第一篇：福建师范大学英语专业论文格式
附件3 福建师范大学外国语学院本科生
毕业论文写作指南
（第三次修订稿，2006年4月25日）
1.选题 Selecting a topic
学生在经过统一动员及论文写作初步指导之后，先自行选题，选题时请考虑以下因素： 1）选题的难度适中、对内容熟悉或有兴趣、范围恰当，切忌太大或太泛；
2）题目力求新颖，忌老生常谈或重复他人研究结论；
3）题目要具有可行性，是否有充足的资料，或能否落实具体的调查和实验；论文所需的篇幅能否在规定时间内完成，并有足够的时间和导师商讨；
4）学生应该在教师指导下完成开题报告（包括本论题的意义、工作内容、大致进度、预期达到的效果或拟解决的问题等）。开题报告经指导教师签字同意后上交学院教学秘书，方可开始撰写论文。
2.论文要求 Requirements of theses 1）论文应与本专业有关； 2）独立完成； 3）用英文撰写；
4）字数8000字左右〖计算方法：word文档中“字数统计”栏中的字符数（不计空格）除以2〗
5）如系翻译方面的研究，可以接受翻译评论，但不接受单纯的翻译文本。6）学生务必在规定时间内提交正式论文定稿，过期不予受理。3.论文结构 Format of the Thesis 根据福建师范大学师大教[2005]6号文件以及本专业特点，对毕业论文格式提出以下要求：
1）所有毕业论文一律用计算机打印。具体格式见附件1；
2）论文结构依次包括（装订顺序）：①封面（学校统一制作，由学生填写）②英文标题③学院、专业、学号、作者姓名、指导教师姓名④英文论文摘要（约400字—--排版后约十行，主要概述论题的背景介绍、目的，以及研究所要解决的主要问题、可能产生的主要结果、结论和建议等）⑤英文关键词（3 至6个）⑥目录（可省项）国际经济与贸易等专业学生可以用汉语撰写论文，论文的结构及装订顺序做相应调整，即下文中的第②④⑤与⑩的顺序进行前后对调调整。⑦正文⑧注释（可省项）⑨参考文献⑩中文论文题目、中文摘要、中文关键词（此项单独一页）；
3）所有论文要求有一定数量和分量的参考文献，文章中所引用的数据和观点应用恰当的方式表明具体出处（有关格式详见附件1的第(十)点及附件2）； 4）严禁任何抄袭或复制他人论文的不道德行为，违者按不及格处理；
5）所有学生在提交打印定稿的同时必须提交一份word格式电子文档（文件名为：学号.DOC），由指导教师统一交给学院教学秘书。
4.论文质量和评分标准 Quality of theses and Grading standard
1)论文评分依据：选题的理论价值和现实意义，内容的开拓性和深度、广度，分析方法，综合表达能力，文字质量，论文的格式，等。
2)论文评分等级：成绩分为“优”、“良”、“中”、“及格”和“不及格”五个等级（每级不再分等）。所有学生论文必须进行答辩，小组答辩成绩不是“优”的，小组成绩作为学生最终成绩；小组答辩成绩为“优”的，需参加学院答辩委员会组织的评优论文答辩，答辩成绩作为学生最终成绩。毕业论文成绩为“及格”的不能获得学士学位资格。毕业论文成绩为“不及格”的学生不能毕业。
附件1 毕业论文（设计）打印格式要求
一、毕业设计（论文）用纸、页面设置要求
毕业设计（论文）应按规定格式单面打印，纸张大小一律使用国际标准A4型复印纸。
页面设置：版心为297×210mm；页边距要求：每一面的上方（T）2.5 cm，下方（B）2.5cm，左（L）2.5 cm，右（R）1.5 cm，装订线（T）0.5 cm，装订线位置（T）左侧，页眉1.5cm，页脚1.75cm，页码设置为：插入页码，居中；其余设置采取系统默认设置。
二、毕业设计（论文）内容打印要求
（一）论文题目：英文用二号“Times New Roman”字体，加粗，居中放置；中文使用二号黑体字，加粗。居中放置。
（二）学院、专业、学号、作者姓名、指导教师姓名（小四号宋体字，加粗），依次排印在论文题目下（上空二行，居中）。
×××学院
×××专业×××（学号）×××（姓名）
指导教师 ×××
（三）摘要（上空二行）
英文摘要：题目采用五号“Times New Roman”字体，加粗，置于粗体方括号【】内，顶格放置；随后的内容与前面的粗体方括号【】之间空一格，不用其他任何标点符号，采用五号“Times New Roman”字体，不加粗；单倍行距。如：
【Abstract】（Times New Roman，五号字，加粗）××××××××××××××××（Times New Roman,五号字，不加粗）
中文摘要：题目采用黑体五号字，加粗，置于粗体方括号【】内，缩进2个汉字字符，方括号中的“摘要”两个字之间空一格；随后的内容与前面的粗体方括号【】之间空一格，不用其他任何标点符号，采用楷体五号字，不加粗，单倍行距；此项内容单独一页，放置于论文的最后；如：
【摘 要】（黑体，五号字，加粗）××××××××××××××××（楷体五号字，不加粗）
（四）关键词
英文关键词：题目采用五号“Times New Roman”字体，加粗，两个单词的首字母要大写，置于粗体方括号【】内，顶格放置；随后的内容与前面的粗体方括号【】之间空一格，不用任何其他标点符号，采用五号“Times New Roman”字体，不加粗，除了专有名词外，其他单词的首字母不大写，各单词之间用分号“；”隔开，分号之后空一格；最后一个关键词之后不用任何标点符号；单倍行距。如： 【Key Words】 xxxx;xxxx;xxxx;xxxx 中文关键词：题目采用黑体五号字，加粗，置于粗体方括号【】内，缩进2个汉字字符；随后的内容与前面的粗体方括号【】之间空一格，不用其他任何标点符号，采用楷体五号字，不加粗，单倍行距；各单词之间用分号“；”隔开，分号之后不空格；最后一个关键词之后不用任何标点符号；单倍行距。如：
【关键词】 ××××；××××；×××；×××
（五）目录（可省项：根据实际情况确定是否需要此项）
采用Times New Roman字体，其中每章题目用小四号，加粗，每节题目用正常字体，并注明各章节起始页码，题目和页码用“„„”相连，如下所示：
Table of Contents（三号字，加粗）
（自然空二行）
1.×××××××
„„„„„„„„„„„„„„（1）（小四号字，加粗）1.1 ××××××
„„„„„„„„„„„„„„（2）（小四号）
1.1.1 ××××××
„„„„„„„„„„„„„„（6）（小四号）2.……
（六）正文字体要求、每章题目左顶格，小四号字，加粗；每节（及小节以下）题目左顶格，小四号字，不加粗但要斜体；正文所有英文文字采用小四号Times New Roman字体，涉及的汉语文字用小四号宋体；每自然段首行缩进4个英文字符。
（七）行间距要求
正文行距设置：设1.5倍行距。
（八）正文章节序号编制 章，编写为：1.，2.，3.，„。
节，编写为：1.1、1.2„，2.1、2.2„。
小节，编写为：1.1.1, 1.1.2„。
小节以下层次，采用希腊数字加括号为序，如（i），（ii）„；之后再采用字母加括号，如(a),(b),„;另外，正文中的例子以（1），（2）„为序号排列，直至最后一个例子；而①, ②„则为脚注或尾注的上标序号〕
（九）毕业设计（论文）的公式、图与表
（略）
（十）中文参考文献（适用于用汉语撰写论文的国贸等专业学生，也适用于英语论文中涉及汉语的参考文献，但相关作者在英语论文夹注中出现的时候，作者姓名必须以拼音××××××
„„„„„„„„„„„„„„（40）（小四号字，加粗）
方式出现，不能以汉语形式出现）参考文献（黑体，小四号字，上空二行）
×××，×××××××××××××××××××××××××××××××××× ×××，××××××××××××××××××××××××××××××××××
参考文献中各文献的排列以作者的姓氏拼音为序；宋体小四号字；参考文献的编写方式为：
期刊文献的格式：“作者，发表时间，文章题目名，《发表的期刊名》,卷号(期数):引文页码.如有第二行，则须缩进4个英文字符”例如：
杨扬，王玉，周洲，2000，油田储层非均质性研究，《高校地质学报》，第3期223-230页。
图书或硕士、博士文献的格式：“作者，出版时间，《著作题目名（硕博论文名）》。出版社名称（硕博毕业院校名），引文页码。如有第二行，则须缩进4个英文字符”例如： 徐通锵,1997，《语言论》。长春：东北师范大学出版社，第222页。张三四，2005,《论非作格动词的习得路径》。江南大学博士论文，第88页。
会议文献的格式：“作者，发表时间，文章题目名。会议名称,卷号(期数):引文页码.如有第二行，则须缩进4个英文字符” 例如：
孙力等，2000,储层条件下水淹油层测井响应机理实验研究。北京国际学术讨论会，第 10-11页。
附件2 英文注释和参考文献格式要求
（说明：本格式主要参阅了Applied Linguistics，《外语教学与研究》等杂志以及部分大学外语学院毕业论文格式要求；日语毕业论文格式另列。）I.注释Endnotes and In-text Citations 1． 脚注（尾注）
在正文需详细注释处的右上方按顺序加注数码①②③……，在全文之后写注文,每条加对应数码, 回行时与上一行注文对齐（注：脚注和尾注主要用以对有关问题、论点做补充说明；偶尔也用以标明、指示参考文献；而以下的夹注则主要只针对参考文献）。
2． 夹注
某些引文或所依据的文献无须详细注释者，以夹注的形式随文在括号内注明。
1）来自文章、专著的直接引语，作者姓名在文中已经出现： 格式：出版年份：页码
例：
Rees said, “As key aspects of …in the process”(1986:241).2)来自文章、专著的直接引语，作者姓名在文中没有出现：
格式：作者姓名，出版年份：页码
例： The underlying assumption is that language “bound up with culture in multiple and
complex ways”(Elli, 1968: 3).3)来自文章、专著的间接引语，作者姓名在文中已经出现：
格式：出版年份：引文页码
例：According to Alun Rees(1986:234)〔也可位于引语的最后〕, the writers focus on
the unique contribution that each individual learner brings to the learning situation 〔(1986:234)〕.4)来自文章、专著的间接引语，作者姓名在文中没有提到：
格式：作者姓名 出版年份：引文页码
