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In Kyushu University, Information Infrastructure Initiative provides an email service for students and staff members, called “Primary Mail Service”. We had operated an on-premises system for this service, and the lifetime of this system would end in early 2019. We needed to reduce costs for replacing this system because our university had just finished a major campus migration. We compared some options such as building a yet another on-premise system and migrating to a cloud-based email service and finally gave up the on-premise option because we couldn’t afford replacement and operational costs of another on-premises system anymore. We selected Microsoft Exchange Online as the new service mainly because we already had a contract with Microsoft and been operating an Office 365 tenant. We had additional requirements for user provisioning and services which were not available in Exchange Online, so we had to implement and maintain additional systems on top of it. On December 18th, 2018, we successfully migrated the email service to Exchange Online. By coincidence, Kyushu University Administration Bureau decided to migrate their in-house Exchange server to Exchange Online. After some discussions, they concluded to migrate their domain to the same tenant with Primary Mail Service. Other than that, there are more than a hundred legacy email servers inside our campus network operated by various departments as subdomains of kyushu-u.ac.jp. We are designing a plan to consolidate them into our tenant of Exchange Online to reduce a budget and human resource costs, and to improve security. In this presentation, we share our experiences about migrating our campus-wide email services to Exchange Online. We also discuss why we want to consolidate other legacy email servers and how to implement the plan.

DOI： 10.1145/3347709.3347817

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

In mathematical modeling of cell physiological processes, measurements required for parameter determination are often available only as aggregated data in the literature. Physiological measurements contain relatively large observation errors due to intrinsic variations in physiological processes, and the errors cause uncertainties in parameter values. This paper reports analyses of the uncertainty in parameter estimates of a simple mathematical model of an ion channel from a set of published experimental data. A conventional approach for estimating model parameters from aggregated data is applying the method of least squares to a series of the mean values of measurements. The parameter estimates by the conventional method significantly differed from those by a statistical approach, maximum likelihood estimation considering the standard errors of the means. Exhaustive analyses on the likelihood of parameter values show high parameter uncertainties and wide distribution of parameter values with no significant differences in the likelihood. These results imply the importance of considering variances of observations and uncertainties in parameter estimates.

DOI： 10.1109/EMBC.2019.8857142

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)   Publisher：電子情報通信学会  

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)   Publisher：大学ICT推進協議会  

九州大学では2016 年からOffice 365 を全学サービスとして正式に提供してきたが、その基盤システムやテナント運用などについて様々な課題が生じていた。そこで、基盤システムとテナントを含めて環境を新たに再構築し、2018 年4 月から新しいサービス環境の提供を開始した。本稿では、従来の環境における課題とその解決策、さらに、新しい環境の構築過程で生じた問題とその解決方法などについて紹介する。

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Intracellular acidosis induced by hypoxia resulted from myocardial ischemia damages myocardium. However, the detailed mechanisms of hypoxic acidosis are not quantitatively explained. The purpose of this study is to create a novel computational model which can reproduce intracellular acidosis caused by myocardial ischemia. We constructed a computational model of myocardium, by using a mathematical ventricular cell model which includes pH regulation and a computational model of myocardial microcirculation for calculating extracellular conditions. The present model reproduced cellular hypoxia in an ischemic condition simulated by a reduced blood flow, and intracellular pH reduction in response to the hypoxia.

DOI： 10.1109/EMBC.2018.8513112

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Other Link： https://dblp.uni-trier.de/conf/embc/2018

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ASSOC COMPUTING MACHINERY  

In Kyushu University, Information Infrastructure Initiative provides email service for students and staff members. Email services for students and staff members were started separately. For students, an email service was started as Unix accounts of "Computer System for Education" in 1995. On the other hand, an email service for staff members was started in 2009, and eventually the two mail services were merged into the current "Kyushu University Primary Mail Service" in 2014. The designs of these mail systems were affected by various operational issues and political decisions at their times. We think that running an in-house mail system is becoming less feasible due to the initial/operational cost, security issues, and our dwindling budget. For the current system, the planned 5-year lifetime ends in this fiscal year. Therefore, we are forced to migrate to a cloud-based mail service. In this presentation, we want to share our past experiences and future plans about our university email services.

DOI： 10.1145/3235715.3235737

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Other Link： https://dblp.uni-trier.de/db/conf/siguccs/siguccs2018.html#KasaharaSIF18

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)   Publisher：電子情報通信学会  

As basic components of ever-expanding internet services, hosting services and cloud computing platforms are expected to satisfy various requirements, such as efficiency, fault-tolerance, resiliency against high load, flexibility, and security. We are trying to solve these problems with a light-weight container based architecture (called FastContainer). To improve FastContainer (especially its auto-scaling function), we are creating an environment for performance and stress tests on a public cloud platform. In this paper, we describe the overview of FastContainer and details of the test environment, its current status, and future plans.

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ASSOC COMPUTING MACHINERY  

Information Infrastructure Initiative of Kyushu University started serving Office 365 Education for all students and staff members at Kyushu University in November 2016. Since 2007, the university had signed Microsoft EES (Enrollment for Education Solutions) including licenses for the latest Microsoft Windows and Office suite. The EES agreement includes an advantage to provide Office 365 Education to the university members with minimum investments, and there was a demand for Skype for Business which is included in Office 365. To deploy Office 365 for our users, we first needed to configure our on-premises user authentication infrastructure to coordinate with Office 365. During trials, we had a couple of difficulties attributed to some disagreements between Microsoft's and our policy on whether the user identifier, namely the user principal name in Active Directory, was open or private. Additionally, we had to consider which services should be applied to the users, because we have been operating an on-premises email service which is competing with Microsoft Exchange mail service. In this presentation, we share our experiences in Office 365 deployment.

DOI： 10.1145/3123458.3123491

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Other Link： https://dblp.uni-trier.de/db/conf/siguccs/siguccs2017.html#KasaharaSOF17

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Institute of Electrical and Electronics Engineers Inc.  

Contributions of interstitial fluid (ISF) flow within the myocardial microcirculation is not well understood despite its importance due to difficulties in measurements. For analysing a contribution of interstitial fluid flow within myocardial microcirculation, we developed a computational model of myocardial microcirculation by introducing convection by the ISF flow into an existing myocardial microcirculation model, and performed simulations with varied ISF flows in normal and hypoperfusion conditions. Simulation results show that the ISF flow has a contribution only with low capillary flow. This might suggest partial comensation of oxygen supply by the ISF flow under ischemic conditions.

DOI： 10.1109/EMBC.2017.8037653

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Other Link： https://dblp.uni-trier.de/conf/embc/2017

Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Institute of Electrical and Electronics Engineers ({IEEE})  

In this paper, we propose a method for reducing the computational cost of strong coupling for multiscale cardiovascular simulation models. In such a model, individual model modules of myocardial cell, left ventricular structural dynamics, and circulatory hemodynamics are coupled. The strong coupling method enables stable and accurate calculation, but requires iterative calculations which are computationally expensive. The iterative calculations can be reduced, if accurate initial approximations are made available by predictors. The proposed method uses the Kalman filter to estimate accurate predictions by filtering out noise included in past values. The performance of the proposed method was assessed with an application to a previously published multiscale cardiovascular model. The proposed method reduced the number of iterations by 90% and 62% compared with no prediction and Lagrange extrapolation, respectively. Even when the parameters were varied and number of elements of the left ventricular finite-element model increased, the number of iterations required by the proposed method was significantly lower than that without prediction. These results indicate the robustness, scalability, and validity of the proposed method.

DOI： 10.1109/JBHI.2015.2436212

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Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)電子情報通信学会  

心壁の拍動現象のシミュレーションでは一般的に、有限要素法による構造力学解析が用いられる。構造力学解析では一般にメッシュ分割が計算結果に影響を与えることが知られている。本論文では、通常の構造力学解析では扱われない、心筋線維方向に生じる心筋細胞の自発的収縮力を考慮した左心室拍動連成シミュレーションにおいて、メッシュ分割の差異が計算結果に与える影響について報告する。本研究では、厚肉回転だ円体の上部を切除した左心室を表現する形状に対して、経緯線に沿って分割したメッシュモデルと、半正多面体である斜方二十・十二面体を細分化して生成したメッシュモデルを比較した。シミュレーション結果の応力分布では心尖部付近に顕著な差が認められたが、ひずみに応じて生じる受動応力成分には大きな差は見られず、心筋線維方向と細胞の自発的収縮力とにおけるメッシュモデル間の差異が主に応力分布の相違を生じていることが明らかとなった。(著者抄録)

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER PHYSIOLOGICAL SOC  

Glucagon-like peptide-1 (GLP-1) is an intestinally derived blood glucose-lowering hormone that potentiates glucose-stimulated insulin secretion from pancreatic β-cells. The secretagogue action of GLP-1 is explained, at least in part, by its ability to stimulate cAMP production so that cAMP may facilitate the release of Ca from inositol trisphosphate receptor (IP R)-regulated Ca stores. However, a quantitative model has yet to be provided that explains the molecular mechanisms and dynamic processes linking GLP-1-stimulated cAMP production to Ca mobilization. Here, we performed simulation studies to investigate how GLP-1 alters the abilities of Ca and IP to act as coagonists at IP R Ca release channels. A new dynamic model was constructed based on the Kaftan model, which demonstrates dual steady-state allosteric regulation of the IP R by Ca and IP . Data obtained from β-cells were then analyzed to understand how GLP-1 facilitates IP R-mediated Ca mobilization when UV flash photolysis is used to uncage Ca and IP intracellularly. When the dynamic model for IP R activation was incorporated into a minimal cell model, the Ca transients and oscillations induced by GLP-1 were successfully reconstructed. Simulation studies indicated that transient and oscillatory responses to GLP-1 were produced by sequential positive and negative feedback regulation due to fast activation and slow inhibition of the IP R by Ca . The slow rate of Ca -dependent inhibition was revealed to provide a remarkable contribution to the time course of the decay of cytosolic Ca transients. It also served to drive and pace Ca oscillations that are significant when evaluating how GLP-1 stimulates insulin secretion. 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 2+ 3 3 3 3 3 3 3 3 3

DOI： 10.1152/ajpcell.00234.2015

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

Many biological findings are continuously reported in the life science area. Most of them are reports on the correlations between some proteins, or correlations between some proteins and macroscopic phenomena such as whole body hemodynamics. In order to understand the underlying mechanisms of the biological systems, simulation and analysis of multiscale biological function models are considered useful. Since the complex calculation schemes are necessary to calculate these models efficiently, it is useful to represent both the biological function models and the calculation schemes in descriptive languages which are readable by the computer programs. In this report, we introduce our simulation system which generates simulation programs from biological function models and calculation schemes both described by description languages. Using our system, we were able to generate simulation programs for a hemodynamic simulation model coupling a ventricular myocyte model and a whole body circulation model, a simulation model that evaluates the changes in action potential of a ventricular myocyte model after drug administration, and a program that calculates the changes in action potential of ventricular myocytes by changing specific parameters.

DOI： 10.11239/jsmbe.53.115

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

Mathematical cell models are effective tools to understand cellular physiological functions precisely. For detailed analysis of model dynamics in order to investigate how much each component affects cellular behaviour, mathematical approaches are essential. This article presents a numerical analysis technique, which is applicable to any complicated cell model formulated as a system of ordinary differential equations, to quantitatively evaluate contributions of respective model components to the model dynamics in the intact situation. The present technique employs a novel mathematical index for decomposed dynamics with respect to each differential variable, along with a concept named instantaneous equilibrium point, which represents the trend of a model variable at some instant. This article also illustrates applications of the method to comprehensive myocardial cell models for analysing insights into the mechanisms of action potential generation and calcium transient. The analysis results exhibit quantitative contributions of individual channel gating mechanisms and ion exchanger activities to membrane repolarization and of calcium fluxes and buffers to raising and descending of the cytosolic calcium level. These analyses quantitatively explicate principle of the model, which leads to a better understanding of cellular dynamics.

DOI： 10.1371/journal.pone.0124970

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

As a well-known property of the heart, many studies has reported that the left ventricular end-systolic pressure-volume relationship (ESPVR) is linear. However, the reason of the linearity is poorly understood. This article presents a multiscale circulation model to be a tool for theoretical analyses on the mechanism of the linearity of ESPVR. The model is composed of three sub-models; a detailed closed-loop lumped-parameter model for cardiovascular system, geometric left ventricle model, a comprehensive ventricular myocyte model. Although the present model integrates nonlinear sub-models, the model can successfully reproduce highly linear ESPVR without any arbitrary modifications.

DOI： 10.1109/EMBC.2014.6945184

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Other Link： https://dblp.uni-trier.de/conf/embc/2014

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

Although there are numerous reports on the electrical heterogeneity of the myocardium, little has been given attention to its relation to cardiovascular mechanics, because of difficulties of simultaneously observing multiple effects in vivo. In this research, a multi-scale cardiovascular simulation model, which describes the myocyte physiology, left ventricular structural dynamics, and hemodynamics, was used to theoretically investigate the relationshipbetween the electrical transmural heterogeneity of myocytes and ventricular energetics. The parameters which describe the characteristics of ion channels of an existing myocyte model were changed to create endo-, mid-, and epi-cardium myocyte models. Simulations were performed with electrically heterogeneous and homogeneous models. As a result, the heterogeneous model had lower contractility and higher total mechanical energy generation per ATP consumption. These findings indicate that electrical heterogeneity contribute to cardiac efficiency.

