三春晖计划代表团访问交流活动日程和内容我们春晖计划代表团第一行程 5 人分别于 2016 年 6 月 7 日 ( 黄胜和章华 ) 9 日 ( 郦永刚 ) 和 11 日 ( 李百炼黄南松 ) 陆续到达兰

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1 2016 年 USACSA 赴兰大云大与理大三校春晖学术交流团总结报告美国华裔教授专家协会一概要 2016 年 6 月 7 日至 17 日我们美国华裔教授学者协会(USCSA)春晖计划交流团一行 6 人在中国国家教育部中国驻洛杉矶总领馆的全力支持下在兰州大学云南大学与大理大学各级领导三校国际合作与交流处领导和老师的悉心安排和帮助下先后成功地对兰大(5 人交流团) 云大(5 人交流团)与理大(4 人交流团)进行了为期 3 至 10 天的学术交流和访问其中参加三校交流者 3 人, 两校(云大与兰大或理大)校交流者 2 人与一校(兰大) 交流者 1 人作为针对三校学科认真挑选的各领域的学术带头人各位专家学者和三校有关院校的领导和学术带头人进行了广泛学术交流举办了一系列的学术专题讲座将自己领域的最新研究动态和成果介绍给三校同仁并且与各院校学者之间展开了活跃的互动交流和商讨春晖计划学者也和各院校认真探讨了在学术研究和教育培养方面今后可能合作的领域与项目美国华裔教授学者协会与兰州大学签订了合作协议书六位专家学者个人亦与所访问的学校在科研教育和师资培养等方面达成了书面或口头合作协议或初步意向通过这次春晖计划我们对三校的科研方向和重点有了深入一步的了解为今后合作和交流奠定了基础各位学者表示将与有关院校保持通畅的联络渠道和争取建立长期科研与教育合作伙伴关系同时也将为三校和南加州地区各学术机构包括南加州大学 (USC) 加州大学各分校(如 UCLA, UCR, UCI)等院校在更多领域的学术交流和合作牵线搭桥访问期间春晖计划专家学者们严谨的学术态度忘我的奉献精神和全力以赴的工作干劲也给所访问的学校留下了深刻的印象二春晖计划代表团成员和交流项目 1).郦永刚教授 (美国南加州大学; 访问三校 : (A) 地震断裂带共震破碎和震后愈合的观察分析和模拟 (兰大资源环境学院: ); (B) 应用断层导波确定汶川地震断裂结构 - 为灾后重建选址提供科学依据 (云大资源环境与地球科学学院: ) 2).黄胜和教授 (美国南加州大学; 访问三校):(A) 宿主为靶向的抗病原微生物药物(兰大药学院: );(B)感染组学共病两极(Sym-Pat)对偶问题解析: 儿科抗感染治疗范式转换(兰大第一医院儿科感染系: ); (C)HIV 感染与血脑屏障损伤研究进展 (理大微生物教研室: ) 3). 章华博士 (美国智泰科技公司; 访问三校 : 美国云计算发展现状和趋势 (兰大计算机网络中心: ) 4. 李百炼教授(美国加州大学河滨分校; 访问兰大与云大两校 : (A) 数学建模及其在复杂生态系统研究中的应用 (兰大生命科学院: ); (B) 未来新经济: 人与自然和谐的生态发展 (云大: ) 5. 周歧发教授(南加州大学生物医学工程学系;访问云大与理大两校): 生物医学工程和医疗仪器 (云大工程系: 下午座谈与讨论; 参观一家医疗仪器公司并进行技术交流) 6). 黄南松教授(美国南加州大东亚研究中心; 访问兰大 : 对外语法教学语法体系之问题暨科学对外汉语教学语法之建立 (兰大文学院: 上午与晚上两个讲座) 1

各院校学者之间展开了活跃的互动交流和商讨春晖计划学者也和各院校认真探讨了在学术研究和教育培养方面今后可能合作的领域与项目美国华裔教授学者协会与兰州大学签订了合作协议书六位专家学者个人亦与所访问的学校在科研教育和师资培养等方面达成了书面或口头合作协议或初步意向通过这次春晖计划我们对三校的科研方向和重点有了深入一步的了解为今后合作和交流奠定了基础各位学者表示

2 三春晖计划代表团访问交流活动日程和内容我们春晖计划代表团第一行程 5 人分别于 2016 年 6 月 7 日 ( 黄胜和章华 ) 9 日 ( 郦永刚 ) 和 11 日 ( 李百炼黄南松 ) 陆续到达兰州机场兰州大学安排专人在机场分批接机, 随后送往兰州大学宾馆入住黄胜和教授和章华博士于 6 月 8 日上午分别参观了兰大药学院与计算机网络中心黄胜和教授应兰大药学院李红玉院长邀请 8 日下午作了题为宿主为靶向的抗病原微生物药物的报告李院长亲自主持报告会 6 月 9 日至 11 日为端午节休假日先期抵达兰州的团员自行安排活动 6 月 12 日黄胜和郦永刚章华李百炼黄南松等 5 个团员分别到对接单位 ( 祥情见上 ) 进行学术交流或讲座并恰谈合作项目 ( 详情见下 : 各自总结 ) 兰大潘保田副校长于 6 月 12 日中午会见与宴请了代表团全体成员 6 月 13 日上午在离开兰州之前郦永刚教授与黄胜和教授代表美国华裔教授学者协会与兰州大学签订了合作协议书 6 月 13 日黄南松教授结束了春晖计划行程飞回北京春晖计划代表团其他 4 位成员继续下一行程 6 月 13 日我们春晖计划代表团第二行程 5 人分别从兰州 ( 黄胜和章华郦永刚李百炼 ) 和西安 ( 周歧发 ) 两地飞往昆明天水机场云南大学安排专人在机场分批接机, 随后送往云南大学连云宾馆入住 6 月 14 日上午李百炼教授代表美国华裔教授学者协会访问团做了一个小时的题为未来新经济 : 人与自然和谐的生态发展的报告当天下午访问团教授专家分别到各院系作学术报告和交流受到云大副校長, 以及云大生态学和环境学院段昌群院长和云南省科技厅王学勤副厅长热诚招待云大张力副校长于 6 月 14 日中午接见与宴请了代团全体成员双方将进一步加强多方位合作 6 月 15 日李百炼教授结束了春晖计划行程飞往深圳春晖计划代表团其他 4 位成员前往理大访问与交流春晖计划代表团第三行程 4 人 ( 黄胜和章华郦永刚周歧发 ) 于 2016 年 6 月 15 日清晨乘飞机抵达大理大学访问期间受到大理大学李小兵副校長, 国际合作处房慧处长, 以及各院系负责人热诚接待在招待座谈会上李副校长和各院院长介绍了大理大学各学科现状, 发展方向和对高水平人才的需求座谈会后, 欢迎仪式后, 理大校方向每位学者赠送了礼品并合影留念随后由校领导陪同共进欢迎午宴当日下午各位专家分别安排在专业院系讲学和交流 6 月 16 日下午章华郦永刚周歧发等三位专家飞回昆明并于 17 日飞往各自目的地结束春晖计划行程黄胜和偕夫人吴春华女士 ( 微生物专家, 完全自费 ) 分别于 6 月 16 日下午和 18 日上午顺便访问了理大微生物教研究室和昆明医科大学儿童医院并进行了卓有成效的学术交流 6 月 18 日下午此次春晖计划行程全部结束总之这次春晖计划是美国华裔教授学者协会在过去工作基础上一个学术和教育合作的良好续篇, 是一个成功的旅程此次春晖计划的成功, 取决于中国国家教育部和中国驻洛杉矶总领馆的全力支持, 我们表示衷心的感谢我们特别感谢洛杉矶总领馆教育组组长与参赞袁东博士和领事柴海鹰老师在百忙中抽出大量时间和精力处理有关的许多繁琐申请事务, 感谢本会会长吴仲和教授付会长郦永刚教授理事会和会员们对此计划的热情关注和帮助我们也由衷地感谢三校各级领导三校国际合作与交流处领导和老师的对交流程序的精心安排和食宿等各方面的关心照顾总而言之, 这次春晖交流计划的成功取决于各个部门领导和同事的大力帮助, 我们全体团员表示深深的谢意! 各位学者的交流汇报摘要如下 : 郦永刚 ( 南加州大学 ) 讲学交流活动简报如下 : 在兰州大学的讲学和交流活动 2

11 日为端午节休假日先期抵达兰州的团员自行安排活动 6 月 12 日黄胜和郦永刚章华李百炼黄南松等 5 个团员分别到对接单位 ( 祥情见上 ) 进行学术交流或讲座并恰谈合作项目 ( 详情见下 : 各自总结 ) 兰大潘保田副校长于 6 月

3 应兰大教育部重点实验室邀请, 本人在兰州大学资源环境学院和地质科学与矿产资源学院作学术报告, 题名为地震断裂带共震破碎和震后愈合的观察分析和模拟约 2 小时的学术报告中, 我介绍了在美国加里福尼亚州断裂带发现断层导波并应用导波研究断层深部精细结构和岩体物理属性的前沿研究工作, 解析和模拟地震断裂带共震破碎和震后愈合的动力学过程, 对地震周期性研究具有指导意义专题报告内容丰富, 博行好评潘校长希望我作为特聘教授定期或不定期参与西部环境重点实验室的中国西北地震带研究项目在云南大学的讲学和交流活动应云大资源环境与地球科学学院邀请, 在该院作学术报告应用断层导波确定汶川地震断裂结构 - 为灾后重建选址提供科学依据本人在 2008 年汶川 8 级大震后及时赶赴中国地震局汶川地震科学考查指挥部受邀参与地震第一线科考工作云大资源环境与地球科学学院院长谈树成教授, 地球物理系主任康国发教授等数十位教师和研究生在座在报告会上, 向云大地球物理系赠送我编写的新书 ( 英文 ) (Seismic Imaging, Fault Damage and Heal, by Li 2014), 供地震研究人员和研究生参考该书荣获 2014 年度中国图书出版优秀图书奖在大理大学的讲学和交流活动美国华裔教授学者协会春辉计划回国访问团受到大理大学李小兵副校長, 国际合作处房慧处长, 以及各院系负责人热诚接待在招待座谈会上李副校长和各院院长介绍了大理大学各学科现状, 发展方向和对高水平人才的需求座谈会后, 各位专家分别安排在专业院系讲学和交流黄胜和 ( 南加州大学 ) 讲学交流活动简报如下 : 团队活动总结 : 在过去 10 年中我组织和参加了本会的两次春晖计划学术交流活动相对于上次新疆春晖四人行活动 ( 单一学校 ), 本次活动具有团体大 (6 人 ) 访问学校多 (3 个加上顺访共 4 个 ) 时间长 (10 天 ) 对接专业面广 ( 文理两大专业六个不同领域 ) 团队作用强 ( 本会与兰大签订合作协议书 ) 和效率高 ( 连续作战平均 3 天访问一个学校 ) 等 6 大优点本次活动中兰大国际处工作最出色与本会互动最佳对接专业最到位和交流成果最卓著缺点 :(A) 准备时间仓促 ;(B) 本会作用发挥欠佳 ;(C) 在与云大和理大专业对接上相对薄弱建议 :(A) 尽早计划提前准备 ( 如春晖计划工作不强的学校需要更多时间作准备 );(B) 进一步加强团员多元化 ( 如增加院士级以上和年轻专家参加 ); (C) 更充分发挥本会组织作用 ( 如成立专门工作小组 ) 个人活动总结 :(1) 兰大活动 : 我分别于 6 月 8 日与 12 日应邀访问了兰大药学院与第一医院并作了题为宿主为靶向的抗病原微生物药物 ( 药学院 ) 和感染组学共病两极 (Sym-Pat) 对偶问题解析 ( 第一医院 ) 的两个学术报告我同第一医院儿科感染系的医护人员座谈讨论与分析了若干诊断不明的疑难病例并签订了协助从感染组学上解决这些疑难问题的协议书 (2) 云大活动 :6 月 14 日上午参加李百炼教授代表本团所做的关于生态发展与未来新经济的报告当天下午随同我多年的合作伙伴李百炼教授 (10 年前春晖活动结缘 ) 与云大生态学和环境学院段昌群院长和他的科研团队座谈和交流随后我与周歧发教授一起参观了一家医疗仪器公司 (3) 理大活动 : 在理大李小兵副校長与国际合作处房慧处长所主持的座谈会上, 李副校长和各院院长介绍了大理大学各学科现状, 发展方向和对高水平人才的需求我代表本团发言介绍了美国华裔教授学者协会的专业特点与人才优势座谈会后, 我到理大儿科医院参观并与该院科研教学骨干座谈和讨论儿科教育体制问题我介绍了美 3

定期参与西部环境重点实验室的中国西北地震带研究项目在云南大学的讲学和交流活动应云大资源环境与地球科学学院邀请, 在该院作学术报告应用断层导波确定汶川地震断裂结构 - 为灾后重建选址提供科学依据本人在 2008 年汶

4 国儿科教育特点该院领导提出了儿科人才培养意向 6 月 16 日上午我应邀到理大微生物教研室介绍了 HIV 感染与血脑屏障损伤研究进展并与该室达成了合作意向 (4) 顺访昆明医科大学儿童医院 : 我偕夫人吴春华女士 ( 微生物专家, 完全自费 ) 于 6 月 18 日上午顺便访问了昆明医大儿童医院在该院院长和刚从我实验室学成回国的博士后李莉医生陪同下参观了新建院区并就该院新建儿科研究所达成了合作意向李百炼 ( 加州大学河滨分校 ) 讲学交流活动简报如下 : 2016 年 6 月 11 号抵达兰州大学,12 号上午在生命科学院做了 2 个小时的学术报告, 题目是数学建模及其在复杂生态系统研究中的应用, 下午与兰大大气科学院进行了学术交流并指导他们的论文写作 13 号下午抵达云南大学,14 号上午代表我们访问团做了一个小时的题为未来新经济 : 人与自然和谐的生态发展, 下午与云大生态学科的教师进行了学术交流并就高原湖泊生态学方面的合作达成协议黄南松 ( 南加州大学 ) 讲学交流活动简报如下 : 本人于 2016 年 6 月日同美国华裔教授协会的其他 4 名教授一起赴兰州大学进行春晖计划学术交流活动现将具体情况报告如下 :1. 为了保证学术报告适应兰州大学文学院的需要, 早在 4 月 20 日本人即将若干学术报告的题目及简要介绍发给兰大文学院, 由他们选定报告的题目 2. 6 月 12 日上午同兰州大学文学院及汉语国际教育专业负责人探讨今后合作的可能性, 包括本人将来继续去兰大进行学术交流协助邀请兰大教师赴美参加学术会议和进行学术访问下午, 同兰大汉语国际教育 ( 硕士 ) 专业的骨干教师就该专业的培养和发展问题进行座谈 3. 6 月 12 日晚上, 举行对外语法教学语法体系之问题暨科学对外汉语教学语法之建立学术报告, 参加者包括兰大文学院的教师研究生及高年级学生共计 200 余人 4. 6 月 13 日上午, 应约同兰大国际交流处长就如何利用海外资源发展兰大人文社会科学的问题进行了长达 2 小时的交流因此, 可以说, 此次活动取得了很好的效果在此, 要感谢美国华裔教授协会前会长黄胜和教授的精心组织和驻洛杉矶领馆教育组的大力支持章华 ( 美国智泰科技公司 ) 讲学交流活动简报如下 : 这次参加教育部赞助和洛杉矶总领馆倡导的春晖计划, 十分荣幸, 收获不少我 6 月 6 号启程,7 号到达兰州大学,8 号就开始了学术交流和我对接的是兰州大学计算机网络中心我给网络中心做了美国云计算发展现状和趋势的讲座, 为网络中心的现有工作和未来发展提出了建设性意见我们草签了联合申请教育部春晖项目的协议 6 月 13 号离开兰州大学, 我们到达昆明, 对云南大学进行学术交流我和云南大学软件学院的代表进行了比较深入交谈, 对将来的合作提出了建设性的建议 6 月 14 号到达大理大学我和大理大学数学和计算机系老师们进行了 2 个多小时的学术交流, 并参观了机房和展览馆 6 月 16 号我们结束了这次学术访问 17 号离开昆明这次学术交流活动, 前后差不多 10 天, 行程紧凑, 富有成效认识了高校新朋友, 也进一步熟悉了国内的学术圈我的领域主要是云计算, 大数据, 物联网等我把美国和西方在这方面的新动向, 新知识和新技术向国内同行进行了汇报建议 : 今后联系学校及对接单位应该由教授本人直接联系为好, 这样便于后面的对接这次到云南大学就出现一些问题建议教授协会主要负责组织工作并提供可能的对接信息周歧发 ( 南加州大学 ) 讲学交流活动简报如下 : 这次本人有幸参加了有黄教授组织的 2016 年六月的教育部春晖教授访问团我是加入了云南大学和大理大学的活动在云南大学, 有科技处安排了一个报告会, 我们全体成员 4

下 : 2016 年 6 月 11 号抵达兰州大学,12 号上午在生命科学院做了 2 个小时的学术报告, 题目是数学建模及其在复杂生态系统研究中的应用, 下午与兰大大气科学院进行了学术交流并指导他们的论文写作 13 号下午抵达云南大学,14

5 都参加了下午我们分组讨论, 我与黄教授一起参观了一位物理系老师合办的一家医疗仪器方面的公司, 并对我们的技术进行了分享双方回来后进一步讨论并商讨合作事宜随后我们一起去了大理大学参观和访问, 下午主管外事的校长介绍了该校的有关情况第二天上午我们分组去了工程学院开会与有关老师分享了有关我们的研究和教学工作发现这个学校是一所刚成立的大学, 老师大部分是硕士毕业我们鼓励他们考在职博士研究生, 来提高研究水平目前已有一到二位老师有保持联系想进一步保持合作通过这次访问收获还是很大, 一是看到了国内变化很大, 另一方面让我们看到了西部人才还是缺乏, 需要多加强合作建议是以后去之前与国内的有关单位联系好, 将可能的合作单位和个人找到, 这样效果会更好! 5

一所刚成立的大学, 老师大部分是硕士毕业我们鼓励他们考在职博士研究生, 来提高研究水平目前已有一到二位老师有保持联系想进一步保持合作通过这次访问收获还是很大, 一