例：It may be true that in the appreciation of medieval art the attitude of the observer is of primary importance(Robertson, 1987: 136).5)互联网资料： 格式：编号
例： “A deconstructive reading is a reading which analyses the specificity of a text’s critical difference from itself”(Net.2).(注:：Net.1, Net.2, Net.3,……只是为了便于注明文内引语的出处，具体格式见下文参考文献中的相关内容)
II.Bibliography(References)（“Times New Roman”字体，小四号，加粗，后面不加任何标点符号；另外，参考文献必须与夹注形成一一对应关系，即文章夹注、脚注中出现的作者必须出现在参考文献中，反之亦然，参考文献中的文献也必须是在文章中出现过的，二者相比，不多也不少）
1.专著：
1).基本格式（还要注意标点符号）：作者的姓名（英文作者的姓，名）.年份.书名（要斜体）.出版地:出版商.如果同一作者两本以上同年出版的参考书，在年份后用a，b，c 等标出； 如有第二行，则须缩进4个英文字符。例：
Chomsky, N.1981a.Lectures on government and binding.Dordrecht: Foris.Chomsky, N.1981b.Theory of markedness in generative grammar.Pisa, Italy: Scuola Normale Superiore.2).书的主编（格式：各项信息的排列顺序基本同上）：
例：Hall, David, ed.1981.The Oxford book of American literary anecdotes.New York: OUP.3).机构作者（格式：各项信息的排列顺序基本同上）：
例：American library association.1983.Intellectual freedom manual.2nd ed.Chicago: ALA.4).翻译著作（格式：各项信息的排列顺序基本同上）：
例：Calvino, Ian.1986.The uses of literature.P.Creagh Trans.San Diego: Harcourt.2.文章：
1)期刊：文章基本格式（还要注意标点符号）：作者姓名.年份.篇名.刊名（要斜体）.刊物的卷号和期号:文章的起止页码。例：
Boling, D.1965.The atomization of meaning.Language 41:555-573.2)论文集的文章：基本格式（还要注意标点符号）：作者姓名.年份.篇名.论文集作者姓名.eds.论文集名称（要斜体）.出版地:出版商.文章的起止页码。例：
Peters, M & T.B.Stephen.1986.Interaction routines as cultural influences upon language acquisition.In Schieffelin, B.B.& E.Ochs, eds.Language Socialization Across Cultures.Cambridge: CUP, 80-96.3.文字资料：（注意：此部分涉及的文献既可能是中文的，也可能是英语的，请使用相应的中、英文标点符号！）)电脑软件
基本格式：制作人姓名，年份，软件名称，型号。2)电影、电视、广播、录像、录音、艺术品等：
基本格式：片名（或节目名），年份或播出日期，导演（或制作者）姓名，出品地（或播出台、地）。3)互联网资料：
基本格式：如果是中文的参考中文参考文献的格式，英文的则参考英文参考文献的格式，例如：
Net 1.Steven Pinker.2006.Second language acquisition of Spanish and French unaccusative verbs.http://。
【论文最后的参考文献中所有文献的排列顺序：英文文献----网络文献----汉语文献，各个文献的先后以作者的姓氏字母或拼音为序；“Times New Roman”字体，1.5倍行距，小四号，不加粗】 日语专业本科毕业论文的格式要求
(空2行)外国语学院
日语专业
2001123 张三
指导教师
李四2
(空2行)
4【摘 要】3 200字左右。内容：处理的对象及主要结论。摘要使用楷体，五号字。第二行开头的位置如本摘要。
【关键词】5 3~5个
论文格式
注释
参考文献6
目录7
1.前言82.正文
2.1 结构2.2 学术史研究3.注释
3.1 引用3.2 夹注3.3 脚注4.版式
4.1 纸张4.2 排版4.2.1 页面设置4.2.2 字体及字号 2 小四号宋体字，加粗。黑体，五号字。4 楷体，五号字。5 黑体，五号字。6 楷体，五号字。7 黑体，四号字。可省项，即作者可根据实际情况确定是否需要设立此项。8 宋体，小四号字。3 8 4.2.3 正文格式4.2.4 编号
5.关于参考文献
5.1 范围5.2 排列顺序
5.2.1 语种之间5.2.2 语种内部5.3 时间5.4 列举的项目及格式5.5 参考文献中的“[类别]”
5.6 例证出处
6.装订顺序7.结论
(空2行)
1.前言
提出问题。明确问题所在，提出大致的思路。
2.正文
2.1 结构
正文可根据需要分成若干部分。2.2 学术史研究
介绍前人对这个问题的研究，并表明自己的研究与前人研究的不同之处。
对学术史的回顾，可以在“前言”中进行，也可以在前言之后单独设一个章节处理。
3.注释
3.1 引用
文章在涉及前人研究成果时，不论是否赞同，都必须声明。引用方法有：
1、用引号直 接引用；
2、通过概括间接引用。不论以哪一种方式引用，都必须注明出处。3.2 夹注
文章中的注释使用夹注(张三2000：35)的形式。这里，“张三”是作者名，“2000”是文献的首次出版时间。如果这个文献是著作，那么有必要注明引文出现的页码，即“35”。
如果张三在1998年发表的两个文献都被引用，则采用“(张三1998a)”和“(张三1998b)”的形式注释。
如果被引用者张三是句子的某个成分，则采取以下方式注释，即：张三(1998a)还指出，„„。
3.3 脚注
如果需要在正文之外进行某种说明，可以使用脚注。脚注以页为单位标注9。
4.版式
4.1 纸张
使用A4纸张(版心为297×210mm)打印。4.2 排版
4.2.1 页面设置
打开“页面设置”对话框，将页边距设定为：上方(T)2.5 cm，下方(B)2.5cm，左(L)2.5 cm，右(R)1.5 cm，装订线(T)0.5 cm，装订线位置(T)左，页眉1.5cm，页脚1.75cm。
每行字数和每页行数均设定为“38”。4.2.2 字体及字号
字体及字号使用以下(1)～(6)的设置。
(1)a.汉语论文题目：黑体，二号字，加粗，居中。
b.如果有副标题，其设置为：黑体，三号字，居中。
(2)a.日语论文题目：MS Gothic字体，二号字，加粗，居中。
b.如果有副标题，其设置为：MS Gothic字体，三号字，居中。
(3)a.每一章的标题，即第1级标题的汉语部分使用“黑体”，四号字。
b.每一章的标题，即第1级标题的日语部分使用「MS Gothic」，四号字。
(4)a.第2级及以下的标题，汉语部分使用“黑体”，小四号字。
b.第2级及以下的标题，日语部分使用「MS Gothic」，小四号字。
(5)a.正文的汉语部分使用“宋体”，小四号字。
b.正文的日语部分使用「MS Mincho」，小四号字。
c.脚注使用小五号字体。
(6)
英语部分使用“Times New Roman”，字号同(1)～(5)。4.2.3 正文格式
如果正文是汉语，则段落的开头缩进2个汉字字符。
如果正文是日语，则段落的开头缩进1个汉字字符。4.2.4 编号
“章节编号”参照本格式，一律使用半角数字。
“例证编号”使用半角的括弧编号，缩进2个汉字字符，如4.2.2中的(1)～(6)。例证实行全文统一编号。
点击word的“插入”，选择“脚注或尾注”。(i)在“插入”栏，选择“脚注”；在“编号方式”栏，选择“自动编号”。(ii)单击“选项”按钮，在“编号方式”栏中，选择“每页重新编号”。
“脚注编号”参照本格式。
“页码编号”的参照本格式10。
5.关于参考文献
5.1 范围
文中提到的他人的研究成果(包括夹注中出现的文献)必须列入“参考文献”。语言词典一般不列入参考文献。
参考文献中列举的项目必须是实际阅读过的。如果是从李四(1992)的论文中看到王五(1985)的观点，那么王五的成果不应列入参考文献。参考文献中列入的是李四(1992)，王五(1985)的出处用脚注说明。处理办法是：王五(1985)11指出，„„。5.2 排列顺序 5.2.1 语种之间
首先是汉语的文献，其次是日语的文献，最后是西方语言的文献。5.2.2 语种内部
汉语：按照人名的汉语拼音字母序排列。
日语：按照人名的五十音图序排列。
英语：按照字母序排列。5.3 时间
参考文献中列举的时间，以该文献的首发时间为准。5.4 列举的项目及格式
期刊文献：[编号](空一格)作者名。文章题目名[类别]。期刊名，年份，卷号(或期数):页码范围。
图书文献：[编号](空一格)作者名。书名[类别]。出版地：出版社名，出版年份。
论文集文献：[编号](空一格)作者名。文章题目名[类别]。论文集名[类别]。出版地：出版社名，出版年份，引文页码。
互联网资料：[编号](空一格)作者名。篇名。网址 5.5 参考文献中的“[类别]”
5.4中，文献名之后的“[类别]”，使用代码标注，规则如(7)。
(7)文献类别： A--论文集中的文章；J—期刊；C—论文集；M—书；D—学位论文；
EB/OL—电子文档
5.6 例证出处
例证的出处不列入参考文献，而是单列“资料出处”。
6.装订顺序
论文按照(i)封面、(ii)论文、(iii)附加信息的顺序装订。
其中，(i)由学校统一制作，作者填写。(ii)论文和(iii)附加信息由作者使用不同的语言写作。
本格式中，(ii)使用汉语，见p1～p5；(iii)使用日语，见p6。(iii)必须单独设一页。
1011 单击“视图”按钮，然后单击“页眉和页脚”；进入页脚，单击“插入自动图文集”按钮，选择“-页码-”。
转引自李四(1992: 123)。7.结论
通过本文的分析，得出哪些结论。只要以条目方式罗列即可。
附记
毕业论文除提交纸质文本外，还必须提交电子文本。电子文本以“WORD文档”格式保存，文件名以自己的学号命名，即：123.doc
参考文献
[1] 侯精一(主编)。现代汉语方言概论[M]。上海：上海教育出版社，2002。
