Faculty Profiles - Shimayoshi Takao

Papers - Shimayoshi Takao

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A Preliminary Study on Gathering SMTP Responses for Email Delivery on the Internet

笠原義晃, 小田知央, 嶋吉隆夫

情報処理学会研究報告(Web) 2023 ( OS-161 ) 2023

A Consideration on a Sender-Side Spam Scoring Header of E-mail Messages

2022 80 - 81 2022.12

Our Design and Implementation of Multi-Factor Authentication Deployment for Microsoft 365 in Kyushu University Reviewed

Yoshiaki Kasahara, Takao Shimayoshi

Proceedings ACM SIGUCCS User Services Conference 56 - 61 2022.3

Publishing type：Research paper (international conference proceedings)

In Kyushu University, Information Infrastructure Initiative manages a Microsoft 365 tenant for our university members. We started offering Office 365 in 2016 and migrated our university-wide email service to Microsoft 365 Exchange Online in 2018. Due to the recent outbreak of COVID-19, off-campus uses of Microsoft 365 have increased, and concerns about account security arose. We discussed how to deploy Multi-Factor Authentication (MFA) to protect our users. Microsoft 365 comes with Azure Active Directory (Azure AD), and it includes built-in MFA functionality. With the basic Azure AD MFA, individual users can register MFA information anytime but have no control to enable or disable MFA. Tenant administrators need to enable MFA for each account. For a gradual deployment, we want to allow users to enroll in MFA and register information at their convenience. In addition to that, we want to prevent malicious attackers from registering their MFA information if an account should be already compromised. Such control was difficult with the basic Azure AD MFA. Since 2020 our tenant subscribes to Azure AD Premium P2 licenses, which provides Azure AD Conditional Access. Conditional Access enables fine controls of MFA and other user access behavior with security groups. We designed an MFA self-enrolling and configuration system, and implemented it with Microsoft Forms, Power Automate, Conditional Access, and in-house web applications. By design, this system prohibits MFA information registration until user's self-enrollment in MFA, and requests the user to register MFA information upon the next sign-in after the self-enrollment. This is supposed to reduce the possible unauthorized registration of MFA information. We extensively discussed implementation of various measures and preparation of documents to counter users' troubles and complaints. We started deploying MFA in April 2021, but we have not yet fully mandated MFA due to a push back from some executives expressing concern about the adverse effects of enforcing MFA too quickly.

DOI： 10.1145/3501292.3511569

心筋虚血・再灌流の数理モデル解析

松岡達, 嶋吉隆夫, 竹内綾子

日本生理学雑誌 84 ( 1 ) 7 - 7 2022.2

透過型SMTPプロキシによるメール送信集約とキュー輻輳回避の検討 Reviewed

小田, 知央, 廣川, 優, 近藤, 宇智朗, 嶋吉, 隆夫, 笠原, 義晃

マルチメディア，分散協調とモバイルシンポジウム2021論文集 2021 ( 1 ) 1479 - 1485 2021.6

Language：Japanese Publisher：情報処理学会

電子メールは古くから用いられているメッセージ交換手段で，依然として世界的に広く利用されている．メールサービスを提供するメールホスティングでは，多数の利用者を同一システムに収容するマルチテナント型によりリソース効率を高め，運用コストを低減している．メールホスティングでは利用可能なグローバル IP アドレス数やメール送信の集中管理のため送信サーバは集約されていることが多いが，大量メール送信や送信先の迷惑メール対策により送信キューの輻輳が発生することで，問題を起こしたテナント以外にも影響が波及し，サービス品質の低下や管理コストの増大をまねいている．本研究では，テナントごとの送信キューの分離と，メール送信の集中管理や送信用グローバル IP アドレスの管理を両立する，メール送信集約用の透過型 SMTP プロキシを提案する．また，送信キューの分離によってキュー輻輳時の影響範囲が限定される効果を確認するための予備実験と，透過型 SMTP プロキシのプロトタイプ実装について述べる．

Other Link： http://hdl.handle.net/2324/4753053

A Supplementation Method for Delegation of Address Management on a Cloud Email Service Reviewed

62 ( 3 ) 810 - 817 2021.3

Authorship：Lead author,　Corresponding author Language：Japanese Publishing type：Research paper (scientific journal)