6 Subsurface Damage Zone of the Calico Fault Viewed by Fault-Zone Trapped Waves from Teleseismic Earthquakes Yong-Gang Li Department of Earth Science, University of Southern California Abstract. The fault-zone trapped waves (FZTWs) are first-time observed at a square seismic array consisting of 40 intermediate-period stations and 60 short-period stations deployed in a 1.5 km by 5.5 km grid adjacent to the Calico Fault (CF) in Mojave Desert, California for teleseismic earthquakes. In the previous study, FZTWs generated by explosions and local earthquakes, traveltimes inverse and InSAR observations have imaged a low-velocity compliant zone along the CF within which seismic velocities are reduced to the maximum of ~40-50% in the center of a ~1-km-wide fault core zone extending to at least 5-6 km depth (Cochran, et al., 2009). In order to obtain further constraints on the deep portion of the CF below the depth coverage of local earthquakes, we innovatively use the FZTWs recorded at this seismic array atop the CF compliant zone for teleseismic earthquakes. This type of FZTWs has not been used before, but they appear to have great promise for providing unprecedented constrains of the depth extension of fault-zone damage structure because these FZTWs arise from seismic waves incident at the fault bottom at deep level. We examined the data from 26 M 6 teleseismic earthquakes occurring at distances of ~40 o -80 o great circles to the Calico array site during We identify this type of FZTWs at dominant frequencies Hz, which show much larger amplitudes and longer wavetrains (~6-8s) starting ~5-s after the first-arrival P-waves at stations located within the ~1-km-wide CF compliant zone than those registered at farther stations out of the zone for teleseismic earthquakes. We synthesize these FZTWs formed by S-waves converted from the first-arrival P waves at the Moho (~30-km depth beneath Mojave Desert) and entering the bottom of the CF compliant zone. Combined with the previous velocity model of the CF, the results from observations and simulations of these FZTWs indicate that the compliant zone with velocity reduction of 40-50% along the CF likely extends to ~8-km depth. 1. Introduction The Calico fault is located midway between the 1992 Mw7.3 Landers and 1999 Mw7.1 Hector Mine ruptures where fault-zone trapped waves (FZTWs) generated by explosions and aftershocks were observed (Li et al., 1994, 2000, 2002, 2003). Some geodetic estimates suggest that the CF has as much as 7 mm/yr dextral slip rates within the eastern California shear zone (Peltzer et al., 2001). Recent trench data indicate that the last earthquake occurred on it at least several hundred years ago (Ganev et al., 2008). Coseismic interferograms for both the Landers and Hector Mine earthquakes showed strain localized on the CF and other nearby faults (Fialko et al., 2002; Fialko, 2004). Line-of-sight displacements with amplitudes of a few centimeters and wavelengths of a few kilometers are clearly associated with the CF (Fig. 1a). Observed interferometric synthetic aperture radar (InSAR) anomalies for the CF are best explained with a 1 2-km-wide zone around the fault with a shear modulus reduced by ~50% extending to at least 5 km depth. Cochran, et al. (2009) conducted a seismic investigation of the compliant zone along the Calico Fault (CF) in the Mojave Desert in 2006 (Fig. 1a, b). Using seismic travel times, FZTWs generated by explosions and local earthquakes as well as interferometric Synthetic Aperture Radar observations, they document seismic velocities within the ~1-km-wide CF compliant core zone reduced by up to ~40%, and shear moduli reduced by up to 60% compared with wall-rock (Fig. 1c). This low-velocity compliant zone extends to at least 5-6 km depth. The velocity reductions observed along the CF compliant zone are likely due to the cumulative mechanical damage from past earthquake ruptures on it and also indicate that faults can affect rock properties at substantial distances from the primary fault slip surfaces and throughout much of the seismogenic zone. This result has implications for the portion of energy expended during rupture to drive cracking and the development of fault systems. Permanent damage 6

5 km grid adjacent to the Calico Fault (CF) in Mojave Desert, California for teleseismic earthquakes.

7 zones may, thus, play a critical role in development and dynamics of faults, intensity of ground motion, and earthquake hazards along the low-velocity fault zone resulting from its waveguide effect. However, the deep portion of the fault damage zone is still less constrained by the FZTWs used in the previous study because those FZTWs generated by near-surface explosions and local earthquakes mostly travel along the fault zone at shallow depths. Recently, we identified a new type of FZTWs in seismograms recorded in the 2006 experiment at the dense square array atop the Calico Fault for teleseismic earthquakes. Since these FZTWs arise from S- wave converted from P-wave at the Moho discontinuity and sub-vertically incident at the bottom of CF compliant zone. These FZTWs are capable to provide unprecedented constraints on the depth extension of fault damage structure beneath the depth that those FZTWs generated by explosions and local earthquakes can approach. In this article, we demonstrate the new type of FZTWs recorded at the dense array atop the CF from the teleseismic earthquakes (Fig. 1d) and use these FZTWs to image the subsurface fault rock damage structure at deep depth. 2. The Data and Waveform Analyses Cochran et al. (2009) installed a dense array of 40 intermediate-period (40T) stations and 60 shortperiod (L22) stations in a 1.5 km 5.5 km square adjacent to the Calico fault (CF) to record three shots detonated within and out of the Calico Fault zone, and then to record earthquakes for six months starting from June in This square array consists of 4 seismic lines (Line A, Line B, Line C and Line D in Fig. 1a) nearly perpendicularly across the CF with 1-km line spacing. The geometry of the array and station intervals is shown in Fig. 1b. Each station has a short-period sensor (L22 2Hz) and/or an intermediate-period sensor (40T 0.025Hz) buried in a m deep dig hole with three components in the vertical, parallel and perpendicular to the fault strike. The seismometers worked in continuous mode at 100 samples per second, and were synchronized by internal GPS clocks. The data recorded at four crossfault lines A, B, C and D for 3 explosions and 5 local on-fault earthquakes have been used for FZTWs analysis, and 20 local and 8 teleseismic earthquakes have been used for travel time tomography (Cochran et al., 2009), showing a ~1-km-wide compliant core zone along the CF extending to at least 5-6 km depth, within which seismic velocities are reduced by up to ~40% and shear moduli reduced by up to 60% compared to wall-rock (Fig. 1c). In the present study, we examine the data recorded at 4 Lines A, B, C and D for 72 teleseismic earthquakes with magnitudes M 6 and occurring at distances of ~40 o -80 o great circles (approximate 5,000-11,000 km) to the Calico seismic array site during June-November of 2006 (Fig. 1d). We use 26 teleseismic earthquakes at depths deeper than 28 km, for which we identify FZTWs closely after the first P-arrivals in teleseisms recorded at 4 cross-fault Lines A, B, C and D (Fig. 1b). These FZTWs likely arise from S-waves that are converted from the first-arrival P-waves at the Moho discontinuity (at ~30-km depth beneath Mojave Desert) and entering the bottom of the low-velocity compliant zone along the CF. Seismograms recorded for shallow teleseismic earthquakes are in general dominated by strong surface waves so that they are not suitable used in this study. In the present article, we show the FZTWs identified in teleseisms from 7 teleseismic earthquakes which locations and magnitudes are listed in Table 1. Table 1. Teleseismic earthquakes and local earthquakes recorded at the seismic array atop the Calico fault, which waveforms are shown in this article Event ID Type Magnitude Latitude Longitude Depth (km) Distance TE162 Teleseism TE244 Teleseism TE271 Teleseism TE272 Teleseism TE276 Teleseism TE288 Teleseism TE317 Teleseism

mostly travel along the fault zone at shallow depths.

8 Fig. 1 (a) Map shows locations of 40 (40T, 0.025Hz) stations (black triangles) and 60 (L22, 2Hz) stations (red circles) along 4 seismic lines A, B, C and D deployed across the Calico Fault in 2006 (Cochran et al., 2009).. Colors in high-pass-filtered co-seismic interferogram from the 10/16/1999 Hector Mine earthquake during 01/13-10/20/1999 denote variations in line of sight (LOS) displacements (Fialko et al., 2002). (b) Map shows locations of intermediate- (triangles) and short-period (dots) stations along seismic lines A, B, C and D deployed across the CF compliant zone (marked by grey color) with the 1-km-wide fault core zone (dark grey). Station spacings are not even, but with denser stations within the compliant zone. (c) Model of P-wave low-velocity zone along Calico fault with 40% reduction in velocity obtained by Cochran et al. (2009). The fault compliant zone is ~1.5 km wide at the surface. The lateral velocity profile across the fault is approximated as a Hanning taper, and the velocity reduction tapers linearly to zero between 0 and 10 km depth. The damage zone is modeled to extend to 10 km depth, but with small relative velocity reductions below ~5-6 km. (d) Map shows locations of 71 teleseismic earthquakes (white circles) with M 6 recorded at 4 seismic lines in the square array atop the CF. Red circles marked by labels with T followed by Julian date, M followed by magnitude and D followed by depth, denote seven teleseismic earthquakes for which FZTWs are identified in teleseisms and shown in this article. Fig. 2a shows seismograms recorded at five 40T stations of seismic Line D across the CF for a M6.7 teleseismic earthquake (TE288 in Table 1) occurring at 39-km depth beneath Hawaii Islands and ~4200 km (37.8 o ) west from the CF seismic array site in Southern California (see Table 1 and Fig. 1d). Because of the low level of noise at the array site, the primary P-wave and S-wave are visible in teleseisms while strong surface waves appear after 1000-s from the event origin time. We apply a band-pass ( Hz) filter on teleseisms to suppress the surface waves, and cut seismograms from 430-s to 470-s, including the first-arrival P-wave (P ) and the wavetrain closely following it. Fig. 2b exhibits the band-pass filtered seismograms at seismic Line D. We observe a wavetrain with large amplitude and ~8-s duration, in which the waveform amplitudes are twice above the background level, staring from ~5.5 s after the firstarrival P at stations D9 and D15 located within the CF compliant zone (see Fig. 1b). We also observe this wavetrain at stations A9, A15 and A21 of Line A, and at stations C9, C15 and C20 of Line C located within the ~1-km wide CF complaint core zone for this teleseismic earthquake (Fig. 2c and Fig. 2d). In contrast, such waveforms do not appear at stations located out of the CF complaint zone. We interpret these long wavetrains with large amplitudes as being fault-zone trapped waves (FZTWs) formed by S- waves that are converted from first-arrival P waves at the Moho discontinuity (~30-km depth beneath 8

. Colors in high-pass-filtered co-seismic interferogram from the 10/16/1999 Hector Mine earthquake during 01/13-10/20/1999 denote variations in line of sight (LOS) displacements (Fialko et al., 2002).

9 Mojave Desert) and sub-vertically enter the bottom of the low-velocity CF compliant zone at certain depth. We call P for the first-arrival refracted P-wave and S for the S-wave converted from P at the Moho discontinuity. The time difference between P and S is ~5.5 s Corresponding to the distance of waves traveling sub-vertically between the Moho at depth of ~30- km and seismic array at the surface. When the S wave enters the bottom of the vertical fault zone at certain depth, S-type FZTWs are produced due to constructive interference of multiple reflected waves at the boundary between the low-velocity compliant zone and high-velocity surrounding rocks, and recorded at stations located within the CF compliant zone. We notice P-type FZTWs in the P coda before the S in perpendicular-component seismograms recorded at stations located within the CF compliant zone for this teleseismic earthquake from which the ray path is nearly perpendicular to the CF strike. Fig. 2 (a) Seismograms in the fault-perpendicular component recorded at six 40T stations along Line D for a M6.7 teleseismic earthquake (TE288 in Table 1). Its location is shown by a red circle labeled with T288 in Fig. 1d. Station D15 is located on the fault trace. Station names and distance with respect to D15, and event date are shown in plot. Surface waves are dominant in raw seismograms, but primary P- and S-waves are visible too. The time scale in plot is s. (b) Band-pass ( Hz) filtered seismograms recorded at Line D show prominent FZTWs (in brackets) with large amplitudes and long wavetrains (~8-s post-s duration marked by a horizontal bar) at stations D9 and D15 located within the ~1-km-wide compliant core zone (denoted by a vertical black bar). Note that the time scale in plot is 40 s starting before the first-p arrival. Seismograms are plotted using a fixed amplitude scale for all stations in each panel. P and S are P-waves and P-S converted waves from the Moho discontinuity between the lower crust and the upper mantle. (c) and (d) Same as in (b) but for seismograms at Line A and Line C, respectively. Stations A15 and C15 are located on the fault trace. Prominent FZTWs with large amplitudes and ~8-s post-s duration recorded at stations between A9 and A21, C9 and C20 located within the ~1-km-wide compliant core zone. Fig. 3a shows three-component seismograms recorded at 15 stations equipped with intermediateperiod 40T sensors and 25 stations equipped with short-period L22 sensors for a M6.3 teleseismic earthquake (TE162 in Table 1) occurring at 140-km depth in Honshu Prefecture of Japan, approximately 9500-km (72.2 o ) west of the CF array site in California (see Fig. 1d). The first-arrival P waves with its coda are dominant around s on seismograms in vertical component, weaker in perpendicularcomponent, but weakest in parallel-component, because the waves come to surface stations nearvertically and are perpendicular to the CF strike. We observe large-amplitude and long-duration (~7-s) wavetrains arriving about 5-s after the P in two horizontal-component teleseisms at stations between B9 and B21 located within the ~1-km-wide CF compliant core zone. In contrast, shorter wavetrains with much lower amplitudes are registered at stations out of the compliant zone, indicating abundance of seismic energy trapped within the CF compliant zone. We interpret that the observed wavetrains with long duration and large amplitudes in horizontal-component teleseisms are S-type FZTWs arising from 9

5 s Corresponding to the distance of waves traveling sub-vertically between the Moho at depth of ~30- km and seismic array at the surface.

10 the S waves converted from P waves at the Moho (~30-km depth) and nearly vertically entering the bottom of the low-velocity compliant zone along the CF at the certain depth. These wavetrains are similar to the FZTWs generated by explosions and local earthquakes, and recorded at the same stations atop the CF (Cochran et al., 2009), but they are recorded for teleseismic earthquakes. Fig.3a Left: Three-component seismograms recorded at fifteen intermediate-period 40T stations and twenty-six L22 2-Hz stations along Line B for a M6.3 teleseismic earthquake (TE162 in Table 1 and Fig. 1d). Station B15 is located on the fault trace. Seismograms have been band-pass (0.5-2 Hz) filtered and are plotted using a fixed amplitude scales for all trace in each plot, showing prominent FZTWs with ~7-s post-s duration (in red brackets) in two horizontal seismograms recorded at stations B9 B21 located within a ~1-km-wide compliant zone (marked by a vertical grey bar). P and S are P-waves and P-S converted waves at the Moho discontinuity. Right: Normalized spectral amplitude contours of teleseisms show large-amplitude (red color) FZTWs at 1-3 Hz with ~7-s duration at on-fault station B15, but lower amplitude with shorter duration (<2-s) at stations B1 and B26 out of the compliant zone. The same amplitude scale is used for three plots. P denotes multiple P-waves between the surface and Moho. We notice (1) the large-amplitude FZTWs following S -waves on two horizontal-component seismograms at stations between B9 and B17 equipped with short-period 2-Hz sensors, indicating that the more seismic energy at higher frequency is trapped within a narrower (~ m wide) fault core zone; (2) the long-duration wavetrains of FZTWs including multiple peaks (starting from P ) like ripple, probably due to waves rebounded between the free surface and Moho; (3) the wavetrains in P coda immediately following the P in vertical- and perpendicular-component seismograms likely being P-type FZTWs arising from P-waves entering at the bottom of compliant zone. In this article, we are interested in the S-type FZTWs following the S converted from P at the Moho. Fig. 3b shows this type of FZTWs with ~7-s durations following S recorded at stations of seismic Lines A, B and C equipped with intermediate-period 40-T sensors located within the CF compliant zone for teleseismic earthquake TE162. These S-type FZTWs are dominant in horizontal-component seismograms, but not clear in vertical-component seismograms. The durations of FZTWs recorded for teleseismic earthquakes are longer than those generated by local earthquakes occurring near the seismic array atop the CF (Cochran et al., 2009; also see Fig. 9 in this article). Observations of these FZTWs suggest the existence of a 1--km-wide remarkable waveguide along the CF compliant zone likely extending from the ground surface through seismogenic depths. We analyze P-to-S converted waves observed for the Moho discontinuity in teleseisms using the receiver function to obtain valuable constraints on the subsurface structure of the CF compliant zone 10

, 2009), but they are recorded for teleseismic earthquakes. Fig.

11 beneath Mojave Desert. The receiver function analysis is helpful to equalize near-source effects in threecomponent seismograms and isolate the receiver effects from the observed waveforms. We compute receiver functions by waveform deconvolution between the radial-component and vertical-component teleseisms for isolating the local response. Fig. 3c shows receiver functions computed for teleseisms recorded at five stations of Line B for teleseismic earthquake TE162. We interpret that the peak amplitudes of first-arrival P-wave (P ) and P-to-S converted wave (S ) from the Moho discontinuity in receiver functions appear at 0 s and ~5 s, respectively, as well as the multiple-phase P at s, according to the Moho depth of ~30-km and Vp in the upper crust beneath Mojave Desert is in average ~6-km/s. The large-amplitudes between ~5 s and 12 s in receiver functions at stations (B13, B14 and B15) located within the CF compliant zone likely correspond S-type FZTWs arising from S wave entering at the bottom of the CF compliant zone at certain depth. In contrast, much lower amplitudes following S in receiver functions at stations (B03 and B24) located outside the compliant zone. We note that high amplitudes following the P -arrivals at stations (B13, B14 and B15) located within the CF compliant zone are likely P-type FZTWs. In contrast, there is no such amplitude peak in P coda at stations (B03 and B24) out of the CF compliant zone. Receiver functions suggest the existence of subsurface low-velocity structure along the CF compliant zone. Fig.3b Left: Same as in Fig.4a, but showing teleseisms recorded at 40T stations along Lines A, C and D. Prominent FZTWs with large amplitudes and long post-s durations (~7-s) at stations located within the ~1-km wide compliant zone. Right: Normalized spectral amplitude contours of teleseisms show large-amplitude FZTWs with ~7-s duration at on-fault stations A15, C15 and D15. P denotes multiple P-waves between the surface and Moho. 11

3c shows receiver functions computed for teleseisms recorded at five stations of Line B for teleseismic earthquake TE162.