[2] 李如龙。闽南方言的介词[A]。介词[C]。广州：暨南大学出版社，2000，122-138。[3] 李艳慧、陆丙甫。数目短语[J]。中国语文，2002，4：326-336。
[4] 张济卿。论现代汉语的时制与体结构（上）[J]。语文研究，1998a，3：17-25。[5] 张济卿。论现代汉语的时制与体结构（下）[J]。语文研究，1998b，4：18-26 [6] 张济卿。对汉语时间系统三元结构的一点看法[J]。汉语学习，1998c，5：20-23 [7] 赵元任。A Grammar of Spoken Chinese[M].1968；吕叔湘译。汉语口语语法[M]。北京：商务印书馆，1979。
[8] 木村英树。付着の“着/zhe/”と「消失」の“了/le/”[J]。中国語，1981，258：24-27/12。[9] 寺村秀夫。日本語のシンタクスと意味 Ⅰ[M]。東京：くろしお出版，1982。[10] Comrie, Bernard.Aspect[M].London: Cambridge University Press, 1976.资料出处
[1] 川端康成。『雪国』，新潮文庫。[2] 倉野憲司(校注)。『古事記』，日本古典文学大系，岩波書店，1958。[3] 『広辞苑』(第五版)，岩波書店。
卒業論文の様式について
——学部生用の場合
外国語学院 日本語科 2001123 張三 指導教官 李四
【要旨】(MS Gothic)200字前後。内容：扱う対象及び主な結論(MS Mincho)
【キーワード】(MS Gothic)3つ~5つ 論文様式 注釈 参考文献(MS Mincho)
第二篇：英语专业论文
英语专业文学方向本科毕业论文写作问题探究
[摘 要]英语毕业论文由于从事英美文学教学的教师理论水平参差不齐、教师对学生文艺理论接受能力的怀疑、商品经济时代文学和文艺理论曲高和寡等因素,造成文学学习和文学方向毕业论文写作中缺乏科学的分析方法。本研究将探索将文艺理论引入本科毕业生的论文写作课程中的必要性和可行性,从而建构以文艺理论为中心的英语专业文学方向毕业论文写作的新模式。
[关键词]文学理论;读者反映理论;认知教学法
依据《高等教育法》(1998)的本科教育学业标准,学生应比较系统地掌握本专业所必需的基础理论知识、基本技能和相关知识,并“具有从事本专业实际工作和研究工作的初步能力”。这一标准强调了研究性教学(research-oriented teaching)的重要性,无疑为英美文学教学中理论研究与实践的有机融合提出了要求,而这种融合往往体现在学生文学论文写作的能力之中。然而,高校中实用主义风气、急功近利思想和“重技能,轻人文”弊端的集中体现冲击着文学课教学,助长了学生轻视与人文修养有关的课程,助长了他们对文学作品敬而远之的倾向(马爱华, 2006)。作为全面考核毕业生综合素质的有效途径,毕业论文写作是本科学生毕业前必须经受的考验关口,是师生教学相长的过程。本文将从文学课教学的现状出发,通过毕业论文写作的过程,在揭示现象、总结经验的基础上,提出重视文艺理论的教学,提高学生的文学素养,培养研究性学习能力的意义。
一、研究现状
部分专家认为英语专业(张冲, 2003)是“英语语言技能的专业训练和对英语语言文化的专门研究”,其特征为“技能加专业,复合而开放”,其培养目标为“纯熟的语言能力,深度的专题研究”。这一专业定位除了强调语言技能之外,着重强调了“文化”和“研究”。文化理解和专题研究的基础在于学生文学课程的给养过程,其中,文学理论分析则既指导了文学课程的学习,又加深了学生对文学作品的理解。文学作品的学习与文艺理论的关系好比材料和工具的关系,“工欲善其事,必先利其器”,如果学生没有相关的文艺理论的学习,就好比一个没有工具的工匠,只能望天兴叹。
二、问题成因
文艺理论是学习英美文学的分析和鉴赏工具,研究生阶段的文艺理论教学已经有了一定的历史,但在英语专业本科教学中文艺理论的教学目前尚未展开。这直接导致学生的文学毕业论文的写作难度增大,出现了许多亟待解决的问题。主要成因如下:
1.从事英美文学教学的教师理论水平参差不齐。部分教师讲授英美文学,而其自身很少涉及文艺理论的使用,或者说自己的文学批评理论知识匮乏,因此不可能在授课时有意识地将文艺理论融入到教学中去。
2.轻视或放低对学生的人文素质和评析能力的生成要求。有些教师担心学生的接受能力,甚至害怕因为学生不能正确理解文艺理论的精髓而将其误用或者滥用。《高等学校英语专业英语教学大纲》(2000)明确规定了文学课程的教学目的“在于培养学生阅读、欣赏、理解英语文学原著的能力,掌握文学批评的基本知识和方法。通过阅读和分析英美文学作品,促进学生语言基本功和人文素质的提高,增强学生对西方文学及文化的了解”,显而易见,加大文学批评理论的讲授和研讨是符合《大纲》要求的。
3.所学知识与研究性写作存在三个“不和谐”关系:文学课的教与学脱节;文学课与语言实践脱节;文学教学理论的研究与外语教学实践脱节(马爱华, 2006)。学生习得的知识孤立于其写作实践之外。人才培养目标不明确,学生急功近利,一成不变的文学课程教学脱离实际人才
培养模式。学生将文艺理论视为纸上谈兵。因而,导致“文学理论教材和教学实践逐渐偏离当今消费时代的审美精神”以及“文学理论的教学被大学生们冷落”(李迪江, 2002)。
三、文艺理论在文学论文写作中的意义
1.文学理论的专业知识学习,铺垫了文学论文的研究能力。“文学理论教学应该优先地培养大学生的理论素养,更多地培养大学生的应用能力,如从文学作品的分析讨论中,来培养大学生的理解能力、分析能力和表达能力等(李迪江, 2002)”。本科学生已经有了一定的文学常识,至少对于著名作品的情节有了一定程度的了解,文学名著选读课使用文学名著的原版书籍作为教材,使得学生有机会对文学文本进行仔细研读,为文艺理论的学习奠定了基础。
2.毕业论文写作,完成学生从读者到理论分析的升华。Guerin认为,“读者参与在文本的创作中”。作品的意义是文本和读者相互作用的结果,它强调读者在阅读过程中的不同参与方式。这一理论代表人物之一伊瑟尔指出,所有文学篇章都有“空白”或“缺口”,这些空白和缺口必须由读者在解读过程中填补或具体化(刘辰诞, 1999)。文学作品须由接受者内化和心灵化,即需要接受者的理解、体验、加工、补充和创造,融入接受者的思想和情感、倾向和评价,只有这样,作品中的时间、人物形象等才会活生生地呈现在自己的头脑中(郭宏安, 1997)。从这个角度暴露了英语专业教育中一贯的“知识单一和技能单一”问题,带来的思考是应该如何培养学生多种语言技能,满足其独立学习的需要。
3.文学史学习为文艺理论的学习奠定基础。心理学、原型批判、女权主义、马克思主义的文学评论等可将传统文学史中作家、作品按照时间排序的方式打破。从各种文艺理论的角度对作家、作品重新排序,不同的文学作品可以用相同的文艺理论进行分析,既起到梳理文学史和文学作品的目的,又使学生对文学作品甚至文学史的认识提升到一个新的高度。如:莎士比亚的《哈姆雷特》,尤金?奥尼尔《榆树下的欲望》,劳伦斯的《儿子与情人》等作品中都蕴含着恋母情结的心理学分析。以此为基础,给学生补充讲述古希腊剧作家索福克里斯的著名悲剧作品《俄狄浦斯王》,能帮助学生探究作品人物的内心世界,为论文写作奠定基础的同时,也有助于选择一个更为可行的题目。
4.结合文本与文艺理论,丰富学生的论文选题。学生文学专业毕业论文选题往往单一,如选择:《伟大的盖茨比》中美国梦破灭的主题或美国梦的悲剧一类的主题;《呼啸山庄》、《傲慢与偏见》中的爱情主题等。选择经典作家的代表作品为研究对象并不是不可以,但对于一般本科生而言,要就这些作品的某一方面进行较为深入、有创意的探讨,还是有相当难度的。因为,对于某一经典文本的某些问题,国内外评论界可能早有定论,而一般的学生“尚不能用当代文论的新视角去解读,很难提出自己的新解”(杜志卿, 2005)。
5.研读诗歌,理论先行。在历届本科英语专业毕业生的论文中,有关诗歌的论文很少有人涉及。究其成因,主要是在较短篇幅的诗歌中大量运用意象和象征等写作手法,再加上诗人用特有的音韵感和
第三篇：福建师范大学协和学院2010级英语专业就业问卷调查
福建师范大学协和学院2010级英语专业就业问卷调查
首先感谢您在百忙之中抽空填写本问卷！
1.请问您的性别是？()
A男B女
2.您是什么时候开始关注就业问题?（）
A初中B高中C大学D目前还未关注
3.您当初选择英语专业的想法是来自？()
A自己对英语有浓厚的兴趣，并打算继续深造。
B为了以后就业方便才选英语专业。
C听从他人或者父母的意见。
D被迫无奈的选择。
4.您对将来毕业就职单位有何取向?()
A国家单位B事业单位C中外企业D私企E无所谓
5.在找工作时您是怎样看待专业和工作性质问题？（）A一定要找与专业对口的工作。
B可以与专业有关联性，不一定对口。
C专业与工作性质无关，先找一份工作在再说。
D根据自己的兴趣喜好选择行业。
6.您对就业地区的选择原因?（可多选，两项以内）（）
A工作待遇好，可观的收入B与国际接轨C岗位多元化D生活条件好
E提供再学习的机会，有较大的发展机会F看重创业环境
7.您认为当今就业困难的主要原因是？（可多选，两项以内）（）A缺乏实际技巧与精练B就业期望过高C就业人数太多D企业的要求过高
E没有找到合适自己的岗位F金融危机带来的企业倒闭
8.您对求职渠道的选择是？（可多选，两项以内）（）
A人才招聘市场B校园招聘会C网上投写简历D父母亲戚朋友介绍
E报纸广播媒体报导F其他
9.您对您第一份工作的薪水期望是多少？（）
A 1000元以内B 1000-1500元C 1500-2000元D 2000-3000 元E 3000元以上
F无所谓多少，只有能够锻炼就可以。
10.工作一段时间后，您发现工作与您理想中的有较大差别，您会？（）
A马上重新找新的工作B先做等有机会再跳槽
C看看再说，或许过段时间会加薪D无所谓，反正都要经历
11.你应聘某企业时，着重该企业哪个方面？（可多选，两项以内）（）A公司的发展前景B薪水的高低C个人的发展空间D公司重视人才的程度E公司的名气
12.您会考虑自主创业吗?（）
A工作难找，就会考虑自主创业B不会，刚刚毕业没什么经验C暂时没考虑
13.如果自主创业，您会选择哪些行业？
A食品饮料等B IT业C网上开店D其他 非常感谢您完成本问卷，祝您身体健康，学业有成！！
第四篇：爱丽丝梦游仙境英语专业论文
Alice adventures in wonder land 主要内容
