Published Article / Magnesium is the second most abundant intracellular cation with many control and regulatory functions. It regulates energy production and utilization and modulates activity of membrane ionic channels. Magnesium has direct control effects on cardiac myocyte ion channels making it useful in certain arrhythmias. Calcium is responsible for pacemaker excitation and for excitation-contraction coupling in myocytes but increased intracellular calcium produces early and late afterdepolarisations initiating arrhythmias. Magnesium regulates calcium channel activity preventing raised intracellular levels. Potassium channel activity is enhanced by magnesium hyperpolarizing the cell reducing arrhythmia generation. Magnesium is effective against long QT Torsade de Pointes. In rapid atrial fibrillation magnesium produces rate control slowing AV nodal conduction. Magnesium prevents digitalis toxicity due to associated hypomagnesemia.

Because games set in persistent virtual game worlds (VGWs) have massive numbers of players, these games need methods of characterisation for playable characters (PCs) that differ from the methods used in traditional narrative media. VGWs have a number of particularly interesting qualities. Firstly, VGWs are places where players interact with and create elements carrying narrative potential. Secondly, players add goals, motives and driving forces to the narrative potential of a VGW, which sometimes originates from the ordinary world. Thirdly, the protagonists of the world are real people, and when acting in the world their characterisation is not carried out by an author, but expressed by players characterising their PCs. How they can express themselves in ways that characterise them depend on what they can do, and how they can do it, and this characterising action potential (CAP) is defined by the game design of particular VGWs. In this thesis, two main questions are explored. Firstly, how can CAP be designed to support players in expressing consistent  characters in VGWs? Secondly, how can VGWs support role-play in their rule-systems? By using iterative design, I explore the design space of CAP by building a semiautonomous agent structure, the Mind Module (MM) and apply it in five experimental prototypes where the design of CAP and other game features is derived from the MM. The term semiautonomy is used because the agent structure is designed to be used by a PC, and is thus partly controlled by the system and partly by the player. The MM models a PC's personality as a collection of traits, maintains dynamic emotional state as a function of interactions with objects in the environment, and summarises a PC's current emotional state in terms of `mood'.   The MM consists of a spreading-activation network of affect nodes that are interconnected by weighted relationships.  There are four types of affect node: personality trait nodes, emotion nodes, mood nodes, and sentiment nodes. The values of the nodes defining the personality traits of characters govern an individual PC's state of mind through these weighted relationships, resulting in values characterising for a PC's personality. The sentiment nodes constitute emotionally valenced connections between entities. For example, a PC can `feel' anger toward another PC. This thesis also describes a guided paper-prototype play-test of  the VGW prototype World of Minds, in which the game mechanics build upon the MM's model of personality and emotion. In a case study of AI-based game design, lessons learned from the test are presented. The participants in the test were able to form and communicate mental models of the MM and game mechanics, validating the design and giving valuable feedback for further development. Despite the constrained scenarios presented to test players, they discovered interesting, alternative strategies, indicating that for game design the `mental physics' of the MM may open up new  possibilities.The results of the play-test influenced the further development of the MM as it was used in the digital VGW prototype the Pataphysic Institute. In the Pataphysic Institute the CAP of PCs is largely governed by their mood. Depending on which mood  PCs are in they can cast different `spells', which affect values such as mental energy, resistance and emotion in their targets. The mood also governs which `affective actions' they can perform toward other PCs and what affective actions they are receptive to. By performing affective actions on each other PCs can affect each others' emotions, which - if they are strong - may result in sentiments toward each other. PCs' personalities govern the individual fluctuations of mood and emotions, and define which types of spell PCs can cast. Formalised social relationships such as friendships affect CAP, giving players more energy, resistance, and other benefits. PCs' states of mind are reflected in the VGW in the form of physical manifestations that emerge if an emotion is very strong. These manifestations are entities which cast different spells on PCs in close proximity, depending on the emotions that the manifestations represent. PCs can also partake in authoring manifestations that become part of the world and the game-play in it. In the Pataphysic Institute potential story structures are governed by the relations the sentiment nodes constitute between entities.Because games set in persistent virtual game worlds (VGWs) have massive numbers of players, these games need methods of characterisation for playable characters (PCs) that differ from the methods used in traditional narrative media. VGWs have a number of particularly interesting qualities. Firstly, VGWs are places where players interact with and create elements carrying narrative potential. Secondly, players add goals, motives and driving forces to the narrative potential of a VGW, which sometimes originates from the ordinary world. Thirdly, the protagonists of the world are real people, and when acting in the world their characterisation is not carried out by an author, but expressed by players characterising their PCs. How they can express themselves in ways that characterise them depend on what they can do, and how they can do it, and this characterising action potential (CAP) is defined by the game design of particular VGWs. In this thesis, two main questions are explored. Firstly, how can CAP be designed to support players in expressing consistent  characters in VGWs? Secondly, how can VGWs support role-play in their rule-systems? By using iterative design, I explore the design space of CAP by building a semiautonomous agent structure, the Mind Module (MM) and apply it in five experimental prototypes where the design of CAP and other game features is derived from the MM. The term \textit{semiautonomy} is used because the agent structure is designed to be used by a PC, and is thus partly controlled by the system and partly by the player. The MM models a PC's personality as a collection of traits, maintains dynamic emotional state as a function of interactions with objects in the environment, and summarises a PC's current emotional state in terms of `mood'.   The MM consists of a spreading-activation network of affect nodes that are interconnected by weighted relationships.  There are four types of affect node: personality trait nodes, emotion nodes, mood nodes, and sentiment nodes. The values of the nodes defining the personality traits of characters govern an individual PC's state of mind through these weighted relationships, resulting in values characterising for a PC's personality. The sentiment nodes constitute emotionally valenced connections between entities. For example, a PC can `feel' anger toward another PC. This thesis also describes a guided paper-prototype play-test of  the VGW prototype World of Minds, in which the game mechanics build upon the MM's model of personality and emotion. In a case study of AI-based game design, lessons learned from the test are presented. The participants in the test were able to form and communicate mental models of the MM and game mechanics, validating the design and giving valuable feedback for further development. Despite the constrained scenarios presented to test players, they discovered interesting, alternative strategies, indicating that for game design the `mental physics' of the MM may open up new  possibilities.The results of the play-test influenced the further development of the MM as it was used in the digital VGW prototype the Pataphysic Institute. In the Pataphysic Institute the CAP of PCs is largely governed by their mood. Depending on which mood  PCs are in they can cast different `spells', which affect values such as mental energy, resistance and emotion in their targets. The mood also governs which `affective actions' they can perform toward other PCs and what affective actions they are receptive to. By performing affective actions on each other PCs can affect each others' emotions, which - if they are strong - may result in sentiments toward each other. PCs' personalities govern the individual fluctuations of mood and emotions, and define which types of spell PCs can cast. Formalised social relationships such as friendships affect CAP, giving players more energy, resistance, and other benefits. PCs' states of mind are reflected in the VGW in the form of physical manifestations that emerge if an emotion is very strong. These manifestations are entities which cast different spells on PCs in close proximity, depending on the emotions that the manifestations represent. PCs can also partake in authoring manifestations that become part of the world and the game-play in it. In the Pataphysic Institute potential story structures are governed by the relations the sentiment nodes constitute between entities.

