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Direct regulation of inward rectifier K+ (Kir) channel by endocannabinoidsAhrari, Ameneh 06 1900 (has links)
This thesis represents the culmination of the main project I have undertaken during my master's program. It is important to note that additional data collection and analysis were conducted by intern students under my supervision, which will be integrated into a forthcoming manuscript where I will be credited as the first co-author. Due to space and focus limitations of this thesis, these additional findings have not been included here. / La famille des canaux potassiques à rectification entrante (Kir), exprimée de manière ubiquitaire, repolarise et maintient le gradient de tension à travers les membranes des cellules excitables et non-excitables. Les canaux Kir sont fortement régulés par divers lipides membranaires, tels que les phosphoinositides, les phospholipides anioniques secondaires, le cholestérol, le Coenzyme A (CoA) à longue chaîne et l'acide arachidonique. Kir2.1 est fortement exprimé dans le tissu musculaire strié des cellules cardiaques auriculaires et ventriculaires. Il joue un rôle essentiel dans la régulation du potentiel de membrane au repos et de la contraction des cellules musculaires cardiaques et lisses en générant le courant K+ à rectification entrante (IK1). (IK1). Les mutations de Kir2.1 avec perte de fonction sont à l'origine du syndrome d'Andersen-Tawil (ATS). Par conséquent, l'altération de la fonction de Kir2.1 est un déterminant essentiel au bon fonctionnement du cœur. Les endocannabinoïdes sont une classe spéciale de lipides naturellement exprimés dans une variété de cellules, y compris les cellules cardiaques, neuronales et immunitaires. Le système endocannabinoïde, y compris les récepteurs cannabinoïdes (CBR), agit comme un système de réponse au stress qui s'active. Des études menées chez l'animal et chez l'homme suggèrent que la modulation pharmacologique de ce système pourrait représenter une nouvelle approche thérapeutique. Cependant, ces dernières années, il est devenu clair que si les endocannabinoïdes peuvent déclencher des changements de signalisation en aval par l'intermédiaire des CBR, ils peuvent également interagir directement avec les canaux ioniques indépendamment des CBR pour moduler la fonction cellulaire.
Dans cette étude, nous avons utilisé la technique de double électrode en voltage imposé pour examiner les effets d'un panel d'endocannabinoïdes sur la fonction de Kir2.1. Nous avons montré qu'un sous-ensemble d'endocannabinoïdes, mais pas tous, peut réguler la fonction de Kir2.1 à des degrés divers, indépendamment des CBR. Nous avons également démontré que les endocannabinoïdes peuvent également réguler les protéines mutées menant à l'ATS (G144S et V302M). Nous avons également observé que l'effet des endocannabinoïdes n'est pas conservé parmi les membres de la famille Kir, avec des différences observées entre les canaux Kir2.1, Kir4.1 et Kir7.1. Ces résultats pourraient avoir des implications plus larges pour les fonctions des cellules cardiaques, neuronales et immunitaires.
Mots clés : Kir2.1, Endocannabinoïdes, LQT7, Rectification entrante, G144S, Kir7.1, Kir4.1 / The ubiquitously expressed family of inward rectifier potassium (Kir) channels repolarizes and maintains the voltage gradient across excitable and non-excitable cell membranes. Kir channels are highly regulated by various membrane lipids, such as phosphoinositides, secondary anionic phospholipids, cholesterol, long chain acyl- Coenzyme A (CoA), and arachidonic acid. Kir2.1 is highly expressed in striated muscle tissue of atrial and ventricular heart cells. It is critically involved in regulating the resting membrane potential and contraction of cardiac and smooth muscle cells through the generation of the current IK1. Loss-of-function mutations in Kir2.1 cause Andersen-Tawil syndrome (ATS). Therefore, altered Kir2.1 function is a critical determinant of proper heart function. Endocannabinoids are a special class of lipids that are naturally expressed in a variety of cells, including cardiac, neuronal, and immune cells. The endocannabinoid system, including cannabinoid receptors (CBRs), acts as a stress response system that is activated. Studies in both animals and humans suggest that pharmacological modulation of this system might represent a novel approach to treatment. However, in recent years, it is becoming clear that while endocannabinoids can trigger downstream signaling changes through CBRs, they can also directly interact with ion channels independently of CBRs to modulate cellular function.
