Simulation studies on the impact of the firing of action potential of myocytes with bipolar pulses

2015 ◽  
Author(s):  
Ruizhe Zhang ◽  
Chengxiang Li ◽  
Chenguo Yao ◽  
Yan Mi
Keyword(s):  
Action Potential ◽  
Simulation Studies ◽  
The Impact

scholarly journals A Simulation Model of Construction Projects Executed in Random Conditions with the Overlapping Construction Works

2021 ◽  
Vol 13 (11) ◽  
pp. 5795
Author(s):  
Sławomir Biruk ◽  
Łukasz Rzepecki
Keyword(s):  
Simulation Model ◽  
Technological Process ◽  
Construction Projects ◽  
Working Time ◽  
Simulation Studies ◽  
Construction Methods ◽  
The Impact ◽  
Construction Works

Reducing the duration of construction works requires additional organizational measures, such as selecting construction methods that assure a shorter realization time, engaging additional resources, working overtime, or allowing construction works to be performed simultaneously in the same working units. The simultaneous work of crews may affect the quality of works and the efficiency of construction processes. This article presents a simulation model aimed at assessing the impact of the overlap period on the extension of the working time of the crews and the reduction of a repetitive project’s duration in random conditions. The purpose of simulation studies is to provide construction managers with guidelines when deciding on the dates of starting the sequential technological process lines realized by specialized working crews, for sustainable scheduling and organization of construction projects.

scholarly journals Ceramide modulates HERG potassium channel gating by translocation into lipid rafts

2010 ◽  
Vol 299 (1) ◽  
pp. C74-C86 ◽  
Author(s):  
Sindura B. Ganapathi ◽  
Todd E. Fox ◽  
Mark Kester ◽  
Keith S. Elmslie
Keyword(s):  
Potassium Channels ◽  
Action Potential ◽  
Lipid Rafts ◽  
Negative Impact ◽  
Cardiac Action Potential ◽  
Cholesterol Depletion ◽  
Cardiac Action ◽  
Herg Channels ◽  
The Impact ◽  
Action Potential Repolarization

Human ether-à-go-go-related gene (HERG) potassium channels play an important role in cardiac action potential repolarization, and HERG dysfunction can cause cardiac arrhythmias. However, recent evidence suggests a role for HERG in the proliferation and progression of multiple types of cancers, making it an attractive target for cancer therapy. Ceramide is an important second messenger of the sphingolipid family, which due to its proapoptotic properties has shown promising results in animal models as an anticancer agent . Yet the acute effects of ceramide on HERG potassium channels are not known. In the present study we examined the effects of cell-permeable C6-ceramide on HERG potassium channels stably expressed in HEK-293 cells. C6-ceramide (10 μM) reversibly inhibited HERG channel current (IHERG) by 36 ± 5%. Kinetically, ceramide induced a significant hyperpolarizing shift in the current-voltage relationship (Δ V1/2 = −8 ± 0.5 mV) and increased the deactivation rate (43 ± 3% for τfast and 51 ± 3% for τslow). Mechanistically, ceramide recruited HERG channels within caveolin-enriched lipid rafts. Cholesterol depletion and repletion experiments and mathematical modeling studies confirmed that inhibition and gating effects are mediated by separate mechanisms. The ceramide-induced hyperpolarizing gating shift (raft mediated) could offset the impact of inhibition (raft independent) during cardiac action potential repolarization, so together they may nullify any negative impact on cardiac rhythm. Our results provide new insights into the effects of C6-ceramide on HERG channels and suggest that C6-ceramide can be a promising therapeutic for cancers that overexpress HERG.

Exposure to low temperature prepares the turtle brain to withstand anoxic environments during overwintering

2021 ◽  
Author(s):  
Ebrahim Lari ◽  
Leslie T. Buck
Keyword(s):  
Membrane Potential ◽  
Low Temperature ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Cellular Damage ◽  
Severe Hypoxia ◽  
Painted Turtle ◽  
Whole Cell ◽  
Voltage Gated ◽  
The Impact

