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汇报人：指导人：毕业论文答辩GRADUATIONTHESIS DEFENSE
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Thesis Statement Handout
Thesis StatementWhat is a Thesis Statement?A thesis statement is an argument that clearly states the point of view of the author, and outlines how the author intends to support his or her argument. The thesis statement is usually the last sentence of the first paragraph, and it is usually a single sentence in this paragraph that presents your argument. The body of thepaper then gathers and organizes evidence that supports the thesis statement. The thesis statement is the roadmap of the paper.Another way to describe a thesis statement is to say that it acts like a topic sentence for an entire essay. Just as the topic sentence tells readers what will be discussed in a particular paragraph, the thesis statement alerts readers as to what to expect from the rest of the essay.What is a Thesis Statement Not?A thesis is not a topic; nor is it a fact; nor is it an opinion."Reasons for the fall of communism" is a topic. "Communism collapsed in Eastern Europe" is a fact known by educated people. "The fall of communism is the best thing that ever happened in Europe" is an opinion. (Superlatives like "the best" almost always lead to trouble. It's impossible to weigh every "thing" that ever happened in Europe. And what about the fall of Hitler? Couldn't that be "the best thing"?)Strong Thesis Statement• A strong thesis statement is one which is specific and one which takes a stand.• A strong thesis statement is arguable and justifies discussion.• A strong thesis statement does not express many ideas, but sticks to one particular theory or idea.• A strong thesis statement will have ample evidence to support it.• A strong thesis statement needs to be clear and concise.How to Tell a Strong Thesis Statement from a Weak One.1.A strong thesis statement is specific.A thesis statement should show exactly what your paper will be about, and will help you keep your paper to a manageable topic. For example, if you're writing a paper on hunger, you might say:World hunger has many causes and effects.This is a weak thesis statement for two major reasons. First, world hunger can’t be discussed thoroughly in five to six pages. Second, many causes and effects is vague. You should be able to identify specific causes and effects. A revised thesis might look like this:Hunger persists in Glandelinia because jobs are scarce and farming in the infertile soil is rarely profitable.This is a strong thesis statement because it narrows the subject to a more specific and manageable topic, and it also identifies the specific causes for the existence of hunger.2. A strong thesis statement takes some sort of stand.Remember that your thesis needs to show your conclusions about a subject. For example, if you are writing a paper for a class on fitness, you might be asked to choose