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Transplantation of human kidney organoids elicited a robust allogeneic response in a humanized mouse model

Kidney International 2025年第6期107卷 1011-1016页

作者： Mon-Wei Yu, Samuel Choi, John Yongjoon Kady, Jamie De Cos, Marina Wong, Jenny S. King, Emily Younis, Nour Al Rahy, Nadim Al Chaar, Soltan Djebli, Houda Eskandari, Siawosh Samuel, Stephen Merhej, Tamara Sukumar, Nivedha Lin, Jia-Ren Chen, Jia-Yun Xu, Yilin Santagata, Sandro Weins, Astrid Yeung, Melissa Cravedi, Paolo Campbell, Kirk N. Lemos, Dario Bonventre, Joseph V. Brehm, Michael A. Azzi, Jamil Department of Medicine Nephrology Division Mount Sinai Hospital New York NY United States Department of Medicine Renal Division Brigham and Women's Hospital Harvard Medical School Boston MA United States Program in Molecular Medicine Diabetes Center of Excellence University of Massachusetts Chan Medical School Worcester MA United States Doctoral School of Science and Technology Lebanese University Beirut Lebanon Institute of Biological Science Faculty of Medical Sciences Mohammed VI Polytechnic University Benguerir Morocco Department of Biotechnology Northeastern University Boston MA United States Department of Systems Biology Harvard Medical School Boston MA United States Department of Pathology Brigham and Women's Hospital Harvard Medical School Boston MA United States Harvard Stem Cell Institute Cambridge MA United States Department of Medicine Division of Engineering in Medicine Brigham and Women's Hospital Harvard Medical School Boston MA United States

Human kidney organoids derived from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have become novel tools for studying various kidney pathologies. Here, we transplanted ESC-derived kidney organoids into humanized mice with a mature human adaptive immune system developed through thymic education. As judged by histology and immunophenotyping, the transplanted HLA-mismatched kidney organoids trigged a robust alloimmune response, characterized by a dense immune cell infiltrate and enhanced memory T cell phenotype in the allograft 30 days post-transplantation. Multiplexed immunofluorescence revealed expression of functional markers of various immune cell infiltrates in response to organoid allografts, mimicking the T cell-mediated rejection process in humans. This validated our model as a novel platform to study various therapeutic strategies to control alloimmunity. Splenocytes isolated from organoid-transplanted hosts showed an alloantigen-specific memory response against 2D kidney organoids ex vivo. Overall, our study indicates that transplanting kidney organoids in humanized mice may be a valuable tool for studying human allogeneic immunity. © 2025 International Society of Nephrology

关键词： human kidney organoids humanized mice model kidney transplantation

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Supply Chain Sustainability in Disruption: SC Intelligence, Customer Knowledge Transfer, and the Mediating Role of IS/IT

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IEEE engineering Management Review 2025年

作者： Ratna, Silvia Saide, Saide Rater, Salya Svyazhanovna, Baizakova Saule Herzavina, Herzavina Faculty of Information Technology Department of Informatics Engineering and Department of Information Systems Banjarmasin Indonesia State Islamic University of Sultan Syarif Kasim Riau Universitas Islam Negeri Sultan Syarif Kasim Riau-UIN SUSKA Riau Department of Information Systems Faculty of Science and Technology Indonesia PRO Knowledge Indonesia Pekanbaru Indonesia Universitas Pahlawan Tuanku Tambusai Indonesia Lembaga Enreach UIN Suska Riau Indonesia Politeknik Aceh Selatan Department of Informatics Engineering Aceh Indonesia Information Communication Technologies Robotics in Arkalyk Pedagogical Institute Master of Natural Sciences Educational Program for the Informatics Computer Science Kazakhstan Universitas Pahlawan Tuanku Tambusai Department of Informatics Engineering Indonesia National Taiwan University of Science and Technology Taiwan

Knowledge resource and information system/technology (IS/IT) capability have been considered to improve firm performance, however there is still a gap regarding the sustainability of supply chain to face and recover from disruption (e.g., COVID-19). Questionnaire-based surveys was adopted and received feedback from sixty (160) Indonesian companies or about 28.07% of response rate. © 1973-2011 IEEE.