《爱丽丝奇境历险记》讲述了小姑娘爱丽丝追赶一只揣着怀表、会说话的白兔，掉进了一个兔子洞，由此坠入了神奇的地下世界。在这个世界里，喝一口水就能缩得如同老鼠大小，吃一块蛋糕又会变成巨人，在这个世界里，似乎所有吃的东西都有古怪。她还遇到了一大堆人和动物：渡渡鸟、蜥蜴比尔、柴郡猫、疯帽匠、三月野兔、睡鼠、素甲鱼、鹰头狮、丑陋的公爵夫人。兔子洞里还另有乾坤，她在一扇小门后的大花园里遇到了一整副的扑克牌，牌里粗暴的红桃王后、老好人红桃国王和神气活现的红桃杰克（J）等等。在这个奇幻疯狂的世界里，似乎只有爱丽丝是唯一清醒的人，她不断探险，同时又不断追问“我是谁”，在探险的同时不断认识自我，不断成长，终于成长为一个“大”姑娘的时候，猛然惊醒，才发现原来这一切都是自己的一个梦境。
《爱丽丝穿镜奇幻记》讲述的是小姑娘爱丽丝刚下完一盘国际象棋，又对镜子里反映的东西好奇不已，以致穿镜而入，进入了镜子中的象棋世界。在这里，整个世界就是一个大棋盘，爱丽丝本人不过是这个棋盘中的一个小卒。小姑娘从自己所处的棋格开始，一步一步向前走，每一步棋都有奇妙的遭遇：爱丽丝会脚不沾地地飞着走路，那里的花朵和昆虫都会说话，白王后变成了绵羊女店主，她手中的编织针变成划船的桨，等等。镜中的故事大多取材于英国传统童谣，作者通过自己的想象加以展开，并详细叙述，童谣里的人和物活灵活现地呈现在读者面前：为一丁点儿小事打架的对头兄弟，行止傲慢的憨蛋和为争夺王冠而战的狮子和独角兽。看来只有发明家兼废品收藏家白骑士无法归类，但他恰好是作者本人的化身。等到爱丽丝终于走到第八格，当了王后之后，为所有这些人准备了一次盛大的宴会，宴会上的烤羊腿会鞠躬，布丁会说话，盛宴最终变成了一片混乱，忍无可忍的爱丽丝紧紧捉住摇晃的红后最后变成了一只小黑猫，爱丽丝也在摇晃中醒来，开始追问这到底是自己的梦呢，还是红国王的梦？ 作者介绍
刘易斯·卡罗尔（Lewis Carroll），原名查尔斯·路德维希·道奇逊，与安徒生、格林兄弟齐名的世界顶尖儿童文学大师。原名查尔斯·路德维希·道奇逊。1832年1月出生于英国柴郡的一个 牧师家庭，1898年卒于萨里。曾在牛津大学基督堂学院任教达30年之久，业余爱好非常广泛，尤其喜爱儿童肖像摄影。他的第一本童书《爱丽丝奇境历险记》于1865年出版，当时就引起了巨大轰动，1871年又推出了续篇《爱丽丝穿镜奇幻记》，更是好评如潮。两部童书旋即风靡了整个世界，成为一代又一代孩子们乃至成人最喜爱的读物。
如果说刘易斯·卡罗尔因为这两部童书而被称为现代童话之父，丝毫没有夸大的成分。至少他的两部《爱丽丝》一改此前传统童话（包括《安徒生童话》、《格林童话》）充斥着杀戮和说教的风格，从而奠定了怪诞、奇幻的现代童话基调。仅从这点来说，就堪称跨时代的里程碑。故事简介
Alice, sitting with her sister, is bored.A White Rabbit scurries by, muttering to himself and pulling a watch from his waistcoat pocket.Curious, Alice follows the animal down a rabbit hole, the first of many instances in which she is propelled by her curiosity.Alice falls, landing in a pile of leaves.She finds herself in a hall and discovers a tiny key to a tiny door leading to a garden.She drinks from a bottle labeled DRINK ME, and shrinks down to ten inches tall.Too short to unlock the garden door, Alice begins to cry.She eats some cake, grows unusually tall, then fans herself and becomes exceedingly small.She finds herself swimming in a pool of her own giant tears.A group of animals gathers around her on the shore.A Mouse gives a speech and then a foot race ensues.Alice is soon left alone and begins to cry again.The White Rabbit approaches.Thinking Alice is his housemaid, he sends her on an errand to fetch some things from his house.Alice drinks from a bottle she finds inside and grows until she fills the house, spilling out windows and bumping her head against the ceiling.Frightened, the Rabbit and his friends throw pebbles at Alice.The pebbles become cakes, which Alice eats to shrink.She escapes and meets a Caterpillar sitting on a mushroom, smoking.While he questions her identity and learning, Alice experiments with eating parts of the mushroom to alter her height.After a brief conversation with a Pigeon, she visits the highly
peppered house of the ill-tempered Duchess and encounters the Cheshire Cat, traveling next to the house of the March Hare.Here the Hare, the Mad Hatter, and the Dormouse have tea.Confused, she leaves the party in disgust and finds her way to the garden she could not reach earlier.In the garden, Alice encounters a very curious croquet game and a Queen of Hearts who threatens to chop off everyone's heads.Alice talks with the moralizing Duchess until the Queen threatens to execute the woman.At the Queen's orders, a Gryphon leads Alice to the Mock Turtle.She listens to his life story and his instructions for dancing the Lobster
Quadrille.The two creatures ask Alice to recount her own adventures, which she does, until a Trial is announced in the distance.The Trial concerns some tarts stolen from the Queen.When she is called to the witness stand, Alice begins to grow again and knocks over the jury box.The King orders her to leave the court because of her height.She refuses and continues to grow as the White Rabbit introduces more evidence.The Queen threatens to chop off Alice's head.Having grown to her full size, Alice calls the Queen and her soldiers a mere deck of cards, at which point the entire pack of them rises up and flies down upon her.Alice awakes.Her sister is brushing off some leaves from Alice's face.She recounts her Adventures and runs off.Her sister watches Alice and begins to dream herself, imagining that the White Rabbit rushes by through the grass.梗概：Alice's Adventures in Wonderland(commonly shortened to Alice in Wonderland)is an 1865 novel written by English author Charles Lutwidge Dodgson under the pseudonym LewisCarroll。[1]It tells of a girl named Alice who falls down a rabbit hole into a fantasy world(Wonderland)populated by peculiar, anthropomorphic creatures.The tale plays with logic, giving the story lasting popularity with adults as well as children.[2] It is considered to be one of the best examples of the literary nonsense genre,[2][3] and its narrative course and structure have been enormously influential,[3] especially in the fantasy genre.