In providing organizational email service, the use of cloud email services contributes to reducing operation and management costs, generally. In most cloud email services, the management of a certain part of email addresses is not delegatable to administrators of organizational units, but this causes operational load concentration on organizational service administrators in large-scale organizations. For solving this issue, this study aims to enable delegations of email address management to administrators of organizational units. This article introduces a method for delegation of email address management and a supplemental system onto a cloud email service. The proposed method divides the management of email addresses within internet subdomains for organizational units from account administration and delegates the email address management to subdomain administrators. The present system for email address management is designed based on microservice architecture and configured in serverless. This microservice architecture and serverless configuration reduces operation and management costs and contributes to the maintainability and extensibility of the present system. Furthermore, the use of an identity-as-a-service for authentification, authorization and storing privilege information ensures confidentiality and security of system accounts.

Challenge for Consolidation of Individual Email Services into a Cloud Service Reviewed

Takao Shimayoshi, Yoshiaki Kasahara, Naomi Fujimura

Proceedings ACM SIGUCCS User Services Conference 26 - 29 2021.3

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

Email is a traditional but still important global communication tool. An email address is a kind of personal identifier, and email addresses printed on publications require persistent reachability. Kyushu University provides a university-wide email service, Primary Mail Service, and assigns a Primary Mail Address for each member. Divisions of the university additionally operate individual email services for their internet subdomains and administer member email addresses. Since email is a major means of cyberattacks nowadays, the secure operation of an email server demands considerable effort and high skill. This article describes a challenge at Kyushu University for consolidating individual email services. Since 2018, the Primary Mail Service has been operated using Microsoft's cloud service, Exchange Online, which supports multiple internet domains on a tenant. The approach employed is registering divisional subdomains to the tenant and configuring forwarding addresses from addresses of the subdomains to the Primary Mail Addresses or external addresses. A desirable scheme is for each domain administrator to manage forwarding addresses of the domain, but Exchange Online is unable to delegate administration to the domains. To overcome this, a system was designed and developed for domain administrators to create, read, update, and delete forwarding addresses. Beginning in July 2020, a new service to import divisional domains was offered. We are now planning measures for promoting the consolidation of individual email services.

DOI： 10.1145/3419944.3441170

Other Link： https://dblp.uni-trier.de/db/conf/siguccs/siguccs2021.html#ShimayoshiKF21

Renovation of the Office 365 environment in Kyushu University: Integration of account management and authentication Reviewed International journal

Takao Shimayoshi, Yoshiaki Kasahara, Naomi Fujimura

Proceedings ACM SIGUCCS User Services Conference 135 - 139 2019.10

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

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.

DOI： 10.1145/3347709.3347819

Other Link： https://dblp.uni-trier.de/db/conf/siguccs/siguccs2019.html#ShimayoshiKF19

Migrate legacy email services in Kyushu university to exchange online Reviewed International journal

Yoshiaki Kasahara, Takao Shimayoshi, Tadayuki Miyaguchi, Naomi Fujimura

Proceedings ACM SIGUCCS User Services Conference 127 - 131 2019.10

Publishing type：Research paper (international conference proceedings) Publisher：ACM

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

Other Link： https://dblp.uni-trier.de/db/conf/siguccs/siguccs2019.html#KasaharaSMF19

Parameter Uncertainty Analysis of a Mathematical Ion Channel Model Reviewed International journal

Takao Shimayoshi

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2019 1952 - 1955 2019.7

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

Other Link： https://dblp.uni-trier.de/conf/embc/2019

個人情報保護と情報セキュリティを考慮したOffice 365 Educationの環境構築方法

嶋吉隆夫, 笠原義晃, 藤村直美

2019‐CSEC‐85 ( 5 ) 1 - 6 2019.5

A Study on Confidential Information Protection in Kyushu University

嶋吉隆夫, 久志昇, 笠原義晃, 藤村直美

IEICE technical report 118 ( 480 ) 91 - 98 2019.3

Restructuring of Service Infrastructure for Office 365 in Kyushu University

嶋吉隆夫, 笠原義晃, 尾花昌浩, 藤村直美

大学ICT推進協議会年次大会論文集 ( 2018 ) 1 - 8 2018.11

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。

A Preliminary Computational Model for Hypoxic Acidosis in Cardiac Myocytes Reviewed International journal