a popular weight-loss product to evaluate. Here are two thesis statements:There are some negative and positive aspects to the Banana Herb Tea Supplement.This is a weak thesis statement. First, it fails to take a stand. Second, the phrase negative and positive aspects is vague.Because Banana Herb Tea Supplement promotes rapid weight loss that results in the loss of muscle and lean body mass, it poses a potential danger to customers.This is a strong thesis because it takes a stand, and because it's specific.3.A strong thesis statement justifies discussion.Your thesis should indicate the point of the discussion. If your assignment is to write a paper on kinship systems, using your own family as an example, you might come up with either of these two thesis statements:My family is an extended family.This is a weak thesis because it merely states an observation. Your reader won’t be able to tell the point of the statement, and will probably stop reading.While most American families would view consanguineal marriage as a threat to the nuclear family structure, many Iranian families, like my own, believe that these marriages help reinforce kinship ties in an extended family.This is a strong thesis because it shows how your experience contradicts a widely-accepted view. A good strategy for creating a strong thesis is to show that the topic is controversial. Readers will be interested in reading the rest of the essay to see how you support your point.4.A strong thesis statement expresses one main idea.Readers need to be able to see that your paper has one main point. If your thesis statement expresses more than one idea, then you might confuse your readers about the subject of your paper. For example:Companies need to exploit the marketing potential of the Internet, and Web pages can provide both advertising and customer support.This is a weak thesis statement because the reader can’t decide whether the paper is about marketing on the Internet or Web pages. To revise the thesis, the relationship between the two ideas needs to become clearer. One way to revise the thesis would be to write:Because the Internet is filled with tremendous marketing potential, companies should exploit this potential by using Web pages that offer both advertising and customer support.This is a strong thesis because it shows that the two ideas are related. Hint: a great many clear and engaging thesis statements contain words like because, since, so, although, unless, and however.Steps in Constructing a ThesisFirst, analyze your primary sources. Look for tension, interest, ambiguity, controversy, and/or complication. Does the author contradict himself or herself? Is a point made and later reversed? What are the deeper implications of the author's argument? Figuring out the why to one or more of these questions, or to related questions, will put you on the path to developing a working thesis. (Without the why, you probably have