关键词： customer knowledge transfer disruption information system/technology (IS/IT) responding knowledge management resource-based view (RBV) Supply chain (SC) sustainability supply chain knowledge transfer

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Enhancing Diagnostic Accuracy for Knee Osteoarthritis Using a Deep Learning Approach

Enhancing Diagnostic Accuracy for Knee Osteoarthritis Using ...

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International Symposium on Applied science 2024, ISAS 2024

作者： Raza, Aquib Ching, Congo Tak Shing Liu, Peng-Ta Phan, Thien-Luan Tran, Ngoc-Luan Nguyen, Ha Anh T. Rameez, Mohammad Li, Hung-Chung Linh, Dao Nguyen Phuong Van Hieu, Nguyen Tran, Trung Nghia National Taiwan University Taipei City10673 Taiwan Research Center for Information Technology Academia Sinica Taipei City11529 Taiwan Graduate Institute of Biomedical Engineering National Chung Hsing University Taichung402 Taiwan Department of Electrical Engineering National Chi Nan University Nantou County Taiwan Advanced Plant and Food Crop Biotechnology Center National Chung Hsing University Taichung402 Taiwan International Doctoral Program in Agriculture National Chung Hsing University Taichung402 Taiwan Fall Prevention Center Department of Physical Medicine & Rehabilitation Changhua Christian Hospital Changhua500 Taiwan Department of Physics and Electronic Engineering University of Science Vietnam National University - Ho Chi Minh City Ho Chi Minh City70000 Viet Nam Department of Computer Science University of York York HeslingtonYO10 5DD United Kingdom Undergraduate Program of Intellectual Creativity Engineering National Chung Hsing University Taichung402 Taiwan Ho Chi Minh City72409 Viet Nam HCMUT Vietnam National University Ho Chi Minh City Thu Duc Ho Chi Minh City71308 Viet Nam

This research introduces a deep learning framework that combines convolutional neural networks with autoencoders to improve the diagnostic accuracy of knee osteoarthritis. The study utilized a publicly available dataset from the Mendeley Data repository, where knee joint images were preprocessed using Contrast Limited Adaptive Histogram Equalization to enhance contrast and ensure consistent image sizing. Initially, an autoencoder was employed in an unsupervised manner to learn compressed representations of the data. These representations were then used to train a CNN to classify knee images into 'healthy' and 'osteoarthritic' categories. The model was trained using an 80:20 split for training and testing data, incorporating early stopping and data augmentation techniques to prevent overfitting and enhance generalization. Performance metrics such as accuracy, precision, recall, and the area under the Receiver Operating Characteristic curve (ROCAUC) were used to evaluate the model, resulting in a high test accuracy of 98.95%. The high precision and recall rates further confirmed the model's robustness in diagnosing KOA. To enhance interpretability, Gradient-weighted Class Activation Mapping (Grad-CAM) was applied to identify critical regions in the images that influenced the model's decisions. Additionally, t-Distributed Stochastic Neighbor Embedding (t-SNE) was used to visualize the high-dimensional encoded features in a two-dimensional space, providing deeper insights into how the model differentiates between classes. The promising results of this deep learning approach suggest its potential for broader applications in medical imaging diagnostics. By providing healthcare professionals with a tool that enhances diagnostic accuracy and operational efficiency, this framework lays the foundation for developing scalable, AI-driven diagnostic systems for various complex medical conditions. © 2025 Institute of Physics Publishing. All rights reserved.

关键词： Joints (anatomy)

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Assistive technology with device for self-inflating bag in neonatology

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Research on Biomedical engineering 2025年第2期41卷

作者： Marcelino, Ana Carolina Rodovanski, Giovana Pascoali Bonetti, Karoline Panes, Caio Rabinovich de Almeida Martins, Fernando Moran, Cristiane Aparecida Araranguá Brazil Graduate Program in Neurosciences and Behavior Department of Experimental Psychology of the Institute of Psychology-University of São Paulo Sao Paulo Brazil Araranguá Brazil Computer Engineering Instituto Mauá de Tecnologia São Caetano do Sul Brazil Electronic Engineering and Computing with Emphasis on Electronic Devices and Systems at Instituto Tecnológico de Aeronáutica–ITA São Caetano do Sul Brazil Department of Physiotheraphy and at the Postgraduate Program in Rehabilitation Science of the Federal University of Santa Catarina-UFCS Ararangua Brazil