第五篇：英语专业论文翻译
A smart copper(II)-responsive binucleargadolinium(III)complex-based magnetic resonanceimaging contrast agent†
Yan-meng Xiao,ab Gui-yan Zhao,ab Xin-xiu Fang,ab Yong-xia Zhao,ab Guan-hua Wang,c Wei Yang*a and Jing-wei Xu*a A novel Gd-DO3A-type bismacrocyclic complex, [Gd2(DO3A)2BMPNA], with a Cu2+-selective binding unitwas synthesized as a potential “smart” copper(II)-responsive magnetic resonance imaging(MRI)contrast agent.The relaxivity of the complex was modulated by the presence or absence of Cu2+;in the absence of Cu2+, the complex exhibited a relatively low relaxivity value(6.40 mM1 s1), while the addition of Cu2+ triggered an approximately 76% enhancement in relaxivity(11.28 mM1 s1).Moreover, this Cu2+-responsive contrast agent was highly selective in its response to Cu2+ over other biologically-relevant metal ions.The influence of some common biological anions on the Cu2+-responsive contrast agent and the luminescence lifetime of the complex were also studied.The results of the luminescence lifetime measurements indicated that the enhancement in relaxivity was mainly ascribed to the increased number of inner-sphere water molecules binding to the paramagnetic Gd3+ core upon the addition of Cu2+.In addition, the visual change associated with the significantly enhanced relaxivity due to the addition of Cu2+ was observed from T1-weighted phantom images.Introduction Copper(II)ion is a vital metal nutrient for the metabolism of life and plays a critical role in various biological processes.1,2 Its homeostasis is critical for the metabolism and development of living organisms.3,4 On the other hand, the disruption of its homeostasis may lead to a variety of physical diseases and neurological problems such as Alzheimer's disease,5 Menkes and Wilson's disease,6 amyotrophic lateral sclerosis,7,8 and prion disease.9,10 Therefore, the assessment and understanding of the distribution of biological copper in living systems by noninvasive imaging is crucial to provide more insight into copper homeostasis and better understand the relationship between copper regulation and its physiological function.A wide variety of organic uorescent dyes have been exploited for the optical detection of ions in the last few decades.11–13However, optical imaging using organic uorescent dyes hasseveral limitations such as photobleaching, light scattering,limited penetration, low spatial resolution and the disturbance of auto uorescence.14 By comparison, magnetic resonance imaging(MRI)is an increasingly accessible technique used as a noninvasive clinical diagnostic modality for medical diagnosis and biomedical research.15 It can provide high spatial resolution three-dimensional anatomical images with information about physiological signals and biochemical events.16 As a powerful diagnostic imaging tool in medicine, MRI can distinguish normal tissue from diseased tissue and lesions in a noninvasive manner,17–19 which avoids diagnostic thoracotomy or laparotomy surgery for medical diagnoses and greatly improves the diagnostic efficiency.Multiple MRI imaging parameters can provide a wealth of diagnostic information.In addition, the desired cross-section for acquiring multi-angle and multi-planar images of various parts of the entire body can be freely chosen by adjusting the MRI magnetic eld;this ability makes medical diagnostics and studies of the body's metabolism and function more and more effective and convenient.Contrast agents are often used in MRI examinations to improve the resolution and sensitivity;the image quality can be signicantly improved by applying contrast agents which enhance the MRI signal intensity by increasing the relaxation rates of the surrounding water protons.20 Due to the high magnetic moment(seven unpaired electrons)and slow electronic relaxation of the
paramagnetic gadolinium(III)ion, gadolinium(III)-based MRI contrast agents are commonly employed to increase the relaxation rate of the surrounding water protons.16,21 However, most of these contrast agents are nonspecific and provide only anatomical information.On the basis of Solomon–Bloembergen–Morgan theory,22–24 several parameters can be manipulated to alter the relaxivity of gadolinium(III)-based MRI contrast agents.These parameters include the number of coordinated water molecules(q), the rotational correlation time(sR)and the residence lifetime of coordinated water molecules bound to the paramagnetic Gd3+ center(sM).Adjusting any of these three factors provides the opportunity to design “smart” MRI contrast agents for specific biochemical events.25–27 In recent years, there have been many studies on the development of responsive gadolinium(III)-based MRI contrast agents;most of them have focused on the development of targeted, high relaxivity and bioactivated contrast agents.These responsive gadolinium(III)-based MRI contrast agents can be modulated by particular in vivo stimuli including pH,28–35 metal ion concentration36–43 and enzyme activity.44–50 Notably, a number of copper-responsive MRI contrast agents have been reported to detect uctuations of copper ions in vivo.51–58 These activated contrast agents exploit the modulation of the number of coordinated water molecules to generate distinct enhancements in longitudinal relaxivity in response to copper ions(Cu+ or Cu2+).In this study, we designed and synthesized a binuclear gadolinium-based MRI contrast agent, [Gd2(DO3A)2BMPNA], that is specically responsive to Cu2+ over other biologicallyrelevant metal ions.The new copper-responsive MRI contrast agent comprises two Gd-DO3A cores connected by a 2,6-bis(3-methyl-1H-pyrazol-1-yl)isonicotinic acid scaffold59,60(BMPNA), which functions as a receptor for copper-induced relaxivity switching.The synthetic strategy for [Gd2(DO3A)2BMPNA] is depicted in Scheme 1.Subsequently, the T1 relaxivity of [Gd2(DO3A)2BMPNA] was studied at 25 C and 60 MHz in the absence or presence of Cu2+.Experiments to determine the selectivity of [Gd2(DO3A)2BMPNA] towards Cu2+ over other biologically-relevant ions were carried out as well.Luminescence lifetime was measured to determine the number of coordinated water molecules(q)of [Gd2(DO3A)2BMPNA] in the absence or presence of Cu2+.In addition, T1-weighted phantom images were collected to visualize the relaxivity enhancement caused by Cu2+, suggesting potential in vivo applications.Experimental section
Materials and instruments
