping force of each individual bolted joint, by means of an instrumented washer. This paper describes the development of a sensor means to be used in the washer, which satisfies the following criteria. 1. Sense changes in the clamping force of the joint and report this fact. 2. Provide compatibility with the large dynamic range of clamping force. 3. Satisfy the limitations in terms of physical size. 4. Provide the means to electronically interface with the washer. 5. Provide a means of powering the washer in situ. 6. Provide a solution at an acceptable cost. Specifically the paper focuses on requirements 1, 2 and 3 and presents the results that support further development of the proposed design and the realization of a pre-prototype system. In the paper, various options for the force sensing element (strain gage, capacitor, piezo-resistive) have been compared, using design optimization techniques. As a result of the evaluation, piezo-resistive sensors in concert with a proprietary force attenuation method, have been found to offer the best performance and cost trade-off The performance of the novel clamping force sensor has been evaluated experimentally and the results show

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

    Science.gov (United States)

    Mesin, Luca

    2015-02-01

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

  17. Modulation Methods for Three-level Neutral-Point-Clamped Inverter Achieving Stress Redistribution under Moderate Modulation Index

    DEFF Research Database (Denmark)

    Ma, Ke; Blaabjerg, Frede

    2016-01-01

    This letter investigates the loss and thermal behaviors of a three-level neutral-point-clamped (3L-NPC) inverter undergoing moderate modulation index, which is typically presented during minor voltage sags of the power grid or speed changes of the electric machines. A series of new space vector m...

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

    Science.gov (United States)

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

    2018-03-01

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

  19. Prostaglandin E2 potentiation of P2X3 receptor mediated currents in dorsal root ganglion neurons

    Directory of Open Access Journals (Sweden)

    Huang Li-Yen

    2007-08-01

    Full Text Available Abstract Prostaglandin E2 (PGE2 is a well-known inflammatory mediator that enhances the excitability of DRG neurons. Homomeric P2X3 and heteromeric P2X2/3 receptors are abundantly expressed in dorsal root ganglia (DRG neurons and participate in the transmission of nociceptive signals. The interaction between PGE2 and P2X3 receptors has not been well delineated. We studied the actions of PGE2 on ATP-activated currents in dissociated DRG neurons under voltage-clamp conditions. PGE2 had no effects on P2X2/3 receptor-mediated responses, but significantly potentiated fast-inactivating ATP currents mediated by homomeric P2X3 receptors. PGE2 exerted its action by activating EP3 receptors. To study the mechanism underlying the action of PGE2, we found that the adenylyl cyclase activator, forskolin and the membrane-permeable cAMP analogue, 8-Br-cAMP increased ATP currents, mimicking the effect of PGE2. In addition, forskolin occluded the enhancement produced by PGE2. The protein kinase A (PKA inhibitors, H89 and PKA-I blocked the PGE2 effect. In contrast, the PKC inhibitor, bisindolymaleimide (Bis did not change the potentiating action of PGE2. We further showed that PGE2 enhanced α,β-meATP-induced allodynia and hyperalgesia and the enhancement was blocked by H89. These observations suggest that PGE2 binds to EP3 receptors, resulting in the activation of cAMP/PKA signaling pathway and leading to an enhancement of P2X3 homomeric receptor-mediated ATP responses in DRG neurons.

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

    NARCIS (Netherlands)

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

    1988-01-01

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

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

    Science.gov (United States)

    Bertrand, Melanie

    2016-01-01

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

  2. Improved non-dimensional dynamic influence function method for vibration analysis of arbitrarily shaped plates with clamped edges

    Directory of Open Access Journals (Sweden)

    Sang-Wook Kang

    2016-03-01

    Full Text Available A new formulation for the non-dimensional dynamic influence function method, which was developed by the authors, is proposed to efficiently extract eigenvalues and mode shapes of clamped plates with arbitrary shapes. Compared with the finite element and boundary element methods, the non-dimensional dynamic influence function method yields highly accurate solutions in eigenvalue analysis problems of plates and membranes including acoustic cavities. However, the non-dimensional dynamic influence function method requires the uneconomic procedure of calculating the singularity of a system matrix in the frequency range of interest for extracting eigenvalues because it produces a non-algebraic eigenvalue problem. This article describes a new approach that reduces the problem of free vibrations of clamped plates to an algebraic eigenvalue problem, the solution of which is straightforward. The validity and efficiency of the proposed method are illustrated through several numerical examples.

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

    Directory of Open Access Journals (Sweden)

    Jack Kent

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

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

    Science.gov (United States)

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

    2016-06-01

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

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

    Science.gov (United States)

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

    2018-07-14

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

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

    CERN Document Server

    Rodionov, V N; Kravtsova, G A

    2002-01-01

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

  7. Pb2+ Modulates Ca2+ Membrane Permeability In Paramecium

    Science.gov (United States)

    Bernal-Martínez, Juan; Ortega Soto, Arturo

    2004-09-01

    Intracellular recording experiments in current clamp configuration were done to evaluate whether Pb2+ modulates ionic membrane permeability in the fresh water Paramecium tetraurelia. It was found that Pb2+ triggers in a dose-dependent manner, a burst of spontaneous action potentials followed by a robust and sustained after hyper-polarization. In addition, Pb2+ increased the frequency of firing the spontaneous Ca2+-Action Potential and also, the duration of Ca2+-Action Potential, in a dose and reversibly-dependent manner. These results suggest that Pb2+ increases calcium membrane permeability of Paramecium and probably activates a calcium-dependent-potassium conductance in the ciliate.