DOI： 10.11239/jsmbe.52.129

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

In standard finite element analysis in structural dynamics, meshing can affect computation results. However, there have been no detailed report about effects of meshing on results of coupling simulation of left ventricular wall motion which involves myocardial spontaneous contractile force and fiber orientation. In this study, we examined an effect of meshing on simulation of left ventricular wall motion, which couples precise ventricular myocyte model and myocardial fiber orientation. We compared two shape models; spheroid mesh divided along graticule and spheroid mesh subdivided from a semi-regular polyhedron. The comparison results show significant differences between two models around the ventricular apex, which are mainly caused by the contractile force and the fiber orientation.

DOI： 10.11239/jsmbe.52.O-186

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

Detailed analysis of oxygen consumption within the myocardial microcirculation is of importance to understand conditions under ischemic heart disease. However, there are currently difficulties in microscopically precise measurements of local oxygen consumptions in myocardial tissue. In this paper, a simulation model of myocardial microcirculation is proposed for analysis of local distribution of oxygen consumption. The proposed model is composed by integrating a theoretical spatially-distributed model of myocardial tissue and a detailed lumped-parameter model of normal cardiac myocyte. The proposed model was validated for an animal research in reproduction of a linear correlation between myocardial oxygen consumption and myocardial contractility. A simulation result of the model shows that local oxygen consumptions under low myocardial blood flow are spatially partitioned into an arteriolar-side normal area and a venular-side low area. Myocytes in the venular-side area lose normal activity under extremely low oxygen concentration. This result indicates the possibility that cardiac tissue is locally damaged under extreme hypoxia in the venular-side area even in case of a slight reduction of mean oxygen consumption of the myocadial tissue caused by decreased myocardial blood flow.

DOI： 10.11239/jsmbe.51.248

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

In this study, we use cardiovascular simulation to gain new insights on the correlation between electrical heterogeneity and ventricular energetics. Although there are numerous in vivo and in vitro studies on the electrical heterogeneity within the ventricular myocardium, not much attention has been directed to its correlation to cardiovascular mechanics, because of difficulties in simultaneously observing and analyzing multiple spatial scales(the cell, the organ, and the system). We performed simulations with two cardiovascular simulation models, one which uses different myocardial cell models for the epicardial, endocardial, and mid-myocardial cells, and another which uses a homogeneous model throughout the entire myocardium. The epicardial, endocardial, and midmyocardial cell models were created by parametrically tuning a homogenous cell model. From the cardiovascular simulation we obtained pressure-volume loops which were used to calculate cardiovascular energetic efficiency and myocardial contractility. We found that energetic efficiency is higher in the electrically heterogeneous model. © 2013 IEEE.

DOI： 10.1109/EMBC.2013.6611132

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Other Link： https://dblp.uni-trier.de/conf/embc/2013

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

The physiological simulation at the tissue and organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and in cases like pharmacokinetics, distributed parameters add to the complexity of the PDE solution. These factors make most PDE solutions and their corresponding program codes tailored for specific problems. We propose a general approach for handling PDEs in computational models using a replacement scheme for discretization. This method allows for the handling of the different PDE types. The replacement scheme involves substituting all the partial differential terms with the numerical solution equations. Once the model equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to determine the simulation loop structure and generate the program code. © 2013 IEEE.

DOI： 10.1109/EMBC.2013.6609795

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Other Link： https://dblp.uni-trier.de/conf/embc/2013

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：INST ENGINEERING TECHNOLOGY-IET  

Energetic efficiency is an important indicator of cardiac function in acute myocardial infarction. However, the relationship between cardiac energetic efficiency and infarct size is not perfectly elucidated. In this study, the relationship is analysed by means of simulation using a theoretical model of the guinea pig left ventricle. In simulation with varied ratios of infarct area, pressure-volume area (PVA), which is an index of total mechanical energy by ventricular contraction, and myocardial oxygen consumption (MVO ) are calculated for each infarct ratio. Then, change of PVA when MVO alters (PVA/MVO ) as a well-known index of energy conversion efficiency is evaluated. In addition, PVA/VO , which represents a ratio of PVA change to alteration of mean oxygen consumption of myocytes except for infarct myocytes, is introduced as an index for real energetic efficiency. In simulation results, PVA/MVO increases but PVA/VO decreases as infarct area expands, because with expansion of infarct area PVA decreases but VO remains almost unchanged because of larger shortening of myocytes. This implies that the enlargement of shortening of noninfarcted myocyte to compensate for depression of cardiac output is a potential cause of myocardial remodelling. © The Institution of engineering and technology 2013. 2 2 2 2 2 2 2

DOI： 10.1049/iet-syb.2011.0080

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：SPRINGER JAPAN KK  

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The coupling of cellular processes at the tissue and organ level usually involves the handling of partial differential equations (PDEs). Since physiological computational models using PDEs have varied greatly in terms of complexity, most solutions are tailored for specific problems. Space-time discretization schemes like FTCS (Forward-Time Centered-Space), BTCS (Backward-Time Centered-Space), Dufort-Frankel, Crank-Nicolson and Lax-Friedrichs exist. We propose a general approach for handling PDEs in computational models using a replacement scheme for discretization. The replacement scheme involves substituting all the partial differential terms with the numerical solution equations. During the replacement algorithm, the time and spatial indices are also appended to the model variables. This method allows for handling of different forms of equation. Once the derivatives are replaced with the discretized terms, the resulting equations are then written in a recurrence relation form. Finally, the equations for solving the unknown variables are generated. The solution to the linear system of equations uses iterative methods like Gauss-Jacobi and Gauss-Seidel algorithm. If the system is explicit, corresponding loop structure is generated as program code to solve the system. We could successfully generate an excitation propagation simulation program for FTCS scheme with a complex cell model.

DOI： 10.11239/jsmbe.50.666

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Other Link： http://search.jamas.or.jp/link/ui/2013307326

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Models written in description languages such as CellML are becoming a popular solution to the handling of complex cellular physiological models in biological function simulations. However, in order to fully simulate a model, boundary conditions and ordinary differential equation (ODE) solving schemes have to be combined with it. Though boundary conditions can be described in CellML, it is difficult to explicitly specify ODE solving schemes using existing tools. In this study, we define an ODE solving scheme description language-based on XML and propose a code generation system for biological function simulations. In the proposed system, biological simulation programs using various ODE solving schemes can be easily generated. We designed a two-stage approach where the system generates the equation set associating the physiological model variable values at a certain time t with values at t + Δt in the first stage. The second stage generates the simulation code for the model. This approach enables the flexible construction of code generation modules that can support complex sets of formulas. We evaluate the relationship between models and their calculation accuracies by simulating complex biological models using various ODE solving schemes. Using the FHN model simulation, results showed good qualitative and quantitative correspondence with the theoretical predictions. Results for the Luo-Rudy 1991 model showed that only first order precision was achieved. In addition, running the generated code in parallel on a GPU made it possible to speed up the calculation time by a factor of 50. The CellML Compiler source code is available for download at http://sourceforge.net/projects/cellmlcompiler. © 2012 Punzalan et al.; licensee BioMed Central Ltd.

DOI： 10.1186/1751-0473-7-11

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Multi-scale models of the cardiovascular system provide new insight that was unavailable with in vivo and in vitro experiments. For the cardiovascular system, multi-scale simulations provide a valuable perspective in analyzing the interaction of three phenomenons occurring at different spatial scales: circulatory hemodynamics, ventricular structural dynamics, and myocardial excitation-contraction. In order to simulate these interactions, multiscale cardiovascular simulation systems couple models that simulate different phenomena. However, coupling methods require a significant amount of calculation, since a system of non-linear equations must be solved for each timestep. Therefore, we proposed a coupling method which decreases the amount of calculation by using the Kalman filter. In our method, the Kalman filter calculates approximations for the solution to the system of non-linear equations at each timestep. The approximations are then used as initial values for solving the system of non-linear equations. The proposed method decreases the number of iterations required by 94.0% compared to the conventional strong coupling method. When compared with a smoothing spline predictor, the proposed method required 49.4% fewer iterations. © 2012 IEEE.

DOI： 10.1109/EMBC.2012.6346157

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

To cope with the complexity of the biological function simulation models, model representation with description language is becoming popular. However, simulation software itself becomes complex in these environment, thus, it is difficult to modify the simulation conditions, target computation resources or calculation methods. In the complex biological function simulation software, there are 1) model equations, 2) boundary conditions and 3) calculation schemes. Use of description model file is useful for first point and partly second point, however, third point is difficult to handle for various calculation schemes which is required for simulation models constructed from two or more elementary models. We introduce a simulation software generation system which use description language based description of coupling calculation scheme together with cell model description file. By using this software, we can easily generate biological simulation code with variety of coupling calculation schemes. To show the efficiency of our system, example of coupling calculation scheme with three elementary models are shown. © 2012 IEEE.

DOI： 10.1109/EMBC.2012.6347513

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

Physiology models written in a description language such as CellML are becoming a popular method to handle complex cellular physiological models in biological function simulations. However, in order to fully simulate a model, boundary conditions and ordinary differential equation (ODE) solving schemes have to be combined with it. Though the former can be described in CellML, it is difficult to explicitly specify ODE solving schemes using existing tools. In this study, we defined an ODE solving scheme description language based on XML and proposed a code generation system for biological function simulations. By using the proposed system, biological simulation programs using various ODE solving schemes can be easily generated. We designed a two-stage approach where the system generates a set of equation associating with the physiological model variable values at a certain time t with values at t plus delta t in the first stage and generates the programs calculating the time evolution of the model in the second stage. This approach enables the flexible construction of code generation modules that can support complex sets of formulas. We evaluated the relationship between models and their calculation accuracies by simulating complex biological models using various ODE solving schemes. Using the FHN model simulation, results showed good qualitative and quantitative correspondence with the theoretical predictions. Results for the LuoRudy1991 model showed that only first order precision was achieved. In addition, running the generated code in parallel on GPU made it possible to speed up the calculations by a factor of 50.

DOI： 10.11239/jsmbe.50.68

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Institute of Electronics, Information and Communication Engineers  

臨床試験を代替する一手段,あるいは,臨床教育の教材として,特に,臨床試験や臨床教育が困難な乳児について,精密に生体機能を再現する計算機シミュレーションの実現が望まれている.生命維持に欠かせない心臓血管系は生体機能シミュレーションにおいて非常に重要な対象であり,その中で中心的な役割を果たす心臓の機能を評価することは重要である.本論文では,ヒト乳児を対象に血圧変化などの循環動態を再現するような,心機能評価が可能なシミュレーションモデルを提案する.提案モデルは,既存の生理特性を詳細に再現した心室筋細胞モデル,及び,全身の血圧変化を表現する血管系モデルを利用し,更に,計測結果に基づき左心室の圧と容積の関係を表現する左心室物理モデルを導入して構築したモデルである.シミュレーション実験により,提案モデルは生現状態のヒト乳児の主要な循環動態パラメータを再現し,心機能の評価に重要な左心室の収縮末期圧容積関係(ESPVR),及び,収縮期圧容積面積と心筋酸素消費量との高い相関(PVA-MVO_2)が再現されていることを確認した.

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Other Link： http://search.jamas.or.jp/link/ui/2012185963

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

To cope with the complexity of the biological function simulation models, model representation with description language is becoming popular. However, simulation software itself becomes complex in these environment, thus, it is difficult to modify target computation resources or numerical calculation methods or simulation conditions. Typical biological function simulation software consists of 1) model equation, 2) boundary conditions and 3) ODE solving scheme. Introducing the description model file such as CellML is useful for generalizing the first point and partly second point, however, third point is difficult to handle. We introduce a simulation software generation system which use markup language based description of ODE solving scheme together with cell model description file. By using this software, we can easily generate biological simulation program code with different ODE solving schemes. To show the efficiency of our system, experimental results of several simulation models with different ODE scheme and different computation resources are shown.

DOI： 10.1109/IEMBS.2011.6090212

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We investigated numerical methods for predictors in a multiscale cardiovascular simulation model. The proposed method predicts initial approximations for the iterative convergence calculations of the strong coupling method using the smoothing spline to remove errors from values of past timesteps and using the linear and second-order extrapolation. The new coupling algorithm was used for coupling a left ventricular finite element model to a myocardial excitation-contraction model. We performed experiments with different values for the smoothing parameter lambda and with linear and second-order extrapolations. lambda = 1 with the linear extrapolation gave the best results. It reduced computation time by 91% compared to the strong coupling method. With the use of the smoothing spline, distance between the initial approximation and converged solution reduced by 62%, while the average number of iterations reduced by 32%. The smoothing spline can be used to improve the accuracy of predictors and reduce the number of iterations needed for the computation of the convergence procedure.

DOI： 10.1109/IEMBS.2011.6089913

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：情報処理学会  

A model of cellular physiological functions is generally defined as a set of ordinary differential equations and algebraic equations. Some models form semi-explicit differential algebraic equations. Numerical simulation of a declaratively defined model requires a calculation condition by selecting parameter constants, the values of which are extrinsically provided. However, manual configuration of consistent calculation conditions for large-scale complicated models is a difficult task. In this paper, we propose a method for efficient configuration of consistent calculation conditions for declaratively defined models. The present method progressively eliminates invalid calculation conditions from candidates in order to assist interactive configuration of a calculation condition, by applying a method based on graph theory for structural solvability of simultaneous equations.

