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BigNeuron: a resource to benchmark and predict performance of algorithms for automated tracing of neurons in light microscopy datasets

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Nature methods 2023年第6期20卷 824-835页

作者： Linus Manubens-Gil Zhi Zhou Hanbo Chen Arvind Ramanathan Xiaoxiao Liu Yufeng Liu Alessandro Bria Todd Gillette Zongcai Ruan Jian Yang Miroslav Radojević Ting Zhao Li Cheng Lei Qu Siqi Liu Kristofer E Bouchard Lin Gu Weidong Cai Shuiwang Ji Badrinath Roysam Ching-Wei Wang Hongchuan Yu Amos Sironi Daniel Maxim Iascone Jie Zhou Erhan Bas Eduardo Conde-Sousa Paulo Aguiar Xiang Li Yujie Li Sumit Nanda Yuan Wang Leila Muresan Pascal Fua Bing Ye Hai-Yan He Jochen F Staiger Manuel Peter Daniel N Cox Michel Simonneau Marcel Oberlaender Gregory Jefferis Kei Ito Paloma Gonzalez-Bellido Jinhyun Kim Edwin Rubel Hollis T Cline Hongkui Zeng Aljoscha Nern Ann-Shyn Chiang Jianhua Yao Jane Roskams Rick Livesey Janine Stevens Tianming Liu Chinh Dang Yike Guo Ning Zhong Georgia Tourassi Sean Hill Michael Hawrylycz Christof Koch Erik Meijering Giorgio A Ascoli Hanchuan Peng Institute for Brain and Intelligence Southeast University Nanjing China. Microsoft Corporation Redmond WA USA. Tencent AI Lab Bellevue WA USA. Computing Environment and Life Sciences Directorate Argonne National Laboratory Lemont IL USA. Kaya Medical Seattle WA USA. University of Cassino and Southern Lazio Cassino Italy. Center for Neural Informatics Structures and Plasticity Krasnow Institute for Advanced Study George Mason University Fairfax VA USA. Faculty of Information Technology Beijing University of Technology Beijing China. Beijing International Collaboration Base on Brain Informatics and Wisdom Services Beijing China. Nuctech Netherlands Rotterdam the Netherlands. Janelia Research Campus Howard Hughes Medical Institute Ashburn VA USA. Department of Electrical and Computer Engineering University of Alberta Edmonton Alberta Canada. Ministry of Education Key Laboratory of Intelligent Computation and Signal Processing Anhui University Hefei China. Paige AI New York NY USA. Scientific Data Division and Biological Systems and Engineering Division Lawrence Berkeley National Lab Berkeley CA USA. Helen Wills Neuroscience Institute and Redwood Center for Theoretical Neuroscience UC Berkeley Berkeley CA USA. RIKEN AIP Tokyo Japan. Research Center for Advanced Science and Technology (RCAST) The University of Tokyo Tokyo Japan. School of Computer Science University of Sydney Sydney New South Wales Australia. Texas A&M University College Station TX USA. Cullen College of Engineering University of Houston Houston TX USA. Graduate Institute of Biomedical Engineering National Taiwan University of Science and Technology Taipei Taiwan. National Centre for Computer Animation Bournemouth University Poole UK. PROPHESEE Paris France. Department of Neuroscience Columbia University New York NY USA. Mortimer B. Zuckerman Mind Brain Behavior Institute Columbia University New York NY USA. Department of Computer Science Northern Illinois Universit

BigNeuron is an open community bench-testing platform with the goal of setting open standards for accurate and fast automatic neuron tracing. We gathered a diverse set of image volumes across several species that is representative of the data obtained in many neuroscience laboratories interested in neuron tracing. Here, we report generated gold standard manual annotations for a subset of the available imaging datasets and quantified tracing quality for 35 automatic tracing algorithms. The goal of generating such a hand-curated diverse dataset is to advance the development of tracing algorithms and enable generalizable benchmarking. Together with image quality features, we pooled the data in an interactive web application that enables users and developers to perform principal component analysis, t-distributed stochastic neighbor embedding, correlation and clustering, visualization of imaging and tracing data, and benchmarking of automatic tracing algorithms in user-defined data subsets. The image quality metrics explain most of the variance in the data, followed by neuromorphological features related to neuron size. We observed that diverse algorithms can provide complementary information to obtain accurate results and developed a method to iteratively combine methods and generate consensus reconstructions. The consensus trees obtained provide estimates of the neuron structure ground truth that typically outperform single algorithms in noisy datasets. However, specific algorithms may outperform the consensus tree strategy in specific imaging conditions. Finally, to aid users in predicting the most accurate automatic tracing results without manual annotations for comparison, we used support vector machine regression to predict reconstruction quality given an image volume and a set of automatic tracings.