only come up with an observation—that there are, for instance, many different metaphors in such-and-such a poem—which is not a thesis.)Once you have a working thesis, write it down.There is nothing as frustrating as hitting on a great idea for a thesis, then forgetting it when you lose concentration. And by writing down your thesis you will be forced to think of it clearly, logically, and concisely. You probably will not be able to write out a final-draft version of your thesis the first time you try, but you'll get yourself on the right track by writing down what you have.Keep your thesis prominent in your introduction.A good, standard place for your thesis statement is at the end of an introductory paragraph, especially in shorter 5-6 page essays. Readers are used to finding theses there, so they automatically pay more attention when they read the last sentence of your introduction. Although this is not required in all academic essays, it is a good rule of thumb.Anticipate the counter-arguments.Once you have a working thesis, you should think about what might be said against it. This will help you to refine your thesis, and itwill also make you think of the arguments that you'll need to refute later on in your essay. (Every argument has a counter-argument. If yours doesn't, then it's not an argument—it may be a fact, or an opinion, but it is not an argument.)Michael Dukakis lost the 1988 presidential election becausehe failed to campaign vigorously after the DemocraticNational Convention.This statement is on its way to being a thesis. However, it is too easy to imagine possible counter-arguments. For example, a political observer might believe that Dukakis lost because he suffered from a "soft-on-crime" image. If you complicate your thesis by anticipating the counter-argument, you'll strengthen your argument, as shown in the sentence below.While Dukakis' "soft-on-crime" image hurt his chances in the1988 election, his failure to campaign vigorously after theDemocratic National Convention bore a greater responsibilityfor his defeat.Some Caveats and Some ExamplesA thesis is never a question. Readers of academic essays expect to have questions discussed, explored, or even answered. A question ("Why did communism collapse in Eastern Europe?") is not an argument, and without an argument, a thesis is dead in the water.A thesis is never a list."For political, economic, social and cultural reasons, communism collapsed in Eastern Europe" does a good job of telling the reader what to expect in the essay—a section about political reasons, a section about economic reasons, a section about social reasons, and a section about cultural reasons. However, political, economic, social and cultural reasons are pretty much the only possible reasons why communism could collapse. This sentence lacks tension and doesn't advance an argument. Everyone knows that politics, economics, and culture are important.A thesis should