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Other Link： http://id.nii.ac.jp/1001/00075767/

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROCKEFELLER UNIV PRESS  

In our companion paper, the physiological functions of pancreatic. cells were analyzed with a new beta-cell model by time-based integration of a set of differential equations that describe individual reaction steps or functional components based on experimental studies. In this study, we calculate steady-state solutions of these differential equations to obtain the limit cycles (LCs) as well as the equilibrium points (EPs) to make all of the time derivatives equal to zero. The sequential transitions from quiescence to burst-interburst oscillations and then to continuous firing with an increasing glucose concentration were defined objectively by the EPs or LCs for the whole set of equations. We also demonstrated that membrane excitability changed between the extremes of a single action potential mode and a stable firing mode during one cycle of bursting rhythm. Membrane excitability was determined by the EPs or LCs of the membrane subsystem, with the slow variables fixed at each time point. Details of the mode changes were expressed as functions of slowly changing variables, such as intracellular [ATP], [Ca2+], and [Na+]. In conclusion, using our model, we could suggest quantitatively the mutual interactions among multiple membrane and cytosolic factors occurring in pancreatic. cells.

DOI： 10.1085/jgp.201110612

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心臓は非常に多くのエネルギーを消費して血液を拍出しており,心筋細胞におけるエネルギー代謝と,心筋細胞の興奮収縮連関の関連性の解明は,病態解明等のために重要なテーマである.特に虚血性心疾患は,細胞への酸素供給低下により,細胞に異常を来す疾病であり,このような疾病における心機能の低下は,第1に酸素濃度の低下によって生じるエネルギーバランスの不均衡が原因と考えられている.虚血時の心機能の低下の主たる原因である低酸素に対する心筋細胞の応答を再現するためには,低酸素状態で活性化される解糖系が重要である.しかしながら,現在提案されている心筋細胞モデルは,解糖系が導入されていないために,低酸素状態の再現性に問題がある.本研究では,低酸素に対する心筋細胞の応答を再現するために,モルモットの心筋細胞モデルであるKyoto modelに解糖系を導入した新たな心筋細胞モデルを構築した.構築したモデルを用いて,動物実験の実験条件に従ったシミュレーションを行い,非ペーシング状態の心筋細胞における低酸素に対する応答の再現を試みた.再現結果は,対応する動物実験結果の傾向と高い類似性を示した.

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Other Link： http://search.jamas.or.jp/link/ui/2010156108

Language：English   Publishing type：Research paper (scientific journal)   Publisher：CELL PRESS  

The action potential, once triggered in ventricular or atrial myocytes, automatically proceeds on its time course or is generated spontaneously in sinoatrial node pacemaker cells. It is induced by complex interactions among such cellular components as ion channels, transporters, intracellular ion concentrations, and signaling molecules. We have developed what is, to our knowledge, a new method using a mathematical model to quantify the contribution of each cellular component to the automatic time courses of the action potential. In this method, an equilibrium value, which the membrane potential is approaching at a given moment, is calculated along the time course of the membrane potential. The calculation itself is based on the time-varying conductance and the reversal potentials of individual ion channels and electrogenic ion transporters. Since the equilibrium potential moves in advance of the membrane potential change, we refer to it as the lead potential, V-L. The contribution of an individual current was successfully quantified by comparing dV(L)/dt before and after fixing the time-dependent change of a component of interest, such as the variations in the open probability of a channel or the turnover rate of an ion transporter. In addition to the action potential, the lead-potential analysis should also be applicable in all types of membrane excitation in many different kinds of cells.

DOI： 10.1016/j.bpj.2009.08.060

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Frank-Starling law, which describes a relation between cardiac contraction energy and end-diastolic volume, is of importance, but the detailed mechanism is not quantitatively understood yet. In this paper, the mechanism of a linear relation between end-diastolic volume and end-systolic pressure as a part of Frank-Starling law is analyzed by means of computer simulation. A hemodynamics model, which is constructed by composing a vascular system model, a left ventricular dynamics model and a myocardial cell model, reproduced a linear relation between end-diastolic volume and end-systolic pressure successfully. In this paper, the simulation results and the detailed analysis are reported.

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Analyzing the microscopic energy balance of cardiac tissue is very important for understanding heart diseases. However, such analysis is difficult with animal experiments. Therefore, the accurate simulation model is expected to be an important tool for such research. We propose a cardiac tissue model which can reproduce accurate distribution of oxygen consumption under hypoxia. The model includes blood tissue exchange model of capillary and oxygen consumption model of cells. The capillary model is based on the model proposed by Dash et al. 2006, and the cell model is based on the model proposed by Kuzumoto et al. 2007. By analyzing the oxygen consumption of the proposed model, the relation between the oxygen consumption and the arterial oxygen concentration was found to be largely different from that of single cell model. This implies that the animal experimental data should be carefully used for constructing a biological simulation model, depending on whether the experiment is performed within a cell or a tissue.

DOI： 10.1109/IEMBS.2009.5332645

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Some models of cellular physiological functions are formulated as ordinary differential equations that contain multiple systems of simultaneous nonlinear equations. Simulation of such a model described in a declarative representation format requires determination of equations to be simultaneously solved with specification of independent and parameter variables in the model. In this report, a method for extracting systems of simultaneous equations in a cell model is presented. The present method analyzes a graph representation of a model and extracts the subgraphs that represent equation systems to be simultaneously solved, by efficiently interactive selection of independent variables of the model.

DOI： 10.1109/IEMBS.2009.5335041

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It is necessary to use complicated myocardial cell model and heart model to evaluate the regional energy production and consumption which leads to the unrealistic computational time. In this research, a left ventricle (LV) simulation model was constructed which includes accurate myocardial cell model. In order to simulate the model in realistic time, we introduced an approximation model of the crossbridge model which can be calculated with weak coupling calculation. The LV model was combined with a circulation model to validate the proposed model by calculating the hemodynamics parameters and ventricular energetics indices. The ESPVR (End Systolic Pressure Volume Relation) showed linear relation, and also the PVA - ATP consumption relation showed linear relation which are widely known as the physiological characteristics of mammalian hearts. From these results, we can say that the model can be used as a model for physiological simulation experiments which are related to the ventricular energetics.

DOI： 10.1109/IEMBS.2008.4649313

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Institute of Electronics, Information and Communication Engineers  

循環系を構成する様々な要素の血圧変化に対する反応を再現可能な循環動態シミュレーションモデルは,左心室の圧容積関係を表現する左心室モデルと,血管系の圧容積関係を表現する血管系モデル,更に循環動態の変化に対しフィードバック制御を行う制御系モデルを用いて実現される.本論文では,カテコールアミンβ刺激系モデルを含むモルモットの心筋細胞モデルであるKyoto modelを導入した左心室モデルと,ヒト成人の循環系モデルであるHeldtらの循環系モデルを組み合わせ,パラメータの変更と制御モデルの変更を行うことによりヒト乳児循環動態シミュレーションモデルを実現した.生理学シミュレーション実験により,シミュレーションモデルの妥当性を確認した.安静時循環動態シミュレーション実験により,左心室拡張末期圧,左心室収縮末期圧,心拍出量,最高・最低動脈圧及び中心静脈圧に関して,生理学的な範囲にあることが確認された.また,圧受容体反射機能を確認する起立負荷(HUT)試験についてのシミュレーション実験を行った.HUT開始前と開始後安定状態における,動脈圧パルス幅の変化率は29%の減少,心拍数は13%の増加であった.これは,生理学実験における23%の減少及び14%の増加と同様の傾向であった.

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Other Link： http://search.jamas.or.jp/link/ui/2008289360

Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

For computer simulations of physiological experiments by physiological models, a machine-readable description of experimental protocols is useful. Although description formats for cell physiological models are already available, there is no specialized representation format for experimental protocols. Here, we propose an XML-based language, PEPML (Physiological Experimental Protocol Markup Language), and a simulation method of experimental protocols in PEPML. In the PEPML, conditions and procedures of an experimental protocol are procedurally described as a list of events, each of which consists of a condition for execution and an action to be executed. By specifying the references of variables in a protocol using an ontology, the protocol can be applied to various models without editing tasks. The proposed simulation method allows unambiguous numerical calculation of a procedural experimental protocol, which is applied to a declaratively represented model by interpretation of the protocol as a set of boundary conditions for the model variables. PEPML and the proposed method allow applying both multiple protocols to a single model and a single protocol to multiple models. This feature facilitates the efficient simulation for verification, comparison and utilization of physiological models.

DOI： 10.11239/jsmbe.46.77

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Other Link： http://search.jamas.or.jp/link/ui/2008208214

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

The heart is an organ with highly complex structure and its pump function is affected by various factors. Many reports showed the strong relation between the excitation-propagation phenomenon in the heart and its pump function. But the experimental studies often failed to provide the mechanistic insights due to the complex cross-talks built in these processes. In this study, we focus on the relation between the activation time and the contraction of the tissue. The contraction simulation coupled with the excitation propagation simulation was performed using the finite element model of the ventricular ring. We performed the simulation with 7 types of stimulation with various pacing sites in the tissue, and compared the pump functions by the area ejection fraction. The results showed that when the activation time became long, the area ejection fraction became nonlinearly small. The results of this study showed the excitation propagation is one of the important parameter of the left ventricular wall motion.

DOI： 10.11239/jsmbe.46.85

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Other Link： http://search.jamas.or.jp/link/ui/2008208215

Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：The Institute of Electrical Engineers of Japan  

Biological simulation has become an important technology for biological research. Though multi-domain simulation technique is required for analysis of complicated biological activities, multi-domain biosimuator system tends to be very complicated and so requires a high developing cost. To improve this situation, we propose a biosimulator development platform, DynaBioS, which can handle complex interactions between phenomena in different domains, such as electrophysiology and mechanics. A biosimulator system is composed of components, each of which is a sub-simulator of a phenomenon, and exchanges event messages to each others as the interaction of the phenomena. This design allows easy replacement of a model for a phenomena by interchanging a corresponding component. This platform reduces costs to develop simulators, by implementation of components by wrapping existing software products, and by reuse of components. Examples of developed simulators are given to show that this platform facilitates the development of biosimulators.

DOI： 10.1541/ieejeiss.127.1928

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHYSIOLOGICAL SOC JAPAN  

The force-velocity (F-V) relationship of filament sliding is traditionally used to define the inotropic condition of striated muscles. A simple circulation model combined with the Laplace heart was developed to get a deeper insight into the relationship between the F-V characteristics and the cardiac ventricular inotropy. The circulation model consists of a preload and an afterload compartments. The linear F-V relationship for filament sliding in the NL model (Negroni and Lascano 1996) was replaced by the exponential F-V relation observed by Piazzesi et al. (2002). We also modified the NL model to a hybrid model to benefit from the Ca2+ cooperativity described by the Robinson model (Robinson et al. 2002). The model was validated by determining the diastolic ventricular pressure-volume relationship of the Laplace heart and the F-V relation of the new hybrid model. The computed parameters of the cardiac cycle agreed well with the physiological data. Computational results showed that the cross-bridge elongation (h in the NL model) temporally undershot the equilibrium h(c) during the ejection period and overshot it during the rapid refilling phase. Thereby the time course of ejection and refilling was retarded. In a simulation where the velocity of the mobile myosin head (dX/dt) was varied, the systolic peak pressure of the ventricle varied from a minimum value at dX/dt = 0 to a saturating value obtained with a constant h, providing in silico evidence for a functional impact of the cross-bridge sliding rate on the ventricular inotropy.

DOI： 10.2170/physiolsci.RP006007

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Other Link： http://search.jamas.or.jp/link/ui/2008155020

Authorship：Lead author   Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

For computer simulations of physiological experiments using physiological models, a machine-readable format of experimental protocols is effective. Here, we propose an XML-based language, PEPML (Physiological Experimental Protocol Markup Language). In the PEPML, conditions and procedures of an experimental protocol are procedurally described as a list of events, each of which consists of a condition for execution and an action to be executed. Since variables used in a protocol can be specified using an ontology, the protocol can be applied to various models without editing tasks. The PEPML allows both application of multiple protocols to a single model and application of a single protocol to multiple models. This feature facilitates the efficient simulation for verifications, comparisons and utilizations of physiological models. © 2007 IEEE.

DOI： 10.1109/IEMBS.2007.4352304

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It is important to use a myocardial cell model to evaluate the effects of the drugs to the hemodynamic parameters. We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential mechanism for reproducing the response of baroreflex control system. The parameters of the published adult human circulation model were modified to fit the infant hemodynamic values. The guinea pig myocardial cell model was introduced to the circulation model whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments. ©2007 IEEE.

DOI： 10.1109/IEMBS.2007.4352465

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：SPRINGER-VERLAG BERLIN  

We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential for the response reproduction of the baroreflex control system. The proposed model was constructed by modifying the parameters of a human adult circulation model with the aid of a guinea pig myocardial cell model, whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments.

DOI： 10.1007/978-3-540-72907-5_20

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Other Link： https://dblp.uni-trier.de/db/conf/fimh/fimh2007.html#NobuakiASLSM07

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Medical and Biological Engineering  

We evaluated the stress distribution in a cylindrical model and a shape model obtained from human heart using two different fiber orientations. For both orientation models, the results showed large differences between the stress distribution in the cylindrical model and the measurement-based shape model. These results suggest that stress distribution is highly dependent on the model geometry, and the usage of a measurement-based shape model is important for evaluating left ventricular (LV) wall stress distribution. This fact may have some influence on the reported homogeneity of stress distribution in an anatomical fiber orientation model that uses a mathematical symmetric shape model.