Purpose: The objectives of this study were to create a device with technological development of the self-inflating bag (SIB) equipment to measure the variables tidal volume, peak inspiratory pressure, and inspiratory flow and to evaluate the knowledge of undergraduate students in handling the SIB. To reduce the risks of mortality, length of hospital stay, and infections, SIB is a resource used to ventilate the patient through the inflation of the device, but it is not capable of measuring the ventilatory parameters. Excess ventilation and incorrect handling of the bag can cause lung injury in newborns. Therefore, measuring these parameters can prevent lung injury resulting from inadequate ventilation. Method: This is a cross-sectional and experimental study, with the development of a device SIB that allows the evaluation of variables of neonatal respiratory mechanics that were tested with an artificial lung. It was approved by the Research Ethics Committee and the research was developed in three stages: the first represents the search for scientific articles for the consensus of neonatal ventilatory variables for the construction of the SIB parameters;the second stage depicts the technological development of a device capable of monitoring such variables through the SIB. In the third stage, the content validation of the device with the handling of the SIB was carried out by students of medicine and physiotherapy courses of Brazil. Results: In this work, a device that analyzes the values of the main ventilatory parameters in neonatology was developed and to generate a safety range for the use of the device, curves with a tolerance of 10% up and down were created. All electronic components were coupled to the equipment, with a display that transmits the parameter values. The web page can be used on a cell phone, tablet, computer, or SmartTv, as long as it is connected to the "RespiratorIoT_AP" network. Among the 29 participants in the study, 8 said they were familiar w

关键词： Students

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Artificial intelligence for modelling infectious disease epidemics

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Nature 2025年第8051期638卷 623-635页

作者： Kraemer, Moritz U. G. Tsui, Joseph L.-H. Chang, Serina Y. Lytras, Spyros Khurana, Mark P. Vanderslott, Samantha Bajaj, Sumali Scheidwasser, Neil Curran-Sebastian, Jacob Liam Semenova, Elizaveta Zhang, Mengyan Unwin, H. Juliette T. Watson, Oliver J. Mills, Cathal Dasgupta, Abhishek Ferretti, Luca Scarpino, Samuel V. Koua, Etien Morgan, Oliver Tegally, Houriiyah Paquet, Ulrich Moutsianas, Loukas Fraser, Christophe Ferguson, Neil M. Topol, Eric J. Duchêne, David A. Stadler, Tanja Kingori, Patricia Parker, Michael J. Dominici, Francesca Shadbolt, Nigel Suchard, Marc A. Ratmann, Oliver Flaxman, Seth Holmes, Edward C. Gomez-Rodriguez, Manuel Schölkopf, Bernhard Donnelly, Christl A. Pybus, Oliver G. Cauchemez, Simon Bhatt, Samir Pandemic Sciences Institute University of Oxford Oxford United Kingdom Department of Biology University of Oxford Oxford United Kingdom Department of Electrical Engineering and Computer Science University of California Berkeley Berkeley CA United States UCSF UC Berkeley Joint Program in Computational Precision Health Berkeley CA United States Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan Section of Epidemiology Department of Public Health University of Copenhagen Copenhagen Denmark Oxford Vaccine Group University of Oxford and NIHR Oxford Biomedical Research Centre Oxford United Kingdom Department of Epidemiology and Biostatistics Imperial College London London United Kingdom Department of Computer Science University of Oxford Oxford United Kingdom School of Mathematics University of Bristol Bristol United Kingdom MRC Centre for Global Infectious Disease Analysis School of Public Health Imperial College London London United Kingdom Department of Statistics University of Oxford Oxford United Kingdom Doctoral Training Centre University of Oxford Oxford United Kingdom Institute for Experiential AI Northeastern University MA Boston Thailand Santa Fe Institute Santa Fe NM United States World Health Organization Regional Office for Africa Brazzaville Congo WHO Hub for Pandemic and Epidemic Intelligence Health Emergencies Programme World Health Organization Berlin Germany Centre for Epidemic Response and Innovation (CERI) School for Data Science and Computational Thinking Stellenbosch University Stellenbosch South Africa African Institute for Mathematical Sciences (AIMS) South Africa Muizenberg Cape Town South Africa Genomics England London United Kingdom Scripps Research La Jolla CA United States Department of Biosystems Science and Engineering ETH Zürich Basel Switzerland Swiss Institute of Bioinformatics Lausanne Switzerland The Ethox Centre Nuffield

