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System Model and Equilibrium Strategy of Mobile Users in a Hybrid Access Network

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Journal of Systems Science and Systems Engineering 2019年第2期28卷 224-237页

作者： Dongmei Zhao Shunfu Jin Wuyi Yue School of Information Science and Engineering Yanshan UniversityQinhuangdao 066000 China Department of Intelligence and Informatics Konan University Kobe Japan

Mobile users usually access the Internet via a hybrid access network, in which cellular and Wi-Fi networks are available alternatively. In the hybrid access network, a mobile user decides to send or not to send a packet according to the number of packets already in the system and the phase of the server. In order to evaluate the system performance of the hybrid access network, in this paper we first establish a fully observable continuous time Markovian queueing system. Then, we present an exact analysis to investigate the behavior of the mobile users in the network. Through iterations and diagonalization, we obtain the expected sojourn time of a newly arriving packet in a closed form. Moreover, with the monotonicity for the expected sojourn time of a newly arriving packet, we prove the existence of the NASH equilibrium strategy. Finally, we analyze the socially optimal strategy and motivate the mobile users to accept the socially optimal strategy by changing the sojourn cost.

关键词： Hybrid access network observable queueing system expected sojourn time NASH equilibriumstrategy socially optimal strategy

Non-alcoholic fatty liver disease: a narrative review of genetics

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The Journal of Biomedical Research 2018年第6期32卷 389-400页

作者： Christopher J.Danford Zemin Yao Z.Gordon Jiang Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center Department of Biochemistry Microbiology and Immunology Ottawa Institute of Systems Biology University of Ottawa

Non-alcoholic fatty liver disease(NAFLD) is now the most common cause of chronic liver diseases worldwide. It encompasses a spectrum of disorders ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis(NASH),fibrosis, cirrhosis, and hepatocellular carcinoma. One of the key challenges in NAFLD is identifying which patients will progress. Epidemiological and genetic studies indicate a strong pattern of heritability that may explain some of the variability in NAFLD phenotype and risk of progression. To date, at least three common genetic variants in the PNPLA3, TM6 SF2, and GCKR genes have been robustly linked to NAFLD in the population. The function of these genes revealed novel pathways implicated in both the development and progression of NAFLD. In addition,candidate genes previously implicated in NAFLD pathogenesis have also been identified as determinants or modulators of NAFLD phenotype including genes involved in hepatocellular lipid handling, insulin resistance,inflammation, and fibrogenesis. This article will review the current understanding of the genetics underpinning the development of hepatic steatosis and the progression of NASH. These newly acquired insights may transform our strategy to risk-stratify patients with NAFLD and to identify new potential therapeutic targets.

关键词： NAFLD NASH genetics PNPLA3 TM6SF2 GCKR MBOAT7

Non-alcoholic Fatty Liver Disease:A Clinical Update

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Journal of Clinical and Translational Hepatology 2017年第4期5卷 384-393页

作者： Joseph M Pappachan Shithu Babu Babu Krishnan Nishal C Ravindran Department of Endocrinology Diabetes&MetabolismRoyal Lancaster InfirmaryUniversity Hospitals of Morecambe Bay NHS TrustLancasterUK Department of Medicine Dorset County HospitalDorchesterUK Department of Gastroenterology&Hepatology Royal Bournemouth HospitalBournemouthUK Department of Gastroenterology&Hepatology Hinchingbrooke HospitalHinchingbrookeHuntingdonUK

Non-alcoholic fatty liver disease(NAFLD)is currently the most common chronic liver disease in developed countries because of the obesity epidemic.The disease increases liverrelated morbidity and mortality,and often increases the risk for other comorbidities,such as type 2 diabetes and cardiovascular disease.Insulin resistance related to metabolic syndrome is the main pathogenic trigger that,in association with adverse genetic,humoral,hormonal and lifestyle factors,precipitates development of NAFLD.Biochemical markers and radiological imaging,along with liver biopsy in selected cases,help in diagnosis and prognostication.Intense lifestyle changes aiming at weight loss are the main therapeutic intervention to manage cases.Insulin sensitizers,antioxidants,lipid lowering agents,incretin-based drugs,weight loss medications,bariatric surgery and liver transplantation may be necessary for management in some cases along with lifestyle measures.This review summarizes the latest evidence on the epidemiology,natural history,pathogenesis,diagnosis and management of NAFLD.