DOI： 10.11239/jsmbe.44.613

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Information Processing Society of Japan  

The development of physiological cell models to support the understanding of biological mechanisms gains increasingly importance. Due to the complexity of biological systems, whole cell models, which are composed of many imported component models of functional elements, get quite complex, making modifications difficult. Here, we propose a method to enhance structural changes of cell models, employing the markup languages of CellML and our original PMSML (Physiological Model Structure Markup Language), in addition to a new ontology for cell physiological modelling, the Cell Model Ontology. In particular, a method to make references from CellML files to the ontology and a method to assist with manipulation of model structures using PMSML together with the Cell Model Ontology are reported. Using these methods two software utilities, an interactive ontology ID assigner, the CellML Ontologizer, and a graphical cell model editor, the Cell Structure Editor, are implemented. Experimental results proved that the proposed method and the implemented software are useful for the modification of physiological models.

DOI： 10.2197/ipsjdc.2.726

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)   Publisher：日本生体医工学会  

DOI： 10.11239/jsmbe.44.613

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

A stretch-induced increase of active tension is one of the most important properties of the heart, known as the Frank-Starling law. Although a variation of myofilament Ca2+ sensitivity with sarcomere length (SL) change was found to be involved, the underlying molecular mechanisms are not fully clarified. Some recent experimental studies indicate that a reduction of the lattice spacing between thin and thick filaments, through the increase of passive tension caused by the sarcomeric protein titin with an increase in SL within the physiological range, promotes formation of force-generating crossbridges (Xbs). However, the mechanism by which the Xb concentration determines the degree of cooperativity for a given SL has so far evaded experimental elucidation. In this simulation study, a novel, rather simple molecular-based cardiac contraction model, appropriate for integration into a ventricular cell model, was designed, being the first model to introduce experimental data on titin-based radial tension to account for the SL-dependent modulation of the interfilament lattice spacing and to include a conformational change of troponin I (TnI). Simulation results for the isometric twitch contraction time course, the length-tension and the force-[Ca2+] relationships are comparable to experimental data. A complete potential Frank-Starling mechanism was analyzed by this simulation study. The SL-dependent modulation of the myosin binding rate through titin's passive tension determines the Xb concentration which then alters the degree of positive cooperativity affecting the rate of the TnI conformation change and causing the Hill coefficient to be SL-dependent. (c) 2006 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.yjmcc.2006.06.003

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The development of electrophyslological whole cell models to support the understanding of biological mechanisms Is Increasing rapidly. Due to the complexity of biological systems, comprehensive cell models, which are composed of many Imported sub-models of functional elements, can get quite complicated as well, making computer modification difficult. Here, we propose a computer support to enhance structural changes of cell models, employing the markup languages CellML and our original PMSML (Physiological Model Structure Markup Language), In addition to a new ontology for cell physiological modelling. In particular, a method to make references from CellML files to the ontology and a method to assist manipulation of model structures using markup languages together with the ontology are reported. Using these methods three software utilities, Including a graphical model editor, are Implemented. Experimental results proved that these methods are effective for the modification of electrophyslological models. © 2006 IEEE.

DOI： 10.1109/iembs.2006.260282

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To realize precise simulation of the left ventricular motion, it is important to utilize an accurate myocardial tissue model which can reproduce various characteristics of myocardial tissue contraction. In this study, we show that the nonlinear characteristics of the passive myocardial tissue property is the essential nature of the nonlinear force-velocity relation and present a formulation for hyperelastic physiological tissue property. Experimental results of our myocardial tissue simulation with the hyperelastic material property proposed are in good agreement with the reported force-velocity relation of real tissue.

DOI： 10.1109/IEMBS.2006.259852

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Other Link： http://orcid.org/0000-0001-8187-9915

Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：IEEE  

We evaluated the stress distribution in a geometrical shape model and a shape model obtained from human heart using two different fiber orientations. For both orientation models, the results showed large differences of the stress distributions between the mathematical shape model and the maesurement based shape model. These results suggest that stress distribution is highly dependent on the model geometry and the usage of a maesurement based shape model is important for the evaluation of the left ventricular (LV) wall stress distribution. This fact may have some influences on the reported homogeneity of stress distribution with anatomical fiber orientation model that uses mathematical shape model.

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DOI： 10.11509/sci.SCI05.0.133.0

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In order to understand the function of biological elements and their interactions, computer analysis and simulation is an essential technique. For higher research efficiency, it is important to provide a system framework for constructing biological simulation systems that handle multiple phenomena. This paper proposes "DynaBioS", a comprehensive system framework for complex biological simulations. This framework consists of three main features, a component-based architecture, a customizable system operation, and an exchangeable model set. The system based on DynaBioS consists of a Simulation Core and System Components. The System Components are sub-simulators for individual functional factors and utility modules corresponding to specific information technologies. The Simulation Core manages and controls all components, in accordance with a Simulation Scenario and a Simulation Model. The DynaBioS makes it possible to implement different simulation systems by combining individual functional components, specific interactions and different simulation models. The versatility of DynaBioS is shown by two examples, a heart pumping simulator and a parameter optimization system for physiological models.

DOI： 10.1109/iembs.2004.1403862

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In order to understand the function of biological elements and their interactions, computer analysis and simulation is an essential technique. For higher research efficiency, it is important to provide a system framework for constructing biological simulation systems that handle multiple phenomena. This paper proposes "DynaBioS", a comprehensive system framework for complex biological simulations. This framework consists of three main features, a component-based architecture, a customizable system operation, and an exchangeable model set. The system based on DynaBioS consists of a Simulation Core and System Components. The System Components are sub-simulators for individual functional factors and utility modules corresponding to specific information technologies. The Simulation Core manages and controls all components, in accordance with a Simulation Scenario and a Simulation Model. The DynaBioS makes it possible to implement different simulation systems by combining individual functional components, specific interactions and different simulation models. The versatility of DynaBioS is shown by two examples, a heart pumping simulator and a parameter optimization system for physiological models.

Scopus

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Language：Japanese   Publishing type：Research paper (conference, symposium, etc.)  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

In recent years, numerical computations are executed using various computing environments such as PC clusters, GPGPU (general-purpose computing on graphics processing units) and cloud computing. Numerical algorithms employed in the numerical computations are generally distributed within libraries implemented in procedural programming languages such as Fortran, C, and MATLAB. This conventional manner has an advantage in computational performance, but also has a problem on availability and productivity that an algorithm has to be ported onto a target environment if any implementations of the algorithm are not available on the environment. In this presentation, a XML-based formal language for root-finding algorithms of nonlinear equations is introduced. In this formal language, a root-finding algorithm is declaratively defined as a set of mathematical recurrence formulas using Content Markup of MathML. This description is independent of any programming languages. By analyzing relationships among mathematical equations and mathematical variables in the description, an abstract calculation procedure of the described algorithm can be obtained. The abstract procedure is convertible into program codes in a concrete programming language. This scheme can reduce costs for implementation of root-finding algorithms on various environments.

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Language：Japanese   Publisher：(一社)日本糖尿病学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

In this paper, we proposed an improved algorithm to derive corresponding loop structure from recurrence relation equation set that are generated by the program code generation system. The system use Ce11ML file as an biological function model, and use TecML file which describes calculation scheme for the model. By using the propoased algorithm, the analysis time improved by 1000 to 10000 fold, and also the limitation of the input recurrence relation equations were relaxed.

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(公社)日本薬学会  

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Language：Japanese   Publisher：(一社)日本生理学会  

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：ELSEVIER IRELAND LTD  

Web of Science

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Language：Japanese  

J-GLOBAL

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Language：Japanese  

J-GLOBAL

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Language：Japanese   Publisher：(一社)日本不整脈心電学会  

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Language：English  

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Language：Japanese  

重大な心臓病態の一つに不整脈がある．特に薬剤投与の副作用による不整脈の発生は大きな問題となっており，未然に副作用の危険性を調べることは重要である．従来では危険性を調べるために動物実験を行われてきたが，近年ではコンピュータシミュレーションにより，比較的低コストで効率的にデータを得ることが有効な手段となっている．本稿では，心筋細胞モデルにパラメタ変化を加えたシミュレーションにより，不整脈の一原因である遅延後脱分極 （DAD） を再現する．DAD に大きく関連するパラメタから，薬剤投与を想定するパラメタと個体別の生理状態を想定するパラメタを選択し，それぞれを変化させたときの DAD 発生の有無を自動判定により調査した．その結果，各パラメタ変化が DAD 発生に与える影響の大きさを解析した．One of serious cardiac diseases is cardiac arrhythmia. It is important to investigate risks of the cardiac arrhythmia by drug side effects before medications. Although animal experminents has been employed to investigate the risks, in recent years, computer simulation is becoming an effective technique to obtain data efficiently at comparatively low cost. In this paper, the delayed afterdepolarization (DAD), which is a cause of arrhythmia, is reproduced by simulation with varying parameters of a ventricular myocyte model. The parameters are selected from model parameter which are deeply relating to DAD, for representing drug dosing and individual physiological conditions. Generations of DAD were evaluated by an automatic DAD detection method introduced in this stydy. From the result, influenced by each parameter change to the risk of DAD was analyzed.

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

Detailed simulation analysis of the cardiovascular system is important because the system is a biological phenomenon indispensable in maintaining life. Since the cardiovascular system is a result of the interaction of myocardial cell physiology, cardiac structural dynamics, and hemodynamics, it is necessary to use multi-physics simulation to couple equations of different scales. For a precise coupling simulation, it is desirable to use the strong coupling method which is computationally expensive. In this paper, a prediction method is proposed for a cardiovascular simulation system using strong coupling calculation. In the proposed method, the smoothing spline and extrapolators are used to predict an approximate solution to the convergence equation, using the predicted value as the initial value to decrease the number of iterations to convergence. Experiments are performed for different values of the smoothing parameter and first to fourth degree extrapolators. Decrease in iterations for the convergence calculation was observed when using the proposed method.

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Other Link： http://search.jamas.or.jp/link/ui/2012002115

Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

To understand conditions under cardiac ischemia or hypoxia, it is of importance to evaluate oxygen consumption in the myocardial microcirculation. However, there are difficulties in accurate measurements of the oxygen consumption experimentlly. Therefore, computer simulation is an important methodology to evaluate the oxygen consumption. For simulation of oxygen consumption in a cardiac tissue, a myocardial microcirculation model is proposed in this report. The model couples a tissue microcirculation model and a myocardial cell model. The simulation results under low oxygen conditions of the arterial blood show that oxygen consumptions decrease from the arterial side to the venous side and that cells in the venous side are under hypoxia.

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Other Link： http://search.jamas.or.jp/link/ui/2011101863

Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

It is of importance to estimate the activity ratios of cardiac cellular ion channels for detecting side effects of drugs under development. A myocardial cell model enables the estimation of the activity ratios by reproducing experimental cardiac cellular action potential (AP) recordings with varied parameters. We analized the relationship between parameters and outputs of the model. Results from the analysis of the distribution of similar AP recordings and myocardial contractility in parameter space show the difficulty in estimating activity ratios of ion channels based on AP recordings or myocardial contractility alone. However, they also show the possibility to improve the estimation accuracy by the combined use of AP recordings and myocardial contractility.

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Other Link： http://search.jamas.or.jp/link/ui/2011101864

Language：English  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER  

Web of Science

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：SPRINGER TOKYO  

Web of Science

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Language：Japanese   Publisher：Information Processing Society of Japan (IPSJ)  

Although there have been many new advances in biology, quantitative explanation about biological phenomenon is still difficult. In this case, computer simulation with biological model is a good tool for quantitative analysis of heart. Also there have been many new advances of the myocardial cell, and many physiological characteristic has been discovered. Since computational complexity increases in proportion to the size of model, computable size of heart model is restricted by computer ability. In this study we performed the simulation using MPI parallel computing for reducing computing time.

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Language：English  

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Language：English   Publisher：Information and Media Technologies Editorial Board  

The development of physiological cell models to support the understanding of biological mechanisms gains increasingly importance. Due to the complexity of biological systems, whole cell models, which are composed of many imported component models of functional elements, get quite complex, making modifications difficult. Here, we propose a method to enhance structural changes of cell models, employing the markup languages of CellML and our original PMSML (Physiological Model Structure Markup Language), in addition to a new ontology for cell physiological modelling, the Cell Model Ontology. In particular, a method to make references from CellML files to the ontology and a method to assist with manipulation of model structures using PMSML together with the Cell Model Ontology are reported. Using these methods two software utilities, an interactive ontology ID assigner, the CellML Ontologizer, and a graphical cell model editor, the Cell Structure Editor, are implemented. Experimental results proved that the proposed method and the implemented software are useful for the modification of physiological models.

DOI： 10.11185/imt.2.144

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Language：Japanese   Publisher：Information Processing Society of Japan (IPSJ)  

The numerical simulation of whole cell models is important to understand cellular mechanisms. However, implementaion of simulation codes of whole cell models, which can include nonlinear equations, formulated as ordinary differential equations demands high effort. This research intends to enable automatic numerical calculation of initial-value problems of explicit method of whole cell models. For this purpose, using a graph theoretical method to analyze the structure of equation systems, a method to set boundary conditions with analysis of structural solvability, and a method to reduce numerical calculation cost by transforming of equations are introduced.

