Hodgkin-Huxley (HH) 模型對於電流生理學的發展有著深遠的影響。它能精確地模擬離子通道的變化。然而，隨著多年來的反覆驗證，研究人員發現HH模型亦有其局限性和不足之處。有見及此，本論文提出一個建基於變形動力學的模型，藉此以更深入的物理層面解釋Hodgkin與Huxley的實驗數據。新的模型為鉀與鈉離子通道建立了新的電導方程。在這模型的詮釋下，HH模型的鉀離子通道電導方程[附圖] 被[附圖]取代，而HH模型的鈉離子通道電導方程 [附圖] 則被 [附圖] 取而代之。縱使 n(t), m(t)和 h(t)在兩個模型中被授予不同的物理意義，但它們均是一階微分方程。此論文詳細闡述模型的建立過程及參數的推導，並論證它能準確地描繪Hodgkin與Huxley對於烏賊巨軸突的實驗數據。模型參數經由遺傳演算法優化後，新的模型不僅能夠準確描述離子通道的電導變化，還能闡述Cole-Moore shift現象。在相同強度的去極化刺激和溫度下，新的模型比HH模型能接近地模擬膜動作電位的實驗數據。 / Hodgkin-Huxley (HH) model has a profound influence on the development of electrophysiology. It is capable of modeling the transient responses of voltage-gated ion channels precisely. Nevertheless, limitations and deficiencies of the model were found as researchers conducted subsequent experiments. In this regard, a new model based on deformation kinetic has been put forth to help explaining the HH experimental data with a deeper level of physical insight. Under the proposed model, the famous HH equation [with formula] for the description of potassium conductance was replaced by [with formula] and the HH sodium conductance equation [with formula] was substituted by [with formula]. Meanwhile, n(t), m(t) and h(t) are still first order differential equations as the HH case. This thesis contributes to illustrate the capability of the new model in approximating HH’s experimental data on squids’ giant axons. Detailed derivation of the new model and identification of the parametric functions are summarized in this report. A customized genetic algorithm was utilized to optimize the model parameters. After fine tuning the new model, we are able to describe the conductance behaviors of voltage-gated ion channels closely, and manage to account for the Cole-Moore shift phenomenon. Under identical initial depolarizing stimuli and temperature as stated in HH’s experiments, close approximations of membrane action potential can also be obtained by the new model. / Detailed summary in vernacular field only. / Yu, Cheuk Him Derek. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 69-70). / Abstracts also in Chinese. / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Overview of Electrophysiological Models --- p.4 / Chapter 1.2 --- The Hodgkin-Huxley Membrane Current Model --- p.4 / Chapter 1.2.1 --- Hodgkin-Huxley Potassium Channel --- p.6 / Chapter 1.2.2 --- Hodgkin-Huxley Sodium Channel --- p.8 / Chapter 1.3 --- Proliferation of the Deformation Kinetic Based Model --- p.10 / Chapter 1.4 --- Thesis Outline --- p.12 / Chapter 2 --- The Deformation Kinetic Based Model --- p.13 / Chapter 2.1 --- The Molecular Theory --- p.13 / Chapter 2.1.1 --- Application of Deformation Kinetics --- p.13 / Chapter 2.1.2 --- The Energy Function E{U+2093} (q) --- p.14 / Chapter 2.1.3 --- The Population Distribution Function P{U+2093} (N,t) --- p.17 / Chapter 2.1.4 --- Conductance Model for Voltage-gated Ion Channels --- p.18 / Chapter 2.2 --- The Approximate Solutions --- p.19 / Chapter 2.2.1 --- Approximation of the General Solution for G{U+2093} (N) --- p.19 / Chapter 2.2.2 --- Approximation of the General Solution for P{U+2093} (N,t) --- p.19 / Chapter 2.2.3 --- The Approximate Solution for Molecular g{U+2093} (t) --- p.23 / Chapter 2.2.4 --- A Convenient Form of the Approximate Solutions --- p.24 / Chapter 2.3 --- Chapter Summary --- p.25 / Chapter 3 --- Voltage-gated Ion Channel Modeling --- p.27 / Chapter 3.1 --- Voltage-gated Potassium Channel Modeling --- p.27 / Chapter 3.2 --- Voltage-gated Sodium Channel Modeling --- p.29 / Chapter 3.3 --- Chapter Summary --- p.31 / Chapter 4 --- The Parametric Functions --- p.32 / Chapter 4.1 --- The Curve Fitting References - HH Experimental Data --- p.32 / Chapter 4.2 --- Curve Fitting through Genetic Algorithm --- p.34 / Chapter 4.3 --- Functional Approximations w.r.t. HH Experimental Data --- p.37 / Chapter 4.3.1 --- Parametric Functions for Voltage-gated Potassium Channel --- p.37 / Chapter 4.3.2 --- Parametric Functions for Voltage-gated Sodium Channel --- p.39 / Chapter 4.4 --- Chapter Summary --- p.46 / Chapter 5 --- The Tracing Results --- p.47 / Chapter 5.1 --- Voltage Clamp Tracings --- p.47 / Chapter 5.1.1 --- Potassium Conductance Tracings --- p.48 / Chapter 5.1.2 --- Sodium Conductance Tracings --- p.49 / Chapter 5.2 --- Membrane Action Potential Tracings --- p.54 / Chapter 5.3 --- Propagated Action Potential Tracings --- p.56 / Chapter 5.4 --- Chapter Summary --- p.59 / Chapter 6? --- The Cole-Moore Shift Phenomenon --- p.60 / Chapter 6.1 --- Cole-Moore shift Phenomenon of Voltage-gated Potassium Channel --- p.61 / Chapter 6.2 --- Cole-Moore Shift Phenomenon of Voltage-gated Sodium Channel --- p.62 / Chapter 6.3 --- Chapter Summary --- p.64 / Chapter 7 --- Discussions --- p.65 / Conclusion --- p.67 / Future Works --- p.68 / References --- p.69 / Chapter Appendix I --- Hodgkin-Huxley’s Analysis of Voltage-gated Channels’ Voltage Clamp Data / Chapter (a) --- HH’s Analysis of Potassium Conductance Change in Voltage Clamp Experiments --- p.71 / Chapter (b) --- HH’s Analysis of Sodium Conductance Change in Voltage Clamp Experiments --- p.71 / Chapter Appendix II --- Numerical Estimations of Hodgkin-Huxley’s Experimental Data / Chapter (a) --- Numerical Estimations of Podium Conductance Change in Voltage Clamp Experiments for HH axon 17 --- p.72 / Chapter (b) --- Numerical Estimations of Sodium Conductance Change in Voltage Clamp Experiments for HH axon 17 --- p.73 / Chapter (c) --- Numerical Estimations of Membrane Action Potential with Different Initial Depolarizations for HH axon 17 --- p.74 / Chapter Appendix III --- Verification of the Replica of HH Model’s Simulations Results / Chapter (a) --- Comparison between HH Membrane Action Potential and Its Replica --- p.75 / Chapter (b) --- Comparison between HH Propagated Action Potential and Its Replica --- p.76

Educators frequently neglect efforts to evaluate the affective components of instructional programs even though most agree that the affective domain is as important, or even more important, than the cognitive domain in learning. Measurement of cognitive attainment is easily accomplished, however, measurement of students' feelings, attitudes, concerns and values is difficult to accomplish.The purpose of the present research was to measure galvanic skin response (GSR) reactions of students to multi-media programs which were created to effect attitude change toward biological concepts in nonscience majors, and to thereby identify learning strategies or combinations of strategies that produce emotional and physiological reactions.The electronic response (ER) system of the Department of Biology at Ball State University was utilized in conducting the study. The effectiveness of producing emotional arousal by the strategies involved in nine ER programs was sampled by using the galvanic skin response (GSR) to measure the change in electrical skin conductance. The population tested for each ER program consisted of 30 subjects. An approximately equal number of males and females and an approximately equal number of morning, mid-day and afternoon sessions were sampled.In the treatment of data, the maximum GSR resistance, following specific ER program events, was calculated using a latency of approximately three seconds. Resistance per unit area of electrode plate surface was calculated in ohms/mm2 and converted to conductance (mhos/mm2). To establish a basis for comparing the emotional and attitudinal impact of each electronic response program, the maximum conductance for each event and information components of each event sequence was averaged for the 30 subjects.A dependent t-test for paired observations was utilized to determine the significant conductance change of corresponding components of the initial and final event sequences in each ER program. In those situations which were significant at the .05 probability level, farther comparisons were made between corresponding components of the initial and middle and middle and final event sequences. The t-test was also utilized to determine the significance of mean changes in conductance between selected information and question and question and answer slides within event sequences which produced a greater or lower conductance than previous event sequences, and those in which little variance or observable differences among components occurred.The principal conclusion drawn from the study is that the electronic response programs provide an effective mechanism for increasing emotional arousal, increasing involvement, and creating attitude change. All of the nine electronic response programs produced a gradual rise in average conductance from the beginning to the end of each program.Extremes in GSR reactions occurred in response to different types and