名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成10年6月4日 李鍾國氏の博士論文として提出された

The purpose of this study was to examine the time course and kinetics of L-type Ca2+ current (ICa,L) from pituitary GH3 cells in response to various action potential (AP) waveforms using the whole-cell configuration of the patch-clamp technique. The major findings in this study are: 1. ICa,L evoked during the AP waveform exhibited an early and a late component. The early component of ICa,L occurred on the rising phase of the AP, whereas the late component coincided with the falling phase. 2. A prolongation of the falling phase of APs led to an increase in Ca2+ charge carried by ICa,L, although the amplitude of the late ICa,L was reduced. 3. When the peak voltage of AP waveforms was prolonged without changing the rising and falling phases, the amplitude of the late components was significantly increased. 4. ICa,L was also found to inactivate during a train of AP waveforms. When Ba2+ ions were used as the charge carriers, current inactivation during a train of APs was decreased. 5. The amplitude of ICa,L evoked by the AP templates with irregular bursting pattern was inactivated. 6. When spontaneous APs with the depolarizing potentials were replayed to GH3 cells, Ca2+ entry was not only spread over the entire AP, but also occurred during the interspike voltage trajectory. 7. When cells were exposed to thyrotropin releasing hormone (TRH; 10

Phosphodiesterases (PDEs) are the enzymes responsible for the hydrolysis of cyclic nucleotides including cAMP and cGMP. We recently discovered that natriuretic peptides elicit effects in the atrial myocardium via a PDE dependant pathway; however, the role(s) of specific PDE subtypes in atrial myocytes are not clear. Thus, I studied the effects of PDE selective blockers on mouse atrial action potentials (APs) and L-type Ca2+ currents (ICa,L). AP duration (APD) was significantly increased in the presence of IBMX (inhibits all PDEs) as well as EHNA (PDE2 inhibitor) and rolipram (PDE4 inhibitor). The PDE 3 inhibitor milrinone had no effect on APD. Applying milrinone and rolipram (PDE3/PDE4 inhibition) or EHNA, milrinone, and rolipram (PDE2/ PDE3/PDE4 inhibition) in combination prolonged APD as effectively as IBMX. A similar pattern of results was obtained for atrial ICa,L. These data provide novel insight into the unique effects of PDE inhibitors in atrial myocytes