All materials for synthesis were purchased from commercial suppliers and used without further purication.1H and 13C NMR spectra were taken on an AMX600 Bruker FT-NMR spectrometer with tetramethylsilane(TMS)as an internal standard.Luminescence measurements were performed on a Hitachi Fluorescence spectrophotometer-F-4600.The time-resolved luminescence emission spectra were recorded on a Perkin-Elmer LS-55 uorimeter with the following conditions: excitation wavelength, 295 nm;emission wavelength, 545 nm;dela time, 0.02 ms;gate time, 2.00 ms;cycle time, 20 ms;excitation slit, 5 nm;emission slit, 10 nm.The luminescence lifetime was measured on a Lecroy Wave Runner 6100 Digital Oscilloscope(1 GHz)using a tunable laser(pulse width ¼ 4 ns, gate ¼ 50 ns)as the excitation(Continuum Sunlite OPO).Mass spectra(MS)were obtained on an auto ex III TOF/TOF MALDI-MS and anIonSpec ESI-FTICR mass spectrometer.Elemental analyses were performed on a Vario EL Element Analyzer.Synthesis Synthesis of compound 3.Methyl 2,6-bis(3-(bromomethyl)-1H-pyrazol-1-yl)isonicotinate(Compound1)59,60 and 4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-4,7,10-triaza-azoniacyclododecan-1-ium bromide(Compound 2)61 were prepared following thereported methods.Compound 2(0.25 g, 0.296 mmol)was suspended in 2 ml anhydrous acetonitrile with 6 equivalents of NaHCO3(0.1492 g)and the mixture was stirred at room temperature for 0.5 h.Compound 1(0.0675 g, 0.148 mmol)was added, and the mixture was slowly heated to reflux(80 C)and stirred overnight.After the reaction was terminated, the mixture was cooled to room temperature, and the solution was ltered.The precipitate was washed several times with anhydrous acetonitrile, and the collected ltrate solution was evaporated under reduced pressure.The residue was puried using silicagel column chromatography eluted with CH2Cl2–n-hexane–CH3OH(10 : 3 : 1, v/v/v)to afford Compound 3(0.1038 g, 53%)as a pale yellow solid.1H NMR(600 MHz, DMSO): 8.22(s, 2H), 8.15(s, 2H), 6.62(s, 2H), 4.53(s, 4H), 3.82(s, 3H), 3.42(m, 4H), 2.98(m, 8H), 2.85(s, 8H), 2.71(m, 24H), 1.33(s, 54H)(Fig.S1†).13C NMR(151 MHz, CDCl3): d 173.21, 172.44, 163.99, 152.38, 150.11, 143.13, 128.07, 109.83, 108.36, 82.59, 57.84, 56.52, 56.06, 55.56, 52.98, 50.55, 48.91, 47.30, 27.96(Fig.S2†).HRMS(ESI): m/z calc.for C67H111N13O14 [M + 2H]2+ 661.92650, [M + H + Na]2+ 672.91747, [M + 2Na]2+ 683.90844, found [M + 2H]2+ 661.92584, [M+ H + Na]2+ 672.91690, [M + 2Na]2+ 683.90682(Fig.S3†).Synthesis of compound 4.Compound 3(0.1 g, 0.0756 mmol)was stirred with triuoroacetic acid in methylene chloride solution(2 ml)at room temperature for 24 h.The solvent was then evaporated under reduced pressure, and the residue was washed three times in CH3OH and CH2Cl2 to eliminate excess acid.The obtained residue was dissolved with a minimum volume of CH3OH and precipitated with cold Et2O.The precipitate was ltered to afford a brown yellow solid(0.1022 g).1H NMR(600 MHz, DMSO): 9.06(s, 2H), 8.17(s, 2H), 6.84(s, 2H), 4.33(s, 4H), 3.98(s, 3H), 3.56(b, 20H), 3.09(m, 24H)(Fig.S4†).13C NMR(151 MHz, D2O): d 174.11, 169.13, 164.64, 150.75, 148.85, 142.10, 129.88, 109.75, 107.99, 55.69, 54.01, 53.10, 52.43, 51.15, 49.59, 48.22, 47.69(Fig.S5†).MALDI-TOFMS spectrum(CH3OH): m/z calc.for C43H63N13O14 [M H] 984.46, found 984.7(Fig.S6†).Anal calc.for C43H63N13O14-$3CF3COOH$2H2O: C, 43.14;H, 5.17;N, 13.35;found C, 42.34;H, 4.999;N, 13.29%.Preparation of [Gd2(DO3A)2BMPNA] and [Tb2(DO3A)2-BMPNA].Compound 4(0.05 mmol)was dissolved in 2 ml of highly-puried water.GdCl3 or TbCl3(0.1 mmol)was added dropwise.The pH was maintained at 6.5–7.0 with NaOH during the whole process.The solution was then stirred at 75 C for 24 h.MALDI-MS(H2O): m/z calc.for C42H55N13O14Gd2 [M + H]+ 1281.46, found 1281.4(Fig.S7†).MALDI-MS(H2O): m/z calc.for C42H55N13O14Tb2 [M + H]+ 1284.3, found 1284.4(Fig.S8†).T1 measurements.The longitudinal relaxation times(T1)of aqueous solutions of [Gd2(DO3A)2BMPNA] were measured on an HT-MRSI60-25 spectrometer(Shanghai Shinning Globe Science and Education Equipment Co., Ltd)at 1.5 T.All of the tested samples were prepared in HEPES-buffered aqueous solutions at pH 7.4.All of the metal ions(Na+, K+, Ca2+, Mg2+, Cu2+, Zn2+, Fe3+, Fe2+)were used as chloride salts.Concentrations of Gd3+ were determined by ICP-OES.Relaxivities were determined from the slope of the plot of 1/T1 vs.[Gd].The data were tted to the following eqn(1),20
(1/T1)obs ¼(1/T1)d + r1[M](1)
where(1/T1)obs and(1/T1)d are the observed values in the presence and absence of the paramagnetic species, respectively, and [M] is the concentration of paramagnetic [Gd].Luminescence measurements.Luminescence emission spectra were collected on a Hitachi uorescence spectrophotometer-F-4600.The luminescence lifetime was measured on a Lecroy Wave Runner 6100 Digital Oscilloscope(1 GHz)using a tunable laser(pulse width ¼ 4 ns, gate ¼ 50 ns)as the excitation(Continuum Sunlite OPO).Samples were excited at 290 nm, and the emission maximum(545 nm)was used to determine luminescence lifetimes.The Tb(III)-based emission spectra were measured using 0.1 mM solutions of Tb complex analog in 100 mM HEPES buffer at pH 7.4 in H2O and D2O in the absence and presence of Cu2+.The number of coordinated water molecules(q)was calculated according to eqn(2):62,63 q= ¼ 5(sH2O1 sD2O1 0.06)(2)T1-weighted MRI phantom images.Phantom images were collected on a 1.5 T HT-MRSI60-25 spectrometer(Shanghai Shinning Globe Science and Education Equipment Co., Ltd).Instrument parameter settings were as follows: 1.5 T magnet;matrix =256 256;slice thickness =1 mm;TE= 13 ms;TR= 100 ms;and number of acquisitions =1.Results and discussion Longitudinal relaxivity of [Gd2(DO3A)2BMPNA] in response to copper(II)ion To investigate the inuence of Cu2+ on the relaxivity of [Gd2(DO3A)2BMPNA], the longitudinal relaxivity r1 for the [Gd2(DO3A)2BMPNA] contrast agent was determined using T1 measurements in the absence or presence of Cu2+ at 60 MHz and 25 C using a 0.2mMGd3+ solution of [Gd2(DO3A)2BMPNA] in 100 mM HEPES buffer(pH 7.4)under simulated physiological conditions.The concentrations of Gd3+ were determined by ICP-OES.The relaxivity r1 was calculated from eqn(1).In the absence of Cu2+, the relaxivity of [Gd2(DO3A)2BMPNA] was 6.40 mM1 s1, which was higher than that of [Gd(DOTA)(H2O)](4.2 mM1 s1, 20 MHz, 25 C)and Gd(DO3A)(H2O)2(4.8 mM1 s1, 20 MHz, 40 C).64 Upon addition of up to 1 equiv.of Cu2+, the relaxivity of [Gd2(DO3A)2BMPNA] increased to 11.28 mM1 s1(76% relaxivity enhancement).As shown in Fig.1, the relaxivity gradually increased with the copper ion concentration, reaching a maximum value of approximately 1.2 equivalents of Cu2+.Due to the use of triuoroacetic acid in the synthesis of Compound 4, triuoroacetic acid residues produced CF3COO in the [Gd2(DO3A)2BMPNA] solution, allowing CF3COO to partially coordinate with Cu2+ to form “Chinese lantern” type structure complexes.65 When the amount of added copper ions was further increased to above 1.2 equiv., the relaxivity was maintained at the same level.The observed difference in Cu2+-triggered relaxivity enhancement demonstrated the ability of this contrast agent to sense Cu2+ in vivo by means of MRI.Our designed contrast agent not only exhibited a higher relaxivity, but also displayed a Cu2+-responsive relaxivity enhancement.Selectivity studies The relaxivity response of [Gd2(DO3A)2BMPNA] exhibited excellent selectivity for Cu2+ over a