关键词： Nonalcoholic fatty liver disease(NAFLD) Nonalcoholic steatohepatitis NASH Insulin resistance Metabolic syndrome Lifestyle interventions Bariatric surgery

紫檀芪抑制血管内皮免疫蛋白酶体介导的抗原递呈并改善肝纤维化的研究

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紫檀芪抑制血管内皮免疫蛋白酶体介导的抗原递呈并改善肝纤维化的...

作者：欧阳颖西南医科大学

学位级别：硕士

目的:中药化学小分子是中草药中的活性成分,现代药理学证明其具有多种药用特性,如抗氧化,抗癌,抗菌等作用,是新药开发的重要来源。紫檀芪(Pterostilbene,PT)属于多羟基二苯乙烯类化合物,是紫檀中抗真菌的重要活性成分。PT对肝脏具有积... 详细信息

目的:中药化学小分子是中草药中的活性成分,现代药理学证明其具有多种药用特性,如抗氧化,抗癌,抗菌等作用,是新药开发的重要来源。紫檀芪(Pterostilbene,PT)属于多羟基二苯乙烯类化合物,是紫檀中抗真菌的重要活性成分。PT对肝脏具有积极的保护作用,然而其具体的作用机制尚不明确,相关研究的文献较少。慢性或重度肝脏损伤常常伴有的纤维化病变是非酒精性脂肪性肝炎(NASH)的重要组织学特征之一,同时也是肝硬化重要的发病原因。肝血管内皮细胞在纤维化过程中起关键的调节作用。在NASH中,主要组织相容性复合体I类(MHC-I)和II类(MHC-II)复合物大量生成,免疫细胞过度激活,使得肝脏内炎症因子大量释放从而加重了肝脏的纤维化。据此,我们主要研究PT是否能够抑制血管内皮免疫蛋白酶体介导的抗原递呈作用同时改善肝纤维化从而减轻NASH的发展,并揭示其潜在机制,进而为NASH治疗新药物的研发提供新思路。方法:A:非酒精性脂肪性肝炎(NASH)模型与药物治疗:首先选取8-10周龄的健康C57BL/6小鼠,随机分为对照组与脂肪性肝炎组。对照组,每日给予普通饲料及灭菌水。非酒精性脂肪性肝炎模型组每日给予高脂饲料(21.1%脂肪+41%蔗糖+1.25%胆固醇)和高糖溶液(23.1 g/L d-果糖+18.9g/L d-葡萄糖),持续12天,并每3天给予腹腔注射20%溶于橄榄油的CCl溶液。于注射CCl后的第二天腹腔给药PT 10 mg/kg(生理盐水稀释),最后一次给药结束后第二天取材(第12天)。将实验小鼠使用戊巴比妥钠注射液腹腔注射安乐死,然后分别进行解剖。采集小鼠的完整肝组织和加入抗凝剂的血清样本。使用ALT和AST试剂盒评估小鼠肝功能。用Sirius Red和Masson评价肝组织损伤。