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iSplit LBI: Individualized partial ranking with ties via split LBI

arXiv

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arXiv 2019年

作者： Xu, Qianqian Sun, Xinwei Yang, Zhiyong Cao, Xiaochun Huang, Qingming Yao, Yuan Key Lab. of Intelligent Information Processing Institute of Computing Technology CAS Microsoft Research Asia State Key Laboratory of Information Security Institute of Information Engineering CAS School of Cyber Security University of Chinese Academy of Sciences School of Computer Science and Tech. University of Chinese Academy of Sciences Key Laboratory of Big Data Mining and Knowledge Management CAS Peng Cheng Laboratory Department of Mathematics Hong Kong University of Science and Technology Hong Kong

Due to the inherent uncertainty of data, the problem of predicting partial ranking from pairwise comparison data with ties has attracted increasing interest in recent years. However, in real-world scenarios, different individuals often hold distinct preferences. It might be misleading to merely look at a global partial ranking while ignoring personal diversity. In this paper, instead of learning a global ranking which is agreed with the consensus, we pursue the tie-aware partial ranking from an individualized perspective. Particularly, we formulate a unified framework which not only can be used for individualized partial ranking prediction, but also be helpful for abnormal user selection. This is realized by a variable splitting-based algorithm called iSplitLBI. Specifically, our algorithm generates a sequence of estimations with a regularization path, where both the hyperparameters and model parameters are updated. At each step of the path, the parameters can be decomposed into three orthogonal parts, namely, abnormal signals, personalized signals and random noise. The abnormal signals can serve the purpose of abnormal user selection, while the abnormal signals and personalized signals together are mainly responsible for individual partial ranking prediction. Extensive experiments on simulated and real-world datasets demonstrate that our new approach significantly outperforms state-of-the-art alternatives. The code is now availiable at https://***/qianqianxu010/ NeurIPS2019-iSplitLBI. Copyright © 2019, The Authors. All rights reserved.

关键词： Forecasting

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Region-wise generative adversarial image inpainting for large missing areas

arXiv

引用

arXiv 2019年

作者： Ma, Yuqing Liu, Xianglong Bai, Shihao Wang, Lei Liu, Aishan Tao, Dacheng Hancock, Edwin State Key Lab of Software Development Environment Beihang University Beijing100191 China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine UBTECH Sydney Artificial Intelligence Centre School of Information Technologies Faculty of Engineering and Information Technologies University of Sydney DarlingtonNSW2008 Australia Department of Computer Science University of York York United Kingdom

Recently deep neutral networks have achieved promising performance for filling large missing regions in image inpainting tasks. They usually adopted the standard convolutional architecture over the corrupted image, leading to meaningless contents, such as color discrepancy, blur and artifacts. Moreover, most inpainting approaches cannot well handle the large contiguous missing area cases. To address these problems, we propose a generic inpainting framework capable of handling with incomplete images on both contiguous and discontiguous large missing areas, in an adversarial manner. From which, region-wise convolution is deployed in both generator and discriminator to separately handle with the different regions, namely existing regions and missing ones. Moreover, a correlation loss is introduced to capture the non-local correlations between different patches, and thus guides the generator to obtain more information during inference. With the help of our proposed framework, we can restore semantically reasonable and visually realistic images. Extensive experiments on three widely-used datasets for image inpainting tasks have been conducted, and both qualitative and quantitative experimental results demonstrate that the proposed model significantly outperforms the state-of-the-art approaches, both on the large contiguous and discontiguous missing areas. Copyright © 2019, The Authors. All rights reserved.

关键词： Generative adversarial networks

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Optimal Design of Wireless-Powered Hierarchical Fog-Cloud Computing Networks

Optimal Design of Wireless-Powered Hierarchical Fog-Cloud Co...