In most vertebrates, anoxia drastically reduces the production of the essential adenosine triphosphate (ATP) to power its many necessary functions, and consequently, cell death occurs within minutes. However, some vertebrates, such as the painted turtle (Chrysemys picta bellii), have evolved the ability to survive months without oxygen by simultaneously decreasing ATP supply and demand, surviving the anoxic period without any apparent cellular damage. The impact of anoxia on the metabolic function of painted turtles has received a lot of attention. Still, the impact of low temperature has received less attention and the interactive effect of anoxia and temperature even less. In the present study, we investigated the interactive impacts of reduced temperature and severe hypoxia on the electrophysiological properties of pyramidal neurons in painted turtle cerebral cortex. Our results show that an acute reduction in temperature from 20 to 5°C decreases membrane potential, action potential width and amplitude, and whole-cell conductance. Importantly, acute exposure to 5°C considerably slows membrane repolarization by voltage-gated K+ channels. Exposing pyramidal cells to severe hypoxia in addition to an acute temperature change slightly depolarized membrane potential but did not alter action potential amplitude or width and whole-cell conductance. These results suggest that acclimation to low temperatures, preceding severe environmental hypoxia, induces cellular responses in pyramidal neurons that facilitate survival under low oxygen concentration. In particular, our results show that temperature acclimation invokes a change in voltage-gated K+ channel kinetics that overcomes the acute inhibition of the channel.

Simulation Studies of the Effect of Shaft's Nonlinear Flexural Stiffness Parameters for Critical States of Rotating Power Transmission Systems

2015 ◽  
Vol 236 ◽  
pp. 62-69
Author(s):  
Tomasz Matyja ◽  
Bogusław Łazarz
Keyword(s):  
Degrees Of Freedom ◽  
Power Transmission ◽  
Flexural Stiffness ◽  
Simulation Studies ◽  
Critical States ◽  
Rotating Machine ◽  
Power Transmission Systems ◽  
Main Component ◽  
6 Degrees Of Freedom ◽  
The Impact

The paper presents simulation studies, performed using Simulink, the impact of nonlinear flexural stiffness of shafts for critical speed range and amplitude of vibration. The tests were performed on the selected model of a rotating machine, consisting of a drive, two torsional vibration dampers, shaft with mounted on it two rigid rotors (discs), supported on a three self-aligning roller bearings and mechanical power receiver (brake). The machine startup and braking with crossing the critical states was simulated using specialized Simulink library, which was developed by authors for analysis of transient states in rotating machines and flexural-torsional couplings. In accordance with the concept of modeling adopted by the authors, rotating system is divided into inertial rigid elements (rotors, bearings, clutches, etc..) and compliance elements (parts of the shaft). The main component of the currently developed library is block modeling rigid rotor with 6 degrees of freedom and with the static and dynamic unbalance. By assumption the library is a modular, expandable and allows modeling the systems of any configuration. The goal of the simulation was to verify how nonlinear flexural stiffness of shaft influences the values of critical speeds and the level of flexural and torsional vibrations.

Simulation Studies of Ultrashort, High-Intensity Electric Pulse Induced Action Potential Block in Whole-Animal Nerves

2008 ◽  
Vol 55 (4) ◽  
pp. 1391-1398 ◽  
Author(s):  
R.P. Joshi ◽  
A. Mishra ◽  
Jiahui Song ◽  
A.G. Pakhomov ◽  
K.H. Schoenbach
Keyword(s):  
Action Potential ◽  
High Intensity ◽  
Electric Pulse ◽  
Simulation Studies

PERFORMANCE MEASURES OF THE VARIABLE STRUCTURE FILTER

2005 ◽  
Vol 29 (2) ◽  
pp. 267-295 ◽  
Author(s):  
Saeid Habibi
Keyword(s):  
Performance Measures ◽  
Internal Model ◽  
Variable Structure ◽  
Simulation Studies ◽  
Initial Estimate ◽  
Modeling Uncertainties ◽  
Corrective Term ◽  
System Output ◽  
Predictor Corrector ◽  
The Impact

A new method for state estimation, referred to as the Variable Structure Filter (VSF), has recently been proposed. The VSF is a model based predictor-corrector method. It uses an internal model to provide an initial estimate of the states and subsequently refines this initial estimate by a corrective term that is a function of the system output and the upper bound of uncertainties. As such, the VSF can explicitly cater for uncertainties in its internal model. In this paper, a conceptual discussion of the VSF strategy and its performance in terms of stability, accuracy, and convergence is provided. The impact of modeling uncertainties on the performance of the VSF is discussed and quantified. The analysis is augmented by comparative simulation studies to further illustrate the concept.