免疫组化实验检测α-SMA和Collagen I蛋白表达及纤维化程度。免疫荧光染色检测炎性细胞因子IL-1β、IL-6、IL-18、免疫蛋白酶体亚基LMP7、MHC-I和MHC-II蛋白的表达;采用Real-time PCR方法检测给药前后小鼠IL-1β、IL-6、IL-18 m RNA基因水平的变化。B:CCl诱导的肝纤维化模型与药物治疗:选取8-10周龄的健康C57BL/6小鼠,随机分为对照组与肝纤维化肝炎组。对照组,每日给予普通饲料及灭菌水。并每3天给予小鼠腹腔注射20%的四氯化碳溶液(1.6mg/kg)。每于第一次注射四氯化碳后第二天开始予以药物处理,一共注射7次,方法同前述。最后一次给药结束后第二天取材。将实验小鼠使用戊巴比妥钠注射液安乐死并分别进行解剖,收集小鼠肝脏组织、血清样品。病理染色法Sirius Red、Masson评估肝脏组织损伤情况;免疫组化评估纤维化指标α-SMA和Collagen-I的表达以及纤维化程度。C:体外细胞模型与药物处理:EOMAs(小鼠血管内皮瘤)细胞长到合适的密度后,用小鼠重组IFN-γ(100 ng/ml)刺激诱导EOMAs小鼠血管内皮瘤细胞表达MHC-I、MHC-II,然后分别同时予以不同浓度PT(10μM,2μM,0.4μM,0.08μM)进行干预,药物干预24小时后,分别收集不同组别细胞的RNA,进行real-time PCR实验进而检测MHC-I和MHC-II m RNA基因表达水平的变化。D:临床患者样本验证:收集4例肝硬化患者以及4例非肝硬化患者肝脏样本,利用免疫荧光染色技术检验肝脏内MHC-II以及免疫蛋白酶体亚基LMP7的表达。结果:(1)PT修复了NASH模型小鼠已经受损的肝脏功能并缓解了肝脏纤维化。PT给药组的血清ALT,AST明显下调(P值NASH小鼠肝组织纤维化面积减少(P值NASH模型小鼠体内的炎症反应。PT给药后关键炎症因子IL-1β,IL-6以及IL-18在肝细胞内表达明显降低(P值<0.01)同时肝细胞内IL-1β,IL-6以及IL-18的m RNA水平亦在给药后呈现出显著下调的趋势(P值<0.05)。(3)PT通过抑制血管内皮免疫蛋白酶体介导的抗原递呈作用从而降低血管内皮细胞性MHC-I和MHC-II的表达,进而减少CD4T和CD8T细胞的异常激活。相比模型组,PT干预治疗后,内皮性MHC-I和MHC-II表达降低,CD4T和CD8T在肝细胞内数量显著性降低(P值<0.01)。(4)删除CD4T细胞减轻慢性肝损伤造成的肝纤维化。病理染色实验结果显示,相比肝纤维化模型组,CD4T细胞删除组小鼠的肝脏组织得到改善,肝纤维化程度明显下降(P值<0.01)。(5)肝硬化患者内皮细胞中蛋白酶体相关抗原递呈细胞表达增高。免疫荧光染色结果显示:与非肝硬化患者相比,肝硬化患者肝内大量表达的MHC-II