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IEEE Global Communications Conference

作者： Jingxian Liu Ke Xiong Derrick Wing Kwan Ng Pingyi Fan Zhangdui Zhong School of Computer and Information Technology Beijing Jiaotong University Beijing China State Key Lab of Rail Traffic Control and Safety Beijing Jiaotong University Beijing China Beijing Key Laboratory of Traffic Data Analysis and Mining Beijing Jiaotong University Beijing China School of Electrical Engineering and Telecommunications University of New South Wales NSW Australia Department of Electronic Engineering Tsinghua University Beijing China

ISBN: (数字)9781728109626

ISBN: (纸本)9781728109633

This paper investigates the optimal design of wireless-powered hierarchical fog-cloud computing networks, where energy-constrained users first harvest energy from a hybrid access point (HAP) and then offload their computation tasks to fog/cloud servers via the HAP or compute the tasks locally by using the harvested energy. An optimization problem is formulated to maximize the minimal energy balance among multiple users by jointly optimizing offloading decisions, communication and computation resource allocations in the system, where computational capacity, processing delay, energy harvesting (EH) and energy consumption constraints are considered. To efficiently solve such a mixed-integer combinatorial non-convex problem, a penalized successive convex approximation (P-SCA)-based algorithm is designed, which is able to converge to a suboptimal solution with the polynomial time computational complexity. Numerical results show that compared to communication and computation resource allocation, the offloading decision is the dominant factor on affecting the system performance. It is also found that local computing is a better choice for users with relatively poor channel gains while fog/cloud computing is a better choice for users with relatively good channel gains. Specifically, cloud computing is preferred if the cloud computational capacity is strong enough and the wired-link data rate is high enough;Otherwise, fog computing is preferred. Besides, more users are served, less max-min energy balance can be obtained.

关键词： Delays Cloud computing Servers Task analysis Edge computing Optimization Energy consumption

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Zero-determinant Strategies for Three-player in Finitely Repeated Games

Zero-determinant Strategies for Three-player in Finitely Rep...

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第37届中国控制会议

作者： Jianzhang Chen Zhihai Rong College of Computer and Information Sciences Fujian Agriculture and Forestry University CompleX Lab Web Sciences CenterUniversity of Electronic Science and Technology of China Big Data Research Center University of Electronic Science and Technology of China School of Computer Science and Engineering University of Electronic Science and Technology of China

Zero-determinant strategies are a new class of probabilistic and conditional strategies, where a player can use a linear relationship between his own payoff and the opponents payoff to determine his opponents expected payoff or extort his opponents unilaterally. This paper will analysis a model of zero-determinant strategies for three players in the finitely repeated public goods game（with a discount factor δ satisfying 0 ＜ δ ＜ 1）. Via analyzing these strategies for three players in the game, including equalizer strategies, extortion strategies and generous strategies, it finds that a player also has an ability to pin the expected total payoff of all other players in a unilateral way as the two-player model by equalizer strategies and can set a ratio between his payoff and the total payoff of all other players by the extortion strategies, and the expected payoffs of three players can obtain the same payoff when they cooperate in the first round by using generous strategies. This provides potential clues to design efficient cooperation protocol in multi-agent systems.

关键词： Zero-determinant Strategies Finitely Repeated Games Direct reciprocity Discount factor

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Assessing the Potential of GPT-4 to Annotate Medical Notes Across Different Languages and Countries: A Model Evaluation Study

SSRN

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SSRN 2024年

作者： Saad Menezes, Maria Clara Hoffman, Alexander F. Tan, Amelia L.M. Nalbandyan, Mariné Omenn, Gilbert S. Mazzotti, Diego R. Hernández-Arango, Alejandro Visweswaran, Shyam Venkatesh, Shruthi Mandl, Kenneth D. Bourgeois, Florence T. Lee, James W.K. Makmur, Andrew Hanauer, David A. Semanik, Michael G. Kerivan, Lauren T. Hill, Terra Forero, Julian Restrepo Castro, Carlos Andrés C.R. Vigna, Matteo Ceriana, Piero Abu-El-rub, Noor Avillach, Paul Bellazzi, Riccardo Callaci, Thomas Gutiérrez-Sacristán, Alba Malovini, Alberto Mathew, Jomol P. Morris, Michele Murthy, Venkatesh Parimbelli, Enea Patel, Lav P. Sáez, Carlos Samayamuthu, Malarkodi Jebathilagam Thompson, Jeffrey A. Tibollo, Valentina Xia, Zongqi Kohane, Isaac S. Harvard Medical School Department of Biomedical Informatics 10 Shattuck Street BostonMA02115 United States School of Medicine and Public Health University of Wisconsin-Madison Office of Informatics and Information Technology 750 Highland Ave MadisonWI53705 United States University of Michigan Department of Computational Medicine & Bioinformatics Internal Medicine Human Genetics Environmental Health 100 Washtenaw Avenue Ann ArborMI48109 United States University of Kansas Medical Center Division of Medical Informatics Division of Pulmonary Critical Care and Sleep Medicine Department of Internal Medicine 3901 Rainbow Blvd Kansas CityKS66160 United States University of Antioquia Hospital Alma Máter de Antioquia Department of Internal Medicine Calle 64 N°51 D - 154 Medellín Colombia University of Pittsburgh Department of Biomedical Informatics 5607 Baum Blvd PittsburghPA15206 United States University of Pittsburgh Department of Neurology 3501 5th Avenue PittsburghPA15206 United States Boston Children's Hospital Computational Health Informatics Program 300 Longwood Avenue BostonMA02115 United States Boston Children's Hospital Department of Pediatrics 300 Longwood Avenue BostonMA02115 United States National University Health System Department of Surgery 1E Kent Ridge Rd Singapore119228 Singapore National University Health System Department of Diagnostic Imaging 1E Kent Ridge Rd Singapore119228 Singapore University of Michigan Department of Learning Health Sciences NCRC 100 2800 Plymouth Road Ann ArborMI48109 United States University of Kansas Medical Center Department of Surgery 3901 Rainbow Blvd Kansas CityKS66160 United States Istituti Clinici Scientifici Maugeri IRCCS Respiratory rehabilitation unit Via Maugeri 10 Pavia27100 Italy University of Kansas Medical Center 3901 Rainbow Blvd Kansas CityKS66160 United States University of Pavia Department of Electrical Computer and Biomedical Engineering via Ferrata 5 Pavia2710