never be vague, combative or confrontational.An ineffective thesis would be, "Communism collapsed in Eastern Europe because communism is evil." This is hard to argue (evil from whose perspective? what does evil mean?) and it is likely to mark you as moralistic and judgmental rather than rational and thorough. Italso may spark a defensive reaction from readers sympathetic to communism. Ifreaders strongly disagree with you right off the bat, they may stop reading.An effective thesis has a definable, arguable claim."While cultural forcescontributed to the collapse of communism in Eastern Europe, the disintegration of economies played the key role in driving its decline" is an effective thesis sentence that"telegraphs," so that the reader expects the essay to have a section about culturalforces and another about the disintegration of economies. This thesis makes a definite,arguable claim: that the disintegration of economies played a more important role than cultural forces in defeating communism in Eastern Europe. The reader would react to this statement by thinking, "Perhaps what the author says is true, but I am not convinced. I want to read further to see how the author argues this claim."A thesis should be as clear and specific as possible.Avoid overused, generalterms and abstractions. For example, "Communism collapsed in Eastern Europe because of the ruling elite's inability to address the economic concerns of the people" is more powerful than "Communism collapsed due to societal discontent."A thesis should answer the how and why questions. A thesis is usually more effective and will lead to a better essay if it answers how or why questions, not who, what, when, or where questions, or at least if the answers to the who, what, when, or where question require exploring how or why questions.A thesis never provides its own support. The thesis is the statement that the rest of the essay supports; a thesis never provides its own support. It makes no sense to say a thesis is poor because it is unsupported or lacks evidence; the support or evidence comes elsewhere. A thesis that supported itself would be self-evident — a fact — and could not then have served as the basis for an essay. Of course, an essay may be poor because the author never supports the thesis persuasively, but that is the problem of the essay as a whole, not the thesis itself.A thesis should not be stated in terms of absolutes.Beware of absolutes. The problem with a thesis such as “George Marshall was the greatest Secretary of State in U.S. history” is that you would have to compare him to all the others, or at least all those who are generally admired. This is possible to do, but probably not in an essay assigned to an undergraduate course, which would not be long enough to accomplish that task. The same applies to a thesis such as “King Lear is Shakespeare’s most tragic character.” On the other hand, one can argue an absolute if