variety of other competing, biologically-relevant metal ions at physiological levels.As depicted in Fig.2(white bars), the addition of alkali metal cations(10 mM Na+, 2 mM K+)and alkaline earth metal cations(2 mM Mg2+, 2 mM Ca2+)did not generate an increase in relaxivity compared to the copper ion turn-on response;even the introduction of d-block metal cations(0.2 mM Fe2+, 0.2 mM Fe3+, 0.2 mM or 2 mM Zn2+)did not trigger relaxivity enhancements.We noted that Zn2+ is also known to replace Gd3+ in transmetalation experiments;however, studies with analogous Gd3+-DO3A complexes demonstrated that this ligand is more kinetically inert to metal-ion exchange.66 To ensure the kinetic stability of the complex, we used MS to monitor [Gd2(DO3A)2BMPNA] in the presence of 1 equiv.of Zn2+.No metal-ion exchange was observed at room temperature after 7 days(Fig.S13†).Relaxivity interference experiments for [Gd2(DO3A)2BMPNA] in the presence of both Cu2+(0.2 mM)and other biologically-relevant metal ions were also conducted;the results are shown as black bars in Fig.2, indicating that these biologically-relevant metal ions(Na+, K+, Mg2+, Ca2+, Fe2+, Fe3+, Zn2+)had no interference on the Cu2+-triggered relaxivity enhancement.In addition, we also tested the Cu2+ response for [Gd2(DO3A)2BMPNA] in the presence of physiologically-relevant concentrations of common biological anions to determine whether the Cu2+-triggered relaxivity enhancement was affected by biological anions at physiological levels.As previously mentioned, Cu2+ binding induced an enhancement in relaxivity from 6.40 mM1 s1 to 11.28 mM1 s1(a 76% increase).As shown in Fig.3, in the presence of citrate(0.13 mM), lactate(0.9 mM), H2PO4(0.9 mM), or HCO3(10 mM), the Cu2+-triggered relaxivity enhancement was approximately 61%(from 6.01 mM1 s1 to 9.66mM1 s1), 66%(from 6.13mM1 s1 to 10.16 mM1 s1), 20%(from 5.88 mM1 s1 to 7.02 mM1 s1), or 55%(from 6.15 mM1 s1 to 9.55 mM1 s1), respectively.Additionally, 100 mM NaCl had almost no effect(an approximately 75% increase), and a simulated extracellular anion solution(EAS, contain 30 mM NaHCO3, 100 mM NaCl, 0.9 mM KH2PO4, 2.3 mM sodium lactate, and 0.13 mM sodium citrate, pH =7),67 resulted in a Cu2+-triggered relaxivity enhancement of approximately 26%(from 6.02 mM1 s1 to 7.56 mM1 s1).Generally, the results revealed that lactate, citrate, and HCO3 had slight impacts on the Cu2+-triggered relaxivity enhancement, while H2PO4 and EAS influenced the enhancement to a greater degree.As shown in Scheme 2, [Gd2(DO3A)2BMPNA] possessed two water molecules after the addition of 1 equiv.Of Cu2+.According to the work of Dickins and coworkers, in lanthanide complexes with two water molecules, the waters can be partially displaced by phosphate, carbonate, acetate, carboxylate, lactate and citrate at different levels.68–70 The influence of these anions on the Cu2+-triggered relaxivity enhancement may be attributed to the partial replacement of coordinated water molecules by these anions.The relatively high concentration of phosphate could likely replace coordinated water molecules to reduce the increased number of water molecules surrounding the paramagnetic Gd3+ centre induced by Cu2+.As shown in Table 1, we measured the number of water molecules in the rst coordination sphere of Tb3+ in the presence of phosphate;the number of coordinated water molecules(q)decreased from 1.5 to 0.8.Coordination features Luminescence lifetime experiments were performed to explore the mechanism of the Cu2+-triggered relaxivity enhancement.Luminescence lifetime measurements of lanthanide complexes have been widely used to quantify the number of inner-sphere water molecules.71 In particular, Tb3+ and Eu3+ have commonly been applied for lifetime measurements because their emission spectra are in the visible region when their 4f electrons are relaxed from higher energy levels to the lowest energy multiplets.72,73 Therefore, the Tb3+ analogue of [Gd2(DO3A)2BMPNA], [Tb2(DO3A)2BMPNA], was prepared according to a similar method, and the luminescence lifetimes of the Tb3+ analogue in HEPES-buffered H2O and D2O in the absence and presence of Cu2+ were measured.As shown in Fig.S9,† the luminescence decay curve of [Tb2(DO3A)2BMPNA] was tted to obtain the luminescence lifetimes74(Table 1), and the number of coordinated water molecules(q)was calculated by eqn(2).The analysis results(Table 1)for [Tb2(DO3A)2BMPNA] in HEPES-bufferedH2OandD2O in the absence and presence of Cu2+ indicated that q increased from 0.6 to 1.5 upon the addition of 1 equiv.of Cu2+;this result indicated that the Cu2+-triggered relaxivity enhancement for [Gd2(DO3A)2BMPNA] was most likely due to the increased number of coordinated water molecules around the Gd3+ ion upon Cu2+ binding to the pyrazole centre(Scheme 2).Aer the addition of Cu2+, Cu2+ removed the pyrazole centre N atom from the paramagnetic Gd3+ ion to generate an open coordination site available for a water molecule.Luminescence emission titrations of [Tb2(DO3A)2BMPNA] towards Cu2+ were also performed to investigate the binding properties of the contrast agent towards Cu2+.Upon addition of 1 equiv.Cu2+, the luminescence of [Tb2(DO3A)2BMPNA] at 545 nm decreased gradually and reached a minimum due to the quenching nature of the paramagnetic Cu2+(Fig.S10†).The titration data indicated a 1 : 1 binding stoichiometry(Scheme 2)Copper-responsive T1-weighted phantom MRI in vitro To demonstrate the potential feasibility of this Cu2+-responsive [Gd2(DO3A)2BMPNA] for copper-imaging applications, T1-weighted phantom images of [Gd2(DO3A)2BMPNA] were acquired in the absence and presence of copper ions.The phantom images depicted in Fig.4 displayed distinct increases in image intensity in the presence of 1 equiv.Cu2+ compared with those without Cu2+(Fig.4D).Moreover, some of the other competing metal ions were also tested to further verify the selectivity of [Gd2(DO3A)2BMPNA] towards Cu2+.Discernible differences were not observed upon the addition of Mg2+(Fig.4C), Zn2+(Fig.4E), or Ca2+(Fig.4F).In addition, we also tested the clinical contrast agent Magnevist(Fig.4G);the image intensity was a bit darker than that of our contrast agent.Conclusions