Background: Physicians invest hours creating patient notes, which are rich in information but difficult for computers to analyze due to their unstructured format. GPT-4 reshaped our ability to process text, yet it is unknown how well this model can handle medical notes. This project aims to compare GPT-4’s ability to annotate medical notes against experienced physicians across three different languages at multiple institutions and countries. Methods: This study included eight sites from four countries - the United States, Colombia, Singapore, and Italy. Each site contributed seven de-identified notes (admission, progress, or consult) from hospitalized patients. GPT-4 assessed each note by answering 14 questions, including demographic information, clinical judgments, data quality, and patients’ eligibility for a hypothetical study enrollment. For validation, two physicians from each site independently evaluated GPT-4's responses. Findings: Overall, 56 medical notes, written in English, Italian, and Spanish, were analyzed. A total of 784 responses from GPT-4 were generated. Both physicians agreed with GPT-4’s response 79% of the time (622/784, 95%CI 76-82%). Only one of the two physicians agreed with GPT-4’s response 10% of the time (82/784, 95%CI 8-13%). Neither physician agreed with GPT-4’s response 10% of the time (80/784, 95%CI 8-13%). Both physicians agreed with GPT-4 more often in notes written in Spanish and Italian than in English, with agreement rates of 88% (86/98, 95%CI 79-93%), 84% (82/98, 95%CI 75-90%), and 77% (454/588, 95%CI 74-80%), respectively. Hallucinations were rare (10/784, 95%CI 0-2%). GPT-4 correctly selected patients for a hypothetical study enrollment based on three criteria 90% of the time (95%CI 81-98%). Interpretation: The findings indicate that GPT-4 annotations demonstrated a high agreement rate with physicians across all languages. We also demonstrate GPT-4's potential to assist in patient selection for studies. Funding: None. Declarati

关键词： Medical computing

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Developments and applications of the OPTIMADE API for materials discovery, design, and data exchange