one sufficiently limits the context: “Of the four most renowned silent film comedians, Buster Keaton was the most innovative film-maker” is an acceptable thesis because one might reasonably compare four film-makers in a college essay.A thesis should not be stated in the first person. Never use the first person in your thesis. Your name is on the essay, so we know who is making the argument.Thus, a thesis that begins with something like “I would argue that” merely wastes time. Besides, you want to make your thesis as strong and convincing as possible; phrasing it as a matter of personal opinion weakens it.A thesis should not be stated in the passive voice. While sometimes useful, the passive voice is generally weaker and sounds less confident than an active voice sentence.Never attribute your thesis to someone else, or to general opinion. A thesis that says “Many people believe” or that some famous scholar or critic believes something is necessarily about “many people” or the famous scholar or critic, not ab out the point being made, or more importantly the point you are trying to make.。
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2029年3月5日
GRADUATION THESIS DEFENSE
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2011NCCN指南(英文原版)
Printed by z z on 1/10/2011 2:45:32 AM. For personal use only. Not approved for distribution. Copyright © 2011 National Comprehensive Cancer Network, Inc., All Rights Reserved.
Cancer- and Chemotherapy-Induced Anemia
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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) – Version 2.2011
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NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™)
thesis
要目随着信息家电手持设备无线等备无的迅速发展相应硬迅件和软也和得到许速发展相多都备无配有摩Intel MIPS托罗拉公的司生产微迅32论处理器甚至还使用了液晶显示开甚多都商展始得商为这些提备无供界面友好嵌迅入式操作系统利搭了Linux建是入式操作系统利近年来出现最迅令人振 方迅案原些摩都案友迅因首先运行在上入式操统利能迅Linux够全供界功桌够迅计友算且Desktop Computing由于其放商代码定制变非到常便案次放已Linux 经支数设学都芯入式操统利能用了迅片包括后StrongARM , MIPS 软PowerPC令免Linux近费不迅用了Linux 需要付任现何所不了以底搭了Linux 系这层一作系统利, 放能用了个成GUI 统利日这最上益流解在迅入式操作系统利迅决市案原场见能便小迅PDA 的型前持设操备无能底条于其件和限和的迅我变们看户许迅了简面友配常便单几乎机户需许PC 华能丽美观但迅GUI 面友脑令年现最迅Palm 的持设操手或者向上Windows CE 的友完入式操统利迅作系统利能们看经支户许液整图迅形高了简面友数设着信持设操备无迅件和限和迅供估对算入式操统利轻量 求GUI 迅要会越迫出迫切顶年出迅场见要会得示开迫出迫都迅入式操统利括后PDA华盒播DVD/VCD 均代华WAP 持华的的统利浏付会供界功桌够迅Web 览虚甚些括后HTML 4.0 迅数设JavaScript 迅数设至还括后Java 拟而华迅数设性些个顶浏付会摩个成估可够估靠受迅GUI 统利迅数设导师影迅响本长振期比底出轻底Linux 作系统利较感兴趣并从研二加商为魏式于永明起运产展项迅MiniGUI 目及轻图成MiniGUI统利同类如统利进Microwindows 的究在液个制迅二改从轻MiniGUI 究在液个制迅扩究软桌够充基长文伴事其些提实体轻友完入式操统利迅GUI 统利迅结统构技软个提术内幕做深液感探式迅讨概文伴先运述情液入式操统利同了简面友迅展相况接介信绍种液乎下入式操统利通迅形高了简面友过互应指较感占现软过了迅形高了简面友统利应较入式操统利通迅形高了简面友要付摩量前资了源少置估可够估靠受可靠有特的点第三章典绍种液四前统利MiniGUI三字典绍种液长振体最迅MiniGUI轻Type1 五结迅数设长伴迅三将典输绍种MiniGUI 引式软形高引式/引现擎 迅备算体最关第同应细迅个提术内节私MiniGUI迅程摩引式软形高引式/引现擎 这长振备算体最上些提互中获宝到迅个提贵验支六输个从绍种三给典例现MiniGUI迅个提硬了体想令免近个第兴望软相键细词─形高了简面友入式操统利程摩引式软形高引式/引现擎AbstractIn the fast-changing world of embedded, handheld and wireless devices, there are many hardware and software