关键词：紫檀芪免疫蛋白酶 MHC 纤维化 NASH

Redefinition of Fatty Liver Disease from NAFLD to MAFLD through the Lens of Drug Development and Regulatory Science

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Journal of Clinical and Translational Hepatology 2022年第2期10卷 374-382页

作者： Yasser Fouad Melissa Palmer Minjun Chen Arie Regev Rajarshi Banerjee Rob Myers Robert Riccio Richard Torstenson Ramy Younes Puneet SArora Henrik Landgren Morten A.Karsdal Martin Blake David A.Shapiro Hans-Juergen Gruss Muhammad Y.Sheikh Dina Attia Steven Bollipo Alastair D.Smith Bradley Freilich Robert G.Gish Detlef Schuppan Department of Gastroenterology Hepatologyand Endemic MedicineFaculty of MedicineMinia UniversityMiniaEgypt Gan-nex/Ascletis Pharma Co Ltd BeijingChina Liver Consulting LLC New YorkNYUSA Division of Bioinformatics and Biostatis-tics National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonARUSA Eli Lilly and Company IndianapolisINUSA Perspectum Diagnostics Ltd OxfordUK Gilead Sciences Inc Foster CityCAUSA Syneos Health LLC MorrisvilleNCUSA Allergan Marlow International BuckinghamshireUKAstraZenecaCambridgeUK Boehringer Ingel-heim International GmbHIngelheimGermany Genentech IncSouth San FranciscoCAUSA AbbVie MarlowBuck-inghamshireUK Nordic Bioscience A/S HerlevDenmark Resonance Health BurswoodWAAustralia Intercept Phar-maceuticals Inc San DiegoCAUSA Fresno Clinical Research Center FresnoCAUSA Gastroenterology and Hepatology Department Beni-Suef UniversityBeni SuefEgypt Department of Gastroenterology and Endoscopy John Hunter HospitalNewcastleNSWAustralia School of Medicine and Public Health University of NewcastleNewcastleNSWAustralia Kan-sas City Research Institute Kansas CityMOUSA Division of Gastroenterology and Hepatology Loma Linda UniversityLoma LindaCAUSA Institute of Translational Immunology and Research Center for Immune Therapy University Medical CenterMainzGermany Division of Gastroenterology Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading cause of liver-related death.Since no effective treatments exist,novel approaches to drug development are required.Unfortunately,outdated terminology and definitions of the disease are hampering efforts to develop new drugs and treatments.An international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLD)to MAFLD,includ-ing a proposal for how the disease should be diagnosed.As allies with the many stakeholders in MAFLD care―including patients,patients’advocates,clinicians,researchers,nurse and allied health groups,regional societies,and others―we are aware of the negative consequences of the NAFLD term and definition.We share the sense of urgency for change and will act in new ways to achieve our goals.Although there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLD initiative provides a firm foundation to build on.It provides a roadmap for moving for-ward toward more efficient care and affordable,sustainable drug and device innovation in MAFLD care.We hope it will bring promising new opportunities for a brighter future for MAFLD care and improve care and outcomes for patients of one of the globe’s largest and costliest public health burdens.From this viewpoint,we have revisited this initiative through the perspectives of drug development and regulatory science.

关键词： NAFLD MAFLD NASH Fatty liver disease Liver Fibrosis

Network Security Situation Awareness Framework based on Threat Intelligence

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Computers, Materials & Continua 2018年第9期56卷 381-399页

作者： Hongbin Zhang Yuzi Yi Junshe Wang Ning Cao Qiang Duan School of Information Science and Engineering Hebei University of Science and TechnologyShijiazhuang050000China Hebei Key Laboratory of Network and Information Security Hebei Normal UniversityShijiazhuang050024China College of Information Engineering Qingdao Binhai UniversityQingdao266000China Department of Information Science&Technology Pennsylvania State University1600 Woodland Rd.AbingtonPa19001USA

Network security situation awareness is an important foundation for network security management,which presents the target system security status by analyzing existing or potential cyber threats in the target system.In network offense and defense,the network security state of the target system will be affected by both offensive and defensive strategies.According to this feature,this paper proposes a network security situation awareness method using stochastic game in cloud computing environment,uses the utility of both sides of the game to quantify the network security situation value.This method analyzes the nodes based on the network security state of the target virtual machine and uses the virtual machine introspection mechanism to obtain the impact of network attacks on the target virtual machine,then dynamically evaluates the network security situation of the cloud environment based on the game process of both attack and defense.In attack prediction,cyber threat intelligence is used as an important basis for potential threat analysis.Cyber threat intelligence that is applicable to the current security state is screened through the system hierarchy fuzzy optimization method,and the potential threat of the target system is analyzed using the cyber threat intelligence obtained through screening.If there is no applicable cyber threat intelligence,using the NASH equilibrium to make predictions for the attack behavior.The experimental results show that the network security situation awareness method proposed in this paper can accurately reflect the changes in the network security situation and make predictions on the attack behavior.

关键词： Situation awareness stochastic game cloud computing virtual machine introspection cyber threat intelligence NASH equilibrium

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“景区+OTA”供应链广告合作决策研究

“景区+OTA”供应链广告合作决策研究

作者：孙倩吉首大学

学位级别：硕士

信息技术的日新月异将“互联网+”与旅游业深度融合,OTA的快速崛起改变了传统旅游运营模式,在线平台作为旅游供应链的中间环节,既联通了上游景区和下游游客,又双向搜集、分析、处理和传递信息,为游客提供更多个性化的旅游服务购买信息... 详细信息