12 Fig.3c Receiver functions computed by deconvolution between the radial- and vertical-component seismograms recorded at 5 stations of Line B. P -arrivals are aligned at time 0 s. P-to-S converted waves (S ) arrive at ~5 s. The S- type fault-zone trapped waves (FZTWs) following S show large amplitudes and ~7-s duration (in grey box) at stations (B-13, B14 and B15) located within the CF compliant zone while much lower amplitudes at stations (B03 and B24) outside the compliant zone. The multiple P arrives at ~14-15 s. To emphasize the converted waves that reverberate between the surface and Moho, computed receive function curves have been smoothed to relieve the ripples from multiple fine layers. Note large amplitudes following P and P related to the P-type FZTWs. In the next example, Fig. 4 exhibits three-component seismograms recorded at four lines A, B, C and D for a M6.3 teleseismic earthquake (TE276 in Table 1) occurring at 161-km depth beneath Solomon Islands, approximately 10,000 km (65.7 o ) west of the CF seismic array in California (see Fig. 1d). We observe consistent large-amplitude wavetrains with long wavetrains (~7-s) after the P-S converted S - wave at ~5-s after the first P-arrive, in two horizontal-component seismograms and spectral contours at stations located within the ~1-km-wide CF compliant core zone, but not at stations out of the compliant zone. These wavetrains are weaker in vertical-component teleseisms than those in horizontal components because waves from this deep teleseismic event propagate nearly-vertically from the Moho at ~30-km depth beneath the seismic array. Fig.4 (a) Three-component seismograms recorded at seventeen 40T stations along Line B for a M6.3 teleseismic earthquake (TE276 in Table 1 and T276 in Fig. 1d). Teleseisms have been band-pass (0.5-2 Hz) filtered, and show prominent FZTWs with ~7-s post-s duration in two horizontal seismograms recorded at stations B9 B21 located within a ~1-km-wide CF compliant core zone. (b) Normalized spectral amplitude contours of teleseisms show largeamplitude FZTWs at 1-3 Hz with 6-s duration at on-fault station B15, but lower amplitude with shorter duration (~3-s) at stations B1 and B26 out of the compliant zone. (c), (d) and (e) Same as in (a), but at Lines A, C and D. Prominent FZTWs with ~7-s post-s duration in two horizontal seismograms recorded at stations located within the compliant zone. (f) Normalized spectral amplitude contours of teleseisms show large-amplitude FZTWs with ~7-s duration at on-fault stations A15, C15 and D15. We note multiple phases starting from P in late coda of teleseisms. Our observations indicate these wavetrains more likely to be the S-type FZTW arising from the S - wave converted from P-wave at the Moho and then entering the bottom of the CF compliant zone at certain depth in the upper crust. We notice the P-type FZTWs immediately following the first P-arrivals 12

The S- type fault-zone trapped waves (FZTWs) following S show large amplitudes and ~7-s duration (in grey box) at stations (B-13, B14 and B15) located within the CF compliant zone while much lower

13 in vertical- and fault-perpendicular-component seismograms for this telemetry earthquake from which the ray path is nearly perpendicular to the fault strike. We notice multiple phases starting from P and other phases in the late coda of teleseisms. Then, we examine the data recorded at 40T stations along Line B for a M6.7 teleseismic earthquake (TE244 in Table 1) occurring at 38-km depth beneath Papua New Guinea Islands ~11,000 km (69.5 o ) west from the CF seismic array site in California (see Fig. 1d). P-waves arrive at ~848-s in the verticalcomponent seismograms. In teleseisms and spectral amplitude contours (Fig. 5a, b), we observe largeamplitude and long-duration (~7.5-s) wavetrains starting from ~5.5 s after the first-p arrivals at stations between B9 and B21 located within the ~1-km-wide CF compliant core zone but not at stations out of the zone, suggesting that these wavetrains are S-type FZTWs arising from the S -wave converted from P- wave at the Moho and sub-vertically entering the bottom of the CF compliant zone at certain depth in the upper crust. These FZTWs are also observed on teleseisms recorded at stations of Lines A, B and C within the CF complaint zone (Figs. 5c, 6d). We notice the P-type FZTWs following the first P-arrival appearing in the vertical- and perpendicular-component seismograms from this shallow telemetry event from which waves propagate nearly perpendicular to the fault strike. We also notice multiple phases in the late coda on teleseisms. Fig. 5e shows receiver functions computed for teleseisms recorded at stations of Line B, Line A and Line C for this teleseismic earthquake. The peak amplitudes of P and P-to-S converted wave S from the Moho in receiver functions arrive at 0 s and ~5 s; the multiple-phase P arrives at ~15 s. Large-amplitudes between 5 s and 12 s in receiver functions at stations B12, B13, A15 and C15) located within the CF compliant zone are likely related to S-type FZTWs arising from S wave. In contrast, much lower amplitudes following S in receiver functions at stations (B01, B26, A04 and C04) outside the compliant zone. We note that amplitude peaks following the P-arrivals registered at stations located within the CF compliant zone are likely P-type FZTWs. Fig.5 (a) and (b) Three-component teleseisms recorded at sixteen 40T stations along Line B for a M6.7 teleseismic earthquake occurring at 38-km depth (TE244 in Table 1 and Fig. 1d), showing prominent FZTWs with large amplitudes and ~7.5-s post-s duration starting at ~5.5-s after the first-p arrivals (in red brackets) on seismograms at stations B9 B21 located within a 1-km-wide compliant zone. Normalized spectral amplitude contours of teleseisms show large-amplitude (red color) FZTWs at 1-3 Hz with ~7.5-s duration at on-fault station B15, but lower amplitude with much shorter duration (2-s) at stations B1 and B26 out of the compliant zone. (c) Perpendicular-component teleseisms recorded at seismic Lines A, C and D. (d) Normalized spectral amplitude contours of teleseisms show large-amplitude FZTWs at 1-2 Hz with ~7.5-s duration at stations A15, C15 and D15 located on the CF surface trace. 13

7 teleseismic earthquake (TE244 in Table 1) occurring at 38-km depth beneath Papua New Guinea Islands ~11,000 km (69.5 o ) west from the CF seismic array site in California (see Fig. 1d).

14 Fig.5 (e) Receiver functions computed by deconvolution between the radial- and vertical-component seismograms recorded at 4 stations of Line B and 2 stations of Line A and Line C for each. P -arrivals are aligned at time 0 s. P- to-s converted waves (S ) appear at ~5 s. The S-type FZTWs following S show large amplitudes and ~7-s duration (in grey box) at stations (B-12, B13, A15 and C15) within the CF compliant zone while lower amplitudes at stations (B01, B26, A04 and C04) outside the compliant zone. The multiple P arrives at ~15 s. Note that large amplitudes following P and P might relate to the P-type FZTWs. Fig. 6 shows another example of this type of FZTWs recorded at both intermediate- and short-period stations along Line B for a M6.8 teleseismic earthquake (TE317 in Table 1 and Fig. 1d) occurring at 548- km depth in Bolivia, approximate 7900-km (78.9 o ) southeast of the CF seismic array in California. Surface waves are invisible in teleseisms for this deepest earthquake in our study (see Fig.2). We observe FZTWs with ~5-6-s duration after the P-S converted S waves on two horizontal-components of teleseisms recorded at stations within the ~1-km-wide CF compliant zone between B9 and B21 (Figs. 6a, b). FZTWs do not appear on the vertical-component seismograms because the ray path from this deep teleseismic earthquake to the CF array is nearly vertical. Normalized spectral amplitude contours of teleseisms show large-amplitude FZTWs at 1-3 Hz with ~6-s duration at on-fault station B15, but much weaker and shorter (2-s) post-s wavetrains at stations B1 and B26 out of the compliant zone (Fig. 6c). We notice the P-type FZTW following the first P-arrival in teleseisms because waves from this deep teleseismic earthquake are nearly-vertical incident to the surface array. We notice that the durations (5-6 s) of FZTWs for this deep teleseismic event are shorter than those (7-8 s) for shallow events because the ray path from the deep event enters the bottom of the CF compliant zone more steeply than that from the shallow event, and thus FZTWs travel shorter distance within the compliant zone to arrive at the CF seismic array. 14

The S-type FZTWs following S show large amplitudes and ~7-s duration (in grey box) at stations (B-12, B13, A15 and C15) within the CF compliant zone while lower amplitudes at stations (B01, B26, A04

15 Fig.6 (a) and (b) Three-component seismograms recorded at sixteen 40T stations and twenty-six L22 2-Hz stations along Line B for a M6.8 teleseismic earthquake (TE317 in Table 1 and Fig. 1d). Teleseisms show prominent FZTWs with ~5-6-s post-s duration in two horizontal seismograms recorded at stations B9 B21 located within a ~1-kmwide compliant zone. (c) Normalized spectral amplitude contours of teleseisms show large-amplitude FZTWs at 1-3 Hz with ~5.5-s duration at on-fault station B15, but lower amplitude with shorter duration (<2-s) at stations B1 and B26 out of the compliant zone. Fig. 6d shows receiver functions computed for teleseisms recorded at stations of Line B, Line C and Line D for this teleseismic earthquake. The peak amplitudes of P and P-to-S converted wave S from the Moho in receiver functions arrive at 0 s and ~5 s, and the multiple-phase P arrives at ~14-15 s. The large-amplitudes between ~5 s and 11.5 s in receiver functions at stations (B11, B13, B15, C15 and D15) located within the CF compliant zone are likely related to S-type FZTWs arising from S wave. In contrast, much lower amplitudes following S in receiver functions at stations (B03, B26, C03 and D03) outside the compliant zone. We note that amplitude peaks following the P-arrivals registered at stations located within the CF compliant zone are likely P-type FZTWs. Fig.6 (d) Receiver functions computed by deconvolution between the radial- and vertical-component seismograms recorded at 5 stations of Line B and 2 stations of Line A and Line C for each. P -arrivals are aligned at time 0 s. P-to- S converted waves (S ) appear at ~4.5 s. The S-type FZTWs following S show large amplitudes and ~6.5-s duration (in grey box) at stations (B11, B13, B15, C15 and D15) within the CF compliant zone while lower amplitudes at stations (B03, B26, C03 and D03) outside the compliant zone. The multiple P arrives at ~15 s. Note that large amplitudes following P and P might relate to the P-type FZTWs. Finally, we examine such type of FZTWs recorded at four seismic Lines A, B, C and D for two teleseismic earthquakes (TE272 and TE271 in Fig. 1d and Table 1) with magnitudes of M6.1 and M6.9, occurring at 53-km depth in South America, and 28-km depth beneath Tonga Islands in Pacific Ocean, ~6,200-km (55 o ) southeast and ~8,700-km (73.5 o ) southwest of the CF, respectively. Fig. 7A shows largeamplitude FZTWs with ~6-7-s post-s duration in teleseisms recorded at stations with either 40T or L22 sensors located within the ~1-km-wide CF compliant zone, but not at farther stations out of the zone for teleseismic earthquake TE272. Fig. 7B shows large-amplitude FZTWs with ~7-8-s post-s duration recorded at stations with either 40T or L22 sensors located within the ~1-km-wide CF compliant zone, but not at farther stations out of the zone for the shallow teleseismic earthquake TE271. The longer duration of FZTWs for this shallow event is probably because the ray path from the shallow event enters the bottom of the CF compliant zone less steeply than that from the deep event, and thus FZTWs travel longer distance within the compliant zone to arrive at the CF seismic array. We notice that P-type FZTWs following the first P-arrivals are obvious in parallel-component teleseisms for teleseismic event TE272 in Fig. 7A (c) because the ray path to the seismic array is sub-parallel to the CF strike. We also notice the multiples in the later coda, probably due to waves rebounded between the free surface and Moho discontinuity. We shall confirm this mechanism using receiver-function method. 15

(c) Normalized spectral amplitude contours of teleseisms show large-amplitude FZTWs at 1-3 Hz with ~5.

16 Fig.7A (a) and (b) Parallel-component seismograms recorded at seventeen 40T stations and twenty-six L22 stations along Line B for a M6.1 teleseismic earthquake (TE272 in Fig. 1d) occurring at 53-km depth. Teleseisms have been band-pass (0.5-2 Hz) filtered, showing prominent FZTWs with ~6-7-s post-s duration in teleseisms recorded at stations located within the ~1-km-wide CF compliant zone. (c) Parallel-component teleseisms recorded at Lines A, C and D for this teleseismic event, showing prominent FZTWs with ~6-s post-s duration at stations within the compliant zone. 16

5-2 Hz) filtered, showing prominent FZTWs with ~6-7-s post-s duration in teleseisms recorded at stations located within the ~1-km-wide CF

17 Fig.7B (a) Perpendicular-component seismograms at Line B with 40T sensors, (b) parallel-component and (c) vertical-component seismograms recorded at Line B with L22 sensors for a M6.9 teleseismic earthquake (TE271 in Fig. 1d) occurring at 28-km depth. Teleseisms have been band-pass (0.5-2 Hz) filtered, showing prominent FZTWs with ~8-s post-s duration in teleseisms recorded at stations located within the ~1-km-wide compliant zone. (d) Perpendicular-component teleseisms recorded at Lines A, C and D, showing prominent FZTWs with ~8-s post-s duration at stations within the compliant zone. In above-mentioned examples, seismograms recorded at the seismic array atop the Calico Fault show the consistent wavetrains with large amplitudes and approximate 5-8-s duration appearing in a time window starting from ~5-6 s after the P-wave first-arrival for teleseismic earthquakes (Fig. 3 to Fig. 7). We interpret these large-amplitude long-duration wavetrains arising from cohesive interference of seismic waves within the low-velocity waveguide along the CF compliant zone when seismic waves from teleseismic earthquakes enter the bottom of the compliant zone at certain depth. Since these wavetrains start at ~5-s after the first-arrival of P-wave (denoted by P in figures), we tentatively interpret that the seismic waves entering the bottom of the CF low-velocity compliant zone are the P-S waves (denoted by S ) converted at the Moho discontinuity at approximate 30-km depth (corresponding to the travel-time difference of ~5-s between P and S ). Because these wavetrains are mostly apparent in horizontalcomponent teleseisms, they are likely the S-type of FZTWs with horizontal polarization. Their waveforms are similar to the fault-zone trapped waves generated by explosions and local earthquakes, and recorded at the same seismic array in the previous study [Cochran et al., 2009], but observed for teleseismic earthquakes D Finite-Simulation of Observed FZTWs for Teleseismic Earthquake We test a model of the Calico fault compliant zone from the surface to ~8-km depth on the basis of the previous model Cochran et al. (2009) combined with observations of FZTWs for teleseismic earthquakes. We use a 3-D finite-difference code (Graves, 1996; Vidale et al., 1985) to compute synthetic seismograms that fits teleseisms recorded at Line B across the CF. The finite-difference computer code is second order in time and fourth order in space, and it propagates the complete wavefield through an elastic media with a free surface boundary and spatially variable anelastic damping (an approximate Q). Our calculation used a element grid in x y z coordinates, with a grid spacing of 62.5 m to simulate a volume of 10 km in width, 10 km in length, and 10 km in depth. The lowvelocity waveguide, composed of a 1.5-km-wide fault zone of maximum velocity reduction of 50% sandwiched embedded in the higher-velocity surrounding rocks with a free surface. The receiver array was placed across the waveguide along the fault strike. In the first stage of our error-and trial forward modeling approach, we used 125-m grid spacing in a 10x10x10 km 3 volume to obtain coarse model parameters at low frequency to save computer memory space and computation time. We then used m grid spacing to increase the resolution of fault-zone structure in the model at higher frequency. Fig. 8a shows the schematic diagram to illustrate the ray path of first-arrival P wave from a teleseismic event hitting the Moho discontinuity at 30-km depth, and transmitting P and converted P-to-S (S ) waves, which sub-vertically enter the bottom of low-velocity fault zone at 10-km depth to produce FZTWs within the fault zone. Fig. 8b exhibits finite-difference seismograms for a double couple source at the Moho with its epicenter 10-km with respect to the cross-fault array using the velocity model in Fig. 10c, in which the velocities within the fault-zone are reduced by 50% from wall-rock velocities. The lowvelocity fault zone extends from the surface to the depth of ~8- km. Synthetic seismic waves are received at the array across the fault zone at surface, showing FZTWs characterized by large amplitudes and long durations arriving at stations located within a 1.5-km-wide low-velocity waveguide. Fig. 8b shows synthetic seismograms to compare with observed teleseisms recorded at Line B for a teleseismic earthquake TE272. The CF compliant zone with velocity reduction of 50% extends from the surface to 8- km depth. Synthetic waveforms developed from our inferred velocity model are in general comparable with observations for this teleseismic earthquake, suggesting that the depth extension of the CF compliant core zone with velocity reduction of 40-50% is approximately 8 km. The value is likely 2-3 km greater than the depth extension (5-6 km) of the Calico fault compliant core zone imaged by Cochran et 17

5-2 Hz) filtered, showing prominent FZTWs with ~8-s post-s duration in teleseisms recorded at stations located within the ~1-km-wide compliant zone.

18 al. (2009). However, since the depth extension and the velocity reduction within the compliant zone are negotiable in the trial-and-error forward modeling, a systematic simulation of teleseisms recorded at the seismic array atop the CF for more teleseismic events with different incident angles to the CF seismic array will provide further constraints on the true depth extension of the CF compliant zone. Fig. 8 (a) Schematic diagram illustrates the first-arrival P wave from teleseismic event hitting the Moho discontinuity between the lower crust and the upper mantle and transmitting P and S waves, which sub-vertically enter the bottom of low-velocity fault zone to produce P-type and S-type fault-zone trapped waves (P-FZTW and S-FZTW). They are recorded at stations (triangles) atop the CF compliant zone (marked by brawn color). (b) Observed (black lines) and synthetic (blue lines) perpendicular-component seismograms at Line B for a teleseismic earthquake TE272 in Table 1. The CF compliant zone with velocity reduction of 50% extends from the surface to 8-km depth. A double-couple source is put on the Moho at 30-km depth and with 10-km epicentral distance from the receiver array. (c) The model of P-wave velocities across the Calico fault with a low-velocity waveguide along the CF compliant zone to ~8-km depth, within which velocities are reduced to the maximum of ~40-50% in the center of a ~1-km-wide fault core zone at shallow depth (Cochran, et al., 2009). The fault zone is ~1.5 km wide at the surface. The lateral velocity profile across the fault is approximated as a Hanning taper, and the velocity reduction tapers linearly to zero between 0 and 10 km depth. 5. Discussion An outstanding question is the depth extent of the low-velocity damage zone along the fault. Some researchers argue that the low-velocity damage zone on faults is a near-surface feature that reaches only down to the top of seismogenic zone at the depth less than 2-3 km (e.g. Ben-Zion et al. 2003; Lewis et al. 2010). Others argue that it extends across seismogenic zone at depths to ~10-km depth (e.g. Korneev et al. 2003; Li et al., 2000; Li and Malin 2008). Wu et al. (2010) showed that the low-velocity waveguide on the SAF at Parkfield extends to the depth of 10 km or more using SAFOD borehole data. Recently, Ellsworth and Malin (2011) document a profound zone of rock damage on the Parkfield San Andreas fault downwards to at least half way (>5-6 km) through the seismogenic crust using both P-type and S- type of FZTWs recorded at the SAFOD mainhole seismograph. FZTWs recorded at Parkfield surface and borehole stations shows that the LVZ on the Parkfield SAF extends to the depth of at least ~7-8 km although the velocity reduction within the damage zone decreases with depth due to the increasing confining pressures. Although FZTWs generated by explosions and local earthquakes have been used for characterization of the subsurface fault damage structure, the wave propagation coverage is lake of resolution for the deep fault zone structure because these seismic sources are located at shallow depths. 18

seismic array atop the CF for more teleseismic events with different incident angles to the CF seismic array will provide further constraints on the true depth extension of the CF compliant zone. Fig.