Takao Shimayoshi, Yuta Yamamoto, Tetsuya Matsuda

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2018-July 4540 - 4543 2018.10

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

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

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

The past, current, and future of our email services in Kyushu University Reviewed

Yoshiaki Kasahara, Takao Shimayoshi, Eisuke Ito, Naomi Fujimura

Proceedings ACM SIGUCCS User Services Conference 103 - 106 2018.9

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

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

精緻に制御可能な恒常性のある高集積マルチアカウント型のメール基盤

松本亮介, 小田知央, 笠原義晃, 嶋吉隆夫, 金子晃介, 栗林健太郎, 岡村耕二

情報処理学会シンポジウムシリーズ(CD-ROM) 2018 ( 1 ) 1383 - 1389 2018.6

Flexible Hosting/Cloud Platform Based on Light-Weight Containers and its Evaluation and Stress Test Environment

笠原義晃, 松本亮介, 近藤宇智朗, 小田知央, 嶋吉隆夫, 金子晃介, 岡村耕二

IEICE technical report 117 ( 471 ) 9 - 14 2018.3

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.

A Design of Elaborately Analyzable Homeostatic E-mail System

松本亮介, 小田知央, 笠原義晃, 嶋吉隆夫, 金子晃介, 栗林健太郎, 岡村耕二

IEICE technical report 117 ( 471 ) 97 - 102 2018.3

Our experience with introducing microsoft office 365 in Kyushu University Reviewed

Yoshiaki Kasahara, Takao Shimayoshi, Masahiro Obana, Naomi Fujimura

Proceedings ACM SIGUCCS User Services Conference Part F131713 109 - 112 2017.10

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

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

A computational model of myocardial microcirculation including interstitial flow Reviewed International journal

Takao Shimayoshi, Yuta Yamamoto, Tetsuya Matsuda

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2017 3668 - 3671 2017.9

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

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

Application of the Kalman Filter for Faster Strong Coupling of Cardiovascular Simulations Reviewed International journal

Yuki Hasegawa, Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

IEEE Journal of Biomedical and Health Informatics 20 ( 4 ) 1100 - 1106 2016.7

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

左心室拍動シミュレーションにおけるメッシュ分割の影響 Reviewed

嶋吉隆夫, 小川貴史, 松田哲也

J99-D ( 5 ) 571 - 578 2016.5

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)

Modeling analysis of inositol 1,4,5-trisphosphate receptor-mediated ca²⁺ mobilization under the control of glucagon-like peptide-1 in mouse pancreatic β-cells Reviewed International journal

Yukari Takeda, Takao Shimayoshi, George G. Holz, Akinori Noma

American Journal of Physiology - Cell Physiology 310 ( 5 ) C337 - C347 2016.3

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

Simulation system for multiscale biological function models that require complex calculation scheme Reviewed

Akira Amano, Florencio Punzalan Rusty, Takao Shimayoshi, Yoshitoshi Kunieda

Transactions of Japanese Society for Medical and Biological Engineering 53 ( 3 ) 115 - 122 2015.10

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

Quantitative decomposition of dynamics of mathematical cell models: Method and application to ventricular myocyte models Reviewed International journal

Takao Shimayoshi, Chae Young Cha, Akira Amano

PLoS ONE 10 ( 6 ) e0124970 2015.6

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

Efficient Algorithm for Extracting the Multiple Loop Structure of the Corresponding Calculation Program from the Complex Recurrence Relation Equation

KOMIYAMA SHIGERU, TATARA TAIKI, PUNZALAN FLORENCIO RUSTY, SHIMAYOSHI TAKAO, KUNIEDA YOSHITOSHI, AMANO AKIRA

電子情報通信学会技術研究報告 114 ( 514(MBE2014 116-179) ) 111 - 116 2015.3

Nonlinear multiscale circulation model reproducable linear end-systolic pressure-volume relationship Reviewed International journal

Takao Shimayoshi, Mitsuharu Mishima, Akira Amano, Tetsuya Matsuda

2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC 2014 2014 6778 - 6781 2014.11

