星野 光

<title>Abstract</title><sec> <title>Background</title> Nondepolarizing neuromuscular blocking drugs (NDNBs) are clinically used to produce muscle relaxation during general anesthesia. To better understand clinical properties of NDNBs, comparative in vitro pharmacologic studies have been performed. In these studies, a receptor binding model, which relies on the assumption that the inhibition, i.e., the effect of an NDNB, is proportional to the receptor occupancy by the drug, has been effectively used to describe obtained experimental data. However, it has not been studied in literature under which conditions the above assumption can be justified nor the assumption still holds in vivo. The purpose of this study is to explore the in vivo relationship between the inhibition and the receptor occupancy by an NDNB and to draw implications on how in vitro experimental results can be used to discuss the in vivo properties of NDNBs. </sec><sec> <title>Methods</title> An ordinary differential equation model is employed to simulate physiologic processes of the activation of receptors by acetylcholine (ACh) as well as inhibition by an NDNB. With this model, the degree of inhibition is quantified by the fractional amount of receptors that are not activated by ACh due to the presence of an NDNB. The results are visualized by plotting the fractional amounts of the activated receptors as a function of the receptor occupancy. </sec><sec> <title>Results</title> Numerical investigations reflecting in vivo conditions show that the degree of inhibition is not proportional to the receptor occupancy, i.e., there is a nonlinear relationship between the inhibition and the receptor occupancy. However, under a setting of high concentration of ACh reflecting a typical situation of in vitro experiments, the relationship between the inhibition and the receptor occupancy becomes linear, suggesting the validity of the receptor binding model. Also, it is found that the extent of nonlinearity depends on the selectivity of NDNBs for the two binding sites of the receptors. </sec><sec> <title>Conclusions</title> While the receptor binding model may be effective for estimating affinity of an NDNB through in vitro experiments, these models do not directly describe in vivo properties of NDNBs, because the nonlinearity between the inhibition and the receptor occupancy causes the modulation of the resultant concentration-effect relationships of NDNBs. </sec>

This paper reports modeling of physiological processes of neuromuscular transmission considering effects of nondepolarizing neuromuscualr blocking drugs (NDNBs) used during general anesthesia. NDNBs are considered to act by interacting with acetylcohine receptors located at pre- and post-junctional sites. This paper proposes an extension of the standard model of synaptic depression used in the field of neuroscience to describe the pre-junctional effect of NDNBs. The extended model is then combined with a previously proposed model of the post-junctional effect to simulate the whole process of neuromuscular transmission. The derived model can be used to predict pharmacologic relationship between the drug concentration and its actual effect of NDNBs. Specifically, the model firstly enables the estimation of Post-tetanic Count (PTC), a clinically used monitoring measure for deep neuromuscular blockade (NMB). The effectiveness of the derived model is discussed by comparing simulation results with clinical data obtained from a patient undergoing a surgical operation.

We report synthesis of reactive controller for a hot-water supply system in a medical institution for dialysis treatment using formal method and its real-time simulation based on measurement data in a practical hospital. Dialysis treatment requires heat to warm a large amount of water to the body temperature. Thus, synthesizing a controller guaranteeing the correctness of heat supply is of critical importance. The hot-water supply system considered in this paper includes heat generation equipments, hot-water storage tanks, and heat loads. We synthesize a reactive controller that reacts to changes of environment of the system affecting the supply such as failure and restarting of equipments, and achieves the continuous supply of heat to a critical load for dialysis treatment. Also, we experimentally demonstrate the synthesized controller with a real-time simulator that can interact with a dynamic analog environment. For this, a dynamic model of the hot-water supply system is developed through the measurement data. We then show that the synthesized reactive controller works effectively while reacting to the analog environment.

This paper focuses on multiscale dynamics occurring in steam supply systems. The dynamics of interest are originally described by a distributed-parameter model for fast steam flows over a pipe network coupled with a lumped-parameter model for slow internal dynamics of boilers. We derive a lumped-parameter model for the dynamics through physically relevant approximations. The derived model is then analyzed theoretically and numerically in terms of existence of normally hyperbolic invariant manifold in the phase space of the model. The existence of the manifold is a dynamical evidence that the derived model preserves the slow-fast dynamics, and suggests a separation principle of short-term and long-term operations of steam supply systems, which is analog to electric power systems. We also quantitatively verify the correctness of the derived model by comparison with brute-force simulation of the original model.

We provide a review of nonlinear instabilities occurring in networks of rotatory generators based on our previous papers. The instability phenomena, which we term the collective instabilities, are of emergent type and observed in networks of synchronous and induction generators. With both the cases, we provide a unified definition of collective instabilities using a coupled dynamical system model. The unified definition is expected to help inquiry to the causes of cascading failure in nation-wide grids and of sudden disconnection of wind turbines following a local disturbance.

This report is concerned with dynamics of steam supply in an energy system that consists of distributed plants producing, consuming, and interchanging steam. This type of steam supply system has been recently addressed and become significant in the context of energy systems integration. In order to consider a novel operation of multiple boilers including cogeneration or heat pump plant, a lumped-parameter model has been derived based on the incompressible gas-flow equations. This report numerically verifies the derived model by comparing with combined simulation of the homogeneous two-phase flow equation and the standard boiler model. The influence of heat loss and pressure drop on dynamics of steam transport is investigated by using COMSOL Multiphysics simulator.

In this paper, we develop a mathematical model of dynamic flows in steam supply networks that include multiple plants producing, consuming, and interchanging steam. This type of steam supply networks have been recently addressed in practice and become significant in the context of energy systems integration. The model contains dynamic characteristics of the steam boilers and the steam transporting pipes as well as a graph-theoretic property of the steam supply networks. We then perform a theoretical analysis of the derived model based on the graph-based formulation. A set of non-isolated equilibrium points is located and proved to form a normally hyperbolic invariant manifold under certain conditions. Its physical meaning and implications are illustrated by a numerical example with a three-plants loop model.

This paper analyzes nonlinear dynamics and stability in a network of fixed-speed induction generators. A typical example of the network appears in windfarms that have recently attracted a lot of interest as an alternative renewable energy resource with large capacity. In this paper, we derive a mathematical model representing nonlinear dynamics occurring in the induction generator network and then present a phenomenon of nonlinear instability. The dynamical mechanism of the phenomenon is discussed in terms of collective variables and mode decomposition.