Negligent Release Litigation: a Proposal for Procedural Reform

1989 ◽  
Vol 17 (4) ◽  
pp. 595-605 ◽  
Author(s):  
Norman G. Poythress
Keyword(s):  
Hindsight Bias ◽  
Simulation Studies ◽  
Social Scientists ◽  
Policy Makers ◽  
Weak Evidence ◽  
Jury Simulation ◽  
Procedural Concerns ◽  
Procedural Reform ◽  
The Impact

Much of what has been written lately regarding tort reform has dealt with substantive as opposed to procedural concerns. This paper offers a preliminary proposal regarding procedural reform that would potentially correct for the hindsight bias in negligent release litigation and have application in other torts contexts involving transferred responsibility. The proposal for bifurcated trial proceedings is worthy of consideration by legal scholars and policy makers as a potential mechanism for ensuring fairness and improving the quality of justice. As a footnote, it might be added that social scientists might contribute to the assessment of the proposed bifurcation procedure by conducting jury simulation studies that investigate the impact of bifurcated vs. non-bifurcated procedures as a function of strong vs. weak evidence of clinician negligence in mock negligent release cases.

scholarly journals Histamine-Induced Excitatory Responses in Mouse Ventromedial Hypothalamic Neurons: Ionic Mechanisms and Estrogenic Regulation

2007 ◽  
Vol 98 (6) ◽  
pp. 3143-3152 ◽  
Author(s):  
Jin Zhou ◽  
Anna W. Lee ◽  
Nino Devidze ◽  
Qiuyu Zhang ◽  
Lee-Ming Kow ◽  
...  
Keyword(s):  
Action Potential ◽  
Brain Slices ◽  
Histamine Receptor ◽  
Ventromedial Hypothalamus ◽  
Patch Clamp Recording ◽  
Action Potential Firing ◽  
Inward Current ◽  
Ovariectomized Mice ◽  
Ionic Mechanisms ◽  
The Impact

Histamine is capable of modulating CNS arousal states by regulating neuronal excitability. In the current study, histamine action in the ventromedial hypothalamus (VMH), its related ionic mechanisms, and its possible facilitation by estrogen were investigated using whole cell patch-clamp recording in brain slices from ovariectomized female mice. Under current clamp, a bath application of histamine (20 μM) caused membrane depolarization, associated with an increased membrane resistance. In some cells, the depolarization was accompanied by action potentials. Histamine application also significantly reduced the latency of action potential evoked by current steps. Histamine-induced depolarization was not affected by either tetrodotoxin or Cd2+. However, after blocking K+ channels with tetraethylammonium, 4-aminopyridine, and Cs+, depolarization was significantly decreased. Under voltage clamp, histamine-induced depolarization was associated with an inward current. The current–voltage relationship revealed that this inward current reversed near EK. The histamine effect was mimicked by a histamine receptor 1 (H1) agonist, but not a histamine receptor 2 (H2) agonist. An H1 antagonist, but not H2 antagonist, abolished histamine responses. When ovariectomized mice were treated with estradiol benzoate (E2), histamine-induced depolarization was significantly enhanced with an increased percentage of cells showing action potential firing. These results suggest that histamine depolarized VMH neurons by attenuating a K+ leakage current and this effect was mediated by H1 receptor. E2 facilitated histamine-induced excitation of VMH neurons. This histamine effect may present a potential mechanism by which estrogens modulate the impact of generalized CNS arousal on a sexual arousal–related neuronal group.

scholarly journals Potential Drugs Targeting Nsp16 Protein May Corroborates a Promising Approach to Combat SARSCoV-2 Virus

2020 ◽  
Author(s):  
Uma Shankar ◽  
Neha Jain ◽  
Prativa Majee ◽  
Subodh Kumar Mishra ◽  
Brijesh Rathi ◽  
...  
Keyword(s):  
Active Site ◽  
Viral Proteins ◽  
Chemical Diversity ◽  
Simulation Studies ◽  
Methyltransferase Activity ◽  
Rna Molecules ◽  
Drug Candidates ◽  
Therapeutic Measures ◽  
The Impact ◽  
Positive Controls

<p>The recent ongoing pandemic caused by SARS-CoV-2 continues to impose devastating impacts and is accountable for the loss of more than 250,000 human lives within a short span of four months. This urges immediate therapeutic measures to control the impact of this disease. One of the most conserved and potentially druggable sites is the Nsp16 active site that performs the 2’-O-methyltransferase activity and puts a 5’ cap on the viral RNA molecules. This allows them to mimic endogenous transcripts for the efficient translation of viral proteins and evasion of the immune response. Herein, we screened three libraries of compounds (>5500) with chemical diversity to identify hits against Nsp16 active site of SARS-CoV-2. From each library a top hit was identified, namely Velpatasvir from the FDA compounds; JFD00244 from the LOPAC library and compound <b>6 </b>from the SAM based analog library. Interestingly, all three hits showed higher affinity than the positive controls. Velpatasvir is a known anti-viral drug used against Hepatitis C virus, and JFD00244 is a SIRT2 inhibitor. 100ns molecular simulation studies showed all three molecules to have stable and energetically favourable interactions with the active site of Nsp16. In summary, this investigation identified three potential drug candidates that are predicted to be potent Nsp16 inhibitors and could be pursued further in cell-based studies. </p>

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