19 In this article, we introduce a new-type of FZTWs recorded at the dense seismic array atop the Calico fault zone for teleseismic earthquakes. We interpret the observed FZTWs arise from S-wave converted from P-wave at the Moho discontinuity and sub-vertically incident at the bottom of CF compliant zone. Therefore, these waves are capable to provide more unprecedented constraints on the depth extension of fault damage structure at seismogenic depth where there is lack of approach of waves generated by explosions and local earthquakes. The data recorded at the dense array of 100 three-component seismographs deployed atop the Calico fault in the central Mojave Desert, Southern California, provide us a good opportunity to detect the seismic phases closely following the first-arrival P wave. The seismic array worked in continuous recording mode at an extremely quiet site for six months and recorded 72 teleseismic earthquakes with magnitudes M 6 and occurring at distances of ~40 o -80 o great circles (approximate 5,000-11,000 km) to the Calico seismic array site. In order to further confirm our observation of this new type of FZTWs, We shall simulate this new type of FZTWs using a full waveform modeling technique with inverse, such as the FD3D tomography method (Chen, 2012). We shall also identify the FZTWs from teleseismic earthquakes recorded at seismic arrays deployed atop other active faults such as San Andreas Fault near Parkfield (Li et al., 2004; 2012) and at the rupture zone of the 2010 M7.1 and 2011 M6.3 Canterbury earthquakes in New Zealand (Li et al., 2014). Acknowledgments This study is supported by Southern California Earthquake Center s award and is benefited by the previous results by Cochran et al. (2009). Thank Elizabeth Cochran for her work on archive of the data recorded at the seismic array deployed at the Calico fault in Thank En-Jui Lee for his help to download the data from IRIS DMC and Y.L. Chen for using his computer program to calculate receiver functions. Reference Ben-Zion, Y., Z. Peng, D. Okaya, L. Seeber, J. G. Armbruster, N. Ozer, A. J. Michael, S. Barris, and M. Aktar, A shallow fault zone structure illuminated by trapped waves in the Karadere-Dusce branch of the North Anatolian Fault, Western Turkey, Geophys. J. Int., 152, , Chen, P., Full-wave seismic data assimilation: a unified methodology for seismic waveform inversion, in Imaging, Modeling and Assimilation in Seismology, edited by Yong-Gang Li, 350pp, published by DE GRUYER and China Higher Education Press, Feburary ISBN , Cochran, E. S., Y. G Li, P. M. Shearer, S. Barbot, Y. Fialko, and J. E. Vidale, Seismic and geodetic evidence for extensive, long-lived fault damage zones, Geology, v9.37; no. 4, , doi: /g25306a.1; Data Repository item , Ellsworth W. L. and P. E. Malin, Deep rock damage in the San Andreas fault revealed by P- and S-type fault zone guided waves, Sibson s volume, Geological Society Special Publication, New Zealand, V359, 39-53, Fialko, Y., Probing the mechanical properties of seismically active crust with space geodesy: Study of the coseismic deformation due to the 1992 Mw7.3 Landers (southern California) earthquake: J. Geophys. Res., v. 109, B03307, doi: /2003JB002756, Fialko, Y., Sandwell, D., Agnew, D., Simons, M., Shearer, P., and Minster, B., Deformation on nearby faults induced by the 1999 Hector Mine earthquake: Science, v. 297, p , doi: /science , Ganev, P.N., Dolan, J.F., Oskin, M.E., Owen, L.A., and Le, K.N., Paleoseismologic evidence for multiple Holocene earthquakes on the Calico fault: Implications for earthquake clustering in the eastern California shear zone: Southern California Earthquake Center Annual Meeting Proceedings and Abstracts, v. XVIII, p , Graves, R.W., Simulating seismic wave propagation in 3D elastic media using staggered-grid finite differences, Bull. Seis. Soc. Am., 86, , Korneev, V. A., R. M. Nadeau, and T. V. McEvilly, Seismological studies at Parkfield IX: Fault-zone imaging using guided wave attenuation, Bull. Seism. Soc. Am. 80, ,

Therefore, these waves are capable to provide more unprecedented constraints on the depth extension of fault damage structure at seismogenic depth where there is lack of approach of waves generated

20 Lewis, M. A. and Y. Ben-Zion, Diversity of fault zone damage and trapping structures in the Parkfield section of the San Andreas Fault from comprehensive analysis of near fault seismograms. Geophys. J. Int., doi: /j X x Li, Y.G., P.C. Leary, K. Aki, and P.E. Malin, Seismic trapped modes in the Oroville and San Andreas fault zones, Science 249, , Li, Y.G., and P.C. Leary, Fault-zone trapped seismic waves, Bull. Seis. Soc. Am., 80, , Li, Y.G. and J.E. Vidale, Low-velocity fault zone guided waves; numerical investigations of trapping efficiency, Bull. Seis. Soc. Am., 86, , Li,Y. G. and P. E. Malin, San Andreas Fault damage at SAFOD viewed with fault-guided waves, Geophys. Res. Lett., 35, L08304, doi: /2007gl032924, Li, Y. G., K. Aki, D. Adams, A. Hasemi, and W. H. K. Lee, Seismic guided waves trapped in the fault zone of the Landers, California, earthquake of 1992, J. Geophys. Res., 99, 11,705-11,722, Li, Y. G., J. E. Vidale, K. Aki, and F. Xu, Depth-dependent structure of the Landers fault zone using fault zone trapped waves generated by aftershocks, J. Geophys. Res. 105, , Li, Y. G., J. E. Vidale, S. M. Day and D. Oglesby, Study of the M7.1 Hector Mine, California, earthquake fault plan by fault-zone trapped waves, Hector Mine Earthquake Special Issue, Bull. Seism. Soc. Am., 92, , Li, Y. G., J. E. Vidale, D. Oglesby, S. M. Day and E. Cochran, Multiple-fault rupture of the M7.1 Hector Mine, California, earthquake from fault-zone trapped waves, J. Geophys. Res., 108, ESE 11, 1-25, Li, Y. G., J. E., Vidale, and S. E. Cochran, Low-velocity damaged structure of the San Andreas fault at Parkfield from fault-zone trapped waves, Geophy. Res. Lett., 31, L12S06, Li, Y. G., P. Malin, and E. Cochran, Fault-zone trapped waves: High-Resolution Characterization of the Damage Zone on the Parkfield San Andreas Fault at Depth, Chapter 3 pp in book: Imaging, Modeling and Assimilation in Seismology, edited by Y. G. Li, China High-Education Press, Beijing, De Gruyter, Boston, February Li, Y.G., G. De Pascale, M. Quigley, and D. Gravely, Fault damage zones of the M7.1 Darfield and M6.3 Christchurch earthquakes characterized by fault-zone trapped waves, Tectonophysics, V618, , ( /j.tecto ), Peltzer, G., Crampe, F., Hensley, S., and Rosen, P., Transient strain accumulation and fault interaction in the Eastern California shear zone: Geology, V29, , doi: / (2001)029<0975: TSAAFI>2.0.CO;2, Vidale, J.E., D.V. Helmberger, and R.W. Clayton, Finite-difference seismograms for SH waves, Bull. Seis. Soc. Am. 75, , Wu, J., J. A. Hole, and J. A. Snoke, Fault-zone structure at depth from differential dispersion of seismic guided waves: Evidence for a deep waveguide on the San Andreas fault, Geophys. J. Int., 182, , doi: j X x

Li, Y.G., and P.C. Leary, Fault-zone trapped seismic waves, Bull. Seis. Soc. Am., 80, 1245-1271, 1990. Li, Y.G. and J.E.

21 ASSESSING STUDENT LRARNING IN ARITHMETIC AND NUMBER SYSTEMS Shuhua An California State University, Long Beach, USA This paper analyzes trends in assessing student learning arithmetic and number systems by discussing two different types of assessments, followed by addressing new trends in assessments in arithmetic and number systems. The paper reviewed and highlighed examples of studies in assessment in conceptual undersanding, procedual fluency, reasoning, and problem sovling, and the paper also reviewed examples of assesment in combined mulitple areas and classroom assessment. Introduction One of the key instructional components for effective elementary mathematics instruction is assessment. National Research Council (1993) specifies mathematics assessment as a way of measuring what students know and of expressing what students should learn (p.1). Assessment is not only a factfinding activity that describes conditions that exist at a particular time (Best & Kahn, 2006), but also should support the learning of important mathematics and furnish useful information to both teachers and students (NCTM, 1995). This important role of assessment requires educators to consider assesment as the process of gathering evidence about a student s knowledge of, ability to use, and disposition towards mathematics and of making inferences from the evidence for a variety of purposes (NCTM, 1995, p.3). The purpose of assessment as a process of gathering evidence and making inferences from that evidence for a variety of goals has played a vital role in mathematics assessment in the last two decades. Recent developments in the new Common Core State Standards for Mathematics (CCSSM) the US have futher heightened the clear purpose of assessment as to support and enhance student learning and called for focusing on mathematics instruction that provide. The three the key shifts are called for by the Common Core: (1) Foucs: Greater focus on fewer topics, (2) Coherence: Linking topics and thinking across grades, and (3) Rigor: Pursue conceptual understanding, procedural skills and fluency, and application with equal intensity (National Governors Association Center for Best Practices, & Council of Chief State School Officers, 2010). The key shift of rigor provided a clear direction in mathematics instruction as well as assessment that requires students to achieve a balance in mathematics learning in conceptual understanding, procedural skill and fluency, and the ability to apply mathematics to solve problems (Wu, 2008; An & Wu, 2014), which is supported by research that effective classroom teachers always use multiple forms of assessments that are meaningful and applicable in classroom to support student learning (An & Wu, 2014; McMillan, 2011). The purpose of this article is to identify and describe examples of the central themes in order to illustrate key aspects of the assessments in arithmetic and number systems. This article provides the overall review on traditional and alternative assessments and addresses new trends and chellenges in assessments in arithmetic and number systems, followed by discussing some specific assesment studies based on a review of related literature on assessing student matheamtical conceptual understanding, procedural skill and fluency, and problem solving teacher in arithmetic and number systems in the recent decades. The article also show an examples of combination of the three areas, and discussion of the classroom assessment. Traditional and alternative assessments in arithmetic and number systems Two main types of assessments have been used in assessing student learning in arithmetic and number systems, traditional and alternative. Traditional assessments, such as standardized tests are mainly multiple-choice tests. According to Thornberg (2001), standardized testing has become a large part of shaping the educational system and its improvements. They measure test-taking skills and a certain degree of what students know, and they cover knowledge-based questions, which students can answer by memorization of factual information, or comprehension, simple problem solving, or even good guessing 21

22 (Fuchs et al. 1999). However, because of their accountability, educators often feel pressured to teach to the test with the hopes that students will score high (Lewis, 2001). The results of standardized tests, such as NAEP mathematics from show an improving trend of elementary childrens learning ourcome, but still no more than 42% percentage of fourth-graders were at or above Proficient level (The Nation s Report Card, 2013). Researchers (Suurtamm, Koch, & Arden 2010) have called that assessment must go beyond focusing on memorization of algorithm and procedures by responding and assessing students mathematical understanding. Therefore, standardized testing should not be the only form of assessment used in schools (NCTM, 2000). In recent decades, the other types of assessments - alternative assessment is becoming an increasingly important area in mathematics education because they are authentic assessments, performance-based (Sweet, 1993), or formative assessments, providing a more reflective evaluation of what students are learning in the classroom, as opposed to a general overview which standardized testing measures. According to Wu and An (2007), alternative assessments offer a wider range of student choice, and allow teachers to monitor their students progress in a much more detailed manner. They offer a more studentcentered approach to learning, and measure students ongoing progress in multiple forms. For example, mathematics portfolios of students work throughout the year are used to mark growth and improvement, while mathematics journals promote students to use their thinking skills and write about their learning (Micklo, 1997). One of the most significant discussions in assessments, no matter what forms of assessments, whether traditional or alternative, concerns which characteristics of assessments work for the students and which characteristics hurt the students. After all, students are at the center of education and their progress marks the quality of education (Wu & An, 2007). In order to appropriately assess student learning in arithmetic and number systems, it is important to know what the assessment entails and what the assessments are actually measuring. New trends and chellenges in assessments in arithmetic and number systems Smarter balanced assessment and four claims. Recent developments and impletementations in the common core standards for mathematics (CCSSM) in the United States have led to a renewed interest in assessing students higher-order thinking with deep understanding and reasoning in mathematics in various froms. For examples, the new Smarter Balanced Assessments, alinged CCSSM, require students to think critically, solve problems, and show a greater depth of knowledge (Smarter Balanced Assessment Consortium, 2012). The Smarter Balanced Assessment has four claims: (1) Concepts and Procedures: Students can explain and apply mathematical concepts and interpret and carry out mathematical procedures with precision and fluency. (2) Problem Solving: Students can solve a range of complex, wellposed problems in pure and applied mathematics, making productive use of knowledge and problemsolving strategies. (3) Communicating Reasoning: Students can clearly and precisely construct viable arguments to support their own reasoning and to critique the reasoning of others. (4) Modeling and Data Analysis: Students can analyze complex, real-world scenarios and can construct and use mathematical models to interpret and solve problems (The Smarter Balanced Assessment Consortium, 2012) The unique feature of the Smarter Balanced summative assessments is that it goes beyond multiple-choice questions to include four types of items: 1) Selected-response items, 2) Technology-enhanced items, 3) Constructed-response items, and 4) Performance tasks. However, It is a chellenging task for elementary teachers to support deeper learning and the development of 21st century competencies essential for students future success (Pellegrino & Hilton, 2012). Drawing on Norman Webb s depth of knowledge (DOK) (Webb, 1997), Herman and Linn (2013) define deep learning in four DOK levels: DOK1- Recall and Reproduction; DOK2 - Basic Application of Skills/Concepts; DOK3 - Strategic Thinking; DOK4 - Extended Thinking. These four levels of DOK now is widely used by classroom teachers in assessing and supporting deep learning in mathematics for their students in the United States. Assessing four claims based on CCSSMPs. The new Common Core State Standards for Mathematical Practice (CCSSMPs) in the US describe a variety of expertise that mathematics educators at all levels 22

23 should seek to develop in their students (National Governors Association Center for Best Practices, & Council of Chief State School Officers, 2010). These CCSSMPs require the development of deep understanding and reasoning in mathematics with a high level of mathematics thinking, reasoning, arguments, communication, and modeling skills. However, these CCSSMPs have posed challenges to classroom teachers on how to forster students deep understanding, sound reasoning and argument skills in math classrooms. In recent released 2015 Smarter Balanced Assement results in California show that more than 40% of elementary students in grades 3-5 scored below standards in the areas of concepts and procedures, followed by more than 38% below standards in problem solving /Modeling and Data Analysis. The area of Communicating Reasoning had more than 39% of students who did not met standards at grades 4 and 5. Areas Below Standard Concepts and Procedures Problem Solving/Model ing and Data Analysis Communicati ng Reasoning The student does not demonstrate the ability to explain and apply mathematical concepts and interpret and carry out mathematical procedures with precision and fluency. The student does not demonstrate the ability to solve a range of complex, well-posed problems in pure and applied mathematics, making productive use of knowledge and problem-solving strategies. The student does not demonstrate the ability to analyze complex, real-world scenarios and construct and use mathematical models to interpret and solve problems. The student does not demonstrate the ability to clearly and precisely construct viable arguments to support the student's own reasoning and to critique the reasoning of others. Table 1: California Elementary Student Smarter Balanced Assessment Results These data show an urgent need to develop an effective approach to support elementary children in improving their learning in arithmetic and number systems as they are the major standards in CCSSM in the US. Performance task and Smarter balanced assessment Another challenge faced by many classroom teachers is supporting students in communicating reasoning and doing performance tasks bescasue Smarter Balanced Assesements include performance task items in its tests at every grade level. Performance- assessments are alternative or authentic assessments (Sweet, 1993). The aim of the authentic assessments is determine what students have learned, and how they are to apply their knowledge to a variety of tasks (Adamson & Darling Hammond, 2010; Caffrey, 2009). According to the Smarter Balanced Assessment Consortium (2012), the performance tasks of Smarter Balanced Assesements measure a student s ability to demonstrate critical-thinking and problem-solving skills. They challenge students to apply their knowledge and skills to respond to complex real-world problems. The forms of the performance tasks can be best described as collections of questions and activities that are coherently connected to a single theme or scenario. Therefore the goals of performance tasks are to measure students capacities of deep learning, understanding, research and writing skills, critical thinking and reasoing, and complex analysis. To support students learning and success in performance tasks, students should be given meaningful and real world related tasks with authentic products to show their understanding of the material in performance tasks (McBee & Barnes, 1998). It provides teachers with the opportunity to promote students interests and engage them in active learning through reflection and demonstration of the thinking processes (Tung, 2010). These student-centered assessments evaluate students at a direct level (Wright, 2001). Examples of assessments in conceptual understanding, compuation, and problem solving 3r d 40 % 38 % 28 % 4t h 47 % 39 % 39 % 5t h 51 % 46 % 41 % 23

24 This section provides examples of asessments focusing conceptul understanding, procedual fluencey, and problem solving, and their impact on teaching and learning mathematics in arithmetic and number systems. The samples of studies were selected and catergorized based on themes and internatioal representation to show trends in assessments in the specific foucses. These samples are orgnized based on five themes: understanding, procedual fluencey, problem solving, combination of the three areas, and classroom assessment. Assessment in conceptual understanding arithmetic and number systems Berman s study (2011) aimed to help teachers assess students understanding of place value, so teachers can ensure what conceptual learning and teaching in arithmetic are needed. The study described how to assess students understanding and manipulation of number system by using the sixtasksofplacevalue (SToPV), which takes about five minutes to do, and can be used to explore students from third grade. The tasks were a combination of doing some hands-on activities and giving responses to the teacher s questions. There were three stages of conceptual understanding in place value in the assessment, understanding, construction, and emergent. Each task gave the rubric of the four different levels of conceptual understanding. According to student s response levels in each task, teachers could determine which stage the student was demonstrating by referring to the definition of the three stages. The author conclused that the SToPV can be administered in daily classroom, and it gives clear definition of where the student is in conceptual understanding of the number system, which helps classroom teachers in their math teaching. The study of Baglici, Codding, and Tryon (2010) followed a cohort of the first grade students for a whole school year, which was an extension of a previous study of the Tests of Early Numeracy (TEN; Chard et al., 2005; Clarke & Shinn, 2002, 2004). The purpose of the study was to determine which TEN measures demonstrate sensitivity to growth from kindergarten to first grade, ascertain whether TEN performance in kindergarten is correlated with first-grade TEN performance, and examine whether TEN performance in kindergarten predicts first-grade mathematics computation skills, year-end mathematics report card grades, and teacher ratings of mathematics skills. The participants were 61 students from three suburban public schools near New York City. The study assessed the student performance from kindergarten to first grade. The assessment used four 1- minute TEN measures to collect students response in arithmetic. The four measures were oral counting, number identification, quantity discrimination, and missing number. Responses for the four measures ranged from 0 to 10 for kindergarten and up to 20 for first grade. Findings showed that In nearly all the analyses, performance on the kindergarten MN measure was a significant predictor of first-grade computation and teacher-determined outcome measures (i.e., ACES-M); it also yielded accept- able reliability coefficients (p. 100). Bailey, Hoard, Nugent, and Geary s study (2012) was designed to determine whether measures of conceptual knowledge of fractions and computational fractions skills concurrently predict mathematics achievement, controlling for other factors (p. 448) by providing a cross-lagged assessment to connect fractions and mathematics achievement across sixth and seventh grades. The study analyzed 212 children who completed at least two tasks given by the researchers. The standardized measures consist of intelligence, achievement, working memory, and mathematical tasks (number sets and number line estimation). The psychometric measures consisted of computational arithmetic, computational fractions, and fractions comparison test. The cross-lagged effects showed that performance on the sixth grade fractions concepts measure predicted 1-year gains in mathematics achievement (ß =.14, p <.01), controlling for the central executive component of working memory and intelligence, but sixth grade mathematics achievement does not predict gains on the fractions concepts measure (ß =.03, p >.50). The research also demonstrated that measures of fluency with computational fractions significantly predicted seventh grade mathematics achievement above and beyond the influence of fluency in computational whole number arithmetic, performance on number fluency and number line tasks, central executive span, and intelligence. The findings indicated the importance of fraction competence for mathematics achievement beyond the elementary school years (Siegler et al., 2011, 2012) and supported the hypothesis 24