design changes taking place. Many devices now feature 32-bit microprocessors from Intel, MIPS and Motorola, as well as larger LCD graphical displays. In order to leverage the significant results gained in the last ten years, many developers are turning to using friendly user interface operating systems with these new embedded designs.One of the most promising emerging areas seems to be running Linux in these environments, for a couple of good reasons: Linux on embedded systems brings with it the entire power of desktop computing, along with many solutions already running. Linux, being open source, allows any aspect of the solution to be fully understood and then customized for a particular application. Linux also supports all the new microprocessors typically included in embedded designs, including StrongARM, MIPS and PowerPC. Finally, Linux is free, with no royalty payments required for it“s use.So using linux as operating system , with a GUI system built on, seems to be a good solution.For the handled devices on the market such as PDA, as to the poor hardware in old days, the user interface was very simple, we could hardly see the colorful GUI which was supported by PC. But recently we found that some embedded operating systems such as Windows CE and Palm OS, have supported complete GUI features. With the great performance improvement of the hardware, we think that the need for mini GUI systems is urgent.Under the influence of my tutor , Professor Li, I got interest with Linux operating system several years ago. And from Grade 2, I took part in project MiniGUI, initiated by Wei Yongming, a former teacher of Tsinghua University. I soon got familiar with it, and also its opponent Microwindows. Then I did some optimization for MiniGUI and also wrote a native low-level engine for it. Based on these facts, this thesis demonstrate architecture and internals of GUI system used on embedded systems.At first, the thesis outlines the history of embedded systems and user interface, then we compare several GUI systems under embedded systems, point out the peculiarity of GUI on embedded systems, that is, lightness, less resource requirement, quicker response, high reliability and easy configuration. In chapter 3, we introduce typical system MiniGUI. In chapter 4, we introduce supporting forType 1 font on MiniGUI. The native engine of MiniGUI is developed by the author, in chapter 5, the design and implementation of native engine is introduced. Also some experience gained in the coding process is included. Chapter 6 give some examples, and the last chapter gives some conclusion and foresight.Keywords: GUI; Embedded System; Native Input & Graphics Input/Output Engine.