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

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

A study on the relationship between electrical transmural heterogeneity and ventricular energetics Reviewed

Yuki Hasegawa, Mitsuharu Mishima, Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

Transactions of Japanese Society for Medical and Biological Engineering 52 ( 3 ) 129 - 135 2014.9

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

An effect of meshing on coupling simulation of left ventricular wall motion Reviewed

Takafumi Ogawa, Takao Shimayoshi, Naoki Kida, Taiji Adachi, Tetsuya Matsuda

Transactions of Japanese Society for Medical and Biological Engineering 52 ( Supplement ) O-186 - O-187 2014.8

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

A simulation model of myocardial microcirculation for local distribution of oxygen consumption Reviewed

Takao Shimayoshi, Yuuta Kubota, Akira Amano, Tetsuya Matsuda

Transactions of Japanese Society for Medical and Biological Engineering 51 ( 4 ) 248 - 253 2013.8

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

A study on the relationship between electrical transmural heterogeneity and ventricular energetics Reviewed International journal

Yuki Hasegawa, Mitsuharu Mishima, Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2013 6854 - 6857 2013.7

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

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

Code generator for distributed parameter biological model simulation with PDE numerical schemes Reviewed International journal

Florencio Rusty Punzalan, Yoshiharu Yamashita, Masanari Kawabata, Takao Shimayoshi, Hiroaki Kuwabara, Yoshitoshi Kunieda, Akira Amano

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2013 1494 - 1497 2013.7

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

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

Theoretical analysis on the relationship between left ventricular energetic efficiency and acute infarct size Reviewed International journal

Takao Shimayoshi, Yuki Hasegawa, Mitsuharu Mishima, Tetsuya Matsuda

IET Systems Biology 7 ( 3 ) 74 - 78 2013.6

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

形式的記述された組織・臓器モデルのための汎用シミュレーションシステム

AMANO AKIRA, SHIMAYOSHI TAKAO, KUNIEDA YOSHITOSHI

心電図 33 ( Supplement 2 ) 59 2013.5

Implementation of a Ventricular Cell Model to a Cardiovascular Model Regulated by the Autonomic Nervous System

Yukiko Himeno, Takao Shimayoshi, Akinori Noma, Akira Amano

JOURNAL OF PHYSIOLOGICAL SCIENCES 63 ( Suppl 1 ) S234 - S234 2013.1

Distributed Parameter Biological Function Model Simulation with User-Provided PDE Numerical Solution Scheme Reviewed

Rusty Punzalan Florencio, YAMASHITA Yoshiharu, KAWABATA Masanari, SHIMAYOSHI Takao, KUWABARA Hiroaki, KUNIEDA Yoshitoshi, AMANO Akira

Transactions of Japanese Society for Medical and Biological Engineering 50 ( 6 ) 666 - 674 2012.12

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

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

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

A CellML simulation compiler and code generator using ODE solving schemes Reviewed International journal

Punzalan, F.R., Yamashita, Y., Soejima, N., Kawabata, M., Shimayoshi, T., Kuwabara, H., Kunieda, Y., Amano, A.

Source Code for Biology and Medicine 7 ( 1 ) 11 - 11 2012.10

Language：English Publishing type：Research paper (scientific journal)

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

A coupling method for a cardiovascular simulation model which includes the Kalman Filter Reviewed International journal

Yuki Hasegawa, Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2012 1222 - 1225 2012.8

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

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

A program code generator for multiphysics biological simulation using markup languages Reviewed International journal

Akira Amano, Masanari Kawabata, Yoshiharu Yamashita, Florencio Rusty Punzalan, Takao Shimayoshi, Hiroaki Kuwabara, Yoshitoshi Kunieda

Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS 2012 6624 - 6627 2012.8

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

連成循環動態シミュレーションモデルにおける数値法

長谷川雄基, 嶋吉隆夫, 天野晃, 松田哲也

第51回生体医工学会大会 2012.5

A CellML Simulation Code Generator using ODE Solving Scheme Description Reviewed

YAMASHITA Yoshiharu, SOEJIMA Naoki, KAWABATA Masanari, Punzalan Florencio Rusty, SHIMAYOSHI Takao, KUWABARA Hiroaki, KUNIEDA Yoshitoshi, AMANO Akira

Transactions of Japanese Society for Medical and Biological Engineering 50 ( 1 ) 68 - 77 2012.2

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

A Computational Model of Infantile Cardiovascular Dynamics for Cardiac Function Assessment Reviewed

WANG Yuwen, SHIMAYOSHI Takao, AMANO Akira, MATSUDA Tetsuya

The IEICE transactions on information and systems (Japanese edetion) 95 ( 2 ) 331 - 338 2012.2

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.