  8. A New Approach of Modified Submerged Patch Clamp Recording Reveals Interneuronal Dynamics during Epileptiform Oscillations

    Czech Academy of Sciences Publication Activity Database

    Morris, G.; Jiruška, Přemysl; Jefferys, J. G. R.; Powell, A. D.

    2016-01-01

    Roč. 10, Nov 9 (2016), č. článku 519. ISSN 1662-453X R&D Projects: GA ČR(CZ) GA14-02634S; GA MZd(CZ) NV15-29835A Institutional support: RVO:67985823 Keywords : in vitro * membrane chamber * LFP * patch clamp * epilepsy * high frequency activity Subject RIV: FH - Neurology Impact factor: 3.566, year: 2016

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

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Poulet, Claire; Diness, Jonas Goldin

    2014-01-01

    (+) currents by ∼15% and prolonged action potential duration (APD), but no effect was observed in myocytes from AF patients. In trabeculae muscle strips from right atrial appendages of SR patients, both compounds increased APD and effective refractory period, and depolarized the resting membrane potential......, while only NS8593 induced these effects in tissue from AF patients. SK channel inhibition did not alter any electrophysiological parameter in human interventricular septum tissue. CONCLUSIONS: SK channels are present in human atria where they participate in repolarization. SK2 and SK3 were down...

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

    Science.gov (United States)

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

    2016-11-01

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

  11. Development of a peptide nucleic acid polymerase chain reaction clamping assay for semiquantitative evaluation of genetically modified organism content in food.

    Science.gov (United States)

    Peano, C; Lesignoli, F; Gulli, M; Corradini, R; Samson, M C; Marchelli, R; Marmiroli, N

    2005-09-15

    In the present study a peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method was developed and applied to the detection of genetically modified organisms (GMO), to test PCR products for band identity and to obtain a semiquantitative evaluation of GMO content. The minimal concentration of PNA necessary to block the PCR was determined by comparing PCRs containing a constant amount of DNA in the presence of increasing concentration of target-specific PNA. The lowest PNA concentration at which specific inhibition took place, by the inhibition of primer extension and/or steric hindrance, was the most efficient condition. Optimization of PCR clamping by PNA was observed by testing five different PNAs with a minimum of 13 bp to a maximum of 15 bp, designed on the target sequence of Roundup Ready soybean. The results obtained on the DNA extracted from Roundup Ready soybean standard flour were verified also on DNA extracted from standard flours of maize GA21, Bt176, Bt11, and MON810. A correlation between the PNA concentration necessary for inducing PCR clamping and the percentage of the GMO target sequence in the sample was found.

  12. Active signal conduction through the sensory dendrite of a spider mechanoreceptor neuron.

    Science.gov (United States)

    Gingl, Ewald; French, Andrew S

    2003-07-09

    Rapid responses to sensory stimulation are crucial for survival. This must be especially true for mechanical stimuli containing temporal information, such as vibration. Sensory transduction occurs at the tips of relatively long sensory dendrites in many mechanoreceptors of both vertebrates and invertebrates, but little is known about the electrical properties of these crucial links between transduction and action potential generation. The VS-3 slit-sense organ of the spider Cupiennius salei contains bipolar mechanosensory neurons that allow voltage-clamp recording from the somata, whereas mechanotransduction occurs at the tips of 100- to 200-microm-long sensory dendrites. We studied the properties of VS-3 sensory dendrites using three approaches. Voltage-jump experiments measured the spread of voltage outward from the soma by observing total mechanically transduced charge recovered at the soma as a function of time after a voltage jump. Frequency-response measurements between pseudorandom mechanical stimulation and somatic membrane potential estimated the passive cable properties of the dendrite for voltage spread in the opposite direction. Both of these sets of data indicated that the dendritic cable would significantly attenuate and retard a passively propagated receptor potential. Finally, current-clamp observations of receptor potentials and action potentials indicated that action potentials normally start at the distal dendrites and propagate regeneratively to the soma, reducing the temporal delay of passive conduction.

  13. Insulin resistance in a large cohort of women with polycystic ovary syndrome: a comparison between euglycaemic-hyperinsulinaemic clamp and surrogate indexes.

    Science.gov (United States)

    Tosi, Flavia; Bonora, Enzo; Moghetti, Paolo

    2017-12-01

    Could surrogate indexes identify insulin resistant individuals among women with polycystic ovary syndrome (PCOS)? Surrogate indexes may be able to rule in, but not rule out, insulin resistance in women with PCOS. Insulin resistance is a typical finding of women with PCOS and most clinical information on this issue is based upon surrogate indexes of insulin resistance. However, data on the performance of these indexes in PCOS women are very limited. A retrospective analysis of 406 women referred to our outpatient clinic for hyperandrogenism and/or menstrual dysfunction and submitted to hyperinsulinemic euglycaemic clamp between 1998 and 2015. In total, 375 of these women had PCOS by the Rotterdam criteria and were included in the study. Six surrogate indexes of insulin sensitivity were calculated from glucose and insulin levels, either at fasting (homeostasis model assessment (HOMA), glucose/insulin (G/I) ratio and quantitative insulin sensitivity check index (QUICKI)) or after oral glucose load (Gutt, Stumvoll0-120 and Matsuda). Overall, insulin resistance, as identified by the M-clamp value, was fo