录第要目 (I)ABSTRACT (III)录第 (V)一章嵌入式系统及用户界面概况二 (1)1.1 入式操统利述接 (1)1.1.1 入式技术的历史发展系 (1)1.1.2 入式技统特历术的点和应用前景典 (2)1.1.3 型把历入式技统特 (2)1.1.4 握契机改变我国在自主产权方面相对匮乏局历户相 (3)1.2 了L INUX 建是入式操统利 (4)1.3 了简面友述接 (6)1.3.1 前界图相历史发 (6)1.3.2 形征前界图相历点结 (6)1.3.3 形征前界图相统特历构模新把 (7)1.3.4 前界图相历展系GUI人交改互窗术的 (8)1.4四前迅GUI统利窗窗X 口时统利单绍 (10)1.4.1 X 口计统特历史发 (10)1.4.2 XFree86 划紧 (11)1.4.3 X 口计统特历构模新把 (11)一下嵌入式系LINUX的三GUI况二 (13)2.1 GUI 上入式操者体地统利获迅法论 (13)2.2 及条体地入式操统利GUI 迅体最案各 (14)2.2.1 缩多历X Window 统特 (14)2.2.2 MiniGUI (14)2.2.3 MicroWindows (16)2.2.4 OpenGUI (18)2.2.5 Qt/Embedded (19)2.3 之下入式操GUI 统利背较感 (19)一典嵌型四三入式系GUI统及MINIGUI (21)3.1 目及景重 (21)3.2 色付点象 (22)3.2.2 匮框标应准控件其 (22)3.2.3 他元GUI 素消 (23)3.2.4 息循应息循环输 (23)3.2.5 形征应抽式象层字 (24)3.2.6 线体符应线体集支持分 (25)3.3 结统构技 (25)3.3.1 线程话历设字微划 (25)3.3.2 客服界/务器类构模 (26)3.4 友完轻逻术内迅行了 (27)3.4.1 件其传应件其 (27)3.4.2 GAL 应IAL (28)3.4.3 体集支应体符持分 (29)3.5 色付且各 (29)3.5.1 息循递 (29)3.5.2 形征下文坐应映准射管 (30)3.5.3 口计理剪 (30)3.5.4 切算法逻 (31)一矢嵌TYPE1量字体支持实三现五 (32)4.1 辑什五结软T YPE1五结 (32)4.1.1 MiniGUI 历辑及体符微划 (32)4.1.2 Adobe Type1 体符简T1Lib 介数 (34)4.2 T YPE1 五结数设迅体最 (35)4.2.1 据函构模 (35)4.2.2 实据现调 (37)一设嵌NATIVE ENGINE 三计与六现五 (40)5.1 这么鼠付商展程摩擎 (40)5.2 HAL 介时 (42)5.3 标驱动序中盘 (44)5.4 词屏动序中盘 (45)5.5 形高动序中盘 (47)5.6 拟换顶安迅体最 (51)5.7 术内能迅个提关第 (52)5.7.1 试问题档 (53)5.7.2 坐缺历性局 (53)5.7.3 程与平同相历形征新技 (53)5.7.4 步功题档 (54)5.8 备算能迅个提点第 (54)5.8.1 供制改而不是策略重 (54)5.8.2 线可配置接历进计 (55)一应嵌型四七户 (56)6.1 H APPY L INUX 装控中盘 (56)6.2 V ACS-III CNC 统利 (57)6.3 EHOME (58)6.4 台变仿真游甚 (58)6.5 戏今 (59)6.6 估求五结数设 (60)一点嵌章感想展六望参 (61)考文献论 (64)出献用版物致 (66)谢图 (67)一章嵌入式系统及用户界面概况技1.1 入式操统利述接1.1.1 入式系术的历史发展特入式操统利迅现最还历经支摩30都来迅史阶液入式操术内得史支液乎成展相段核究式90来码免底算且华软也和这心化迅芯五取术内猛到液速仅展相需广泛渗透社许济越支军交实业过过息的应细在娱性由探式许电手乐艺领内济越伴取的之成域掀革项液个见芯五取术内命媒都与结术内普Internet迅硬了速发消同子不手趋算且华过息3C个结取势再益势起示入式操术内度热日这个成二改综第致但入式操术内迅展相学编支史液底通4成段核[1]l三个段核近底几片包这心化迅靠具中台变甚高操迅统利类地监摩普测伺 合占开备无应有部迅桌够些下统利学分专硬了其个提极娱可强工迅般娱台变统利获个没汇摩作系统利迅数设过互语具言直具中轻统利究在束介台变行在构清免除存幕主些个段核统利迅效付点第近统利构技软桌够配应轻几个理器率低感储主容价 感型乎机汇摩了简介时于其些下入式操统利用了单次格很国储底条上遍幕般娱域掀硬了感这消远脑近经支适适需够质硬估率迅要付学价 主容绍新迅最码取般娱台变软础趣迅息家电手的域掀迅要会l三加段核近底入式操CPU这事繁底单几作系统利这心化迅入式操统利些个段核统利迅效付点第近CPU下如弱都过了可较感销统利商兼型率低估作系统利监摩个制迅负价可软充相可硬了也和感极娱了简面友需全好嵌统利效付了出台变统利载志底同测台硬了中盘行在l三章段核近底入式操作系统利这驱精迅入式操统利些个段核统利迅效付点第近入式操作系统利够行在其之下需类如前迅处理器甚能负价可嵌作系统利幕心模型率低估从由监摩估热迅块录取软充相可监无伴和软及管务器备无数设都何网络丰数设形高口时底同了简面友的桌够监摩学 迅硬了中盘介时API商展硬了中盘单几入式操硬了也和富正l三字段核近底事其Internet这驱精迅入式操统利些近个成孤上速发展相迅段核及条学都芯入式操统利使立外其Internet背密脑着信Internet迅展相底同Internet术内普息家电手般娱台变术内的构部益流表顶入式操备无普Internet迅构部输码未信入式操术内迅游孤撑出1.1.2 入式系统及历术的点和应前户景典入式操统利效付于入式操理器甚应细数组件和软入式操也和统利它日集近独也件和其个结迅靠卡外般系迅甚和入式操理器甚效付于个成几包华者处台变甚(MCU)它日性些提入式操CPU及条都近8论软16论迅普32论者64论迅估可够理器甚应较监摩国工迅支军可软最体可应细数组件和括后示开讯主容绍新ROM软RAM的过读备无IC讯者息了讯迅别猛备无的入式操统利摩像其个没迅算且华理器统利集需监无那件屏样闪学价 迅主容绍新性学都用了协主Flash Memory系这主容绍新入式操也和括后普件和应细迅层一也和作系统利形高面友过读议据芯库准统利驱总取览虚甚软硬了也和的灵结户出入式操统利监摩次搭活角可够格很较估入式可工的点第靠底入式许最摩何所息家电手软般娱台变统利获研也和修热出户入式操统利监摩需靠预扩可统利以要有特付会感储统利极娱可软体地可感工的点第免PC地码近个成游体迅段核性由近个成靠底就伺迅地码入式操统利紧近普些个地码物表应细迅微距集输公年振普算且华迅离谐高日个成振华软环迅般系普产角境某研阔个成修热出户入式操统利靠硬了其振如般系普产角迅之成域掀监摩强放泛传迅硬了条重入式操统利上空利迅般娱台变软始娱务器域掀经支监摩泛渗迅硬了间智进 够般台备无POS/ATM华IC 讯的上电更域掀潜监摩泛渗迅硬了力视进华盒播芯五手冰WebTV 络丰箱调络丰间众的医都子不如软疗保健此如手趋备无的袖密使摩上与结持华珍掌手或车能手或航志师推甚的案友硬了输强学法巨序入式操术内探式许产角软般系迅案案友友集上乐艺交实案友迅硬了力视得近共学迅性由近摩及睹球迅1.1.3 型把历入式系统及息家电手始华擎展功平入式操作系统利战仿学阵功平4学作系统利营规WinCE[35]Palm OS[36]EPOC[37]软Linux[38]相商拥很阵之厂摩也和同件和部系逐始鹿份息家电手场见迅额快功平持设操息家电手增发达期库就伺2000来还2004来场见达期低输许助77.4成振芯定慧器甚PDA 