In this study, we used the electrophysiology technique called two-electrode-voltage-clamp (TEVC) in combination with mutagenesis studies to examine the effects of a panel of endocannabinoids on the function of Kir2.1. We showed that a subset of endocannabinoids, but not all, can regulate the Kir2.1 function to varying degrees, independent of CBRs. We also demonstrated that endocannabinoids can also regulate mutants linked with ATS (G144S and V302M). We also observed that the effect of endocannabinoids is not conserved among Kir family members, with differences observed between Kir2.1, Kir4.1 and Kir7.1 channels. These findings could have broader implications for cardiac, neuronal, and immune cell functions.
Key words: Kir2.1, Endocannabinoids, LQT7, Inward rectification, G144S, Kir7.1, Kir4.1
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Reduction of the Global Human Population : A Rectificatory Argument based on Environmental ConsiderationsKoenraads, Stijn January 2016 (has links)
Contrary to what many scholars hold, a case can be made for human population reduction (the practice of artificially decreasing the number of human beings on the Earth). Robin Attfield's, Paul Taylor's, Arne Næss's and J. Baird Callicott's theories are considered for justifying human population reduction; however, only Næss's actually justifies reduction. Another argument for human population reduction is developed, based on rectification: humans have unjustly harmed other living entities and themselves, and they should provide rectification for the harm done. Human population reduction is a way in which this rectification can be given.
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The geometric stochastic resonance and rectification of active particlesGlavey, Russell January 2015 (has links)
This thesis describes the work of three research projects, the background research that motivated the work, and the resultant project findings. The three projects concerned: (i) Geometric stochastic resonance in a double cavity, (ii) Synchronisation of geometric stochastic resonance by a bi-harmonic drive, and (iii) Rectification of Brownian particles with oscillating radii in asymmetric corrugated channels. In the project 'Geometric stochastic resonance in a double cavity', we investigated synchronisation processes for the geometric stochastic resonance of particles diffusing across a porous membrane and subject to a periodic driving force. Non-interacting particle currents were driven through a symmetric membrane pore either parallel or perpendicular to the membrane. Then, harmonic mixing spectral current components were generated by the combined action of parallel and perpendicular drives. The role of the repulsive interaction of particles as a controlling factor with potential applications to the transport of colloids and biological molecules through narrow pores was also investigated. In 'Synchronisation of geometric stochastic resonance by a bi-harmonic drive', we simulated the stochastic dynamics of an elliptical particle using the Langevin equation. The particle was simultaneously driven by low and high frequency harmonic drives across a porous inter-cavity membrane. It was observed that the particle oscillated out of phase with the low frequency drive. This effect was due to the absolute negative mobility the particle would have exhibited if the low frequency drive had been replaced by a dc static force. It was also observed that the magnitude of this out-of-phase stochastic resonance depends on how the combined action of the driving forces and noise fluctuations affect the particle orientation, and as such was shown to be sensitive to the particle shape. This emphasises the importance of particle geometry, in addition to chamber geometry, to the realisation and optimisation of geometric stochastic resonance. In the project 'Rectification of Brownian particles with oscillating radii in asymmetric corrugated channels', we simulated the transport of a Brownian particle with an oscillating radius freely diffusing in an asymmetric corrugated channel over a range of driving forces for a series of temperatures and angular frequencies of radial oscillation. It was observed that there was a strong influence of self-oscillation frequency upon the average particle velocity. This effect can be used to control rectification of biologically active particles as well as for their separation according to their activity, for instance in the separation of living and dead cells. The background research is described in Chapter One and the research findings are described along with their related projects in Chapters Two and Three.