combinations of narrative, pictorial presentations and musicalselections. Situations which created a mood or conveyed a feeling, possessed emotionally toned narrative or slides, or required a value stance or judgment produced the greatest GSR reactions. Calming, quiet, and relaxing music, unmoving slides, unemotional narration, questions lacking challenge or treating non-controversial subject matter, produced the smallest GSR reactions.The present study supports the contention that multiple stimuli, which increase the number of senses incorporated in the learning process and the interaction (response-reinforcement) of the learner, produce a greater emotional reaction than stimuli in one sense modality.The author considers that emotional responses involved and related with affective learning are as important, or more important, than cognitive attainment. Further investigations of the relationship between multimedia components and emotional arousal need to be carried out to ascertain the appropriate blending or combinations of stimuli which provide the best or most effective learning situations. Data obtained through research in the cognitive and affective aspects of instructional designs should also be correlated to determine how the most effective learning strategies can be developed.

Thesis. 1976. Ph.D.--Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science. / Microfiche copy available in Archives and Engineering. / Bibliography: leaves 377-385. / Ph.D.

Stretch of cardiac muscle is known to activate various physiological processes that result in changes to cardiac function, contractility and electrophysiology. To date, however, the precise relationship between mechanical stretch and changes in the electrophysiology of the heart remain unclear. This relationship, termed mechanoelectric feedback (MEF), is thought to underlie many cardiac arrhythmias associated with pathological conditions. These electrophysiological changes are observed not only in the whole heart, but also at the single cardiomyocyte level, and can be explained by the presence of stretch-activated ion channels (SACs). Most investigations of the actions of stretch have concentrated on these sacrolemmal ionic currents thought responsible for the proposed MEF-induced changes in contractility. While these studies have provided some useful insight into possible mechanisms, the inappropriate use of solutions and non-physiological degrees of stretch, may have caused somewhat misleading results. Currently, little is known about the involvement or contribution of non-selective or K+ selective SACs to the normal cardiac cycle. Here, I investigate the concept that stretch-induced changes in cardiac electrophysiology (MEF) are important in normal cardiac cycle and demonstrate the effects of stretch on the Frank-Starling mechanism (stretch induced increases in cardiac contractility) while pharmacologically manipulating stretch-activated ion currents. Experiments were conducted using a number of agents known to influence stretch-activated channels either in a positive or antagonistic manner. Results proved somewhat negative toward MEF theory with only substantial or pathological levels of stretch being able to elicit any electrophysiological change in the heart. Furthermore, where electrophysiological changes were associated with pathological stretch they were not consistently modulated by stretch-activated ion channel activators or blockers. Of equal importance was the observation that smaller levels of myocardial stretch associated with positive changes in contractility via the Frank-Starling mechanism were not associated with any electrophysiological changes in the Langendorff perfused heart (as observed by monophasic action potentials) nor in isolated muscle preparations (as observed through transcellular membrane potential recordings). As such, the present research undertaken in this thesis confirms an absence of electrophysiological changes with stretch except under extreme conditions suggesting that MEF is not a robust and necessarily repeatable phenomenon in the mammalian heart. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1320476 / Thesis (Ph.D.) - University of Adelaide, School of Molecular and Biomedical Science, 2008