国立情報学研究所で電子化したコンテンツを使用している。

国立情報学研究所で電子化したコンテンツを使用している。

Abstract Stretch of the cardiac muscle activates several physiological processes leading to changes in the function of the muscle. These changes include increase of the contraction force accompanied by changes in the intracellular calcium concentration. This phenomenon is known as Frank-Starling relation of the heart. In addition to this, stretch also influences the membrane voltage of individual myocytes predisposing the cardiac muscle to arrhythmias. In atrial muscle stretch augments the secretion of the atrial natriuretic peptide (ANP). Although several cellular components are known to be sensitive to mechanical stimulus the precise mechanisms participating to these stretch-induced changes are not known in detail. Further it is not known if these changes are causally related or if they share a common causal factor. This research was aimed to study the stretch-induced changes in the rat atrium. The possible interactive mechanisms were studied by recording intracellular action potentials, changes in the intracellular calcium concentration, contraction force and ANP secretion during stretch. The plausible mechanosensitive cellular components were incorporated into a mathematical model that was used to further study the mechanisms. The role of intracellular acidosis as a possible modulator of the mechanotransduction was of special interest. In isolated rat left atrium moderate stretch produced by increasing the intra-atrial pressure increased the contraction force in a biphasic manner. The immediate increase of the force was caused by altered properties of the contractile element, but the following slow increase was accompanied by an increase of the Ca2+ transient. These changes were followed by lengthening of the late phase of action potentials and augmented secretion of the ANP. Intensive sustained stretch was also found to induce delayed afterdepolarizations (DADs). Gadolinium (Gd3+), blocker of stretch-activated ion channels reduced the stretch-dependent activation of the contraction and inhibited the stretch-induced DADs. The mathematical model simulated the experimental findings at best when stretch-activated channel (SA-channel) activation and increased troponin-C affinity were used to mimic the stretch. The modelling data suggested that the SA-channel current increases the sarcoplasmic reticulum calcium content in a time dependent manner leading to Ca2+ transient augmentation during systole. Bigger Ca2+ transients induce a depolarizing current during the late phase of the action potential (AP) repolarization via the Na+/Ca2+ exchanger causing the lengthening of the action potentials. A small reduction of the intracellular pH (0.18 units) with 20 mM propionate was found to modulate the stretch-induced changes in the rat atrium. Acidosis leads to an increase in the diastolic [Ca2+]i during stretch, inhibits the stretch-induced changes in action potentials and slows down the contraction development during stretch by inhibiting the fast component of the force increase. These changes in E-C-coupling (excitation-contraction-coupling) were accompanied by a simultaneous augmentation of the ANP secretion. Furthermore, it was shown that contraction force and diastolic [Ca2+]i of the stretched tissue are more sensitive to acidosis than in non-stretched tissue. In conclusion, the stretch-induced changes in rat atrial myocytes are mediated by at least two mechanisms; stretch-activated Ca2+ influx and change in the properties of the contractile element. The action potential changes can be largely explained by modulation of the membrane voltage by intracellular calcium via Na+/Ca2+-exchanger. The co-occurrence of the changes in the [Ca2+]i and ANP secretion suggests that the stretch-induced ANP secretion can be mediated by [Ca2+]i.

An electrophysiology research laboratory at the Wake Forest University School of Medicine in the Physiology/Pharmacology Department currently carries out memory research by recording neural signals from laboratory animals with a wire tethering the animal to nearby signal conditioning and recording equipment. A wireless neural signal recording system is desirable because it removes the cumbersome wires from the animal, allowing it to roam more freely. The result is an animal that is more able to behave as it would in its natural habitat, thus opening the possibility of testing procedures that are not possible with wired recording systems. While there are wireless neural recording systems in existence, this thesis presents a new approach to recording neural signals wirelessly. The firings of neurons in the hippocampus are manifested as action potentials or voltage "spikes" on the order of 100 to 400uV in magnitude. Though the information content of the neural signal is riding on these action potentials, the spikes comprise a small fraction of the complete neural signal. A unique feature of the neural signal transceiver presented in this thesis is its ability to digitally isolate and transmit the action potentials, leaving out the remaining, unimportant part of the neural signal. This approach to recording neural signals makes efficient use of the limited bandwidth available with portable short range wireless devices. This thesis will present the spike isolating neural transmitter, which was built using commercially available electronic components. Then, the proper function of assembly language code written for a PIC18F458 microcontroller will be demonstrated. Finally, a discussion of the performance of the neural signal transmitter will be provided. / Master of Science

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