信息技术的日新月异将“互联网+”与旅游业深度融合,OTA的快速崛起改变了传统旅游运营模式,在线平台作为旅游供应链的中间环节,既联通了上游景区和下游游客,又双向搜集、分析、处理和传递信息,为游客提供更多个性化的旅游服务购买信息。现阶段各旅游主体为抢占旅游市场提升旅游收益,均会大手笔的进行旅游宣传,增加旅游广告投资成本,这种盲目的广告投资与增加旅游收益的目标相悖。为了助推旅游业的发展,增加旅游供应链和各成员之间的总利润,建立“景区+OTA(Online Travel Agency,OTA)”供应链广告合作投资决策模型,以期能实现旅游供应链的协调。从“景区+OTA”供应链的视角着手,首先,通过文献检索法查阅整理目前广告投资的背景,总结分析相关问题,并梳理“景区+OTA”供应链相关概念和理论基础;接着,基于契约理论景区和OTA形成委托代理关系,构建旅游供应链广告投资决策NASH模型、Stackelberg模型和系统合作模型,得到分散式非合作决策、分散式合作决策和集中式合作决策模式下的最优利润和最优投资决策;然后,重点分析了三种博弈情景下的最优利润、最优决策对比,并进一步分析广告投资的影响因素;最后,使用MATLAB软件通过数值模拟仿真验证“景区+OTA”供应链广告合作投资决策博弈推理结论。研究所得结论如下:(1)集中式系统投资决策的旅游供应链利润大于分散决策的旅游供应链利润,旅游广告合作投资的旅游供应链利润大于分散决策的利润。(2)景区可通过自身的投资行为和激励措施诱导OTA的投资行为,使得景区更喜欢Stackelberg博弈。(3)景区和OTA的声誉广告、销售广告、佣金分担比例、边际利润和对于风险的态度均会对旅游收益产生影响。

关键词： “景区+OTA”供应链广告合作契约理论 NASH Stackelberg

Perspectives on Nonalcoholic Fatty Liver Disease:An Overview of Present and Future Therapies

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Journal of Clinical and Translational Hepatology 2017年第1期5卷 67-75页

作者： John Vizuete Alfredo Camero Mazyar Malakouti Karthik Garapati Julio Gutierrez Department of Medicine Division of GastroenterologyUniversity of Texas Health Science Center San AntonioSan AntonioTXUSA The Texas Liver Institute San AntonioTXUSA

Nonalcoholic fatty liver disease(NAFLD)represents a major public health epidemic.Pharmacologic therapies for this condition are scarce,but multiple agents with novel mechanisms of action are in development.Here we review the pathophysiology and natural history of NALFD,diagnostic testing and data for currently available treatment strategies.We then turn our attention to promising developmental drugs and their respective trials.As the prevalence of fatty liver disease increases,clinicians will have more tools at hand for management of this condition.We conclude the horizon is bright for patients and doctors who deal with NAFLD.

关键词： Nonalcoholic fatty liver disease Fatty liver Steatohepatitis NAFLD NAFL NASH Developmental drugs Hepatic steatosis

On Dynamics and NASH Equilibriums of Networked Games

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IEEE/CAA Journal of Automatica Sinica 2014年第1期1卷 10-18页

作者： Daizhan Cheng Tingting Xu Fenghua He Hongsheng Qi the Institute of Systems Science Chinese Academy of Sciences the Institute of Sstronautics Harbin Institute of Technology

Networked noncooperative games are investigated,where each player(or agent) plays with all other players in its neighborhood. Assume the evolution is based on the fact that each player uses its neighbors current information to decide its next strategy. By using sub-neighborhood, the dynamics of the evolution is obtained. Then a method for calculating NASH equilibriums from mixed strategies of multi-players is proposed.The relationship between local NASH equilibriums based on individual neighborhoods and global NASH equilibriums of overall network is revealed. Then a technique is proposed to construct NASH equilibriums of an evolutionary game from its one step static NASH equilibriums. The basic tool of this approach is the semi-tensor product of matrices, which converts strategies into logical matrices and payoffs into pseudo-Boolean functions, then networked evolutionary games become discrete time dynamic systems.

关键词： Networked non-cooperative game local infor-mation sub-neighborhood fundamental evolutionary equation NASH equilibrium