arXiv

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arXiv 2024年

作者： Evans, Matthew L. Bergsma, Johan Merkys, Andrius Andersen, Casper W. Andersson, Oskar B. Beltrán, Daniel Blokhin, Evgeny Boland, Tara M. Balderas, Rubén Castañeda Choudhary, Kamal Díaz, Alberto Díaz García, Rodrigo Domínguez Eckert, Hagen Eimre, Kristjan Montero, María Elena Fuentes Krajewski, Adam M. Mortensen, Jens Jørgen Duarte, José Manuel Nápoles Pietryga, Jacob Qi, Ji de Jesús Trejo Carrillo, Felipe Vaitkus, Antanas Yu, Jusong Zettel, Adam de Castro, Pedro Baptista Carlsson, Johan Cerqueira, Tiago F.T. Divilov, Simon Hajiyani, Hamidreza Hanke, Felix Jose, Kevin Oses, Corey Riebesell, Janosh Schmidt, Jonathan Winston, Donald Xie, Christen Yang, Xiaoyu Bonella, Sara Botti, Silvana Curtarolo, Stefano Draxl, Claudia Cobas, Luis Edmundo Fuentes Hospital, Adam Liu, Zi-Kui Marques, Miguel A.L. Marzari, Nicola Morris, Andrew J. Ong, Shyue Ping Orozco, Modesto Persson, Kristin A. Thygesen, Kristian S. Wolverton, Chris Scheidgen, Markus Toher, Cormac Conduit, Gareth J. Pizzi, Giovanni Gražulis, Saulius Rignanese, Gian-Marco Armiento, Rickard Chemin des Étoiles 8 Louvain-la-Neuve1348 Belgium Matgenix SRL 185 Rue Armand Bury Gozée6534 Belgium École Polytechnique Fédérale de Lausanne Avenue de Forel 3 Lausanne1015 Switzerland Institute of Biotechnology Life Sciences Center Vilnius University Sauletekio av. 7 VilniusLT-10257 Lithuania SINTEF P.O. Box 4760 Torgarden TrondheimNO-7465 Norway Materials Design and Informatics unit Department of Physics Chemistry and Biology Linköping University Sweden Baldiri i Reixac 10-12 Barcelona08028 Spain Tilde Materials Informatics Straßmannstraße 25 Berlin10249 Germany Materials Platform for Data Science Sepapaja 6 Tallinn15551 Estonia Computational Atomic-Scale Materials Design Technical University of Denmark Kgs. Lyngby Denmark Av. Miguel de Cervantes 120 Complejo Industrial Chihuahua Chihuahua Chih. 31136 Mexico Material Measurement Laboratory National Institute of Standards and Technology GaithersburgMD20899 United States Department of Mechanical Engineering and Materials Science Duke University DurhamNC27708 United States Center for Extreme Materials Duke University DurhamNC27708 United States École Polytechnique Fédérale de Lausanne Lausanne1015 Switzerland Universidad Autónoma de Chihuahua Facultad de Ciencias Quimicas Chihuahua31125 Mexico Department of Materials Science and Engineering The Pennsylvania State University University ParkPA16802 United States Department of Materials Science and Engineering Northwestern University EvanstonIL60208 United States Department of NanoEngineering University of California 9500 Gilman Drive La Jolla San DiegoCA92093-0448 United States National Institute for Materials Science 1-2-1 Sengen Ibaraki Tsukuba305-0047 Japan Dassault Systèmes Germany GmbH Am Kabellager 11-13 Cologne51063 Germany CFisUC Department of Physics University of Coimbra Rua Larga Coimbra3004-516 Portugal Dassault Systèmes 22 Science Park CB4 0FJ United Kingdom Theory of Condensed Matter Cavendis

The Open databases Integration for Materials Design (OPTIMADE) application programming interface (API) empowers users with holistic access to a growing federation of databases, enhancing the accessibility and discoverability of materials and chemical data. Since the first release of the OPTIMADE specification (v1.0), the API has undergone significant development, leading to the v1.2 release, and has underpinned multiple scientific studies. In this work, we highlight the latest features of the API format, accompanying software tools, and provide an update on the implementation of OPTIMADE in contributing materials databases. We end by providing several use cases that demonstrate the utility of the OPTIMADE API in materials research that continue to drive its ongoing development. © 2024, CC BY.

关键词： Electronic data interchange

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Age-Based Utility Maximization for Wireless Powered Networks: A Stackelberg Game Approach

Age-Based Utility Maximization for Wireless Powered Networks...

引用

IEEE Global Communications Conference

作者： Haina Zheng Ke Xiong Pingyi Fan Zhangdui Zhong Khaled Ben Letaief School of Computer and Information Technology Beijing Jiaotong University Beijing China Beijing Key Laboratory of Traffic Data Analysis and Mining Beijing Jiaotong University Beijing China Department of Electronic Engineering Tsinghua University Beijing China State Key Lab of Rail Traffic Control and Safety Beijing Jiaotong University Beijing China The Hong Kong University of Science and Technology Hong Kong