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Language：English   Publisher：Information Processing Society of Japan (IPSJ)  

The development of physiological cell models to support the understanding of biological mechanisms gains increasingly importance. Due to the complexity of biological systems, whole cell models, which are composed of many imported component models of functional elements, get quite complex, making modifications difficult. Here, we propose a method to enhance structural changes of cell models, employing the markup languages of CellML and our original PMSML (Physiological Model Structure Markup Language), in addition to a new ontology for cell physiological modelling, the Cell Model Ontology. In particular, a method to make references from CellML files to the ontology and a method to assist with manipulation of model structures using PMSML together with the Cell Model Ontology are reported. Using these methods two software utilities, an interactive ontology ID assigner, the CellML Ontologizer, and a graphical cell model editor, the Cell Structure Editor, are implemented. Experimental results proved that the proposed method and the implemented software are useful for the modification of physiological models.

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Language：English  

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Language：Japanese   Publisher：Information Processing Society of Japan (IPSJ)  

The importance of whole cell electrophysiological models to support the understanding of biological mechanisms is increasing rapidly. Due to the complexity of the biological systems, comprehensive cell models, which are composed of many sub-models, get complicated. Therefore, the construction and the modification of these models are very difficult. To solve this problem, we have been developing a graphical editor of cell model structure. The editor has intelligent assistant function for manipulation of model structures using markup languages together with an ontology for cell physiological models. However, to use this function, model files must contain the ontology ID. Here, we propose an ontology annotation method of CellML files. The experimental results proved that the method is effective for the modification of electrophysiological models.

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Language：English  

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Language：English  

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

In the development of cell physiological models, it is useful to evaluate simulation results produced by using description files that include a model definition and the information required for the simulation. Although several description languages for the cell physiological models are proposed, they are not sufficient or efficient to describe required information in developing models. In this research, we propose a XML based description language "CPSML" for cell physiology simulation. CPSML describes three contents in different formats : model definition, model structure and experimental protocol. This separated description facilitates efficient simulation of a model with various experimental methods and model improvements.

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Other Link： http://search.jamas.or.jp/link/ui/2006032007

Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

Accuracy of cell model is very important for the realization of the precise biological simulation. However, the construction and authoring of a cell model is complicated work that require both biological and information science knowledge. To realize an efficient authoring of a cell model, we examined the intelligent support function of a cell model authoring tool. We also examined the knowledge required to realize this support function. In this report, we propose the cell physiology ontology suitable for this purpose.

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Other Link： http://search.jamas.or.jp/link/ui/2006032008

Language：English  

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Language：English  

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

To understand the complicated mechanism of the biological functions, it is important to analyze the interactions between various phenomena in developing simulation systems. We have been developing a software environment for general biological simulation, which is capable of multi-physics simulation with intensive interaction. The software environment composes of several individual sub-components with common interfaces, and the interactions between such components are described using a simulation scenario. Various simulation systems of different purposes can be easily developed by combining different function components. Using this environment, a simulator of left ventricle motion was implemented, which computes deformation of left ventricle according to a cell physiological model, a 3D shape, and a cell orientation model.

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Other Link： http://search.jamas.or.jp/link/ui/2004199798

Language：English  

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Language：Japanese   Publisher：Information Processing Society of Japan (IPSJ)  

Many architectures which can assure the QoS (quality of service) are already proposed. To apply those architectures to the network, rules for the decision of the allocation of resources are needed. These rules are called "policies". Each network domain has own policies. Therefore, when contents go through many domains, it is very difficult to assure the contents QoS. In this paper, we propose the policy definition and the framework which choose the contents assigned resources according to policies.

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Language：Japanese  

現在では，ネットワークの側でデータの帯域保証や優先制御を行うことができるような技術がいくつか提案されている．それらの技術を利用するためにはポリシーと呼ばれるネットワーク内での資源配分ルールが必要であるが，個々のネットワークドメインには独自のポリシーが存在し，さらにはその基準は多岐にわたるため，ドメインをまたぐようなコンテンツのQoSを保証するためにはそれらをとりまとめる必要がある．本論文では，複数のネットワークドメインをまたぐデータ配送の品質を保証することを前提とした，ネットワークドメインのポリシー設計と複数ドメインの持つポリシーを取りまとめるためのフレームワークを提案する．Many architectures which can assure the QoS(quality of service) are already proposed. To apply those architectures to the network, rules for the decision of the allocation of resources are needed. These rules are called "policies". Each network domain has own policies. Therefore, when contents go through many domains, it is very difficult to assure the comtents QoS. In this paper, we propose the policy definition and the framework which choose the contents assigned resources according to policies.

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

Many architectures which can assure the QoS (quality of service) are already proposed. To apply those architectures to the network, rules for the decision of the allocation of resources are needed. These rules are called "policies". Each network domain has own policies. Therefore, when contents go through many domains, it is very difficult to assure the contents QoS. In this paper, we propose the policy definition and the framework which choose the contents assigned resources according to policies.

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Language：Japanese   Publisher：Information Processing Society of Japan (IPSJ)  

We propose a method to satisfy QoS request by cooperating resource reservation with QoS technology. First, it is discussed to incorporate of resource reservation with QoS-based routing, in order to reserve resource along a suited path for a QoS request for the flow. Issues of the cooperation are discussed, then requirements of QoS-based routing and extensions of RSVP for the cooperation are considered. Next, resource reservation and hierarchical transmission are coordinated, aimed to enable heterogeneous reservations. Schemes of reserving resource for a layered flow are compared, Then extensions of RSVP for the adopted scheme are proposed.

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Language：Japanese  

インターネットを利用してリアルタイムにデータの送受信を行うアプリケーションにおいて要求される通信品質QoSを保証するため, 資源予約を行うプロトコルとしてRSVP (Resource ReSerVation Protocol)が提案されている。また, QoS保証可能なネットワーク技術としてATM (Acynchronous Transfer Mode)があり, 受信側で異なる帯域に応じて, 品質の異なる有効なデータを受け取れる符号化方法として, 階層符号化方式がある。本稿では, まず, RSVPを用いた資源予約をIP over ATM上で行う方法を提案する。ここでは, RSVPを拡張しCSR (Cell Switch Router:セル文換ルータ)を利用することにより, 送受信端末間での継ぎ目のない資源予約を実現する。次に, 階層符号化された実時間データを, 複数のVCを使って, 複数のQoSを選択可能な資源予約を行う方法を提案する。

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Event date： 2019.11.3 - 2019.11.6

Language：English  

Venue：New Orleans  

In Kyushu University, Information Infrastructure Initiative provides an email service for students and staff members, called “Primary Mail Service”. We had operated an on-premises system for this service, and the lifetime of this system would end in early 2019. We needed to reduce costs for replacing this system because our university had just finished a major campus migration. We compared some options such as building a yet another on-premise system and migrating to a cloud-based email service and finally gave up the on-premise option because we couldn’t afford replacement and operational costs of another on-premises system anymore. We selected Microsoft Exchange Online as the new service mainly because we already had a contract with Microsoft and been operating an Office 365 tenant. We had additional requirements for user provisioning and services which were not available in Exchange Online, so we had to implement and maintain additional systems on top of it. On December 18th, 2018, we successfully migrated the email service to Exchange Online. By coincidence, Kyushu University Administration Bureau decided to migrate their in-house Exchange server to Exchange Online. After some discussions, they concluded to migrate their domain to the same tenant with Primary Mail Service. Other than that, there are more than a hundred legacy email servers inside our campus network operated by various departments as subdomains of kyushu-u.ac.jp. We are designing a plan to consolidate them into our tenant of Exchange Online to reduce a budget and human resource costs, and to improve security. In this presentation, we share our experiences about migrating our campus-wide email services to Exchange Online. We also discuss why we want to consolidate other legacy email servers and how to implement the plan.

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Event date： 2019.11.3 - 2019.11.6

Language：English  

Venue：New Orleans  

Office 365 Education is a suite of cloud services for students and educators. Kyushu University has provided Office 365 accounts for all students and staff. The first generation of an environment for Office 365 provisioning in the university had several issues about associating between Office 365 accounts and member identifications of the university. All university members are randomly assigned unique identifiers by the central ID management system for using commonly in university-wide information services. Since the IDs are for internal use only, the first environment authenticated a user with another ID and password specific for Office 365. In addition, processes for assigning licenses and giving privilege to users of Office 365 depending on modifications to member information in the ID management system were not fully automated. This paper shows how we resolved problems integrating Office 365 into the ID management of the university by rebuilding the infrastructure. We configured a federated authentication system and developed a system for processing in events of the account life cycle.

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Event date： 2019.7.23 - 2019.7.27

Language：English  

Venue：Berlin  

In mathematical modeling of cell physiological processes, measurements required for parameter determination are often available only as aggregated data in the literature. Physiological measurements contain relatively large observation errors due to intrinsic variations in physiological processes, and the errors cause uncertainties in parameter values. This paper reports analyses of the uncertainty in parameter estimates of a simple mathematical model of an ion channel from a set of published experimental data. A conventional approach for estimating model parameters from aggregated data is applying the method of least squares to a series of the mean values of measurements. The parameter estimates by the conventional method significantly differed from those by a statistical approach, maximum likelihood estimation considering the standard errors of the means. Exhaustive analyses on the likelihood of parameter values show high parameter uncertainties and wide distribution of parameter values with no significant differences in the likelihood. These results imply the importance of considering variances of observations and uncertainties in parameter estimates.

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Event date： 2019.5

Language：Japanese  

Venue：徳島県鳴門市  

九州大学では組織的に取り扱う情報に対して機密性の格付けを指定することが規定されたが，
電子化された情報を取り扱う際に職員が実施すべき具体的な手順は明示されていなかった．
そこで，
機密性を要する情報を電子的に保存，授受する際に保護する方法について検討を行い，
職員が従うべき規則を制定した．
本稿では検討の内容と取り決めた規則について報告する．
保護方法は，
九州大学において実現可能かつ実務的に運用可能であることを前提に，
機密性保持を確保する中で業務効率について最大限に配慮し，
技術的手段だけで漏洩を防止するのではなく，
一部のリスクは受容し，ルールとして予防することも含めて検討した．
検討の結果，
電子化された機密性を要する情報を保存，授受する方法，
および，その際に用いる暗号化の方法やパスワードの扱いなどについて，規則を定めた．
さらに本稿では，
検討の中で明らかとなった今後解決が期待される技術的な課題についても報告する．

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Event date： 2019.5

Language：Japanese  

Venue：北海道札幌市  

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Event date： 2019.5

Language：Japanese  

Venue：福井県あわら市  

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Event date： 2018.10.7 - 2018.10.10

Language：English  

Venue：Orlando  

In Kyushu University, Information Infrastructure Initiative provides email service for students and staff members. Email services for students and staff members were started separately. For students, an email service was started as Unix accounts of "Computer System for Education" in 1995. On the other hand, an email service for staff members was started in 2009, and eventually the two mail services were merged into the current "Kyushu University Primary Mail Service" in 2014. The designs of these mail systems were affected by various operational issues and political decisions at their times. We think that running an in-house mail system is becoming less feasible due to the initial/operational cost, security issues, and our dwindling budget. For the current system, the planned 5-year lifetime ends in this fiscal year. Therefore, we are forced to migrate to a cloud-based mail service. In this presentation, we want to share our past experiences and future plans about our university email services.

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Event date： 2018.7.18 - 2018.7.21

Language：English  

Venue：Honolulu  

Intracellular acidosis induced by hypoxia resulted from myocardial ischemia damages myocardium. However, the detailed mechanisms of hypoxic acidosis are not quantitatively explained. The purpose of this study is to create a novel computational model which can reproduce intracellular acidosis caused by myocardial ischemia. We constructed a computational model of myocardium, by using a mathematical ventricular cell model which includes pH regulation and a computational model of myocardial microcirculation for calculating extracellular conditions. The present model reproduced cellular hypoxia in an ischemic condition simulated by a reduced blood flow, and intracellular pH reduction in response to the hypoxia.

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Event date： 2018.2

Language：Japanese  

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Event date： 2018.2

Language：Japanese  

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Event date： 2017.12.12

Language：Japanese  

Numerical algorithms are generally published along with reference implementations in procedural programming languages such as Fortran, C, and MATLAB, and distributed and utilized within libraries with mainly concerning computational performance. However, a necessary algorithm has to be ported onto a target environment if no implementation of the algorithm is available on the environment. Especially in recent years, numerical computations are executed using various computing environments. Therefore, that conventional manner has a problem on availability and productivity. In this presentation, a XML-based formal language is introduced, the domain of which is specialized for root-finding algorithms of nonlinear equations. In the present formal language, a root-finding algorithm is not defined as a procedure but as a set of mathematical recurrence formulas, and declaratively described using Content Markup of MathML independently of any programing languages. By analyzing relationships among mathematical equations in the description and mathematical variables referred in the equations, an abstract calculation procedure of the described algorithm can be obtained as a partial order relation. From the abstract procedure, program codes in concrete programming languages can be generated. A generator of C99 or Fortran 95 source codes is presented, and a performance evaluation of a generated source code compared to a common source code is reported.