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

A general CellML simulation code generator using ODE solving scheme description. Reviewed International journal

Amano, A., Soejima, N., Shimayoshi, T., Kuwabara, H., Kunieda, Y.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 2011 940 - 944 2011.8

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

A study on prediction methods for a cardiovascular strong-coupling simulation. Reviewed International journal

Hasegawa, Y., Shimayoshi, T., Amano, A., Matsuda, T.

Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 2011 137 - 140 2011.8

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

Efficient Configuration of Solvable Calculation Condition for Differential Algebraic Equations in Cell Models Reviewed

嶋吉隆夫, 天野晃, 松田哲也

情報処理学会論文誌 52 ( 8 ) 2412 - 2421 2011.8

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.

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

Time-dependent changes in membrane excitability during glucose-induced bursting activity in pancreatic beta cells Reviewed International journal

Chae Young Cha, Enrique Santos, Akira Amano, Takao Shimayoshi, Akinori Noma

JOURNAL OF GENERAL PHYSIOLOGY 138 ( 1 ) 39 - 47 2011.7

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

イオンチャンネルやトランスポーターの膜電位変化への定量的寄与度;リードポテンシャル解析法 Invited

車采映, 姫野友紀子, 嶋吉隆夫, 天野晃, 野間昭典

日本生理学雑誌 72 ( 5 ) 146 2010.5

Construction of Myocardial Cell Model Including Glycolysis Model for Reproducing Hypoxic Reaction Reviewed

AMANO Akira, TOMITA Sachiko, MATSUOKA Satoshi, SHIMAYOSHI Takao, LU Jianyin, MATSUDA Tetsuya

The IEICE transactions on information and systems 93 ( 3 ) 398 - 408 2010.3

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

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.

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

A Novel Method to Quantify Contribution of Channels and Transporters to Membrane Potential Dynamics Reviewed International journal

Chae Young Cha, Yukiko Himeno, Takao Shimayoshi, Akira Amano, Akinori Noma

BIOPHYSICAL JOURNAL 97 ( 12 ) 3086 - 3094 2009.12

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

Analysis of the underlying mechanism of frank-starling law of a constructive hemodynamics model Reviewed

Mitsuharu Mishima, Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

Asia Simulation Conference 2009, JSST 2009 2009.10

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

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.

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

膵β細胞シミュレーションモデルによる膜電位オシレーション機構の解析

中村靖彦, 藤本新平, WANG Jian‐Wu, 姫野友紀子, CHA Chae Young, 嶋吉隆夫, 野間昭典, 稲垣暢也

生化学 ROMBUNNO.4T6A-13 2009.9

Evaluation of Cardiac Oxygen Consumption under Hypoxia with Tissue Model integrating Microcirculation Model and Cell Model Reviewed International journal

Akira Amano, Yuuta Kubota, Takao Shimayoshi, Tetsuya Matsuda

2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 2009 3885 - 3888 2009.9

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

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

A Method for Analysis of Simultaneous Equations in Cell Models Reviewed International journal

Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 2009 2343 - 2346 2009.9

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

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

Estimating Contribution Of Individual Ionic Components To The Cardiac Pacemaker Potential

Yukiko Himeno, Chae Young Cha, Takao Shimayoshi, Yasuhiko Nakamura, Jian-Wu Wang, Akinori Noma, Nobuya Inagaki

BIOPHYSICAL JOURNAL 96 ( 3 ) 259A - 259A 2009.2

EVALUATION OF CELL AND TISSUE HYPOXIC REACTION - MODEL STUDY Reviewed

Akira Amano, Yuuta Kubota, Takao Shimayoshi, Tetsuya Matsuda

JOURNAL OF PHYSIOLOGICAL SCIENCES 59 261 - 261 2009.1

COMPARING CONTRIBUTIONS OF EACH IONIC COMPONENT TO CARDIAC PACEMAKER POTENTIAL BETWEEN DIFFERENT MODELS USING THE LEAD POTENTIAL ANALYSIS Reviewed