In conclusion, we designed and synthesized a novel bismacrocyclic DO3A-type Cu2+-responsive MRI contrast agent, [Gd2(DO3A)2BMPNA].The new Cu2+-responsive MRI contrast agent comprised two Gd-DO3A cores connected by a 2,6-bis(3-methyl-1H-pyrazol-1-yl)isonicotinic acid scaffold(BMPNA)that functioned as a Cu2+ receptor switch to induce a distinct relaxivity enhancement in response to Cu2+;the relaxivity was increased up to 76%.Importantly, the complex exhibited high selectivity for Cu2+ over a range of other biologically-relevant metal ions at physiological levels.Luminescence lifetime experiment results showed that the number of inner-sphere water molecules(q)increased from 0.6 to 1.5 upon the addition of 1 equiv.Cu2+.When Cu2+ was coordinated in the central part of the complex, the donor N atom of the pyrazole centre was removed from the paramagnetic Gd3+ ion and replaced by a water molecule(Scheme 2).Consequently, the Cu2+-triggered relaxivity enhancement could be ascribed to the increase in the number of inner-sphere water molecules.The designed contrast agent had a longitudinal relaxivity of 6.40 mM1 s1, which was higher than that of [Gd(DOTA)(H2O)](4.2 mM1 s1, 20 MHz, 25 C)and Gd(DO3A)(H2O)2(4.8 mM1 s1, 20 MHz, 40 C).In addition, the visual change associated with the signicantly enhanced relaxivity from the addition of Cu2+ was observed in T1-weighted phantom images.Acknowledgements We are grateful to the State Key Laboratory of Electroanalytical Chemistry for nancial support.Notes and references 1 S.Puig and D.J.Thiele, Curr.Opin.Chem.Biol., 2002, 6, 171.2 S.C.Leary, D.R.Winge and P.A.Cobine, Biochim.Biophys.Acta, Gen.Subj., 2009, 146, 1793.3 D.D.Agranoff and S.Krishna, Mol.Microbiol., 1998, 28, 403.4 H.Kozlowski, A.Janicka-Klos, J.Brasun, E.Gaggelli, D.Valensin and G.Valensin, Coord.Chem.Rev., 2009, 253, 2665.5 K.J.Barnham, C.L.Masters and A.I.Bush, Nat.Rev.Drug Discovery, 2004, 3, 205.6 D.J.Waggoner, T.B.Bartnikas and J.D.Gitlin, Neurobiol.Dis., 1999, 6, 221.7 J.S.Valentine and P.J.Hart, Proc.Natl.Acad.Sci.U.S.A., 2003, 100, 3617.8 L.I.Bruijn, T.M.Miller and D.W.Cleveland, Annu.Rev.Neurosci., 2004, 27, 723.9 G.L.Millhauser, Acc.Chem.Res., 2004, 37, 79.10 D.R.Brown and H.Kozlowski, Dalton Trans., 2004, 1907.11 A.W.Czarnik, Acc.Chem.Res., 1994, 27, 302.12 L.Prodi, F.Bolletta, M.Montalti and N.Zaccheroni, Coord.Chem.Rev., 2000, 205, 59.13 H.N.Kim, M.H.Lee, H.J.Kim, J.S.Kim and J.Yoon, Chem.Soc.Rev., 2008, 37, 1465.14 M.Mahmoudi, V.Serpooshan and S.Laurent, Nanoscale, 2011, 3, 3007.15 P.A.Rinck, Magnetic Resonance Imaging, Blackwell Science, Berlin, 4th edn, 2001, p.149.16 A.E.Merbach and ´E.T´oth, The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging, John Wiley & Sons, Ltd., New York, 2001.17 S.Aime, E.Terreno, D.D.Castelli and A.Viale, Chem.Rev., 2010, 110, 3019.18 S.Aime, M.Fasano and E.Terreno, Chem.Soc.Rev., 1998, 27, 19.19 M.Woods, D.E.Woessner and A.D.Sherry, Chem.Soc.Rev., 2006, 35, 500.20 R.B.Lauffer, Chem.Rev., 1987, 87, 901.21 J.Kowalewski, D.Kruk and J.Parigi, Adv.Inorg.Chem., 2005, 57, 42.22 I.Solomon, Phys.Rev., 1955, 99, 559.23 N.Bloembergen, J.Chem.Phys., 1957, 27, 572.24 N.Bloembergen and L.O.Morgan, J.Chem.Phys., 1961, 34, 842.25 E.L.Que and C.J.Chang, Chem.Soc.Rev., 2010, 39, 51.26 C.S.Bonnet and ´E.T´oth, Future Med.Chem., 2010, 2, 367.27 L.Prodi, F.Bolletta, M.Montalti and N.Zaccheroni, Coord.Chem.Rev., 2000, 205, 59.28 S.Aime, S.G.Crich, M.Botta, G.Giovenzana, G.Palmisano and M.Sisti, Chem.Commun., 1999, 1577.29 J.Hall, R.Haner, S.Aime, M.Botta, S.Faulkner, D.Parker and A.S.de Sousa, New J.Chem., 1998, 22, 627.30 M.P.Lowe and D.Parker, Chem.Commun., 2000, 707.31 S.Aime, A.Barge, M.Botta, D.Parker and A.S.De Sousa, J.Am.Chem.Soc., 1997, 119, 4767.32 S.Aime, F.Fedeli, A.Sanino and E.Terreno, J.Am.Chem.Soc., 2006, 128, 11326.33 M.P.Lowe, D.Parker, O.Reany, S.Aime, M.Botta, G.Castellano, E.Gianolio and R.Pagliarin, J.Am.Chem.Soc., 2001, 123, 7601.34 R.Hovland, C.Glogard, A.J.Aasen and J.Klaveness, J.Chem.Soc., Perkin Trans.2, 2001, 929.35 ´E.T´oth, R.D.Bolskar, A.Borel, G.Gonz´alez, L.Helm, A.E.Merbach, B.Sitharaman and L.J.Wilson, J.Am.Chem.Soc., 2004, 127, 799.36 W.H.Li, S.E.Fraser and T.J.Meade, J.Am.Chem.Soc., 1999, 121, 1413.37 K.Dhingra, M.E.Maier, M.Beyerlein, G.Angelovski and N.K.Logothetis, Chem.Commun., 2008, 3444.38 H.Hifumi, A.Tanimoto, D.Citterio, H.Komatsu and K.Suzuki, Analyst, 2007, 132, 1153.39 L.M.De Le´on-Rodr´ıguez, A.J.M.Lubag, J.A.L´opez, G.Andreu-de-Riquer, J.C.Alvarado-Monz´on and A.D.Sherry, MedChemComm, 2012, 3, 480.40 R.Trokowski, J.Ren, F.K.Kalman and A.D.Sherry, Angew.Chem., Int.Ed., 2005, 44, 6920.41 W.S.Li, J.Luo, F.Jiang and Z.N.Chen, Dalton Trans., 2012, 41, 9405.42 K.Hanaoka, K.Kikuchi, Y.Urano and T.Nagano, J.Chem.Soc., Perkin Trans.2, 2001, 1840.43 R.Ruloff, G.v.Koten and A.E.Merbach, Chem.Commun., 2004, 842.44 M.Giardiello, M.P.Lowe and M.Botta, Chem.Commun., 2007, 4044.45 M.Andrews, A.J.Amoroso, L.P.Harding and S.J.A.Pope, Dalton Trans., 2010, 3407.46 W.Xu and Y.Lu, Chem.Commun., 2011, 47, 4998.47 R.A.Moats, S.E.Fraser and T.J.Meade, Angew.Chem., Int.Ed., 1997, 36, 726.48 A.Y.Louie, M.M.Huber, E.T.Ahrens, U.Rothbacher, R.Moats, R.E.Jacobs, S.E.Fraser and T.J.Meade, Nat.Biotechnol., 2000, 18, 321.49 B.Yoo and M.D.Pagel, J.Am.Chem.Soc., 2006, 128, 14032.50 Q.Wei, G.K.Seward, P.A.Hill, B.Patton, I.E.Dimitrov, N.N.Kuzma and I.J.Dmochowski, J.Am.Chem.Soc., 2006, 128, 13274.51 E.L.Que and C.J.Chang, J.Am.Chem.Soc., 2006, 128, 15942.52 E.L.Que, E.Gianolio, S.L.Baker, A.P.Wong, S.Aime and C.J.Chang, J.Am.Chem.Soc., 2009, 131, 8527.53 E.L.Que, E.Gianolio, S.L.Baker, S.Aime and C.J.Chang, Dalton Trans., 2010, 39, 469.54 W.S.Li, J.Luo and Z.N.Chen, Dalton Trans., 2011, 484.55 E.L.Que, E.J.New and C.J.Chang, Chem.Sci., 2012, 3, 1829.56 M.Andrews, A.J.Amoroso, L.P.Harding and S.J.A.Pope, Dalton Trans., 2010, 3407.57 D.Kasala, T.S.Lin, C.Y.Chen, G.C.Liu, C.L.Kao, T.L.Cheng and Y.M.Wang, Dalton Trans., 2011, 5018.58 D.Patel, A.Kell, B.Simard, B.Xiang, H.Y.Lin and G.Tian, Biomaterials, 2011, 32, 1167.59 E.Brunet, O.Juanes, R.Sedano and J.C.Rodr´ıguez-Ubis, Photochem.Photobiol.Sci., 2002, 1, 613.60 Z.Q.Ye, G.L.Wang, J.X.Chen, X.Y.Fu, W.Z.Zhang and J.L.Yuan, Biosens.Bioelectron., 2010, 26, 1043.61 S.Mizukami, K.Tonai, M.Kaneko and K.Kikuchi, J.Am.Chem.Soc., 2008, 130, 14376.62 W.D.Horrocks and D.R.Sudnick, Acc.Chem.Res., 1981, 14, 384.63 S.Quici, M.Cavazzini, G.Marzanni, G.Accorsi, N.Armaroli, B.Vcntura and F.Barigelletti, Inorg.Chem., 2005, 44, 529.64 P.Caravan, J.J.Ellison, T.J.McMurry and R.B.Laufer, Chem.Rev., 1999, 99, 2293.65 O.G.Polyakov, B.G.Nolan, B.P.Fauber, S.M.Miller, O.P.Anderson and S.H.Strauss, Inorg.Chem., 2000, 39, 1735.66 M.F.Tweedle, J.J.Hagan, K.Kumar, S.Mantha and C.A.Chang, Magn.Reson.Imaging, 1991, 9, 409.67 D.Parker, Coord.Chem.Rev., 2000, 205, 109.68 R.S.Dickins, T.Gunnlaugsson, D.Parker and R.D.Peacock, Chem.Commun., 1998, 1643.69 J.I.Bruce, R.S.Dickins, L.J.Govenlock, T.Gunnlaugsson, S.Lopinski, M.P.Lowe, D.Parker, R.D.Peacock, J.J.B.Perry, S.Aime and M.Botta, J.Am.Chem.Soc., 2000, 122, 9674.70 R.S.Dickins, S.Aime, A.S.Batsanov, A.Beeby, M.Botta, J.I.Bruce, J.A.K.Howard, C.S.Love, D.Parker, R.D.Peacock and H.Puschmann, J.Am.Chem.Soc., 2002, 124, 12697–12705.71 W.D.Horrocks and D.R.Sudnick, Acc.Chem.Res., 1981, 14, 384.72 C.C.Bryden and C.N.Reilley, Anal.Chem., 1982, 54, 610.73 K.Binnemans, Chem.Rev., 2009, 109, 4283.74 S.Quici, M.Cavazzini, G.Marzanni, G.Accorsi, N.Armaroli, B.Vcntura and F.Barigelletti, Inorg.Chem., 2005, 44, 529.This journal is © The Royal Society of Chemistry 2014 RSC Adv., 2014, 4, 34421–34427 | 34427
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