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Investigation of the principle of flame rectification in order to improve detection of the propane flame in absorption refrigeratorsMöllberg, Andreas January 2005 (has links)
<p>Electrical properties of a propane flame was investigated to improve detection of the flame in absorption refrigerators. The principle of flame rectification, which uses the diode property of the flame, was studied. A DC voltage in the range 0–130V was applied, between the burner and an electrode in the flame, and the current through the flame in the forward and reverse direction was measured. This measurements were performed with the electrode top in different horizontal and vertical positions. AC voltages at various frequencies was also applied and the average current through the flame was measured.</p><p>A linear relation was found between the applied DC voltage and the current through the flame which means that the resistance, in the investigated voltage range, is independent of the applied voltage. The resistance in the forward direction was almost constant for different electrode positions but the reverse resistance varied many hundred MOhm when the electrode was moved vertically away from the burner. The gas flow also influenced the reverse resistance to a large extent.</p> / <p>Elektriska egenskaper hos en propanlåga undersöktes i syfte att förbättra detekteringen av lågan i absorptionskylskåp. Rektifieringsprincipen, vilken utnyttjar lågans diodegenskap, undersöktes. En likspänning i intervallet 0–130V lades på, mellan brännaren och en elektrod i lågan, och strömmen genom lågan i fram- och backriktningen mättes. Dessa mätningar gjordes med elektroden i olika horisontella och vertikala positioner. Växelspänning med olika frekvenser lades också på och medelvärdet av strömmen genom lågan mättes.</p><p>Ett linjärt samband upptäcktes mellan pålagd likspänning och strömmen genom lågan vilket betyder att resistansen, i det undersökta spänningsintervallet, är oberoende av pålagd spänning. Resistansen i framriktningen var i princip konstant vid olika elektrodplaceringar medan backresistansen varierade flera hundra MOhm när elektroden flyttades bort från brännaren vertikalt. Gasflödet påverkade också backresistansen i stor utsträckning.</p>
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International Debt Cancellation and the Question of Global Justice: A Case Study of Nigeria.Aniago, Wilfred Onyekachi January 2006 (has links)
<p>There is so much hunger in the developing poor countries of the world that the extent of inequality calls for a re-examination of global resources distribution especially as it concerns global debt crisis. The debts and their servicing obligation worsen the condition of the poor. Their cancellation could grant some respite to these global poor. This is why the call for a total and unconditional cancellation of Third World debt becomes a moral imperative. This needs to be given a normative approach especially as most of the debts were said to have arisen from morally questionable contracts. The demand for their cancellation is therefore a demand for global justice viewed from the stand point of rectification and distribution.</p>
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International Debt Cancellation and the Question of Global Justice: A Case Study of Nigeria.Aniago, Wilfred Onyekachi January 2006 (has links)
There is so much hunger in the developing poor countries of the world that the extent of inequality calls for a re-examination of global resources distribution especially as it concerns global debt crisis. The debts and their servicing obligation worsen the condition of the poor. Their cancellation could grant some respite to these global poor. This is why the call for a total and unconditional cancellation of Third World debt becomes a moral imperative. This needs to be given a normative approach especially as most of the debts were said to have arisen from morally questionable contracts. The demand for their cancellation is therefore a demand for global justice viewed from the stand point of rectification and distribution.