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Event date： 2017.11.7 - 2017.11.9

Language：English  

Venue：Toronto  

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Event date： 2017.10.1 - 2017.10.4

Language：English  

Venue：Seattle  

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Event date： 2017.10.1 - 2017.10.4

Language：English  

Venue：Seattle  

Information Infrastructure Initiative of Kyushu University started serving Office 365 Education for all students and staff members at Kyushu University in November 2016. Since 2007, the university had signed Microsoft EES (Enrollment for Education Solutions) including licenses for the latest Microsoft Windows and Office suite. The EES agreement includes an advantage to provide Office 365 Education to the university members with minimum investments, and there was a demand for Skype for Business which is included in Office 365. To deploy Office 365 for our users, we first needed to configure our on-premises user authentication infrastructure to coordinate with Office 365. During trials, we had a couple of difficulties attributed to some disagreements between Microsoft's and our policy on whether the user identifier, namely the user principal name in Active Directory, was open or private. Additionally, we had to consider which services should be applied to the users, because we have been operating an on-premises email service which is competing with Microsoft Exchange mail service. In this presentation, we share our experiences in Office 365 deployment.

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Event date： 2017.7.11 - 2017.7.15

Language：English  

Venue：Jeju Island  

Contributions of interstitial fluid (ISF) flow within the myocardial microcirculation is not well understood despite its importance due to difficulties in measurements. For analysing a contribution of interstitial fluid flow within myocardial microcirculation, we developed a computational model of myocardial microcirculation by introducing convection by the ISF flow into an existing myocardial microcirculation model, and performed simulations with varied ISF flows in normal and hypoperfusion conditions. Simulation results show that the ISF flow has a contribution only with low capillary flow. This might suggest partial comensation of oxygen supply by the ISF flow under ischemic conditions.

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Event date： 2017.7.11 - 2017.7.15

Language：English  

Venue：Jeju  

Contributions of interstitial fluid (ISF) flow within the myocardial
microcirculation is not well understood despite its importance due to
difficulties in measurements. For analysing a contribution of
interstitial fluid flow within myocardial microcirculation, we
developed a computational model of myocardial microcirculation by
introducing convection by the ISF flow into an existing myocardial
microcirculation model, and performed simulations with varied ISF
flows in normal and hypoperfusion conditions. Simulation results show
that the ISF flow has a contribution only with low capillary flow.
This might suggest partial comensation of oxygen supply by the ISF
flow under ischemic conditions.

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Event date： 2017.6.8 - 2017.6.9

Language：Japanese  

Venue：静岡県静岡市  

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Event date： 2017

Language：Japanese  

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Event date： 2016.10.24 - 2016.10.25

Language：Japanese  

Venue：福岡県福岡市  

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Event date： 2016.9.17 - 2016.9.18

Language：Japanese  

Venue：北海道旭川市  

心筋細胞ではエネルギー産生の98%以上は細胞内のミトコンドリアにより行われる.単離ミトコンドリアを 用いた実験では,その機能は外液カルシウムイオン濃度に依存することがわかっている.また,心筋細胞への 負荷が高まると細胞内カルシウムイオン濃度は上昇する.しかし,実環境において一心拍中に急激に変化す る細胞内カルシウムイオン濃度がミトコンドリアにどのような影響を与えるかについては,実験で確かめる ことが非常に困難である.そこで本研究では,シミュレーションによりミトコンドリアの機能の変化を解析 することを目的とする.これまでに,実験結果に基づく詳細なミトコンドリアの数理モデルが開発されてお り,クエン酸回路や電子伝達系,ミトコンドリア内外での基質量,イオン濃度の変化などが連立微分方程式と して表現されている.一方,詳細な心筋細胞モデルとしてKyotoモデルがあり,膜興奮,イオン動態,基礎代謝 および筋収縮によるエネルギー消費などを表現する.そこで,詳細なミトコンドリアモデルをKyotoモデルに組 みこむことで,細胞内におけるミトコンドリアの機能をシミュレーションする.このモデルを用いて,細胞 への刺激頻度を変えることで細胞内カルシウム濃度を変化させるシミュレーションを行い,ミトコンドリア の機能がどのように変化するかを解析した結果を報告する.

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Event date： 2016.9.17 - 2016.9.18

Language：Japanese  

Venue：北海道旭川市  

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Event date： 2016.8.23 - 2016.8.26

Language：English  

Venue：Seoul  

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Event date： 2016.8.16 - 2016.8.20

Language：English  

Venue：Orland, FL  

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Event date： 2016.8.16 - 2016.8.20

Language：English  

Venue：Orland, FL  

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Event date： 2016.1.13 - 2016.1.14

Language：Japanese  

Venue：福岡市  

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Event date： 2016

Language：Japanese  

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Event date： 2015.3.16

Language：Japanese  

In this paper, we proposed an improved algorithm to derive corresponding loop structure from recurrence relation equation set that are generated by the program code generation system. The system use Ce11ML file as an biological function model, and use TecML file which describes calculation scheme for the model. By using the propoased algorithm, the analysis time improved by 1000 to 10000 fold, and also the limitation of the input recurrence relation equations were relaxed.

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Event date： 2015.3.16

Language：Japanese  

In this paper, we proposed an improved algorithm to derive corresponding loop structure from recurrence relation equation set that are generated by the program code generation system. The system use Ce11ML file as an biological function model, and use TecML file which describes calculation scheme for the model. By using the propoased algorithm, the analysis time improved by 1000 to 10000 fold, and also the limitation of the input recurrence relation equations were relaxed.

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Event date： 2015

Language：Japanese  

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Event date： 2015

Language：Japanese  

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Event date： 2015

Language：Japanese  

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Event date： 2014.11

Language：English  

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Event date： 2014.8.26 - 2014.8.30

Language：English  

Venue：Chicago  

As a well-known property of the heart, many studies has reported that the left ventricular end-systolic pressure-volume relationship (ESPVR) is linear. However, the reason of the linearity is poorly understood. This article presents a multiscale circulation model to be a tool for theoretical analyses on the mechanism of the linearity of ESPVR. The model is composed of three sub-models; a detailed closed-loop lumped-parameter model for cardiovascular system, geometric left ventricle model, a comprehensive ventricular myocyte model. Although the present model integrates nonlinear sub-models, the model can successfully reproduce highly linear ESPVR without any arbitrary modifications.

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Event date： 2014.8.26 - 2014.8.30

Language：English  

Venue：Chicago  

As a well-known property of the heart, many studies has reported that the left ventricular end-systolic pressure-volume relationship (ESPVR) is linear. However, the reason of the linearity is poorly understood. This article presents a multiscale circulation model to be a tool for theoretical analyses on the mechanism of the linearity of ESPVR. The model is composed of three sub-models; a detailed closed-loop lumped-parameter model for cardiovascular system, geometric left ventricle model, a comprehensive ventricular myocyte model. Although the present model integrates nonlinear sub-models, the model can successfully reproduce highly linear ESPVR without any arbitrary modifications.

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Event date： 2013.7.3 - 2013.7.7

Language：English  

Venue：Osaka  

In this study, we use cardiovascular simulation to gain new insights on the correlation between electrical heterogeneity and ventricular energetics. Although there are numerous in vivo and in vitro studies on the electrical heterogeneity within the ventricular myocardium, not much attention has been directed to its correlation to cardiovascular mechanics, because of difficulties in simultaneously observing and analyzing multiple spatial scales(the cell, the organ, and the system). We performed simulations with two cardiovascular simulation models, one which uses different myocardial cell models for the epicardial, endocardial, and mid-myocardial cells, and another which uses a homogeneous model throughout the entire myocardium. The epicardial, endocardial, and midmyocardial cell models were created by parametrically tuning a homogenous cell model. From the cardiovascular simulation we obtained pressure-volume loops which were used to calculate cardiovascular energetic efficiency and myocardial contractility. We found that energetic efficiency is higher in the electrically heterogeneous model.

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Event date： 2013.7.3 - 2013.7.7

Language：English  

Venue：Osaka  

The physiological simulation at the tissue and organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and in cases like pharmacokinetics, distributed parameters add to the complexity of the PDE solution. These factors make most PDE solutions and their corresponding program codes tailored for specific problems. We propose a general approach for handling PDEs in computational models using a replacement scheme for discretization. This method allows for the handling of the different PDE types. The replacement scheme involves substituting all the partial differential terms with the numerical solution equations. Once the model equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to determine the simulation loop structure and generate the program code.

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Event date： 2013.7.3 - 2013.7.7

Language：English  

Venue：Osaka  

In this study, we use cardiovascular simulation to gain new insights on the correlation between electrical heterogeneity and ventricular energetics. Although there are numerous in vivo and in vitro studies on the electrical heterogeneity within the ventricular myocardium, not much attention has been directed to its correlation to cardiovascular mechanics, because of difficulties in simultaneously observing and analyzing multiple spatial scales(the cell, the organ, and the system). We performed simulations with two cardiovascular simulation models, one which uses different myocardial cell models for the epicardial, endocardial, and mid-myocardial cells, and another which uses a homogeneous model throughout the entire myocardium. The epicardial, endocardial, and midmyocardial cell models were created by parametrically tuning a homogenous cell model. From the cardiovascular simulation we obtained pressure-volume loops which were used to calculate cardiovascular energetic efficiency and myocardial contractility. We found that energetic efficiency is higher in the electrically heterogeneous model.

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Event date： 2013.7.3 - 2013.7.7

Language：English  

Venue：Osaka  

The physiological simulation at the tissue and organ level typically involves the handling of partial differential equations (PDEs). Boundary conditions and in cases like pharmacokinetics, distributed parameters add to the complexity of the PDE solution. These factors make most PDE solutions and their corresponding program codes tailored for specific problems. We propose a general approach for handling PDEs in computational models using a replacement scheme for discretization. This method allows for the handling of the different PDE types. The replacement scheme involves substituting all the partial differential terms with the numerical solution equations. Once the model equations are discretized with the numerical solution scheme, instances of the equations are generated to undergo dependency analysis. The result of the dependency analysis is then used to determine the simulation loop structure and generate the program code.

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Event date： 2013.5.30

Language：Japanese  

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Event date： 2013.5

Language：Japanese  

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Event date： 2012.8.28 - 2012.9.1

Language：English  

Venue：San Diego, CA  

To cope with the complexity of the biological function simulation models, model representation with description language is becoming popular. However, simulation software itself becomes complex in these environment, thus, it is difficult to modify the simulation conditions, target computation resources or calculation methods. In the complex biological function simulation software, there are 1) model equations, 2) boundary conditions and 3) calculation schemes. Use of description model file is useful for first point and partly second point, however, third point is difficult to handle for various calculation schemes which is required for simulation models constructed from two or more elementary models. We introduce a simulation software generation system which use description language based description of coupling calculation scheme together with cell model description file. By using this software, we can easily generate biological simulation code with variety of coupling calculation schemes. To show the efficiency of our system, example of coupling calculation scheme with three elementary models are shown.

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Event date： 2012.8.28 - 2012.9.1

Language：English  

Venue：San Diego, CA  

Multi-scale models of the cardiovascular system provide new insight that was unavailable with in vivo and in vitro experiments. For the cardiovascular system, multi-scale simulations provide a valuable perspective in analyzing the interaction of three phenomenons occurring at different spatial scales: circulatory hemodynamics, ventricular structural dynamics, and myocardial excitation-contraction. In order to simulate these interactions, multiscale cardiovascular simulation systems couple models that simulate different phenomena. However, coupling methods require a significant amount of calculation, since a system of non-linear equations must be solved for each timestep. Therefore, we proposed a coupling method which decreases the amount of calculation by using the Kalman filter. In our method, the Kalman filter calculates approximations for the solution to the system of non-linear equations at each timestep. The approximations are then used as initial values for solving the system of non-linear equations. The proposed method decreases the number of iterations required by 94.0% compared to the conventional strong coupling method. When compared with a smoothing spline predictor, the proposed method required 49.4% fewer iterations.

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Event date： 2012

Language：English  

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Event date： 2011.11.24

Language：Japanese  

重大な心臓病態の一つに不整脈がある．特に薬剤投与の副作用による不整脈の発生は大きな問題となっており，未然に副作用の危険性を調べることは重要である．従来では危険性を調べるために動物実験を行われてきたが，近年ではコンピュータシミュレーションにより，比較的低コストで効率的にデータを得ることが有効な手段となっている．本稿では，心筋細胞モデルにパラメタ変化を加えたシミュレーションにより，不整脈の一原因である遅延後脱分極 （DAD） を再現する．DAD に大きく関連するパラメタから，薬剤投与を想定するパラメタと個体別の生理状態を想定するパラメタを選択し，それぞれを変化させたときの DAD 発生の有無を自動判定により調査した．その結果，各パラメタ変化が DAD 発生に与える影響の大きさを解析した．One of serious cardiac diseases is cardiac arrhythmia. It is important to investigate risks of the cardiac arrhythmia by drug side effects before medications. Although animal experminents has been employed to investigate the risks, in recent years, computer simulation is becoming an effective technique to obtain data efficiently at comparatively low cost. In this paper, the delayed afterdepolarization (DAD), which is a cause of arrhythmia, is reproduced by simulation with varying parameters of a ventricular myocyte model. The parameters are selected from model parameter which are deeply relating to DAD, for representing drug dosing and individual physiological conditions. Generations of DAD were evaluated by an automatic DAD detection method introduced in this stydy. From the result, influenced by each parameter change to the risk of DAD was analyzed.