ISBN: (数字)9781728109626

ISBN: (纸本)9781728109633

This paper investigates the efficient cooperation in wireless-powered communication networks, where an access point (AP) and multiple helpers first together charge up a sensor via radio-frequency (RF)-based wireless power transfer (WPT), and then the sensor uses the harvested energy to transmit real-time status updates to the AP. Due to the selfishness of the helpers, payment is provided as an incentive to them by the sensor-AP communication pair. For such a system, a Stackelberg game approach is designed to establish efficient cooperation between the helpers and the sensor-AP communication pair. An Age of information (AoI)-based utility and a profit-based utility are defined for the sensor-AP pair and the helpers, respectively. Optimization problems are formulated to maximize their utilities. An explicit expression of the optimal transmit power of the helper is derived, with which a Dinkelbach's Programming (DP)-based algorithm is designed to jointly find the optimal payment price and transmit power at the AP, and at the same time, the Stackelberg equilibrium (SE) is achieved. Moreover, a closed-form expression of the minimum AoI of the system is also presented. Numerical results show that the more helpers there exist, the higher payment price the AP should fix, and meanwhile, the lower AoI of the sensor-AP communication pair can be achieved. Besides, it is shown that by increasing the transmit power at the AP, the optimal average AoI could not be reduced evidently.

关键词： Games Real-time systems Energy harvesting Wireless communication Measurement Batteries Wireless sensor networks

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The effect of non-Markovian recovery on reversible failure propagation on networks

arXiv

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arXiv 2019年

作者： Lin, Zhaohua Feng, Mi Tang, Ming Liu, Zonghua Hui, Pak Ming Lai, Ying-Cheng Department of Physics East China Normal University Shanghai200062 China School of Information Science Technology East China Normal University Shanghai200241 China Web Sciences Center University of Electronic Science and Technology of China Chengdu611731 China Big Data Research Center University of Electronic Science and Technology of China Chengdu611731 China Shanghai Key Laboratory of Multidimensional Information Processing East China Normal University Shanghai200241 China Department of Physics Chinese University of Hong Kong Shatin Hong Kong School of Electrical Computer and Energy Engineering Arizona State University TempeAZ85287 United States

Compared with the classical irreversible failure propagation, the spontaneous recovery model can better depict the failure propagation on network systems such as financial and transportation networks. In this paper, we study how the non-Markovian recovery process influences cascading failure dynamics in the spontaneous recovery systems. To this end, we compare two kinds of failure-recovery models: the non-Markovian recovery (NMR) model and the corresponding Markovian recovery (MR) model. We first develop a Pairwise approximation theory for the MR and NMR models, which can predict the time evolution, steady state, and hysteresis behaviour of failure-recovery systems more accurately than the classical mean-field (MF) method. We find that although the non-Markovian recovery mechanism does not essentially affect the steady state and hysteresis behaviour of failure-recovery systems, the two models exhibit distinct evolution processes. When investigating the effect of initial conditions on the phase transition and hysteresis behavior, we find in the hysteresis region, the NMR model exhibits a non-monotonic growth characteristic: with the increase of initial failed nodes, the steady state staying in relative low-failure phase first turns into relative high-failure phase, and then into relative low-failure phase again. We then use the MF theory to explain the phenomenon qualitatively and point out when considering non-Markovian dynamics, we should study the steady state not only from the perspective of the variation of parameters, but also from the initial conditions. Copyright © 2019, The Authors. All rights reserved.

关键词： Hysteresis

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Neuroprotective effects of Ginkgo biloba extract and GinkgoUde B against oxygen-glucose deprivation/reoxygenation and glucose injury in a new in vitro multicellular network model

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Frontiers of Medicine 2018年第3期12卷 307-318页

作者： Xiaohan Yang Tiezheng Zheng Hao Hong Nan Cai Xiaofeng Zhou Changkai Sun Liying Wu Shuhong Liu Yongqi Zhao Lingling Zhu Ming Fan Xuezhong Zhou Fengxie Jin Department of Biomedical Engineering Faculty of Electronic Information and Electrical Engineering Dalian University of Technology Dalian 116024 China Research Center for the Control Engineering of Translational Precision Medicine Dalian University of Technology Dalian 116024 China State Key Laboratory of Fine Chemicals Dalian R&D Center for Stem Cell and Tissue Engineering Dalian University of Technology Dalian 116024 China Liaoning Provincial Key Laboratory of Cerebral Diseases Institute for Brain Disorders Dalian Medical University Dalian 116044 China Institute of Basic Medical Sciences Academy of Military Medical Sciences Beijing 100850 China School of Computer and Information Technology and Beijing Key Lab of Traffic Data Analysis and Mining Beijing Jiaotong University Beijing 100044 China College of Biotecknology Dalian Polytechnic University Dalian 116034 China

Acute ischemic stroke （AIS）, as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract （GBE） against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell- astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B （GB）, against oxygenglucose deprivation/reoxygenation and glucose （OGD/R） injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein （Na-F）, and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.

关键词： acute ischemic stroke Ginkgo biloba extract Ginkgolide B network model neuroprotection

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