Infectious disease threats to individual and public health are numerous, varied and frequently unexpected. Artificial intelligence (AI) and related technologies, which are already supporting human decision making in economics, medicine and social science, have the potential to transform the scope and power of infectious disease epidemiology. Here we consider the application to infectious disease modelling of AI systems that combine machine learning, computational statistics, information retrieval and data science. We first outline how recent advances in AI can accelerate breakthroughs in answering key epidemiological questions and we discuss specific AI methods that can be applied to routinely collected infectious disease surveillance data. Second, we elaborate on the social context of AI for infectious disease epidemiology, including issues such as explainability, safety, accountability and ethics. Finally, we summarize some limitations of AI applications in this field and provide recommendations for how infectious disease epidemiology can harness most effectively current and future developments in AI. © Springer Nature Limited 2025.

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Pan-cancer analysis of CDC7 in human tumors: Integrative multi-omics insights and discovery of novel marine-based inhibitors through machine learning and computational approaches

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computers in Biology and Medicine 2025年 190卷 110044-110044页

作者： Saif, Ahmed Islam, Md. Tarikul Raihan, Md. Obayed Yousefi, Niloofar Rahman, Md. Ajijur Faridi, Hafeez Hasan, Al Riyad Hossain, Mirza Mahfuj Saleem, Rasha Mohammed Albadrani, Ghadeer M. Al-Ghadi, Muath Q. Ahasan Setu, Md. Ali Kamel, Mohamed Abdel-Daim, Mohamed M. Aktaruzzaman, Md. Department of Pharmacy Faculty of Science University of Rajshahi Rajshahi6205 Bangladesh Department of Genetic Engineering and Biotechnology Faculty of Biological Science and Technology Jashore University of Science and Technology Jashore7408 Bangladesh Jashore7408 Bangladesh Department of Pharmaceutical Sciences College of Health Sciences and Pharmacy Chicago State University ChicagoIL United States Department of Industrial Engineering and Management Systems University of Central Florida USA OrlandoFL United States Department of Pharmacy Faculty of Biological Science and Technology Jashore University of Science and Technology Jashore7408 Bangladesh Department of Computer Science and Engineering Faculty of Engineering and Technology Jashore University of Science and Technology Jashore7408 Bangladesh Department of Laboratory Medicine Faculty of Applied Medical Sciences Al-Baha University Al-Baha65431 Saudi Arabia Department of Biology College of Science Princess Nourah bint Abdulrahman University 84428 Riyadh11671 Saudi Arabia Department of Zoology College of Science King Saud University P.O. Box 2455 Riyadh11451 Saudi Arabia Department of Microbiology Faculty of Biological Science and Technology Jashore University of Science and Technology Jashore7408 Bangladesh Department of Medicine and Infectious Diseases Faculty of Veterinary Medicine Cairo University Giza12211 Egypt Department of Pharmaceutical Sciences Pharmacy Program Batterjee Medical College P.O. Box 6231 Jeddah21442 Saudi Arabia Pharmacology Department Faculty of Veterinary Medicine Suez Canal University Ismailia41522 Egypt

Cancer remains a significant global health challenge, with the Cell Division Cycle 7 (CDC7) protein emerging as a potential therapeutic target due to its critical role in tumor proliferation, survival, and resistance. However, a comprehensive analysis of CDC7 across multiple cancers is lacking, and existing therapeutic options have come with limited clinical success. The aim of this is to integrate a comprehensive pan-cancer analysis of CDC7 with the identification of novel marine-derived inhibitors, bridging the understanding of CDC7's role as a prognostic biomarker and therapeutic target across diverse cancer types. In this study, we conducted a pan-cancer analysis of CDC7 across 33 tumor types using publicly available datasets to evaluate its expression, genetic alterations, immune interactions, survival, and prognostic significance. Additionally, a marine-derived compound library of 31,492 molecules was screened to identify potential CDC7 inhibitors using chemoinformatics and machine learning. The top candidates underwent rigorous evaluations, including molecular docking, pharmacokinetics, toxicity, Density Functional Theory (DFT) calculations, and Molecular Dynamics (MD) simulations. The findings revealed that CDC7 is overexpressed in several cancers and is associated with poor survival outcomes and unfavorable prognosis. Enrichment analysis linked CDC7 to critical DNA replication pathways, while its role in modulating tumor-immune interactions highlighted its potential as a target for immunotherapy. Among all tested compounds, Tetrahydroaltersolanol D (CMNPD21999) exhibited the strongest binding affinity and stability, along with better drug-likeness and zero toxicity. These attributes highlight its potential as a promising drug candidate for CDC7 inhibition and future cancer treatment development. Furthermore, additional in vitro and in vivo studies are required to confirm the effectiveness of this drug candidate against the CDC7 protein. © 2025