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Event date： 2011.11.24

Language：Japanese  

重大な心臓病態の一つに不整脈がある．特に薬剤投与の副作用による不整脈の発生は大きな問題となっており，未然に副作用の危険性を調べることは重要である．従来では危険性を調べるために動物実験を行われてきたが，近年ではコンピュータシミュレーションにより，比較的低コストで効率的にデータを得ることが有効な手段となっている．本稿では，心筋細胞モデルにパラメタ変化を加えたシミュレーションにより，不整脈の一原因である遅延後脱分極 （DAD） を再現する．DAD に大きく関連するパラメタから，薬剤投与を想定するパラメタと個体別の生理状態を想定するパラメタを選択し，それぞれを変化させたときの DAD 発生の有無を自動判定により調査した．その結果，各パラメタ変化が DAD 発生に与える影響の大きさを解析した．One of serious cardiac diseases is cardiac arrhythmia. It is important to investigate risks of the cardiac arrhythmia by drug side effects before medications. Although animal experminents has been employed to investigate the risks, in recent years, computer simulation is becoming an effective technique to obtain data efficiently at comparatively low cost. In this paper, the delayed afterdepolarization (DAD), which is a cause of arrhythmia, is reproduced by simulation with varying parameters of a ventricular myocyte model. The parameters are selected from model parameter which are deeply relating to DAD, for representing drug dosing and individual physiological conditions. Generations of DAD were evaluated by an automatic DAD detection method introduced in this stydy. From the result, influenced by each parameter change to the risk of DAD was analyzed.

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Event date： 2011.8.30 - 2011.9.3

Language：English  

Venue：Boston, MA  

To cope with the complexity of the biological function simulation models, model representation with description language is becoming popular. However, simulation software itself becomes complex in these environment, thus, it is difficult to modify target computation resources or numerical calculation methods or simulation conditions. Typical biological function simulation software consists of 1) model equation, 2) boundary conditions and 3) ODE solving scheme. Introducing the description model file such as CellML is useful for generalizing the first point and partly second point, however, third point is difficult to handle. We introduce a simulation software generation system which use markup language based description of ODE solving scheme together with cell model description file. By using this software, we can easily generate biological simulation program code with different ODE solving schemes. To show the efficiency of our system, experimental results of several simulation models with different ODE scheme and different computation resources are shown.

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Event date： 2011.8.30 - 2011.9.3

Language：English  

Venue：Boston, MA  

We investigated numerical methods for predictors in a multiscale cardiovascular simulation model. The proposed method predicts initial approximations for the iterative convergence calculations of the strong coupling method using the smoothing spline to remove errors from values of past timesteps and using the linear and second-order extrapolation. The new coupling algorithm was used for coupling a left ventricular finite element model to a myocardial excitation-contraction model. We performed experiments with different values for the smoothing parameter and with linear and second-order extrapolations. 1 with the linear extrapolation gave the best results. It reduced computation time by 91% compared to the strong coupling method. With the use of the smoothing spline, distance between the initial approximation and converged solution reduced by 62%, while the average number of iterations reduced by 32%. The smoothing spline can be used to improve the accuracy of predictors and reduce the number of iterations needed for the computation of the convergence procedure.

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Event date： 2011.7.1

Language：Japanese  

Detailed simulation analysis of the cardiovascular system is important because the system is a biological phenomenon indispensable in maintaining life. Since the cardiovascular system is a result of the interaction of myocardial cell physiology, cardiac structural dynamics, and hemodynamics, it is necessary to use multi-physics simulation to couple equations of different scales. For a precise coupling simulation, it is desirable to use the strong coupling method which is computationally expensive. In this paper, a prediction method is proposed for a cardiovascular simulation system using strong coupling calculation. In the proposed method, the smoothing spline and extrapolators are used to predict an approximate solution to the convergence equation, using the predicted value as the initial value to decrease the number of iterations to convergence. Experiments are performed for different values of the smoothing parameter and first to fourth degree extrapolators. Decrease in iterations for the convergence calculation was observed when using the proposed method.

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Other Link： http://search.jamas.or.jp/link/ui/2012002115

Event date： 2010.11.11

Language：Japanese  

To understand conditions under cardiac ischemia or hypoxia, it is of importance to evaluate oxygen consumption in the myocardial microcirculation. However, there are difficulties in accurate measurements of the oxygen consumption experimentlly. Therefore, computer simulation is an important methodology to evaluate the oxygen consumption. For simulation of oxygen consumption in a cardiac tissue, a myocardial microcirculation model is proposed in this report. The model couples a tissue microcirculation model and a myocardial cell model. The simulation results under low oxygen conditions of the arterial blood show that oxygen consumptions decrease from the arterial side to the venous side and that cells in the venous side are under hypoxia.

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Other Link： http://search.jamas.or.jp/link/ui/2011101863

Event date： 2010.11.11

Language：Japanese  

It is of importance to estimate the activity ratios of cardiac cellular ion channels for detecting side effects of drugs under development. A myocardial cell model enables the estimation of the activity ratios by reproducing experimental cardiac cellular action potential (AP) recordings with varied parameters. We analized the relationship between parameters and outputs of the model. Results from the analysis of the distribution of similar AP recordings and myocardial contractility in parameter space show the difficulty in estimating activity ratios of ion channels based on AP recordings or myocardial contractility alone. However, they also show the possibility to improve the estimation accuracy by the combined use of AP recordings and myocardial contractility.

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Other Link： http://search.jamas.or.jp/link/ui/2011101864

Event date： 2010.11

Language：Japanese  

新薬開発における副作用の予測には各種イオンチャネルの阻害率を推定することが重要である。一方、心筋細胞モデルを用いることで、実計測した細胞の膜電位波形からイオンチャネル阻害率の推定が期待できる。そこで本研究では、薬物作用推定を目的に、心筋細胞モデルの出力とパラメタとの関係を解析する。各パラメタを軸とする5次元パラメタ空間内での膜電位及び収縮力の変化を解析した。その結果、膜電位や収縮力単独による特定のパラメタの推定は困難であるが、両者を併用することにより推定精度が向上する可能性が示された。(著者抄録)

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Event date： 2010.11

Language：Japanese  

虚血性心疾患や低酸素症の病態を解明するためには、微小循環における酸素消費量を評価することが重要となる。しかし、微小循環の酸素消費量を正確に計測することは困難であり、精密なモデルを用いた生体機能シミュレーションが有効な手段となる。本研究では、微小循環モデルであるDashモデルに心筋細胞モデルであるKyotoモデルを導入することにより、低酸素状態において微小循環の酸素消費量が計算可能な心筋組織微小循環モデルを提案する。構築したモデルを用いて、低酸素状態における心筋組織毛細血管の動脈側から静脈側にかけての酸素消費分布を求めると、動脈側に比べて精脈側の酸素消費量が減少していることが分かり、特に静脈側で虚血状態に陥っていることが示唆された。(著者抄録)

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Event date： 2010.10

Language：English  

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Event date： 2009.10.7 - 2009.10.9

Language：English  

Venue：Shiga  

Frank-Starling law, which describes a relation between cardiac contraction energy and end-diastolic volume, is of importance, but the detailed mechanism is not quantitatively understood yet. In this paper, the mechanism of a linear relation between end-diastolic volume and end-systolic pressure as a part of Frank-Starling law is analyzed by means of computer simulation. A hemodynamics model, which is constructed by composing a vascular system model, a left ventricular dynamics model and a myocardial cell model, reproduced a linear relation between end-diastolic volume and end-systolic pressure successfully. In this paper, the simulation results and the detailed analysis are reported.

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Event date： 2009.9.2 - 2009.9.6

Language：English  

Venue：Minneapolis, MN  

Some models of cellular physiological functions are formulated as ordinary differential equations that contain multiple systems of simultaneous nonlinear equations. Simulation of such a model described in a declarative representation format requires determination of equations to be simultaneously solved with specification of independent and parameter variables in the model. In this report, a method for extracting systems of simultaneous equations in a cell model is presented. The present method analyzes a graph representation of a model and extracts the subgraphs that represent equation systems to be simultaneously solved, by efficiently interactive selection of independent variables of the model.

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Event date： 2009.9.2 - 2009.9.6

Language：English  

Venue：Minneapolis, MN  

Analyzing the microscopic energy balance of cardiac tissue is very important for understanding heart diseases. However, such analysis is difficult with animal experiments. Therefore, the accurate simulation model is expected to be an important tool for such research. We propose a cardiac tissue model which can reproduce accurate distribution of oxygen consumption under hypoxia. The model includes blood tissue exchange model of capillary and oxygen consumption model of cells. The capillary model is based on the model proposed by Dash et al. 2006, and the cell model is based on the model proposed by Kuzumoto et al. 2007. By analyzing the oxygen consumption of the proposed model, the relation between the oxygen consumption and the arterial oxygen concentration was found to be largely different from that of single cell model. This implies that the animal experimental data should be carefully used for constructing a biological simulation model, depending on whether the experiment is performed within a cell or a tissue.

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Event date： 2009.9

Language：English  

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Event date： 2009

Language：English  

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Event date： 2008.8.20 - 2008.8.25

Language：English  

Venue：Vancouver, BC  

It is necessary to use complicated myocardial cell model and heart model to evaluate the regional energy production and consumption which leads to the unrealistic computational time. In this research, a left ventricle (LV) simulation model was constructed which includes accurate myocardial cell model. In order to simulate the model in realistic time, we introduced an approximation model of the crossbridge model which can be calculated with weak coupling calculation. The LV model was combined with a circulation model to validate the proposed model by calculating the hemodynamics parameters and ventricular energetics indices. The ESPVR (End Systolic Pressure Volume Relation) showed linear relation, and also the PVA - ATP consumption relation showed linear relation which are widely known as the physiological characteristics of mammalian hearts. From these results, we can say that the model can be used as a model for physiological simulation experiments which are related to the ventricular energetics.

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Event date： 2008.8.6

Language：Japanese  

Although there have been many new advances in biology, quantitative explanation about biological phenomenon is still difficult. In this case, computer simulation with biological model is a good tool for quantitative analysis of heart. Also there have been many new advances of the myocardial cell, and many physiological characteristic has been discovered. Since computational complexity increases in proportion to the size of model, computable size of heart model is restricted by computer ability. In this study we performed the simulation using MPI parallel computing for reducing computing time.

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Event date： 2008

Language：English  

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Event date： 2007.8.23 - 2007.8.26

Language：English  

Venue：Lyon  

For computer simulations of physiological experiments using physiological models, a machine-readable format of experimental protocols is effective. Here, we propose an XML-based language, PEPML (Physiological Experimental Protocol Markup Language). In the PEPML, conditions and procedures of an experimental protocol are procedurally described as a list of events, each of which consists of a condition for execution and an action to be executed. Since variables used in a protocol can be specified using an ontology, the protocol can be applied to various models without editing tasks. The PEPML allows both application of multiple protocols to a single model and application of a single protocol to multiple models. This feature facilitates the efficient simulation for verifications, comparisons and utilizations of physiological models.

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Event date： 2007.8.23 - 2007.8.26

Language：English  

Venue：Lyon  

It is important to use a myocardial cell model to evaluate the effects of the drugs to the hemodynamic parameters. We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential mechanism for reproducing the response of baroreflex control system. The parameters of the published adult human circulation model were modified to fit the infant hemodynamic values. The guinea pig myocardial cell model was introduced to the circulation model whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments.

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Event date： 2007.6.7 - 2007.6.9

Language：English  

Venue：Salt Lake City, UT  

We developed an infant circulation model which incorporates an accurate myocardial cell model including a beta adrenergic system. The beta adrenergic system is essential for the response reproduction of the baroreflex control system. The proposed model was constructed by modifying the parameters of a human adult circulation model with the aid of a guinea pig myocardial cell model, whose baseline heart rate is close to that of an infant. The presented model is in good agreement with results obtained in physiological experiments.

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Event date： 2007

Language：English  

The development of physiological cell models to support the understanding of biological mechanisms gains increasingly importance. Due to the complexity of biological systems, whole cell models, which are composed of many imported component models of functional elements, get quite complex, making modifications difficult. Here, we propose a method to enhance structural changes of cell models, employing the markup languages of CellML and our original PMSML (Physiological Model Structure Markup Language), in addition to a new ontology for cell physiological modelling, the Cell Model Ontology. In particular, a method to make references from CellML files to the ontology and a method to assist with manipulation of model structures using PMSML together with the Cell Model Ontology are reported. Using these methods two software utilities, an interactive ontology ID assigner, the CellML Ontologizer, and a graphical cell model editor, the Cell Structure Editor, are implemented. Experimental results proved that the proposed method and the implemented software are useful for the modification of physiological models.

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Event date： 2006.12.21

Language：Japanese  

The numerical simulation of whole cell models is important to understand cellular mechanisms. However, implementaion of simulation codes of whole cell models, which can include nonlinear equations, formulated as ordinary differential equations demands high effort. This research intends to enable automatic numerical calculation of initial-value problems of explicit method of whole cell models. For this purpose, using a graph theoretical method to analyze the structure of equation systems, a method to set boundary conditions with analysis of structural solvability, and a method to reduce numerical calculation cost by transforming of equations are introduced.

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Event date： 2006.12.21

Language：Japanese  

The numerical simulation of whole cell models is important to understand cellular mechanisms. However, implementaion of simulation codes of whole cell models, which can include nonlinear equations, formulated as ordinary differential equations demands high effort. This research intends to enable automatic numerical calculation of initial-value problems of explicit method of whole cell models. For this purpose, using a graph theoretical method to analyze the structure of equation systems, a method to set boundary conditions with analysis of structural solvability, and a method to reduce numerical calculation cost by transforming of equations are introduced.