Yukiko Himeno, Chae Young Cha, Takao Shimayoshi, Akinori Noma, Nobuya Inagaki

JOURNAL OF PHYSIOLOGICAL SCIENCES 59 259 - 259 2009.1

A NOVEL METHOD TO QUANTIFY CONTRIBUTION OF CELLULAR COMPONENTS TO AUTOMATIC CHANGES OF MEMBRANE POTENTIAL IN MATHEMATICAL MODELS Reviewed

Chae Young Cha, Yukiko Himeno, Takao Shimayoshi, Akinori Noma

JOURNAL OF PHYSIOLOGICAL SCIENCES 59 260 - 260 2009.1

An Approximation Model of Myocardial Crossbridge for Weak Coupling Calculation of Left Ventricle Model and Circulation Model Reviewed International journal

Akira Amano, Yasuhiro Takada, Jianyin Lu, Takao Shimayoshi, Tetsuya Matsuda

2008 30TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-8 2008 957 - 960 2008.8

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

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

A Model for Simulation of Infant Cardiovascular Response to Orthostatic Stress Reviewed

AMANO Akira, NOBUAKI Yutaka, SHIMAYOSHI Takao, LU Jianyin, SHIM Eun B., MATSUDA Tetsuya

The IEICE transactions on information and systems (Japanese edition) 91 ( 8 ) 2177 - 2187 2008.8

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.

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

形式的記述による細胞シミュレーションの効率化

嶋吉隆夫, 天野晃, 松田哲也

心電図 28 ( Supplement 1 ) S.1.79 2008.3

A Simulation Method of Cell Physiological Experiments with a Novel Description Language for Experimental Protocols Reviewed

SHIMAYOSHI Takao, AMANO Akira, MATSUDA Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering 46 ( 1 ) 77 - 84 2008.2

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

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

The Influence of Activation Time on Left Ventricular Wall Motion : Simulation Study of Ring Shape Left Ventricular Model Reviewed

TAKADA Yasuhiro, AMANO Akira, SONG Inhwan, LU Jianyin, SHIMAYOSHI Takao, ISHIKAWA Satoshi, KOTERA Hidetoshi, MATSUDA Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering 46 ( 1 ) 85 - 92 2008.2

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

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

DynaBioS : A Platform for Cell/Biodynamics Simulators Reviewed

SHIMAYOSHI Takao, HORI Kenta, LU Jianyin, AMANO Akira, MATSUDA Tetsuya, NOMA Akinori

IEEJ Transactions on Electronics, Information and Systems 127 ( 11 ) 1928 - 1936 2007.11

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

The cross-bridae dynamics during ventricular contraction predicted by coupling the cardiac cell model with a circulation model Reviewed

Eun Bo Shim, Akira Amano, Takayuki Takahata, Takao Shimayoshi, Akinori Noma

JOURNAL OF PHYSIOLOGICAL SCIENCES 57 ( 5 ) 275 - 285 2007.10

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

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

A generic representation format of physiological experimental protocols for computer simulation using ontology Reviewed

Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 2007 382 - 385 2007.8

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

Infant circulation model based on the electrophysiological cell model Reviewed

Yutaka Nobuaki, Akira Amano, Takao Shimayoshi, Jianyin Lu, Eun B. Shim, Tetsuya Matsuda

Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 2007 1010 - 1013 2007.8

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

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

A model for simulation of infant cardiovascular response to orthostatic stress Reviewed

Yutaka Nobuaki, Akira Amano, Takao Shimayoshi, Jianyin Lu, Eun B. Shim, Tetsuya Matsuda

FUNCTIONAL IMAGING AND MODELING OF THE HEART, PROCEEDINGS 4466 190 - 199 2007.6

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

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

Stress Distribution in a Cylinder and a Measurement-based Left Ventricular Shape Model Reviewed

TAKADA Yasuhiro, LU Jianyin, SHIMAYOSHI Takao, ISHIKAWA Satoshi, AMANO Akira, KOTERA Hidetoshi, MATSUDA Tetsuya