关键词： Gene expression

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Testing the Inference Accuracy of Accelerator-Friendly Approximate Phylogeny Tracking

Testing the Inference Accuracy of Accelerator-Friendly Appro...

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Computational Intelligence in Artificial Life and Cooperative Intelligent systems (ALIFE-CIS), IEEE Symposium on

作者： Matthew Andres Moreno Anika Ranjan Emily Dolson Luis Zaman Department of Ecology and Evolutionary Biology University of Michigan Ann Arbor United States Center for the Study of Complex Systems University of Michigan Ann Arbor United States Michigan Institute for Data and AI in Society University of Michigan Ann Arbor United States Undergraduate Research Opportunities Program University of Michigan Ann Arbor United States Department of Computer Science and Engineering Michigan State University East Lansing United States Program in Ecology Evolution and Behavior Michigan State University East Lansing United States

ISBN: (数字)9798331508371

ISBN: (纸本)9798331508388

computer simulations are an important tool for studying the mechanics of biological evolution. In particular, agent-based approaches provide an opportunity to collect high-quality records of ancestry relationships. Such phylogenies can provide insight into evolutionary dynamics within these simulations. Previous work generally tracks lineages directly, yielding an exact phylogenetic record of evolutionary history. However, challenges exist in scaling direct ancestrytracking approaches to highly-distributed, many-processor evolution in silico. An alternative approach is to estimate phylogenetic history via noncoding annotations on digital genomes, akin to how bioinformaticians build phylogenies by assessing genetic similarities between organisms. Recent work has extended this “hereditary stratigraphy” approach to support powerful hardware accelerator platforms, such as the Cerebras Wafer-Scale Engine. Although these second-generation “surface”-based hereditary stratigraphy algorithms have demonstrated order-ofmagnitude speedups over first-generation “column”-based algorithms, it remains unknown how they impact the accuracy of reconstructed phylogenies. To address this question, we assessed reconstruction accuracy under alternative configurations across a matrix of evolutionary conditions varying in selection pressure, spatial structure, and ecological dynamics. Encouragingly, we find that the second-generation approaches provide higher reconstruction quality across most surveyed conditions.

关键词： Surface reconstruction Accuracy Annotations Heuristic algorithms Computational modeling Biological system modeling Stratigraphy Phylogeny History Bars

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Testing the Inference Accuracy of Accelerator-Friendly Approximate Phylogeny Tracking

Testing the Inference Accuracy of Accelerator-Friendly Appro...

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2025 IEEE Symposium on Computational Intelligence in Artificial Life and Cooperative Intelligent systems, ALIFE-CIS 2025

作者： Moreno, Matthew Andres Ranjan, Anika Dolson, Emily Zaman, Luis University of Michigan Department of Ecology and Evolutionary Biology Ann Arbor United States Center for the Study of Complex Systems University of Michigan Ann Arbor United States Michigan Institute for Data and Ai in Society University of Michigan Ann Arbor United States Undergraduate Research Opportunities Program University of Michigan Ann Arbor United States Michigan State University Department of Computer Science and Engineering East Lansing United States Program in Ecology Evolution and Behavior Michigan State University East Lansing United States