25 that improving children s competence with fractions is likely to facilitate gains in mathematics achievement. Assessment in computation and procedural fluency in arithmetic and number systems Liu s study (2009) aimed at collecting baseline data for computational estimation by Chinese students. About 403 third graders and fifth graders participted in the study from four different types of elementary schools in different areas in China. The instrument of the study was based on the Multiplication Estimation Test (MET) with some revisions to the original one. The revised MET had 32 items with an equal number of problems on all the dimensions. The author concluded that students often will not estimate simply at the request to estimate if an exact answer is within their mental computation capability, and a two-step process is suggested for helping students decide what route to take when given arithmetic problems. The longitudinal study by Muldoon, Towse, Simms, Perra, and Menzies (2013) aimed at assessing the relationships between number line estimation, counting, and mathematical abilities, in response to claims that the quality (and in particular linearity) of children s mental representation of number acts as a constraint on number development. The pariticipants were 99 five-year-old students from four primary schools in Edinburg, Scotland. They were tested individually using the three tasks in number estimation, counting, and math ability in four testing sessions with varied focuses in each session 3 monthly intervals. For all analyses the researchers used the ability score. The finding showed that there were correlations between the three types of ability, but while the quality of children s estimations changed over time and performance on the mathematical tasks improved over the same period, changes in one were not associated with changes in the other. The findings suggested that the linearity of number representation is not significantly privileged in its impact over and above simple procedural number skills. The authors proposed that both early arithmetic success and estimating skill are bound closely to developments in counting ability. Assessment in problem solving in arithmetic and number systems Kalyuga (2006) described an alternative schema-based rapid assessment technique and investigated how to apply it in arithmetic word problem solving in the study. Fifity five eighth graders from a Sydney school participatec in the assessment. The students were asked to finish two different tests, the traditional test and the first-step diagnosis test. In the first-step diagnosis test, 20 arithmetic problems were given, and students only needed to write their first solution in 30s. If a response to a task was an immediate next step expected in the fully worked out, detailed fine-grained solution procedure according to the first schema for that task, the response was allocated a score 1. If an answer was not an immediate next but one of the following steps towards the solution (or even the final step of the solution), it was al- located an additional score for each skipped step. The study showed that a rapid measure of learners schematic knowledge structures based on monitoring immediate traces of cognitive processes in working memory can be constructed and used for valid diagnostic inferences in a relatively complex instructional domain. A case study by Mundia (2012) aimed at identifying the degree and nature of problems in math for fifth graders, finding and recommending ways the child s math problems could be investigated further to gain additional insights. The participants were 29 Grade 4 children. The data for this case study were collected through observations, school assessment reports and documents, an in-take interview with one of the parents, a researcher constructed 16- item diagnostic test covering contents (addition, subtraction, multiplication, division); an error analysis of the child s mistakes in mathematics from the diagnostic class wide test; and a think-aloud diagnostic interview based on the error analyses. The survey data were analyzed quantitatively while observational and interview data were analyzed qualitatively. The study identified some learning difficulties of the fourth graders. The difficulties were inability to use the four arithmetic operations (addition, subtraction, multiplication, and division) efficiently; not understanding the relationship between units, tens and hundreds; using any two of the four arithmetic processes (+, -, x, 25

26 ) in combination within one operation; treating each column as a separate problem; place value problems or wrong alignment of numbers; poor eye-hand coordination leading to dysgraphia; and shortterm memory / memory lapses (p. 361). Assessing student learning in muliple areas and forms in arithmetic and number systems The effective assessment task should be an open-ended task, and it should include the three components (NRC, 1993): 1) Involving significant mathematics; 2) Enhancing mathematics learning and supporting good instructional practice; 3) Supporting every student s opportunity to learn important mathematics. Various studies suggest using rich mathematical tasks to develop students capacity in reasoning and argument (Mok & Kaur, 2006; Shimizu, Kaur, Huang, & Clarke, 2010). Mathematics tasks are important vehicles for classroom instruction that aims to enhance students learning. To achieve quality mathematics instruction, then, the role of mathematical tasks to stimulate students cognitive processes is crucial (Hiebert & Wearne, 1993). Current research evidence indicates that students who are given opportunities to work on their problem solving skills in rich mathematical tasks enjoy the subject more, are more confident and are more likely to continue studying mathematics, or mathematics-related subjects (Hewson, 2015). One example of rich mathematical tasks in arithmetic and number systems demonstrated in Wu and An s study (2015) is using the Model-Strategy-Application with Reasoning (MSAR) in assessing the effects of children learning in diverse classrooms. The results shows that applying the MSAR approach in teaching and assessing student learning helped diverse students at grades 2, 3, and 5 understand arithmetic and number systems from drawing visual models, developing procedural fluency using various strategies, and building competence in problem solving in real world applications. The findings of Wu and An s support Hopkins s (2011) idea of combining concepts and procedures and problem solving together. Hopkins (2011) indicated that students will have mathematical learning difficulties when some students conceptual understanding and procedural learning of arithmetic becomes less integrated. For example, various research studies showed the effects of integral nature of understanding place value numeration with applying it in arithmetic and problem solving on children s learning place value acknowledged (Steffe & Cobb, 1988; Wright, 1996; Hopkins; 2011). Seethaler and Fuchs study (2006) aimed at examining the relations of various cognitive abilities and aspects of math performance with computational estimation skill of third graders. Students (n = 315) were assessed on language, nonverbal reasoning, concept formation, processing speed, long-term memory, working memory, inattentive behavior, basic reading skill, arithmetic number combination skill, doubledigit computation skill, and computational estimation ability. The researchers conducted a one-way analysis of variance (ANOVA) on estimation skill, using computation performance status as the betweengroups factor. Then, correlation and multiple regression were used to explore the extent to which the predictor variables under examination correlated with, and accounted for variance in, estimation skill. The conclusion of the study was that skills in arithmetic number combinations, nonverbal reasoning, concept formation, working memory, and inattentive behavior may play significant roles in the prediction of estimation outcome. Classroom Assessment According to Callingham (2010), The classroom is the powerhouse of learning (p.2). Teachers play a major role in making student learning successful (Hattie, 2009). Sandra Horn, and William Sanders (1997) have corroborated the conclusions and indicated that the most important factor affecting student learning is the teacher. It is important to provide a varity of assesments in classroom to support student mathematics learning. These type of assessments include preassessent that address a student readiness to learn to support planning for achieving maximally effectiveness in student learning, and formative assessment that occurrs during teaching (McMillan, 2011). Formative assessment is an interactive and ongoing process (Airasian, 1994) and focuses on active feedback by teachers to support learning (Marzano, 2006; Shavelson, 2006). According to Marzano (2006), research on effective classroom assessment lead to the following four gereralizations: 26

27 . Feedback from classroom assessments should give students a clear picture of their progress and how they might improve. Feedback on classroom assessments should encourage students to improve their learning. Classroom assessment should be formative in nature. Formative classroom assessments should be frequent. A study on formative classroom assessment conducted by An and Wu (2011) showed that teachers can provide more and better feedback to students when they use the sampling strategy addressed in the study for assessing and analyzing student work. Their study engaged ten classroom teachers in an inquiry process of the four steps of identifying errors, analyzing reasons for the errors, designing approaches for correction, and taking action for correction. The teachers, include a 5 th grade teacher, made obvious progress in their knowledge of assessing students thinking, understanding the difficulties and challenges their students had in learning mathematics through analyzing their daily homework. Summary and reflection In summary, the list of studies reviewed in this artilce is not intended to be exhaustive. The purpose of this article was to address and highlight some examples of studies related to assessment in student learning in arithmetic and number systems. The results of these studies demenstrated recent trends in assesments in arithmetic and number systems, focusing the process of assessing student learning in conceptual undersanding, procedual fluency, reasoning, and problem sovling in real world application with mulitple forms. These studies showed that classroom teachers are the key in assessing and supporting studnet learning, and effective classroom teachers should use multiple forms of assessments that are interactive and meaningful in classroom to support student learning in arithmetic and number systems. References Airasian, P. W. (1994). Classroom assessment (2nd ed.). New York: McGraw Hill An. S. & Wu, Z. (2011). Enhancing Mathematics Teachers' Knowledge of Students' Thinking from Assessing and Analyzing Misconceptions. International Journal of Science and Mathematics Education, Springer. An, S., & Wu, Z. (2014). Using the Evidence-Based MSA Approach to Enhance Teacher Knowledge in Student Mathematics Learning and Assessment. Journal of Mathematics Education, Vol 7, No. 2, Adamson, F., & Darling-Hammond, L. (2010, April). Beyond Basic Skills: The Role of Performance Assessment in Achieving 21st Century Standards of Learning. Stanford, CA: Stanford Center for Opportunity Policy in Education. California Department of Education. (2015). Mathematics framework for California public schools Sacramento, CA: California Department of Education. Caffrey, E. D. (2009). Assessment in Education and Secondary Education: A Primer.Washington: Congressional Research Service. Callingham, R. (August 16, 2010). Mathematics assessment in primary classrooms: Making it count. Research Conference ACER Research Conferences. Paper 7. Retrived from Hattie, J. A. C. (2009). Visible learning: A synthesis of meta-analyses relating to achievement. Abingdon: Routledge. Herman, J.L. & Linn, R.L. (2013). On the road to assessing deeper learning: The status of Smarter Balanced and PARCC assessment consortia. (CRESST Report 823). Los Angeles, CA: University of California, National Center for Research on Evaluation, Standards, and Student Testing (CRESST). 27

28 Hiebert, J., & Wearne, D. (1993). Instructional tasks, classroom discourse, and students learning in secondgrade arithmetic. American Educational Research Journal, 30, Horn, S., & Sanders, W. (1997). Teacher and Classroom Context Effects on Student Achievement: Implications for Teacher Evaluation. Journal of Personnel Evaluation in Education, 11: 57±67, Lewis, A. (2001). Heads in the sand. Phi Delta Kappan, 83(1), 3-5. Marzano, Robert, J Classroom Assessment and Grading that Work. ASCD. Alexandria, Virginia. McMillan, J. H. (2000). Fundamental assessment principles for teachers and school administrators. Practical Assessment, Research & Evaluation, 7(8). Retrieved April 27, 2016 from Micklo, S.J. (1997). Math portfolios in the primary grades. Childhood Education, 73(4), Mok, I.A.C. & Kaur, B. (2006). Learning Tasks. In Clarke, D., Emanuelsson, J., Jablonka, E., and Mok, I.A.C. (eds.) Making Connections: Comparing Mathematics Classrooms Around the World (pp ). Rotterdam: Sense Publishers B.V. National Council of Teachers of Mathematics (NCTM). (1995). Assessment standards. Reston, VA: NCTM. National Council of Teachers of Mathematics (NCTM). (2000). Principles and Standards for School Mathematics. Reston: VA: NCTM. National Governors Association Center for Best Practices, & Council of Chief State School Officers. (2010). Common Core State Standards for Mathematics. Washington D.C.: National Governors Association Center for Best Practices, Council of Chief State School Officers. National Research Council (1993). Measuring what counts: a conceptual guide for mathematics assessment. Washington, DC: National Academy Press. Sanders, W. L., Wright, S. P., & Horn, S. P. (1997). Teacher and classroom context effects on student achievement: Implications for Teacher Evaluation. Journal of Personnel Evaluation in Education. Volume 11, Issue 1, pp Sweet, D. (1993, September). Performance Assessment. (Office of Research, Office of Educational Research and Improvement (OERI) of the U.S. Department of Education.) Retrieved from Education Research Consumer Guide: Smarter Balanced Assessment Consortium. (2012). Claims for the Mathematics Summative Assessment. Retrieved from: Mathematics-Claims.pdf The Nation s Report Card (2013). What level of knowledge and skills have the nation's students achieved? Retrived from Thornberg, D. (2001). Pencils down! How decontextualized standardized testing can destroy education. Multimedia Schools, 8(3), 6-8. Tung, R. (2010). Including Performance Assessments in Accountability Systems: A Review of Scale Up Efforts. Center for Collaborative Education and the Nellie Mae Education. Pellegrino, J. W., & Hilton, M. L. (Eds.). (2012). Education for life and work: Developing transferable knowledge and skills in the 21st century. Washington, DC: The National Academies Press. Webb, N. (1997). Research Monograph Number 6: Criteria for alignment of expectations and assessments on mathematics and science education. Washington, D.C.: CCSSO. Wright, A. (2001). The ABCs of assessment. The Science Teacher, 68(7), Wu, Z. & An, S. (2007). Using alternative assessments to assess students learning: Discussion of 28

29 traditional and authentic assessments. In N. Idris (Ed.), Classroom assessment in mathematics education (pp ). Selangor, Malaysia: McGraw-Hill Education. Wu, Z. (2008). Using the MSA model to assess Chinese sixth graders mathematics proficiency. Journal of Mathematics Education. 1(1), Wu, Z., & An, S. (2015). Teaching elementary and middle school mathematics using the MSA approach: Model, strategy, and application (2 nd ed). Irvine, CA: Education for All Publisher. 29

30 Game Theory Models for Infectious Diseases Sheng-He Huang 1, Wensheng Zhou 2, Ambrose Jong 1, Huan Qi 3 1 Childrens Hospital Los Angeles, University of Southern California, Los Angeles, CA, 2 HRL Laboratories, Malibu, CA, 3 Institute of Systems Engineering, Huazhong University of Science & Technology, Wuhan, China Corresponding author: shhuang@hsc.usc.edu Abstract The reductionism and Manichaean view of the microbe human host relationship are the two major limitations in the conventional theories of microbial infection. Three focal point theory-based game models (pure cooperative, dilemma and pure conflict) are proposed for resolving those problems. There exists a dynamic duality relationship (DDR) between symbiosis (Sym) and pathogenesis (Pat) in microbial infection, which is the most fundamental problem in infectomics. Our health is associated with the dynamic interactions of three microbial communities [nonpathogenic microbiota (NP) (Cooperation), conditional pathogens (CP) (Dilemma), and unconditional pathogens (UP) (Conflict)] with the hosts at three different health statuses [nonsusceptibility (NS), conditional susceptibility (CS), and unconditional susceptibility (US)]. Sym and Pat can be quantitated by measuring symbiotic index (SI), which is quantitative fitness for the symbiotic partnership, and pathogenic index (PI), which is quantitative damage to the symbiotic partnership, respectively. The values of SI and PI can be used for calculation of the symbiotic point (SP). 1. Introduction Infectious diseases caused by bacterial, viral, fungal or parasitic pathogens continue to be the leading cause of morbidity and mortality worldwide despite the availability of effective anti-microbial agents and vaccines over the last fifty years [1]. The continual emergence of previously undescribed new pathogens, reemergence of old pathogens, and the rising crisis of antibiotics resistance will certainly heighten the global impact of microbial infections in the 21st century. These problems are mainly due to inadequate knowledge of the dynamic duality relationships (DDR) between symbiosis (Sym) and pathogenesis (Pat) in microbial infections [2]. The term symbiosis, which may have many variations on its definition, in this paper refers to living together through a close and prolonged association between two or more organisms of different species [3, 4]. Duality is defined as different ways of looking at the same thing [5]. There are two major limitations inherent in the conventional theories of microbial infection. On the one hand, in the past century biology and medicine including infectious diseases have been dominated by the reductionistic approaches. Focusing research on individual virulence genes and the important pathogens has been the traditional approach to human infectious diseases. On the other hand, as Joshua Lederberg pointed out [6, 7], medical science is imbued with the Manichaean view of the microbe human host relationship: we good; they evil. Almost all broad-spectrum antimicrobial agents, which are in the best interest of pharmaceutical industries, kill both the good microbes as well as the bad germs. Even though narrow-spectrum anti-infective agents are not narrow for pathogens, they also target both the good and bad microorganisms with a limited range of species. 2. Research Questions Animals and plants are continually infected by an extensive diversity of symbiotic or invading organisms including bacteria, virus, fungus or parasites. Infection of bacteria by phages started long before the emergence of animals and plants [8]. Microbial infection is an evolutionary paradigm which is associated 30