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Event date： 2006.10

Language：English  

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Event date： 2006.10

Language：English  

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Event date： 2006.8.30 - 2006.9.3

Language：English  

Venue：New York, NY  

We evaluated the stress distribution in a geometrical shape model and a shape model obtained from human heart using two different fiber orientations. For both orientation models, the results showed large differences of the stress distributions between the mathematical shape model and the maesurement based shape model. These results suggest that stress distribution is highly dependent on the model geometry and the usage of a maesurement based shape model is important for the evaluation of the left ventricular (LV) wall stress distribution. This fact may have some influences on the reported homogeneity of stress distribution with anatomical fiber orientation model that uses mathematical shape model.

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Event date： 2006.8.30 - 2006.9.3

Language：English  

Venue：New York, NY  

To realize precise simulation of the left ventricular motion, it is important to utilize an accurate myocardial tissue model which can reproduce various characteristics of myocardial tissue contraction. In this study, we show that the nonlinear characteristics of the passive myocardial tissue property is the essential nature of the nonlinear force-velocity relation and present a formulation for hyperelastic physiological tissue property. Experimental results of our myocardial tissue simulation with the hyperelastic material property proposed are in good agreement with the reported force-velocity relation of real tissue.

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Event date： 2006.8.30 - 2006.9.3

Language：English  

Venue：New York, NY  

The development of electrophyslological whole cell models to support the understanding of biological mechanisms Is Increasing rapidly. Due to the complexity of biological systems, comprehensive cell models, which are composed of many Imported sub-models of functional elements, can get quite complicated as well, making computer modification difficult. Here, we propose a computer support to enhance structural changes of cell models, employing the markup languages CellML and our original PMSML (Physiological Model Structure Markup Language), In addition to a new ontology for cell physiological modelling. In particular, a method to make references from CellML files to the ontology and a method to assist manipulation of model structures using markup languages together with the ontology are reported. Using these methods three software utilities, Including a graphical model editor, are Implemented. Experimental results proved that these methods are effective for the modification of electrophyslological models.

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Event date： 2006.7

Language：English  

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Event date： 2006.6.15

Language：Japanese  

The importance of whole cell electrophysiological models to support the understanding of biological mechanisms is increasing rapidly. Due to the complexity of the biological systems, comprehensive cell models, which are composed of many sub-models, get complicated. Therefore, the construction and the modification of these models are very difficult. To solve this problem, we have been developing a graphical editor of cell model structure. The editor has intelligent assistant function for manipulation of model structures using markup languages together with an ontology for cell physiological models. However, to use this function, model files must contain the ontology ID. Here, we propose an ontology annotation method of CellML files. The experimental results proved that the method is effective for the modification of electrophysiological models.

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Event date： 2006.2

Language：English  

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Event date： 2006

Language：English  

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Event date： 2005.11

Language：English  

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Event date： 2005.10.14

Language：Japanese  

Accuracy of cell model is very important for the realization of the precise biological simulation. However, the construction and authoring of a cell model is complicated work that require both biological and information science knowledge. To realize an efficient authoring of a cell model, we examined the intelligent support function of a cell model authoring tool. We also examined the knowledge required to realize this support function. In this report, we propose the cell physiology ontology suitable for this purpose.

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Other Link： http://search.jamas.or.jp/link/ui/2006032008

Event date： 2005.10.14

Language：Japanese  

In the development of cell physiological models, it is useful to evaluate simulation results produced by using description files that include a model definition and the information required for the simulation. Although several description languages for the cell physiological models are proposed, they are not sufficient or efficient to describe required information in developing models. In this research, we propose a XML based description language "CPSML" for cell physiology simulation. CPSML describes three contents in different formats : model definition, model structure and experimental protocol. This separated description facilitates efficient simulation of a model with various experimental methods and model improvements.

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Other Link： http://search.jamas.or.jp/link/ui/2006032007

Event date： 2005.4

Language：English  

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Event date： 2005.3

Language：English  

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Event date： 2004.9.1 - 2004.9.5

Language：English  

Venue：San Francisco, CA  

In order to understand the function of biological elements and their interactions, computer analysis and simulation is an essential technique. For higher research efficiency, it is important to provide a system framework for constructing biological simulation systems that handle multiple phenomena. This paper proposes "DynaBioS", a comprehensive system framework for complex biological simulations. This framework consists of three main features, a component-based architecture, a customizable system operation, and an exchangeable model set. The system based on DynaBioS consists of a Simulation Core and System Components. The System Components are sub-simulators for individual functional factors and utility modules corresponding to specific information technologies. The Simulation Core manages and controls all components, in accordance with a Simulation Scenario and a Simulation Model. The DynaBioS makes it possible to implement different simulation systems by combining individual functional components, specific interactions and different simulation models. The versatility of DynaBioS is shown by two examples, a heart pumping simulator and a parameter optimization system for physiological models.

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Event date： 2004.3.10

Language：Japanese  

To understand the complicated mechanism of the biological functions, it is important to analyze the interactions between various phenomena in developing simulation systems. We have been developing a software environment for general biological simulation, which is capable of multi-physics simulation with intensive interaction. The software environment composes of several individual sub-components with common interfaces, and the interactions between such components are described using a simulation scenario. Various simulation systems of different purposes can be easily developed by combining different function components. Using this environment, a simulator of left ventricle motion was implemented, which computes deformation of left ventricle according to a cell physiological model, a 3D shape, and a cell orientation model.

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Other Link： http://search.jamas.or.jp/link/ui/2004199798

Event date： 2002.4

Language：English  

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Language：English   Presentation type：Poster presentation  

Venue：Online  

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Language：Japanese  

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Language：Japanese  

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Language：English   Presentation type：Poster presentation  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Auckland, New Zealand  

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Language：Japanese   Presentation type：Poster presentation  

Venue：兵庫県神戸市  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：東京都町田市  

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Language：Japanese  

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Language：Japanese  

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Language：Japanese  

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Language：English   Presentation type：Oral presentation (general)  

Venue：Chicago, IL, USA  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：宮城県仙台市  

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Language：Japanese   Presentation type：Oral presentation (general)  

In standard finite element analysis in structural dynamics, meshing can affect computation results. However, there have been no detailed report about effects of meshing on results of coupling simulation of left ventricular wall motion which involves myocardial spontaneous contractile force and fiber orientation. In this study, we examined an effect of meshing on simulation of left ventricular wall motion, which couples precise ventricular myocyte model and myocardial fiber orientation. We compared two shape models; spheroid mesh divided along graticule and spheroid mesh subdivided from a semi-regular polyhedron. The comparison results show significant differences between two models around the ventricular apex, which are mainly caused by the contractile force and the fiber orientation.

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Language：Japanese   Presentation type：Oral presentation (invited, special)  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese   Presentation type：Poster presentation  

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Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Bar Harbor, ME, USA  

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Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：San Diego, CA, USA  

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Language：Japanese   Presentation type：Poster presentation  

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Language：Japanese  

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Language：English   Presentation type：Symposium, workshop panel (public)  

Venue：Auckland, New Zealand  

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Language：Japanese  

Venue：東京都調布市  

重大な心臓病態の一つに不整脈がある．特に薬剤投与の副作用による不整脈の発生は大きな問題となっており，未然に副作用の危険性を調べることは重要である．従来では危険性を調べるために動物実験を行われてきたが，近年ではコンピュータシミュレーションにより，比較的低コストで効率的にデータを得ることが有効な手段となっている．本稿では，心筋細胞モデルにパラメタ変化を加えたシミュレーションにより，不整脈の一原因である遅延後脱分極 （DAD） を再現する．DAD に大きく関連するパラメタから，薬剤投与を想定するパラメタと個体別の生理状態を想定するパラメタを選択し，それぞれを変化させたときの DAD 発生の有無を自動判定により調査した．その結果，各パラメタ変化が DAD 発生に与える影響の大きさを解析した．One of serious cardiac diseases is cardiac arrhythmia. It is important to investigate risks of the cardiac arrhythmia by drug side effects before medications. Although animal experminents has been employed to investigate the risks, in recent years, computer simulation is becoming an effective technique to obtain data efficiently at comparatively low cost. In this paper, the delayed afterdepolarization (DAD), which is a cause of arrhythmia, is reproduced by simulation with varying parameters of a ventricular myocyte model. The parameters are selected from model parameter which are deeply relating to DAD, for representing drug dosing and individual physiological conditions. Generations of DAD were evaluated by an automatic DAD detection method introduced in this stydy. From the result, influenced by each parameter change to the risk of DAD was analyzed.

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Language：Japanese  

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Language：Japanese  

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Language：English  

Venue：Oxford, UK  

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Language：English  

Venue：Auckland, New Zealand  

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Language：Japanese   Presentation type：Public lecture, seminar, tutorial, course, or other speech  

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Language：English  

Venue：Shiga, Japan  

Frank-Starling law, which describes a relation between cardiac contraction energy and end-diastolic volume, is of importance, but the detailed mechanism is not quantitatively understood yet. In this paper, the mechanism of a linear relation between end-diastolic volume and end-systolic pressure as a part of Frank-Starling law is analyzed by means of computer simulation. A hemodynamics model, which is constructed by composing a vascular system model, a left ventricular dynamics model and a myocardial cell model, reproduced a linear relation between end-diastolic volume and end-systolic pressure successfully. In this paper, the simulation results and the detailed analysis are reported.

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Language：English  

Venue：Auckland, New Zealand  

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Language：Japanese  

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Language：English  

Venue：Auckland, New Zealand  

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Language：English  

Venue：Kyoto, Japan  

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Language：English  

Venue：San Francisco, CA, USA  

In order to understand the function of biological elements and their interactions, computer analysis and simulation is an essential technique. For higher research efficiency, it is important to provide a system framework for constructing biological simulation systems that handle multiple phenomena. This paper proposes "DynaBioS", a comprehensive system framework for complex biological simulations. This framework consists of three main features, a component-based architecture, a customizable system operation, and an exchangeable model set. The system based on DynaBioS consists of a Simulation Core and System Components. The System Components are sub-simulators for individual functional factors and utility modules corresponding to specific information technologies. The Simulation Core manages and controls all components, in accordance with a Simulation Scenario and a Simulation Model. The DynaBioS makes it possible to implement different simulation systems by combining individual functional components, specific interactions and different simulation models. The versatility of DynaBioS is shown by two examples, a heart pumping simulator and a parameter optimization system for physiological models.

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Language：English  

Venue：Kyoto, Japan  

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：沖縄県名護市  

Many architectures which can assure the QoS (quality of service) are already proposed. To apply those architectures to the network, rules for the decision of the allocation of resources are needed. These rules are called "policies". Each network domain has own policies. Therefore, when contents go through many domains, it is very difficult to assure the contents QoS. In this paper, we propose the policy definition and the framework which choose the contents assigned resources according to policies.

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：山口県山口市  

本稿では，資源予約とその周辺技術とを連携して，受信者のQoS要求を満たすことを考える．まず，フローが必要とするQoSに適した経路で資源予約するために，QoSルーティング技術と資源予約を連携することを考える．その場合の問題点を明らかにし，QoSルーティングに求められる条件とRSVPに必要となる変更について考察する．次に，受信者によってQoS要求が異なる場合に対応するために，階層伝送との連携を考える．階層伝送されるフローをRSVPを用いて予約する場合の手法について比較した後，そのために必要となる拡張方法を提案する．We propose a method to satisfy QoS request by cooperating resource reservation with QoS technology. First, it is discussed to incorporate of resource reservation with QoS-based routing, in order to reserve resource along a suited path for a QoS request for the flow. Issues of the cooperation are discussed, then requirements of QoS-based routing and extensions of RSVP for the cooperation are considered. Next, resource reservation and hierarchical transmission are coordinated, aimed to enable heterogeneous reservations. Schemes of reserving resource for a layered flow are compared. Then extensions of RSVP for the adopted scheme are proposed.

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Language：Japanese   Presentation type：Oral presentation (general)  

Venue：福岡県福岡市  

インターネットを利用してリアルタイムにデータの送受信を行うアプリケーションにおいて要求される通信品質QoSを保証するため, 資源予約を行うプロトコルとしてRSVP (Resource ReSerVation Protocol)が提案されている。また, QoS保証可能なネットワーク技術としてATM (Acynchronous Transfer Mode)があり, 受信側で異なる帯域に応じて, 品質の異なる有効なデータを受け取れる符号化方法として, 階層符号化方式がある。本稿では, まず, RSVPを用いた資源予約をIP over ATM上で行う方法を提案する。ここでは, RSVPを拡張しCSR (Cell Switch Router:セル文換ルータ)を利用することにより, 送受信端末間での継ぎ目のない資源予約を実現する。次に, 階層符号化された実時間データを, 複数のVCを使って, 複数のQoSを選択可能な資源予約を行う方法を提案する。

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Applicant：三菱電機株式会社

Application no：特願2001-135269  Date applied：2001.5.2

Announcement no：特開2002-330134  Date announced：2002.11.15

J-GLOBAL

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Applicant：三菱電機株式会社

Application no：特願2001-135261  Date applied：2001.5.2

Announcement no：特開2002-328668  Date announced：2002.11.15

J-GLOBAL

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Applicant：三菱電機株式会社

Application no：特願2000-402777  Date applied：2000.12.28

Announcement no：特開2002-204254  Date announced：2002.7.19

Patent/Registration no：特許第4346815号  Date registered：2009.7.24  Date issued：2009.7.24

J-GLOBAL

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Applicant：三菱電機株式会社

Application no：特願2000-257849  Date applied：2000.8.28

Announcement no：特開2002-077249  Date announced：2002.3.15

Patent/Registration no：特許第4316123号  Date registered：2009.5.29  Date issued：2009.5.29

J-GLOBAL

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