ISBN: (纸本)9798331508371

computer simulations are an important tool for studying the mechanics of biological evolution. In particular, agent-based approaches provide an opportunity to collect high-quality records of ancestry relationships. Such phylogenies can provide insight into evolutionary dynamics within these simulations. Previous work generally tracks lineages directly, yielding an exact phylogenetic record of evolutionary history. However, challenges exist in scaling direct ancestrytracking approaches to highly-distributed, many-processor evolution in silico. An alternative approach is to estimate phylogenetic history via noncoding annotations on digital genomes, akin to how bioinformaticians build phylogenies by assessing genetic similarities between organisms. Recent work has extended this 'hereditary stratigraphy' approach to support powerful hardware accelerator platforms, such as the Cerebras Wafer-Scale Engine. Although these second-generation 'surface'-based hereditary stratigraphy algorithms have demonstrated order-ofmagnitude speedups over first-generation 'column'-based algorithms, it remains unknown how they impact the accuracy of reconstructed phylogenies. To address this question, we assessed reconstruction accuracy under alternative configurations across a matrix of evolutionary conditions varying in selection pressure, spatial structure, and ecological dynamics. Encouragingly, we find that the second-generation approaches provide higher reconstruction quality across most surveyed conditions. © 2025 IEEE.

关键词： Biostratigraphy

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Biomedical data and AI

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science China Life sciences 2025年第5期68卷 1536-1540页

作者： Hao Xu Shibo Zhou Zefeng Zhu Vincenzo Vitelli Liangyi Chen Ziwei Dai Ning Yang Luhua Lai Shengyong Yang Sergey Ovchinnikov Zhuoran Qiao Sirui Liu Chen Song Jianfeng Pei Han Wen Jianfeng Feng Yaoyao Zhang Zhengwei Xie Yang-Yu Liu Zhiyuan Li Fulai Jin Hao Li Mohammad Lotfollahi Xuegong Zhang Ge Yang Shihua Zhang Ge Gao Pulin Li Qi Liu Jing-Dong Jackie Han Peking-Tsinghua Center for Life Sciences (CLS) Academy for Advanced Interdisciplinary StudiesPeking University Center for Quantitative Biology (CQB) Academy for Advanced Interdisciplinary StudiesPeking University Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program Academy for Advanced Interdisciplinary StudiesPeking University Department of Physics University of Chicago School of Life Sciences Southern University of Science and Technology Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies College of Chemistry and Molecular Engineering Peking University Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Biology Massachusetts Institute of Technology Lambic Therapeutics Inc. Changping Laboratory Al for Science Institute Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Fudan University Department of Obstetrics and Gynecology West China Second University HospitalSichuan University Peking University International Cancer Institute and Peking University-Yunnan Baiyao International Medical Institute and State Key Laboratory of Natural and Biomimetic Drugs Department of Molecular and Cellular PharmacologySchool of Pharmaceutical SciencesPeking University Health Science CenterPeking University Channing Division of Network Medicine Department of MedicineBrigham and Women's Hospital and Harvard Medical School Center for Artificial Intelligence and Modeling the Carl R.Woese Institute for Genomic BiologyUniversity of Illinois Urbana-Champaign Department of Genetics and Genome Sciences School of Medicine and Department of Computer and Data Sciences and Department of Population and Quantitative Health SciencesCase Western Reserve University Department of Biochemistry and Biophysics University of California Sanger Institute Department of Automation Tsinghua University State Key Laboratory of Multimodal Artificial Intelligence Systems I

The development of artificial intelligence(AI) and the mining of biomedical data complement each other. From the direct use of computer vision results to analyze medical images for disease screening, to now integrating biological knowledge into models and even accelerating the development of new AI based on biological discoveries, the boundaries of both are constantly expanding, and their connections are becoming closer.

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CONVEXITY AND CHARACTERIZATION OF OPTIMAL POLICIES IN A DYNAMIC ROUTING PROBLEM

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JOURNAL OF OPTIMIZATION THEORY AND APPLICATIONS 1984年第1期44卷 105-136页

作者： TSITSIKLIS, JN Doctoral Student Laboratory for Information and Decision Systems Department of Electrical Engineering and Computer Science Massachusetts Institute of Technology Cambridge Massachusetts

An infinite horizon, expected average cost, dynamic routing problem is formulated for a simple failure-prone queueing system, modelled as a continuous time, continuous state controlled stochastic process. We prove that the optimal average cost is independent of the initial state and that the cost-to-go functions of dynamic programming are convex. These results, together with a set of optimality conditions, lead to the conclusion that optimal policies are switching policies, characterized by a set of switching curves (or regions), each curve corresponding to a particular state of the nodes (servers).

关键词： Stochastic control unreliable queueing systems average cost jump disturbances

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