31 with co-evolution between hosts and microbes [6, 7, 9]. This co-evolution can be defined as the process of reciprocal and dynamic genetic changes in two or more species [2]. The conventional wisdom in medicine holds that microbial infection is a pathogenic process in which a pathogen enters, establishes itself and multiplies in the host [10]. The emphasis is on the antagonism or conflict, not the mutualism. This represents zero-sum thinking the belief that if one player gains, other player must inevitably lose. Methods and concepts of the zero-sum game theory have proved successful in studying the strategy of pure conflict. The most challenging issue in infectious diseases is how to dissect the dynamic Sym/Pat duality relationships in microbial infections using infectomics and mathematics such as game theory. Game theory, defined in the broadest sense, is the study of the strategies of conflict, cooperation and mixed situations in which both coexist. This article attempts to enlarge the scope and application of game theory in infectious diseases, extending from the zero-sum games to the nonzero-sum games. CP..Microbial Community Subhealth Uncond.Sus. (US) Host Conditional Sus. (CS) Host Non-susceptible (NS) Host UP Microbial Community Infect. Disease Health Non-Pathogenic (NP) Microbial Community Fig.1 Schematic representation of interactions of three microbial communities [non-pathogenic (NP), conditional pathogenic (CP) and unconditional pathogenic (UP)] with with the hosts at three different health statuses [non-susceptibility (NS), conditional susceptibility (CS), and unconditional susceptibility (US)]. 3. Research Evidence and Methods 3.1. Three Community Principles of Microbial Infections Our health is associated with the dynamic interactions of three microbial communities [2] [nonpathogenic microbiota (NP), conditional pathogens (CP), and unconditional pathogens (UP)] with the hosts at three different health statuses [nonsusceptibility (NS), conditional susceptibility (CS), and unconditional susceptibility (US)] (Fig.1). NP is the major microbial community which forms a healthy symbiotic superorganism with the hosts. The ecology and evolution of NP-NS interaction is essential and fundamental for health. From birth to death, we share a benign coexistence with a vast, complex, and dynamic consortium of microbes. Most of our microbial commensals reside in our gastrointestinal (GI) track packed with up to 100 trillion (10 14 ) microbes [1, 11]. The GI tract harbors a rich microbiota of >600 different bacterial species. Some of these microorganisms have important health functions. These include stimulating the immune system, protecting the host from invading bacteria and viruses, and aiding digestion. The gut microbiota, which is essential for human homeostasis, is established rapidly after birth and remains relatively stable throughout the life [1]. The GI mucosa provides a protective interface between the internal environment and the constant external challenge from food-derived antigens and microbes. CP and UP are minor microbial communities that mainly contribute to the pathogenesis of microbial diseases. The distinction between the commensal and the pathogen in the CP community can be blurred because they may cause diseases under certain sub-health conditions of the hosts, or in immunocompromised hosts. For example, pneumococcus, meningococcus and Haemophilus bacteria regularly exist as part of the normal microbiota of the host respiratory track and are mostly carried asymptomatically despite the fact that they can cause well-defined diseases [12, 13]. Microbes in the CP community dynamically evolve in two opposite directions, which are 31

32 toward either the NP (more cooperative or mutualistic) or UP (more pathogenic) microbial community. Microbes with high pathogenicity belong to the UP microbial community. The three microbial communities and three statuses of the hosts are subjected to dynamic reciprocal changes driven by intraspecies, crossspecies or cross-kingdom transfer of genetic materials. Maximum SP= f (SI, PI) Minimum NP-NS CP-CS UP-US Non-Zero Sum Zero Sum Cooperation Dilemma Noncooperation Ecologic Infectomics Immunoinfectomics & Chemical Infectomics Fig.2. A continuum model of host-microbe interactions coupling with infectomic approaches to dissect the problems in microbial infections Duality Representations of Microbial Infections: Sym and Pat. Extending along the dynamic continuum from conflict to cooperation, microbial infections always involve symbiosis and pathogenesis, which are two fundamental components of the host-microbe interactions (Fig.2). There exists a Sym-Pat dynamic duality relationship (DDR) in microbial infection, which is the most fundamental issue of infectomics [2]. DDR is reflected in the genotypic and phenotypic infectomes, which are encoded by both host and microbial genomes. The opposition and unity of Sym and Pat are indispensable, and the academic viewpoint that the unity of opposites of Sym and Pat gives impetus to the development of microbial infection is considered as the core idea and radical principle of the duality representations of microbial infections. In certain circumstances and at a certain stage of the development of microbial infection, each of the two aspects of Sym and Pat will transform from antagonism into mutualism or from mutualism into antagonism. Sym and Pat can be quantitated by measuring symbiotic index (SI), which is quantitative fitness for the symbiotic partnership, and pathogenic index (PI), which is quantitative damage to the symbiotic partnership, respectively. The most crucial experiments are to identify infectomic signatures specific for SI and PI. The set of symbiotic or pathogenic parameters is defined as a function SI(x) or PI(x*). SI(x) and PI(x*) are continuous functions ranging from 0 to 1 to admit different degrees of Sym and Pat, respectively (Fig.3). SI(x)=0 and PI(x*)=0 indicate that x and x* are perceived to be zero-symbiotic and zero-pathogenic, respectively. SI(x)=1 and PI(x*) =1 indicate that x and x* are perceived to be completely symbiotic and completely pathogenic, respectively. Intermediate values of SI(x) and PI(x*) indicate that x and x* are perceived to be partially symbiotic and partially pathogenic, respectively. The hosts have large influences on SI and PI. For example, polydnaviruses have evolved complex life cycles in which they interact as symbionts with one host and pathogens with another. Their genomes reflect the dual roles as mutualists and pathogens [14]. Symbiotic points (SP) are used to determine the DDR between Sym and Pat. The values of SI and PI can be used for calculation of the symbiotic point (SP), which is a function of SI and PI. SP= f (SI, PI) The focus of the DDR research is to examine the ability of SP to transform situations of potential conflict (UP-US & CP-CS) into situations of cooperation (NP-NS). SP bears analogy to Schelling s focal point, 32

33 which is any feature of such a game that provides a focus of convergence [15]. In the games with multiple Nash equilibria, one equilibrium usually stands out from the others (salient). Such an equilibrium is a focal point which can be easily recognized by all the players [16]. Thomas Schelling s Strategy of Conflict (1960) has been recognized as one of the most important works of game theory [17]. There is no doubt that focal points play a central role in Schelling s game theory. Schelling has made a significant contribution to a reorientation of game theory. Understanding focal points is not only a key to improving game theory but also a key to dissecting SPs. 1 α (SI) β (PI) α (SI) I II III IV β (PI) 0.5 β I II 0.5 III Fig.3. A relationship between SI (αi) and PI (βi). A cooperative relationship (NP-NS: health and mutualism) (I) occurs between the host and the NP microbial α community. A competitive relationship (CP- CS) (II and III) exists between the host and β the CP microbial community. There are two types of competitions, better (II) and worse (III). An antagonistic 0.5 relationship 1 (UP-US) (IV) between the host and the UP microbial community Game Theoretical Models (GTMs) of Microbial Infections. In this paper, three types of GTMs are proposed for studies on NP-NS interactions (cooperative game), UP-US interactions (noncooperative games), and CP-CS interactions (dilemma or bargaining game). First, the NS-NS interactions are dissected with pure cooperative games in which each player chooses the strategy corresponding with the focal point in the expectation that the others will do the same. The significance of focal points can be shown most clearly in the pure cooperative games (Fig.4(a)). As there is no conflict of interests in these games, all the players merely want to cooperate and they do not choose the alternative ways. Analysis of the cooperative game issues is to focus on coalition formation and distribution of the gains through cooperation. The SP in the NP-NS games tends to be maximal (Fig.2). Secondly, noncooperative GTMs are used for analysis of the UP-US interactions. In contrast to cooperative games which focus on collective rationality and common interest, noncooperative games emphasize individual rationality and individual optimal strategy. The SP in the UP-US games tends to be minimal (Fig.2). In games of pure conflict, defection is the equilibrium strategy and the total benefit to all players in the game, for every combination of strategies, always adds to zero (zero-sum). This situation is depicted in Fig.4(b) as a two-player game. In the antagonistic UP-US interaction model, the surviving strategies of the UP community conflict with that of the US host. The UP evolves to exploit the host as much as possible, and the host adapts to exclude or limit the damage caused by the UP. Thirdly, we consider the strategic use of focal point theory in mixed situations to analyze the CP-CS interactions in which there is both conflict and mutual dependence. The most well-known example is the Prisoner s Dilemma game (a two player game) in which each player chooses between a cooperating and defecting strategy. As shown in Fig.4(c), each player receives a higher playoff by defecting than by cooperating, no matter what the other player chooses. However, they receive a higher playoff if both cooperate than both defect. The two player game can be extended to the N-player Prisoner s Dilemma game with arbitrary numbers of players. The CP-CS interactions can co-evolve toward two different directions, increasing or decreasing the SP. α IV 1 33

34 4. Outcome In this paper, focal point theory-based game models are proposed for analysis of the dynamic duality relationships (DDR) of Sym-Pat in microbial infections. DDR is the most fundamental problem in infectomics, which is the integration of omics and mathematical/computational approaches. There are three types of infectomic approaches that can be used for the control of microbial infections: ecological infectoimcs, immunoinfectomics and chemoinfectomics [2]. Ecological infectomics will explore symbiotic solutions to microbial infections. Developing novel immunological intervention strategies for the prevention and treatment of microbial infections using infectomic signatures and immunomic approaches falls within the field of immunoinfectomics. Chemoinfectomics represents the most powerful approach to the development of a new generation of drugs for antimicrobial chemotherapy. Microbes 1,1 0,0 0,0 0,0 1,1 0,0 Host 0,0 0,0 1,1 0,0 0,0 0,0 M M H 2, -2-1, 1 H -1, 1 3, -3 Microbes C D Host C 3, 3 4, 1 D 1, 4 2, 2 0,0 0,0 0,0 1,1 Pure Conflict Game Dilemma Game (a) (b) (c) Fig.4. (a) Pure cooperative game. (b) Pure conflict game. H: host; M: microbes. (c) Dilemma game. The number in the left of each pair indicates the payoff for Microbes; the right, Host. Higher numbers represent greater payoff for the individual. Two strategies [Cooperation (C) and Defection (D) ] are used Symbiosis Point Converting (SPC): Ecological infectomics-based approaches for rational control of microbial infections. As microbial infection is an ecological and evolutionary paradigm which is associated with co-evolution between hosts and microbes (such as human host and microorganisms, phages and bacteria) in dynamic ecosystems, two ecological infectomics-based SPC approaches (increasing and decreasing SP) can be used for rational control of infectious diseases [2]. The focus in SP increasing approaches is how to transform situations of potential conflict (pathogenesis) into cooperation (symbiosis) by dissecting the dynamic duality relationships (DDR) between Sym and Pat in microbial infections and developing symbiotic agents (symbiotics) that favor a healthy symbiosis [2]. Symbiotics are defined as products that are beneficial to symbiotic ecology of the super-organisms consisting of microbes and their human hosts. These include microbial (e.g., probiotic bacteria) and nonmicrobial agents (e.g., prebiotics) [2]. The introduction of beneficial symbiotics with higher SP in our body should be a very attractive rationale for modulating the microbiota, improving the symbiotic homeostasis of the superorganism and providing a microbial stimulus to the host immune system against pathogens. Decreasing SP is another rational strategy for control of microbial infections. As phages, which specifically kill bacteria, play an important role in the ecology, evolution and virulence of a number of pathogens, there is a rational use of phages for treatment and prevention of bacterial infections. The use of phages to treat bacterial infections has a long history dating back to mid 1910 s [2]. Due to the availability of effective broad spectrum antibiotics in the early 1940 s, phage therapy was discarded in Western medicine at that time. The rising crisis of antibiotic resistance has recently increased great interest in phages and their use as natural antimicrobial agents to fight microbial infections [2]. Compared with commonly used antibiotics, a great advantage of phages is their narrow host range. Recent studies showed that co-infection with GB virus C (GBV-C) is associated with a decreased mortality in HIV-infected patients [18]. Therefore, reducing SP between microbial agents (such as phages and GBV-C) and targeted pathogens is another excellent ecological approach for the development of novel antimicrobial agents Specific Pathogen-Targeting (SPT): Immunoinfectomics- and chemoinfectomics-based approaches for prevention and treatment of infectious diseases. In contrast to the ecological infectomics-based SPC approaches that focus on the symbiotic relationships (such as NP-NS and CP-CS 34

35 interactions) between the hosts and microbial communities, immunoinfectomics- and chemoinfectomicsbased SPT approaches emphasize the use of antagonistic relationships (such as UP-US interactions) between the hosts and microorganisms. It is important to point out that the SPT approaches are intrinsically different from the conventional pathogen-targeting antimicrobial agents, which kill both pathogens and nonpathogens [2]. The availability of the genomic information from both microbes and their hosts has resulted in exciting new progress in the field of immunoinfectomics. Nanobody-based technologies and immune epitope mapping have emerged as the very powerful tools for the discovery and development of novel antimicrobial agents. Concurrent advances in both high-throughput chemistry and infectomics have given rise to the field of chemoinfectomics for elucidating and validating drug targets, and generating novel therapeutics. Chemoinfectomics refers to the use of small synthetic molecules that are highly specific for defined infectomic targets, for biological function analysis and to discover new drug leads. The progress towards understanding the DDR of Sym-Pat in microbial infections using focal point theory-based game models will greatly facilitate the use of ecological infectomics, immunoinfectomics and chemoinfectomics for the rational control of infectious diseases. 5. References [1]. S.H. Huang, T. Triche and A.Y. Jong, Infectomics: genomics and proteomics of microbial infections, Functional & Integrative Genomics. Vol.1, pp , [2]. S.H. Huang, X. Wang and A. Jong, The evolving role of infectomics in drug discovery, Expert Opinion in Drug Discovery, Vol. 2, pp.1-15, [3]. M.J. Roossinck, Symbiosis versus competition in plant virus evolution, Nature Review Microbiology, Vol. 3, pp , [4]. G.G. Dimijian, Evolving together: the biology of symbiosis, Baylor University Medical Center Proceedings, Vol. 13, pp , [5]. S. Lee, Three roads to Quantum Gravity, Basic Books, 2001, page 113. [6]. J. Lederberg, Infectious history, Science, Vol. 288, pp , [7]. J. Lederberg. The future of infectious diseases, Journal of Urban Health. Vol.75, pp , [8]. H. Brussow, C. Canchaya, W.D. Hardt, Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion, Microbiology and Molecular Biology Reviews, Vol. 68, pp , [9]. M.E. Woolhouse, J.P. Webster, E. Domingo, B. Charlesworth, B.R. Levin, Biological and biomedical implications of the co-evolution of pathogens and their hosts, Nature Genetics, Vol.32, pp , [10]. A. Casadevall and L.A. Pirofski, Host-pathogen interactions: basic concepts of microbial commensalism, colonization, infection, and disease, Infection and Immunity, Vol. 68, pp , [11]. R.E. Ley, D.A. Peterson, J.I. Gordon, Ecological and evolutionary forces shaping microbial diversity in the human intestine, Cell. Vol.124, pp , [12]. S. Falkow, Is persistent bacterial infection good for your health? Cell, Vol.124, pp , [13]. D. Kuklinska, M. Kilian, Relative proportions of Haemophilus species in the throat of healthy children and adults, European Journal of Clinical Microbiology, Vol.3, pp , [14]. B.A. Webb, M.R. Strand, S.E. Dickey, et. al., Polydnavirus genomes reflect their dual roles as mutualists and pathogens, Virology, Vol. 347, pp , 2006 [15]. K. Benmore, L. Samuelson, The evolution of focal points, Games and Economic Behavior, Vol.55, pp.21-42, 2006 [16]. J. Metha, C. Starmer, R. Sugden, Focal points in pure coordination games: an experimental investigation, Theory and Decision, Vol. 36, pp , [17]. R. Sugden, I.E. Zamarron, Finding the key: the riddle of focal points, Journal of Economic Psychology, Vol. 27, pp ,

36 [18]. D.E Yirrell, E. Wright, L.A. Shafer, et. al., ssociation between active GB virus-c (hepatitis G) infection and HIV-1 disease in Uganda, International Journal of STD & AIDS, Vol. 18, pp.244-9, *Published in Frontiers in the Convergence of Bioscience and Information Technologies, FBIT 2007 Date of Conference: Oct

37 Clinical Course of Chronic Hepatitis B (CHB) Presented with Normal ALT in Asian American Patients Kelvin Nguyen 1*, Calvin Pan 2*, Victor Xia 3, Jennifer Hu 2, Ke-Qin Hu 1 1 Division of GI/Hepatology, University of California, Irvine, School of Medicine, Orange, CA, United States; 2 Division of Gastroenterology and Hepatology, NYU Langone Medical Center, NYU School of Medicine, NY; 3 Dept of Anesthesiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States ABSTRACT BACKGROUND: The clinical course for chronic hepatitis B (CHB) patients with normal ALT and with or without minimal histologic activity remains unclear. GOAL: We assessed frequency, amplitude, disease activities, and associated factors of ALT and/or AST flares in this subpopulation. STUDY: 47 consecutive treatment naïve Asian CHB patients were enrolled from two liver clinics between December 2003 and January 2013, who had normal baseline ALT by routine clinical biochemical testing done 6 weeks before or after the liver biopsy (LB). Flare is defined as elevation of ALT/AST above ULN of ALT/AST. RESULTS: The mean post-lb follow-up was 37.6 (C.I. = 12, 88) months. The mean age at the LB was 43.3 (C.I. = 19, 65); 22/47 (46.8%) were males; 15/45 (33.3%), HBeAg+; 68.1% had stage 0-1 fibrosis; 63.8% had grade 0-1 inflammation. During follow-up, 13/47 (27.7%) cases developed ALT flare at least once in a mean of 13.5 (C.I. = 2, 43) months after LB; ALT flare was not associated with baseline ALT level, fibrosis stage, inflammation grade, hepatitis B virus (HBV) DNA load, HBeAg status, HBV genotype, HBV pre-core, and basal core promoter mutations. 11/13 (84/6%) of ALT flares resolved during follow-up. 13/13 (100%) of ALT flares met AASLD treatment criteria but only 6/13 (46.2%) were on HBV treatment. CONCLUSIONS: Serum ALT and/or AST flares occur frequently in CHB carriers who initially presented with normal ALT during pre-treatment period. Thus, regular follow-up is warranted despite status of ALT/AST. No clinical factors were found to be associated with ALT flares. Key Words: Chronic hepatitis B; Normal ALT; Liver biopsy; ALT flare; AST flare INTRODUCTION Chronic hepatitis B virus (HBV) infection affects more than 400 million people worldwide. Vast majority of chronic hepatitis B (CHB) patients are located in Asia. (1) CHB causes ongoing liver injury that can be associated with cirrhosis and hepatocellular carcinoma (HCC). Compared to people without HBV infection, HBV carriers have a 100 fold higher relative risk of developing HCC. (2) It is estimated that 15-40% of CHB patients will progress to cirrhosis that can be complicated by hepatic decompensation and end stage liver disease, while 25% of these patients will develop HCC. (2-5) The rate of developing cirrhosis in patients with chronic HBV infection at tertiary centers ranges from 2-7% 37