<p>Bed bugs (<i>Cimex lectularius</i> L.) are globally important human ectoparasites. Their management necessitates the use of multiple control techniques. Plant-derived essential oils are extracts from aromatic plants that represent one of the alternative control measures for bed bug control, in addition to mechanical options and synthetic pesticides. However, there is limited information available on the efficacy and toxicology of plant essential oils against bed bugs. This project was designed with the aim to provide in-depth information on efficacy, toxicology and mode-of-action of essential oils and their insecticidal constituents in bed bugs. Initially, I evaluated topical and fumigant toxicity of fifteen essential oil components against adult male bed bugs of the Harlan strain (an insecticide susceptible strain). Neurological effects of the six most toxicologically active compounds were also determined. In both topical and fumigant bioassays, carvacrol and thymol were the most active compounds. Spontaneous electrical activity measurements of the bed bug nervous system demonstrated neuroinhibitory effects of carvacrol, thymol and eugenol, whereas linalool and bifenthrin (a pyrethroid class insecticide) produced excitatory effects. Further, I evaluated the efficacy and neurological impacts of a mixture of three neuroinhibitory compounds; carvacrol, eugenol and thymol in 1:1:1 ratio against adult male bed bugs of the Harlan strain. This mixture of monoterpenoids as well as the mixture of synthetic insecticides exhibited a synergistic affect in topical bioassays. In electrophysiology experiments, the monoterpenoid mixture led to higher neuroinhibitory effects, whereas a mixture of synthetic insecticides caused higher neuroexcitatory effects in comparison to single compounds. </p> <p>In the next objective of my dissertation, I compared the efficacy of five plant essential oils (thyme, oregano, clove, geranium and coriander), their major components (thymol, carvacrol, eugenol, geraniol and linalool) and EcoRaider^® (commercial product) between pyrethroid susceptible (Harlan) and field collected (Knoxville) bed bug populations. Initially, I found that the Knoxville strain was 72,893 and 291,626 fold resistant to topically applied deltamethrin (a pyrethroid class insecticide) compared to the susceptible Harlan strain at the LD₂₅ and LD₅₀ lethal dose levels, respectively. Synergist bioassays and detoxification enzyme assays showed that the Knoxville strain possesses significantly higher activity of cytochrome P450 and esterase enzymes. Further, Sanger sequencing revealed the presence of the L925I mutation in the voltage gated sodium channel gene. The Knoxville strain, however, did not show any resistance to plant essential oils, their major components or EcoRaider^® in topical bioassays (resistance ratios of ~ 1). In the final objective, I evaluated the efficacy of binary mixtures of above-mentioned essential oils or their major components or EcoRaider^® with deltamethrin in susceptible and resistant bed bugs. In topical application bioassays, binary mixtures of essential oils or their major components or EcoRaider^® and deltamethrin at the LD₂₅ dose caused a synergistic increase in toxicity in resistant bed bugs. Further, I studied the inhibitory effects of major essential oil components on detoxification enzyme activities (cytochrome P450s, esterases and glutathione transferases). Detoxification enzyme assays conducted using protein extracts from bed bugs pre-treated with essential oil constituents showed that these compounds significantly inhibited cytochrome P450 activity in the resistant strain, but esterase and glutathione transferase activity were unaffected. No inhibition of detoxification enzyme activities was observed in the Harlan strain bed bugs pre-treated with essential oil constituents.</p> <p>In conclusion, my dissertation research has created the foundation for utilization of natural products for bed bug management by (i) describing the efficacy of plant essential oils and their components against bed bugs, (ii) discovering synergistic interactions between essential oil components at the nervous system level, (iii) determining susceptibility of deltamethrin-resistant bed bugs to plant essential oils and their constituents and (iv) identifying synergistic effects of essential oils or their components on toxicity of pyrethroid insecticides and underlying mechanisms of this synergistic interaction. </p> <br>