Transactions of Japanese Society for Medical and Biological Engineering 44 ( 4 ) 613 - 620 2006.12

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

Other Link： http://search.jamas.or.jp/link/ui/2007253872

A Method to Support Cell Physiological Modelling Using Description Language and Ontology Reviewed

Shimayoshi Takao, Komurasaki Kazuhiro, Amano Akira, Iwashita Takeshi, Matsuda Tetsuya, Kanazawa Masanori

IPSJ Digital Courier 2 ( 2 ) 726 - 735 2006.11

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

実心臓に基づく形状及びリング形状を用いた左心室拍動シミュレーションにおける収縮末期応力分布の比較

高田康弘, 陸建銀, 嶋吉隆夫, 石川覚志, 天野晃, 小寺秀俊, 松田哲也

生体医工学シンポジウム2006予稿集 222 2006.9

Mechanism of the Frank-Starling law - A simulation study with a novel cardiac muscle contraction model that includes titin and troponin I Reviewed International journal

Natalie S. Schneider, Takao Shimayoshi, Akira Amano, Tetsuya Matsuda

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 41 ( 3 ) 522 - 536 2006.9

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

Computer Support for Physiological Cell Modelling using an Ontology on Cell Physiology Reviewed

Shimayoshi Takao, Komurasaki Kazuhiro, Amano Akira, Iwashita Takeshi, Kanazawa Masanori, Matsuda Tetsuya

2006 International Conference of the IEEE Engineering in Medicine and Biology Society 4171 - 4174 2006.8

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

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

Reproducing nonlinear force velocity relation of myocardial tissue by a nonlinear parallel elastic component Reviewed

Yutaka Nobuaki, Yu Kamei, Jianyin Lu, Takao Shimayoshi, Satoshi Ishikawa, Akira Amano, Hidetoshi Kotera, Tetsuya Matsuda

2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15 1 612 - 615 2006.8

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

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

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

Stress distribution in a rotationally symmetric and a measurement based left ventricular shape model Reviewed

Yasuhiro Takada, Akira Amano, Jianyin Lu, Takao Shimayoshi, Satoshi Ishikawa, Tetsuya Matsuda, Hidetoshi Kotera

2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY 1 624 - 627 2006.8

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.

DOI： 10.1109/IEMBS.2006.259854

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

心筋組織における非線形張力速度関係再現のための非線形並列弾性要素モデル

信秋裕, 瓶井悠, 陸建銀, 嶋吉隆夫, 石川覚志, 天野晃, 小寺秀俊, 松田哲也

複合医工学シンポジウム予稿集, pp.172-175, 京都府京都市, 複合医工学インスティテュート 2006.5

Design of DynaBioS Architecture for Distributed Biodynamics Simulator Reviewed

Hori Kenta, Lu Jianyin, Shimayoshi Takao, Nishi Toshifumi, Ashihara Takashi, Terashima Keisuke, Amano Akira, Matsuda Tetsuya

Proceedings of the Annual Conference of the Institute of Systems, Control and Information Engineers 5 237 - 238 2005.5

A software environment for simulators suitable for complex biological analysis Reviewed

T. Shimayoshi, K. Hori, J.Y. Lu, A. Amano, T. Matsuda

The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society 26 3047 - 3050 2004.9

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

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

マルチフィジックス細胞・生体機能シミュレーションのための統合シミュレーション環境

嶋吉隆夫, 堀謙太, 陸建銀, 皿井伸明, 天野晃, 松岡達, 松田哲也

生体医工学 42 ( 特別号 ) 437 - 437 2004.5

A software environment for simulators suitable for complex biological analysis

T. Shimayoshi, K. Hori, J. Y. Lu, A. Amano, T. Matsuda

Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings 26 IV 3047 - 3050 2004

Publishing type：Research paper (international conference proceedings)

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.

階層符号化を用いた受信能力の異なる複数の受信者に対応できるマルチキャスト ATM上での階層符号化によるQoS選択可能な資源予約方法 (文部省S)

SHIMAYOSHI TAKAO, FUJIKAWA KENJI, IKEDA KATSUO

ATM網におけるインターネット技術を基盤とした多地点・多品質同時伝送方式平成9-11年度 No.09305027 97 - 98 2000

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