38 annually. (6-10) In order to evaluate the severity of liver injury, liver biopsy remains the gold standard modality to accurately evaluate fibrosis/cirrhosis in patients with CHB. (11) Serum ALT level has been used as one of the parameters in determining clinical phases of HBV infection and serum ALT elevation, also called ALT flare, is an indication of hepatic necroinflammation. (12-13) Acute exacerbation, manifested with ALT flare, occurs in patients with CHB, especially in those with elevated ALT levels at presentation. (14) Most of these exacerbations were associated with reactivation of HBV replication and ended with spontaneous resolution and ALT normalization, though the exacerbation could recur. Although CHB patients with persistently normal ALT are thought to have mild hepatic necroinflammatory activity on liver biopsy and have good prognosis, (15-16) several studies have demonstrated that CHB patients with significant inflammation and fibrosis on liver biopsy can present with normal or minimally elevated ALT, questioning the accuracy of current standard ALT criteria in reflecting HBV-related liver injury. (17-25) Serum ALT is an important parameter used in all major guidelines for HBV treatment from different organizations. (26-29) In general, the decision to initiate HBV treatment is based on CHB natural history and possible risks for disease progression. Both Asian Pacific Association for the Study of the Liver (APASL) and American Association for the Study of Liver Diseases (AASLD) recommend treatment once the patients ALT is above 2 x Upper Limit of Normal (ULN), while European Association for the Study of the Liver (EASL) and Keffee and Tong s algorithms recommend to consider treatment once ALT is more than 1 x ULN (12, 26-29) as studies have shown that when ALT gets close to ULN, the patients may potentially have increased liver related mortality. (30-31) On the other hand, it is well known that single elevations of ALT level might not indicate significant severe histologic disease. (22-23, 32) However, it is still unclear about the clinical course of CHB patients with normal ALT with or without minimal histologic activity. A good understanding about disease progression will facilitate the discussion when it is appropriate to start treatment for CHB patients with normal ALT and AST at baseline. In the present study, we evaluate CHB patients with normal ALT and AST at baseline for frequency of HBV infection flare, specifically ALT and AST flare from the time of liver biopsy. We also assess risk factors of ALT flare in these Asian American patients with CHB. PATIENTS AND METHODS Patients and Enrollment Criteria. This study was conducted via a consecutive and retrospective chart review of patients with CHB who were regularly followed in 2 outpatient liver clinics at University of California, Irvine medical center and Elmhurst Hospital of Mount Sinai School of Medicine between December 2003 and January The Institutional Review Board at both centers approved this study and the informed consent was exempt. Patients were enrolled if they met the following inclusion criteria: Asian American patients who carried diagnosis of CHB with detectable serum HBV DNA; underwent a liver biopsy with report of normal or mild liver histology i.e. METAVIR Staging 2 and Fibrosis 2; regular follow-up every 6 months at minimum with liver function tests and HBV DNA for minimal 12 months; and serum ALT level ULN. The ULN of ALT is 60 IU/L at University of California, Irvine liver clinic while the ULN is 40 IU/L at Mount Sinai clinic. Exclusion criteria include coinfection with HIV, Hepatitis C or D, or HCC. A total of 47 patients who met above inclusion criteria were included in the present study. Clinical Data Collection. Chart review was performed to collect clinical information that includes date of birth, age, gender, ethnicity, date of clinic entrance, date of biopsy, date of treatment 38

39 initiation if applied. Follow up time started from the time the patient had entered the clinic till January 2013 or the time that treatment was started. Once a patient received treatment for hepatitis B, that patient s clinical data will no longer be followed by our study. Laboratory Data Collection. The following laboratorial data were collected at the time of liver biopsy as the baseline results, then every 3-6 months with a two-week variation. Biologic and hematologic laboratory data included ALT, AST, total bilirubin, albumin, protime/inr, and platelet count. HBV serological and virological test results included HBsAg, HBeAg, HBeAb, HBV DNA level, HBV genotype, pre-core (PC) mutations (G1896A and C1858T), and basal core promoter (BCP) mutations (A1762T and G1764A). ALT 60 IU/L is considered within normal limit (WNL) at University of California, Irvine liver clinic whereas ALT 40 IU/L is the reference for WNL at Mount Sinai clinic. AST 40 IU/L is WNL at both clinics. Pathology Data Collection. All percutaneous liver biopsies were performed at our centers. Liver histology was assessed by pathologists specialized in liver diseases without any knowledge of the clinical data. A liver sample was considered adequate if it was longer than 15 mm and contained six portal tracts or more. The METAVIR scoring system was used to evaluate histologic grades and stages of the liver biopsy. (33-35) The severity of necroinflammation was graded from A0 (no activity) to A3 (severe activity) and the stage of fibrosis was graded from F0 (no fibrosis) to F4 (cirrhosis). (35) Statistical Analysis. The descriptive data were shown as whole numbers and percentages. Chisquare tests were performed in order to evaluate univariate analysis of predictive risk factors for ALT flare. Student t-tests were also performed. A p-value of less than 0.05 is considered statistically significant. The primary endpoints were frequency of ALT/AST flares and associated factors with ALT flare in this subpopulation of patients with mild histologic disease activity and normal liver enzymes at the time of biopsy. RESULTS Baseline Characteristics of the Patients. As summarized in Table 1, of 47 patients in the study, all were of Asian American background and had biopsy with ALT ULN, specific for each institution s laboratory reference. Mean follow-up was 37.6 ± 19.0 months with the range of months. Mean age was 43.3 ± 13.5 years with 22/47 (46.8%) being male. Mean ALT at biopsy was 26.5 ± 10.3 IU/L, while mean AST at biopsy was 24.6 ± 6.7 IU/L. Mean HBV DNA level at biopsy was 2.0x10 8 ± 1.0x10 9 IU/mL. All patients with liver biopsy reported histologic stage and grade 2, 68.1% and 63.8% had fibrosis stage 1 and inflammatory grade 1, respectively. Of 45 patients, 33.3% were HBeAg positive, 71.1% developed HBeAb; 2 cases were positive for both HBeAg and HBeAb. Ninety-eight percent of the participants had genotype B or C, 66.7% had genotype B infection. HBV PC mutations accounted for 62.8% of all cases, HBV BCP mutations accounted for 32.6% of cases, while 20.9% of all cases had both PC and BCP mutations, i.e. at least one PC mutation (G1896A or C1858T) and one BCP mutation (A1762T and G1764A). Frequency and Clinical Features of CHB Flares. Of 47 participants, 13/47 (27.7%) were found to have ALT flares defined as ALT > ULN (Figure 1), 10/13 (76.9%) had a single flare; 2/13 (15.4%), 2 flares; and 1/13 (7.7%), 5 flares during follow-up. In these ALT flare events, 10/13 (76.9%) were associated with AST flares. The first episodes of ALT flare occurred between 2 and 43 months after liver biopsy with a mean interval of 13.5 ± 13.3 months. The mean ALT of these flares was ± IU/L. Only 1/13 (7.7%) case with first ALT flare was associated with further HBV DNA increase by more than 1 log of 10. In 11/13 (84.6%) patients, the first episodes of ALT flare resolved eventually, in 19.7 ± 20.0 weeks. However, only 5/13 of those cases experienced spontaneous resolution of ALT flare i.e. resolving within 12 weeks. The episodes of ALT flare achieved the highest ALT at a mean 39

40 value of 148 ± IU/L, after a mean interval of 21.2 ± 15.7 months since biopsy, and resolved after a mean interval of 17.8 ± 16.4 weeks, ranging from 2 to 52 months. (Table 2) Among 12 (25.5%) cases with first episode of AST flare, 2/12 (16.7 %) were AST flare only and not accompanied with ALT flare. The first episode of AST flare reached a mean AST of 79.0 ± 86.2 IU/L, ranging from 39 to 344 IU/L. These episodes occurred at a mean interval of 17.2 ± 16.2 months and resolved within 19.7 ± 20.0 weeks. The AST flares with the highest AST level were obtained at a mean AST of 95.4 ± 85.7 IU/L, varying from 41 to 344 IU/L. They occurred after an interval of 24.5 ± 17.1 months since liver biopsy, and resolved in 15.7 ± 15.9 weeks, ranging between 2-52 weeks. (Table 2) Outcomes and Factors Associated with CHB Flares. During the followup, none of these 13 cases with ALT flare or 12 cases with AST flare experienced hyperbilirubinemia, hepatic decompensation, or required hospitalization. As shown in Figure 1, in 13 patients with ALT flare, 6 (6/13, 46.2%) met criteria of AASLD recommendations (27) and were started on HBV treatment, and 7 (7/13, 53.8%) met the criteria of AASLD recommendations, but chose not to undergo HBV treatment. In these 7 non-treated patients, 3 cases (42.9%) had spontaneous resolution of ALT flare, defined as ALT returning to normal range within 12 weeks. However, 2/7 (28.6%) non-treated cases with ALT flare experienced recurrent ALT flare after a mean period of 17.5 months since resolution of the first flare. As shown in Table 4, the univariate analysis has shown no significant association between ALT flare and all assessed clinical factors, including age 50, gender, ALT at biopsy ½ ULN, fibrosis stage > 1, inflammation grade > 1, HBV DNA 100,000 IU/mL or 20,000 IU/mL, HBeAg positivity, HBV PC mutation, HBV BCP mutation, any combination of PC and BCP mutations, and genotype B or C. DISCUSSION Although biochemical flare is well known as part of natural history of CHB, the outcomes of ALT flare remains to be determined in patients with normal baseline ALT and AST and mild histologic disease activity on liver biopsy. In the present study, a good number of patients developed flares, especially ALT flares (27.7%). Amongst patients with ALT flares, most (76.9%) have both ALT and AST flares. Most episodes of ALT flare are single flares, except one case with five flares, which was the highest among all flares. Although most of these flares resolved eventually, 2/13 (15.4%) cases of ALT flares did not show flare resolution in a mean follow-up of 24 (0-48) months since the flares occurred and probably due to lack of closer and longer follow-up. HBV-related biochemical flare can be classified as either host induced, virus induced, or indeterminate. A host induced flare could be a signal of HBeAg seroconversion, whereas a virus induced flare means either the virus is replicating rapidly and causing liver damage or reactivation of HBV or reversion from anti-hbe to HBeAg. (36-42) An ALT flare with elevated HBV DNA level indicates significant infectivity with potential liver damage, prompting immediate hepatitis B treatment. Biochemical flares in our study are mostly not associated with elevations in HBV DNA levels, which deemed most of the flares in our patient population as host-induced. It should be noted, as a retrospective study, we could not rule out other possible non-hbv causes for ALT flare, such as alcohol use, other virus infection, medications, or even herbal supplements. Is HBV DNA a better marker than ALT for liver injury? As mentioned by Iloeje et al. in the REVEAL HBV study, risk for cirrhosis increases significantly with increasing HBV DNA levels and is independent of HBeAg status and serum ALT. (43) Most of the flares in our study were not associated with more than one log increase in HBV DNA level. Only one flare was 40

41 observed to have an increase by three logs of 10 in HBV DNA viral load. This observation shows there is no clear association between HBV DNA elevation and biochemical flares in CHB patients in our cases. As long-term changes in serum levels of HBV DNA and ALT are independent predictors for HCC, regular monitoring of HBV DNA levels and ALT is important in clinical management of chronic carriers of HBV. (44) Currently, no simple and readily available markers were able to predict biochemical flares accurately in CHB patients. We assessed potential risk factors for ALT flares, including gender, age, ALT and HBV DNA levels at biopsy, histology of liver biopsy, HBeAg status, HBV PC and/or BCP mutations, and genotypes. However, we found no significant correlation between these factors and ALT flares. A larger patient population study will be needed to confirm our findings. Although no flare associated factor was identified, this study has shown that CHB patients with significant viremia, even with normal ALT and minimal or normal liver histology, will have significant risk of disease activity during the follow-up period. Thus, close monitoring is needed for this population of patients. In this cohort of patients, only 46.2% of patients with ALT flare were treated with antiviral therapy. The continuous follow-up on the natural history of ALT/AST flare had to be interrupted to comply with the good clinical practice. However, majority of patients reviewed in this study with ALT/AST flare did not enter into the treatment. Our observation pointed to the direction of a treatment barrier from both physicians and patients due to the lack of recognition on the impact of ALT flare. Therefore, further physician and patient education is needed on HBV monitoring for treatment candidate selection. One of the main reasons that patients met criteria for treatment, but not receiving treatment is due to patient s refusal. It is difficult to have patients convinced on starting HBV treatment when most of patients with flares are asymptomatic. (12-13, 45) In addition, most of the patients with flares had one flare only and their ALT elevation resolved quickly, evidenced by normal follow-up liver function tests. This creates a false alarm that the disease rarely exacerbates and even if it flares up, it will become quiescent quickly so that close monitor is an acceptable option. Of all 12 cases of AST flare, 6 (50%) cases received HBV treatment. 2/12 AST flares were AST flare without ALT flare and only one of these two cases underwent HBV treatment due to significant high HBV DNA level in the billion IU/mL range. AST has not been used as one of the criteria considered for HBV treatment. However, all of the cases of AST flare have met AASLD treatment criteria, based on ALT and HBV DNA viral load. Therefore, the utility of AST as one of the treatment criteria is still questionable. According to findings of our study, patients with CHB, regardless HBeAg status i.e. HBeAgnegative or HBeAg-positive, are at risk for ALT flares. With the emergence of more updated, less stringent guidelines for HBV treatment, we are anticipating more patients will receive early treatments. In the mean time, frequent and close follow-ups are very important. Regarding surveillance for HCC in Asian Americans with hepatitis B, the common guideline consists of alpha fetoprotein (AFP) and abdominal ultrasound every 6 months. (12) Surveillance candidates are high-risk patients who are at advanced stages of liver disease such as cirrhosis, HCC in blood relatives, or low to moderate risk patients such as inactive carriers, immune tolerant patients, HBsAg positive males < 40 years old, HBsAg positive females < 50 years old or patients with HBsAg loss. (12) Patients in our clinic are routinely seen every 3-6 months and we would recommend these frequent follow-ups. HBeAg seroconversion indicates immune clearance, which reduces risk of hepatic decompensation and improves survival. (46-47) However, there is a concern that up to 30% of CHB 41

42 patients continue to have elevated ALTs and high HBV DNA levels after HBeAg seroconversion, (37, 48-49) making them more prone to develop complications of liver cirrhosis. (6, 39, 50) 66.7% of our study participants are HBeAg negative. Of 12 patients with ALT flares and known HBeAg status, 8 (66.7%) patients were tested as HBeAg negative and 6/7 (85.7%) of them had high level of HBV DNA (i.e. more than 100,000 IU/mL). This finding is critical as the association between HBV DNA and HCC is greater in the subset of patients with HBeAg negative with normal ALT levels and no cirrhosis at entry. (51) Therefore, these patients should be highly considered for HBV treatment as well as continuing close follow-ups. There are a few limitations in this study. We were not able to identify any clinical factors associated with ALT flare in our study, possibly due to a low power effect. A larger patient population might be able to show a statistically significant correlation between some of these factors and ALT flare. Despite a negative result, our study has established a foundation for future studies to look into the natural disease progression of CHB as well as risk factors for serologic flares. According to Prati et al, ULN for ALT should be 30 IU/L for men and 19 IU/L for women as patients with higher levels of ALT than the above suggested values and less than 40 IU/L, which was traditionally the common ULN, were found to have histologic disease activities. (30) Our study includes patients from 2 different clinics where the reference ranges for ALT and AST are not the same. Therefore, a subset analysis for ALTs lower than the common ULN by Prati standard was not performed. In conclusion, our study has shown a significant proportion of CHB patients with ALT/AST ULN developed flares during follow-up after biopsy. These biochemical flares were not associated with worsening HBV DNA level and were not associated with seroconversion. The fact that many of these patients with flares did not receive treatment brought attention to closer follow-ups on these patients. Threshold for treatment in CHB patients should be lower than it is now and early treatment for these patients is highly recommended. So far, no risk factors have been identified as being associated with ALT flare. ACKNOWLEDGEMENTS An early analysis of the study was presented at the 2012 AASLD meeting in Boston. DISCLOSURE Dr. Ke-Qin Hu has received research or educational grants from Gilead, Bristol Myers Squibb, Genentech, and Merck. He also serves as speaker bureau for Gilead, Bristol Myers Squibb, Genentech, and Merck. Dr. Calvin Q. Pan has received research grants from Gilead, Bristol Myers Squibb, Novartis, and Roche. He also serves as a consultant, advisor and speaker bureau for Gilead and Bristol Myers Squibb. 42

43 Table 1. Baseline Clinical Presentation Variables Cases Percentage or Mean ± SD Age (years old) 47/ ± 13.5 Gender (male) 22/ % Post-Biopsy follow up (months) 47/ ± 19.0 ALT at biopsy (IU/L) 47/ ± 10.3 AST at biopsy (IU/L) 47/ ± 6.7 HBV DNA (IU/mL) 45/ x10 9 HBV DNA log at biopsy 45/ ± 2.0 Histologic stage 1 32/ % Histologic grade 1 30/ % No fatty liver on histology 39/ % Genotype B 28/ % Genotype C 13/ % HBeAg+ at biopsy 15/ % HBeAb+ at biopsy 32/ % Precore mutation (G1896A or C1858T) 27/ % HBeAg+ 3/ % HBeAg- 23/ % BCP mutation (A1762T or G1764A) 14/ % HBeAg+ 5/ % HBeAg- 9/ % Pre-core AND BCP mutations 9/ % HBeAg+ 1/9 11.1% HBeAg- 8/9 88.9% 43

44 Table 2. Clinical Presentation and Clinical Course after Liver Biopsy Variables Cases Percentage or Mean ± SD Patterns of ALT flares All with ALT flares 13/ % Cases of single ALT flares 9/ % Cases of 2 ALT flares 3/ % Cases of 5 ALT flares 1/13 7.7% All cases of AST flares 12/ % Cases with only AST flares 2/12 4.3% Cases of ALT flares associated AST flares 10/ % Presentation of ALT flares ALT flares and HBeAg status HBeAg-positive 4/ % HBeAg negative 8/ % First ALT flare (IU/L) 13/ ± Biopsy to first ALT flare (months) 13/ ± 13.3 Recovery from first ALT flare (weeks) 11/ ± 19.1 HBV DNA at first ALT flare (IU/mL) 11/47 7.5x10 7 ± 2.3x10 8 Flare with highest ALT (IU/L) 13/ ± Biopsy to flare with highest ALT (months) 13/ ± 15.7 Flare with highest ALT resolves in (weeks) 10/ ± 16.4 First AST flare (IU/L) 12/ ± 86.2 HBV DNA at first AST flare (IU/mL) 11/47 1.5x10 7 ± 3.1x10 7 Biopsy to first AST flare (months) 12/ ± 16.2 First AST flare resolves in (weeks) 11/ ± 20.0 Flare with highest AST (IU/L) 12/ ± 85.7 Biopsy to flare with highest AST (months) Flare with highest AST resolves in (weeks) 12/47 10/ ± ±

45 Table 3. Summary of the Outcomes from CHB Biochemical Flares Outcomes Cases Percentage HBV Tx started in general 15/ % HBV Tx started with ALT or ALT/AST flares 6/ % HBV Tx started with AST flares only 1/15 6.7% % of ALT flares that met Rx criteria 13/ % % of ALT flares, meeting Rx criteria and started on Rx 6/ % % of ALT flares without treatment 7/ % Table 4. Univariate Analysis of Possible Risk Factors for CHB Biochemical Flares Variables Cases/Total ALT flares (%) P- value Age 50 17/47 (36.2%) 0.3 Male gender 8/13 (61.5%) 0.3 ALT at biopsy ½ ULN 10/13 (76.9%) 0.3 Fibrosis stage > 1 9/13 (69.2%) 1.0 Inflammation grade > 1 8/13 (61.5%) 1.0 HBV DNA 20,000 IU/mL 12/12 (100.0%) 0.2 HBV DNA 100,000 IU/mL 10/12 (83.3%) 0.2 HBeAg positivity 4/12 (33.3%) 1.0 Any combined precore/bcp mutations 2/12 (16.6%) 1.0 Genotype B 10/12 (83.3%) 0.3 Genotype C 2/12 (16.7%) 0.3 Genotype B or C 12/12 (100.0%) 1.0 Precore mutation G1896A only 4/12 (57.1%) 1.0 Any precore mutation (G1896A or C1858T) 6/12 (50.0%) 0.5 BCP mutations (both A1762T AND G1764A) 3/7 (42.9%) 0.1 Any BCP mutation (A1762T OR G1764A) 3/12 (25.0%) 0.7 G1896A with both A1762T and G1764A mutations 2/7 (28.6%) 0.2 Any combination of precore and BCP mutations 2/12 (16.7%)

47/47 (100%) 13/47 (28%) 6/13 (46%) Total number of cases Cases with ALT flare Cases with ALT flare and HBV treatment started Figure 1. Distribution of ALT flare and HBV treatment References 1.