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Investigation of the principle of flame rectification in order to improve detection of the propane flame in absorption refrigeratorsMöllberg, Andreas January 2005 (has links)
Electrical properties of a propane flame was investigated to improve detection of the flame in absorption refrigerators. The principle of flame rectification, which uses the diode property of the flame, was studied. A DC voltage in the range 0–130V was applied, between the burner and an electrode in the flame, and the current through the flame in the forward and reverse direction was measured. This measurements were performed with the electrode top in different horizontal and vertical positions. AC voltages at various frequencies was also applied and the average current through the flame was measured. A linear relation was found between the applied DC voltage and the current through the flame which means that the resistance, in the investigated voltage range, is independent of the applied voltage. The resistance in the forward direction was almost constant for different electrode positions but the reverse resistance varied many hundred MOhm when the electrode was moved vertically away from the burner. The gas flow also influenced the reverse resistance to a large extent. / Elektriska egenskaper hos en propanlåga undersöktes i syfte att förbättra detekteringen av lågan i absorptionskylskåp. Rektifieringsprincipen, vilken utnyttjar lågans diodegenskap, undersöktes. En likspänning i intervallet 0–130V lades på, mellan brännaren och en elektrod i lågan, och strömmen genom lågan i fram- och backriktningen mättes. Dessa mätningar gjordes med elektroden i olika horisontella och vertikala positioner. Växelspänning med olika frekvenser lades också på och medelvärdet av strömmen genom lågan mättes. Ett linjärt samband upptäcktes mellan pålagd likspänning och strömmen genom lågan vilket betyder att resistansen, i det undersökta spänningsintervallet, är oberoende av pålagd spänning. Resistansen i framriktningen var i princip konstant vid olika elektrodplaceringar medan backresistansen varierade flera hundra MOhm när elektroden flyttades bort från brännaren vertikalt. Gasflödet påverkade också backresistansen i stor utsträckning.
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Fabrication and characteristics of diamond PN junction deviceChen, Hong-Ruei 07 January 2009 (has links)
This work has employed the Micro-wave Plasma enhanced Chemical Vapor Deposition (MPCVD) method to fabricate diamond PN junction device. The n+ <111> orientation single-crystal silicon has used as substrates. P-type diamond layer is doped with B(OCH3)3 and the N-type diamond layer is doped with ammonia. The surface structure of diamond film has been observed by scanning electron microscope; and the device rectification property of a PN junction has measured by current-voltage characteristic. The carrier density and mobility of diamond films have been analyzed by Hall measurement. Furthermore, the Cathodoluminescence (CL) spectroscopy showed the defect spectra in diamond PN junction. The N-type diamond film and P-type diamond film have deposited at temperature of 800 ¢J, for 30 minutes and 90 minutes, respectively. The process CVD has performed in the same chamber continually. A I-V curve of sample showed the set on positive voltage 0.5 V and the reverse breakdown voltage of 6 V. Further, CL results revealed a peak at 285 nm (4.4 eV), which represents the CVD diamond band and the other one is at 500 nm (2.5 eV), which stands for donor-acceptor recombination from defect in these diamond films.
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Operation of Battery Power Modules with Serial ConnectionHu, Jin-shin 20 July 2009 (has links)
This thesis presents a novel configuration of battery power by the outputs with serial connection of battery power modules (BPMs) for high voltage level loads. As compared to the conventional application of series-connected battery bank, this configuration operates the BPMs individually, and thus has the advantages of flexible control, convenient maintenance, and easily favorable battery management. The associated converter is equipped to a single battery pack, so that has lower component stresses leading to a higher circuit efficiency.
The operation and the design of a lead-acid battery power with series boost-typed BPMs are illustrated. The operation and the design of the converter are illustrated. The control of the power converters is accomplished by a complex programmable logic device (CPLD). To improve the converter efficiency, the technique of synchronous rectification is introduced. For the BPMs designed for discontinuous conduction mode (DCM) operation, charge equalization can be automatically achieved under the same duty-ratio, but is adequate only for batteries with a small difference. On the other hand, charge equalization for the BPMs with continuous conduction mode (CCM) can easily be accomplished by regulating the duty-ratios of the converters.
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Microwave photovoltage effects in thin-film magnetic bilayer systemsHyde, Paul 13 January 2015 (has links)
The field of Spintronics, which utilizes the spin polarization of electrons as a means to transport energy and information, is currently undergoing a massive expansion due to the numerous recent discoveries of electron spin-based effects only visible at the micro and nano scale. With all these new material and current based properties being discovered, it has become increasingly difficult to experimentally isolate the effects of each of them individually. In this work one of the main proposals is an experimental method for separating the voltage signals generated by the spin rectification effect and spin pumping in bilayer samples, a topic currently of much interest to the spintronics community. After demonstrating this new method for separating voltage signals, it is utilized to reveal new details about how the layers of ferromagnetic bilayer samples interact with each other and the behaviours of spin currents within these systems.
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