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48 29. Liaw YF, Leung N, Guan R, et al. Asian-pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int. 2005; 25: Prati D, Taioli E, Zanella A, et al. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137: Kim HC, Nam CM, Jee SH, et al. Normal serum aminotransferase concentration and risk of mortality from liver diseases: prospective cohort study. BMJ 2004: 328: Seto WK, Lai CL, Philip PCI, et al. A large population histology study showing the lack of association between ALT elevation and significant fibrosis in chronic Hepatitis B. PLoS ONE 2012; 7: e Ma J, Jiang Y, and Gong G. Evaluation of seven non-invasive models in staging liver fibrosis in patients with chronic hepatitis B virus infection. European Journal of Gastroenterology & Hepatology 2013; 25: Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis C. The French METAVIR Cooperation Study Group. Hepatology 1994; 20: Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR cooperative study group. Hepatology 1996; 24: Liaw YF, Tai DI, Chu CM, et al. Acute exacerbation in chronic type B hepatitis: comparison between HBeAg and antibody positive patients. Hepatology 1987; 7: Perrillo RP, Campbell CC, Sanders GE, et al. Spontaneous clearance and reactivation of hepatitis B virus infection among male homosexuals with chronic type B hepatitis. Ann Intern med 1984; 100: Lok ASF, Lai CL, Wu PC, et al. Spontaneous hepatitis B e antigen to antibody seroconverion and reversion in Chinese patients with chronic hepatitis B virus infection. Gastroenterology 1987; 92: Tong MJ, Sampliner RE, Govindajaran S, et al. Spontaneous reactivation of hepatitis B in Chinese patients with HBsAg-positive chronic active hepatitis. Hepatology 1987; 7: Chu CM, Sheen IS, and Liaw YF. The etiology of acute hepatitis in Taiwan: acute hepatitis superimposed on HBsAg carrier state as the main etiology of acute hepatitis in areas with high HBsAg carrier state. Infection 1988; 16: Koike K, Iino S, Kurai K, et al. IgM anti-hbc in anti-hbe positive chronic type B hepatitis with acute exacerbations. Hepatology 1987; 7: Tassopoulos NC, Papaevangelou GJ, Sjogren MH, et al. Natural history of acute hepatitis B surface antigen-positive hepatitis in Greek adults. Gastroenterology 1987; 92: Iloeje UH, Yang HI, Su J, et al. Risk evaluation of viral load elevation and associated liver disease/cancer-in HBV (REVEAL-HBV) study group. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology 2006; 130: Chen CF, Lee WC, Yang HI, et al. Risk evaluation of viral load elevation and associated liver disease/cancer in HBV (REVEAL-HBV) study group Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology 2011; 141: Tong MJ, Hsu L, Chang PW, et al. Evaluation of current treatment recommendations for chronic hepatitis B: A 2011 update. Journal of Gastroenterology and Hepatology 2011; 26: Fattovich G, Brollo L, Giustina G, et al. Natural history and prognostic factors for 48

49 chronic hepatitis type B. Gut 1991; 32: Chen CJ, Iloeje UH, and Yang HI. Long-term outcomes in hepatitis B: The REVEAL- HBV Study. Clin Liver Dis 2007; 11: Chan HL, Hui Y, Leung NW, et al. Risk factors for active liver disease in HBeAgnegative chronic hepatitis B virus-infected patients. Am J Gastroenterol 2000; 95: Davis GL, Hoofnagle JH, and Waggoner JG. Spontaneous reactivation of chronic hepatitis B virus infection. Gastroenterology 1984; 86: McMahon BJ, Holck P, Bulkow L, et al. Serologic and clinical outcomes 1536 Alaska natives chronically infected with hepatitis B virus. Ann Intern Med 2001; 135: Chen CJ, Yang HI, Hu J, et al. The REVEAL-HBV study group. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295:

50 Many-to-One in Blended Learning Imperial Learning in the Cloud Age 混合教学集众师教一人云端太学教学法 Ming Yang (Ph.D.) University of Califonia, Rioverside Introduction 1. Refletions on Imperial Learning Imperial Learning for the prince described in the following Chinese classical passage summarizes the best Chinese imperial way in teaching a little prince to become an emperor. When the prince was a little toddler, the emperor assigned his best martial to train and protect him, his best experienced premier to be his coach, and his wisest scholar to be the teacher. The emperor created these three highest teaching positions of the country to ensure the prince to develop a strong and healthy body by learning from his lead martial, to acquire high virtues and honor from the best premier, and to learn valuable lessons from the best scholar. As if this is not enough, the emperor created three more assistant teaching positions from his best young royal officials: best young warrior, best young experienced tutor, and best young scholar to accompany the prince during his daily life, and banquet meetings. The pupose is for the prince to learn knowledge, principles, filial piety, benevolence, propriety, righteousness conducts with best learning approach from the best men young and old. In this way, the prince is guarded against meeting bad people and shielded from seeing evil things. 汉书贾谊传第 26 节昔者成王幼在襁抱之中召公为太保周公为太傅太公为太师保保其身体傅傅之德意师道之教训此三公之职也于是为置三少皆上大夫也曰少保少傅少师是与太子宴者也故乃孩提有识三公三少固明孝仁礼义以道习之逐去邪人不使见恶行于是皆选天下之端士孝悌博闻有道术者以卫翼之使与太子居处出入故太子乃生而见正事闻正言行正道左右前后皆正人也 Gu Ban) As if this is still not enough, the emperor selected many more people from his country with all necessary knowledge and skills as assistants, helpers, and guards for the little prince such as the people with virtuous conduct, filial piety, best learned, and approved theory. These people serve as peers surrounding the little prince. Therefore, the prince will see right things, listen to right words, grow up in right ways, because people around him are all good influences. Teaching the prince to gain the imperial quality requires even more quality and valuable resources. From the classical passage below, Confucius, our best imperial sage and teacher, professed that formal learning for the prince should start immediately after he develops his sexual orientation. Then from the imperial School East, he learns love and care, there he understands what to love and what not to love, how and who to care as well as what to guard against. From the imperial School South, he learns trust worthiness and propriety, and there he understands what to say and what not to say, how to respect elders and how to set example for the younger ones. The prince then goes to the imperial School West, the imperial School North and finally reaches the the imperial School Center to learn the best governing theories and practices. The five imperial schools together bring the prince to his royalty and he is prepared as the best leader to govern the country. 孔子曰少成若天性习贯如自然 Confucius 及太子少长知妃色则入于学学者所学之官也学礼曰帝入东学上亲而贵仁则亲疏有序而恩相及矣帝入南学上齿而贵信则长幼有差而民不诬矣帝入西学上贤而贵德则圣智在位而功不遗矣帝 50

51 入北学上贵而尊爵则贵贱有等而下不隃矣帝入太学承师问道退习而考于太傅太傅罚其不则而匡其不及则德智长而治道得矣此五学者既成于上则百姓黎民化辑于下矣 Gu Ban) After the prince graduates from the formal imperial school learning, he still needs many resources to better himself as a great emperor. From the classical passage below, we see that he is provided with many top assistants, collaborators, and educational services to maintain his highest imperial values as the future emperor ready for governing the country. 及太子既冠成人免于保傅之严则有记过之史彻膳之宰进善之旌诽谤之木敢谏之鼓瞽史诵诗工诵箴谏大夫进谋士传民语习与智长故切而不愧化与心成故中道若性三代之礼春朝朝日秋暮夕月所以明有敬也春秋入学坐国老执酱而亲馈之所以明有孝也行以鸾和步中采齐趣中肆夏所以明有度也其于禽兽见其生不食其死闻其声不食其肉故远庖厨所以长恩且明有仁也 Gu Ban) How can every common kid be taught today in the same best way as the little price? Traditional teaching in a traditional school obviously seems impossible to fill in the role. However, in the Cloud Age with advances of educational technology, best knowledge, skills and practices from best teachers can be selected. WIth advanced approach they can be collectively blended into the best learning methodology to serve each individual learner in the efficient way. This is what I propose below as a unique teaching methodology: Many to one in Blended Learning. 2. Reflections on Cloud-Based Blended Learning With the advancement of educational technology, Net-Gen learners start to enter colleges and they brought in fresh needs and expectations to Higher Education. By carefully analyzing their needs and expectations, we propose here the project of Scaling the Blended Learning for Net-Gen Learners. We designed a working model of Blended Learning (BL) to reposition higher education in its fast tracks. We emphasize scaling as a way to power up the engine of blended learning so that it will shift forward the heavy load of educational paradigm. The learner-centered learning model supported by our technology infrastructure will achieve significant increases in learning efficiency and effectiveness. This is because with this model professors can reduce their lecture preparation and presentation time from 70% to 30% to better render their lectures. So an efficiency teaching equation of = 10 for F2F (Face to Face) teaching becomes a magical one: = 10 for BL. Furthermore, when the 40% professor s saved time from F2F is appropriated to a better learning for students, their success and satisfaction will increase significantly. And the BL efficiency equation will also be a magical one: = 10. Figure 1. Content enhancement in Cloud-based Blended Learning Model In addition to the magical increase of efficiency and effectiveness, we envision that technology innovation in BL will enhance the quality of instructional content from C = C 1 to C = C + 1 where C stands for intended content input. With F2F teaching in a big lecture hall, part of instructional 51

52 content gets lost into noises and interruptions. So the result is expressed as C = C 1. In BL, through content optimization, presentation concentration, and noise filtering enhancements, we have designed enhancements for the instructional content so that the formula is achieved through Content = Content + Multimedia Enhancement + Multichannel Access + Anytime/Anywhere availability. This results in an optimized content for BL that can be expressed as C = C + 1. Cost reduction is a big advantage favoring BL. While the cost to attend a college is rising sharply and the financial support for incoming students is falling quickly, the big scissors formed by these differences will cut off many students from completing a quality education. Our BL model will significantly reduce the expected educational fees and costs from a fraction of +30% to -50%, resulting in a total of 80% reduction of educational expenses for students. The significance of reducing costs for higher education on the whole is that BL will save the public education from either becoming noncompetitive or going bankruptcy. For learners, the low BL educational costs will enable our kids from low income families to complete their quality education. Part I: Blended Learning Framework with Updated Learning Theories Blended learning uses a methodology to blend instructions with online delivery so that students will be able to access the content online; and they can choose the desired content modules anywhere and anytime. With blended learning, the instructional and learning paradigm shifts from instructorcentered to student-centered. The instructor more often takes a directing or coaching role, rather than the acting and teaching role. As such, educators need to harness technology and take creative approaches to address the learning needs of these Net-gen learners; understand their new learning behavior; and provide assistance and solutions around their preferences. Instructors should also understand that while technology and online delivery free them from these routine tasks of preparing, teaching, and testing, they should spend more time creating individualized intervention plans, increasing the timeliness and frequency of direct instruction for the students who need it most. Without specialized training in blended learning course design and methodology, instructors may not take advantage of technology and online delivery in their traditional approach. Furthermore, without spending more time helping students individually, Blended learning processes only make teaching easy and convenient for the instructor, without increasing effectiveness in student-centered learning. Figure 2. Advantages of Cloud-based Blended Learning Model With the advancement of educational technology, Net-Gen learners start to enter colleges and they bring new challenges and expectations to Higher Education. Higher education in the technology era can not afford to ignore the social and economic changes driven forward by technology. The teaching paradigm has to embrace technology advancement so as to satisfy expectations of net-gen learners. As technology doubles its advancement almost every two years, education should not continue its way of teaching as it had been without it for 150 years. 52

53 Our vision is that teaching paradigm is bound to be shifted by technology advancement as well as the net-gen college learners. The power and energy of technology has been so vast and far-reaching to net-gen learners that higher education should be repositioned to make a sea change to embrace them. The new paradigm shifted by blended learning will be one that is student-centered, communityembraced, and with finger-tip access of content. The enclosed classroom becomes open in 24/7 in the new learning environment. Quality education is no longer enclosed within a campus but available anytime and anywhere. Students can reach their destination through their preferred paths, not just one pre-defined path that requires students to follow, with success or failure, as described in the following 4 dilemmas. Dilemma 1: Learning at a Shifted Teaching Paradigm Blended learning is a technology enhanced learning framework that shifts conventional teaching to a learner-centered approach by mixing class instructions and learning activities with multimedia presentation and online multichannel delivery. Students in a blended learning program will be able to access course instructions and content at their finger tips, choose the desired content modules anytime, and interact with peers and the instructor anywhere. With blended learning, the instructional and learning paradigm shifts from instructor-centered, class-based, and textbook-dependent framework to a student-centered, community-based, and media dependent framework. In a blended course, the instructor often takes a role of a coach, rather than that of a presenter. As such, educators need to be savvy in technology and develop creative approaches to address learning needs of the Net-gen learners; understand the new learner-centered learning behavior; and provide assistance and solutions around their preferences. However, instructors also need to understand that, they should be prepared that while multimedia technology and online delivery can free 30-70% of their time from routine tasks in preparing, teaching, and testing their classes, they will also need to spend more time creating individualized intervention plans, lead class discussions and group interactions, and increase the timeliness and frequency of specialized instructions for the students who need them most. Without training instructors in appropriate course design and methodology in blended learning, the purpose of blended learning may not be well served in that instructors may simply apply technology and online delivery to their traditional teaching methods. Without spending more time with students individually, technology can only make the instructors teaching easier and more convenient at most, without substantially increasing learning effectiveness in the students learning process. Recent findings show an increasing trend in online learning and a declining trend in faceto-face learning gradually moves away from each other. Furthermore, online learning is gaining momentum. For example, companies similar to the University of Phoenix (UOP, under Apollo Group) increase in value, while the poor economy has reduced the value of most other companies. This situation may have resulted from the University of Phoenix increasing their online programs and the access of higher education online became a much favored approach for students who had to work while earning a degree. 53

Figure 3. Simulation of learning space for Net-Generation in Cloud-based learning The teaching paradigm also shifts with wide acceptance of new technologies on campuses.

Institutions have adopted course management systems for academic content, Internet networking tools, collaboration tools, and community building tools for interactivity.

54 Figure 3. Simulation of learning space for Net-Generation in Cloud-based learning The teaching paradigm also shifts with wide acceptance of new technologies on campuses. Education has been influenced by continued expansion of personal learning devices such as laptops, smart phones, ipods, and ipads among learners. Institutions have adopted course management systems for academic content, Internet networking tools, collaboration tools, and community building tools for interactivity. Here are some key technology drivers that influence changes in education: Ubiquity of Internet access, gig-byte connectivity, and Web 2.0 functionality. Advances in graphics, multimedia and interactivity: authoring, publishing, lecture capturing, and content delivery in multiple modes and channels. Dilemma 2: Large Courses with Less Individual Attention Either an online or a face-to-face learning model alone may not maximize student success in today s learning environment. With classroom teaching serving as the norm in colleges and universities, online teaching is often undervalued and mostly used to supplement or fill the void of direct teaching. On the other hand, classroom teaching itself has limitations. The most notable factor is that classes become much larger. Faculty members and students feel that teaching, discussion, and interactions become unmanageable and ineffective. This circumstance causes students to watch presentations passively, with little interaction, Instructor do not have enough time to give enough direct guidance and individualized attention to students. Let s take UC Riverside as an example. In general, undergraduate classes at University of California Riverside are generally big. Each quarter there are about 200 courses with enrollment over 100 students. Table 1. Undergraduate currilum full of large classes in a typical university Let s take a UCR first-year business student, Cole Brian, as an example. Out of 10 courses he has taken so far, six out of 10 had a class size of more than 200 students, averaging 230 students per class. When each course accounts for about 1/3 of an instructor's total work time in a quarter, how much time would Cole Brian be allowed to speak to his instructors? Well, here is the data: 54

Table 2. Large classes in a undergraduate currilum With such big classes, one can reckon why C instructor may not be able to help him individually for a half hour during the whole quarter.

55 Table 2. Large classes in a undergraduate currilum With such big classes, one can reckon why C instructor may not be able to help him individually for a half hour during the whole quarter. Cole s TA sections are also alarmingly large, averaging 45 students per discussion section. Maybe a TA can afford to help him individually for one hour during the whole quarter. Figure 3. Discussion sections are too large in a ndergraduate currilum For students in this dilemma, blended learning offers a solution. When class teaching is supplemented with online lecture captures, communication tools, and interactive functions, a student s access to course content becomes frequent and instant. With a virtual community where a student s classmates, peers, group members, TAs and the instructor are instantly available, the student s learning process becomes authentic, manageable, and effective. Time and space can be simulated to make teaching an amazing art. For example, if Albert Einstein s lectures had been captured, students would not have to depend upon anecdotes, stories, and readings to learn from him. They would have learned with the great master by simply repeating the lectures as comfortably, as conveniently, and as frequently as they would like. Dilemma 3: Learning at Higher Costs and Less Resources Low-income young adults who need to combine work with learning may benefit substantially from blended learning programs. Under the pressure of the economic downturn, college students face the dilemma of learning at a record level of expenses which further pressures their personal lives. Recent headline news at the LA Times revealed that some UCLA students became homeless. They could not afford rent for a dorm and had to sleep in their cars at night. They had to either skip meals or depend upon donated meals to stay out of hunger. Let s take an UCR MBA student, Jayanti Dash, as an example. She came from India last year to attend the UCR MBA program. She was married and her loved ones were left behind in India. In 2009, the annual fees and costs for an international MBA student at UCR amounted to about $48,000. And tuition is still on a sharp rise. She had to spend all savings from her family; ask help from her uncle's family in the US; and work part time at UCR to make ends meet. Jayanti would have to quit 55

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2008年1月11日に岩手県釜石沖で発生した地震（M4.7）について

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