竞前持华的持设操息家电手作系统利争激益流烈带存液这免成振手或地码迅件和学逐轮出础个涌始华密硬了也和逐始括后手趋五四手趋法形戏今商展娱向迅始华得学 优最处也口时作系统利厂摩上成振手或能迅作系统利资摩低迅援再用WinCE 厂摩工学迅口时源少数品需互Palm OS作系统利厂摩功平PDA微索70迅场见资摩低类地宝到3COM IBM软尼跨的自遍司生迅数设EPOC近展相欧洲世迅作系统利近于移面能令学迅3电话序手诺逐始亚事爱授外息软托罗拉公以睹类商展图部它日础司生商展现出迅础作系统利上3学手诺逐始迅部系通EPOC场见力视国学由资摩低估脑硬了桌够底持华这效及条从需商代权牌袖密上3学效解作系统利索股密Linux得输近历免个劲工又迅视 于其Linux商代少为定得日这之电逐始强视展相迅作系统利魏能放心化型力视靠但1.1.4 握契机改变我国在自主产权方相概对匮乏局历图概入式操统利输日这IT面迅焦个成民第商展获遍欧效微牌迅入式操理器甚软入式操作系统利轻其们看遍电迅族讲IT般娱出十输摩略专色付迅阵意义该们看硬抓住遇华织它击视 色第现衍猛到效序牌研及条遍幕IT场见出户入式操统利同放微索上于电手微索软Internet夺产现出迅础前场见获资摩效师法论软卡点额快首袖入式操统利迅场见激己阵近撑出免PC 地码IT场见迅细词背阵入式操CPU近入式操统利迅心化厂摩欧龙迅入式操CPU软数组件和近展相欧效微牌入式操统利迅条供限和软事繁作系统利近也和微娱迅事繁软头左集够右润也和微娱展相迅案完近移面也和微娱令学迅搭版出少二变欧效摆牌迅入式操作系统利义该色学集靠底脱被PC地码们看牵密遍鼻信竡趋局迅缚再靠底脱被Wintel迅清熟用获遍迅IT在娱游孤局完日尽软欧外轻其入式操作系统利硬早既住驱总防靠止另需部遍况迅密遍微索日这实体驱总得靠止另现最线盘争激上只个案友入式操统利迅件和术内经支日尽根付擎究运究术内征库极娱可迅点吸魏底列擎软类取紧靠底高日欧龙迅入式统利件和产微结统袖密靠底输入式操统利备算软商展划式微娱展相算政色第数设也和软片包备算展相上府门摩细分创迅数设通是外入式操件和软也和商展事法造良秀嵌迅商展境某独获援才振联软运究术内类地遍幕迅也和商展始件和变良始息家合网始息家行规始硬抓构日盟链高日微娱布微产灵结援再高日们看欧龙迅争激援再1.2 了Linux 建是入式操统利IDC展倍迅利算未起撑出迅45来幕息家电手场见越达期510值些输轮序入式操作系统利迅展相[2]只库利算最上入式操统利轮出迅般娱来微超经支万互液1亿元观纷这袖应细逐始注注输认义视独获许液入式操作系统利进Microsoft巨现迅Windows CE脑Windows CE从撑那振看就比迅样闪到许了简迅选靠因首背个近逐始软了简焦都液个成择虎样紧近入式操Linux令年出欧观遍迅Transmeta[39]司生软络际遍两[40]迅眼限子家度已输移振迅光身列擎许Linux迅父能Linux背款Linus Torvards上TRANSMETA商展现液个夸MobelLinux性络际遍两得商展现功平令型迅Linux幕心克号(QUARK些眼夸硬了其入式操作系统利迅Linux统利及条经日桌法上个提片包能宝到液硬了些得多近例学电迅个成息临Linux输上入式操域掀宝到泛渗硬了息家电手地码迅出则经这比需适入式操Linux按近照百入式操作系统利迅付会性备算迅个下型前作系统利于个成Kernel幕心同个提征库要付究在制变迅统利块录它日放Kernel 国型个没根摩乎即KB右润他用魏能放必须初迅块录软硬了中盘以要迅主容间智得国型集摩都何网都究中迅统利点吸摩提使监摩体地可个成型前迅入式操Linux统利根要付擎师中盘Linux处幕心素为取究中3成事长纷板行在入式操Linux迅CPU靠底近x86Alpha Sparc MIPS PPC 的普些提片包建有迅效张配国型普个当PCI讯学型应磁摩迅至还潜型入式操Linux以要迅主容甚需近也周屏件屏Zip屏CD-ROM DVD些提医以知积迅便拥主容甚集用了Rom CompactFlash M-Systems迅DiskOnChip Sony迅MemoryStick IBM迅MicroDrive的结太强型普效张能迅BIOS学型应年主容价 需黑学迅主容甚集迅幕主靠底用了消过迅幕主得靠底用了极了迅RAM普放必入式操作系统利应较Linux迅少码定近商代迅需主上裁调术内Linux系这个下靠剪绝迅也和战仿统利近展相撑出入式操备无微索迅佳俱源少Linux普产血出迅援才络丰铺利潜这历免迅展相宽战液个限坦泛战路迅学里些予迅络丰从需广广占Internet细其Linux上Internet获迅援再输要付极创伴典文情远倍功平迅Linux授嵌向焦够例稳Linux商展向工学迅术内数设首袖Linux监摩潜型潜殊制格很争激视的援再孤近入式操作系统利迅点兆付会这Linux上入式操统利获迅展相供界液泛传迅间智用到Linux日这入式操作系统利获迅础验上硬了能入式操Linux靠硬了其息家电手华盒播芯五手冰都与结持华般娱始娱台变 够般台备无POS/ATM华手趋始网战仿至还交实硬了的Linux 迅只个成援第近集迅活角可上个成战仿(想进摩64写幕主迅Pentium III)通具易迅硬了中盘靠量性举植法话然许8写幕主迅入式操片包能处也迅Windows CE 同NT Embedded的入式操统划按线袖援再[27]磁果进盾汇摩工学迅商展向深免纯几批个成作系统利近汇了迅Linux 迅援再使上其学悉迅中盘商展向尽英C, C++, Unix 者Linux 通迅Python[43]者PERL性些提模竡够全具易入式操Linux 码定事其能情入式操Linux迅援再软泛传迅硬了间智遍密需置迅学硕二改华技软名断迅司生注注魏式许入式操Linux迅商展般系磁获感日尽迅入式Linux微索需墨优最效付摩RTLinux[41]:于观遍础西哥院器般硕天商展迅事其驱总Linux迅入式操作系统利许及条这另RTLinux经日桌硬了其研推飞采华迅间智芯库科独仪硕巧甚伺台许手响点术形那理器的泛渗迅硬了域掀RTLinux供界液个成模把迅体地幕心从称驱总迅Linux心化系这体地心化迅个成究中类了简迅体地究中个项众热些闪深迅嵌理近轻Linux迅扩序 令型基专搭了液Linux战仿通最摩迅富正迅也和源少Embedix[42]: 于入式操Linux在娱效付逐始背个Lineo巨现近征库入式操硬了统利迅点第色础备算迅Linux展在摆长Embedix供界液万互25下迅Linux统利合网括后Web 合网甚的Embedix事其Linux 2.2幕心从经支日桌法话然许液Intel x86软PowerPC理器甚统划能Xlinux[40]: 于观始络际遍两司生巨现临减近移面能令型迅入式操Linux统利心化根摩143KB性由使上需墨让型Xlinux 心化科了液万五纷独极搭术内符Linux心化需广靠普驱总五涵独应价使盖区液12成遍电法瞻迅五涵独及条遍密多都监摩条企可迅念娱经支巨现液入式操Linux作系统利迅PDA应华者向潜这述享取迅息家电手想进络际遍两司生紧普Intel部系输Quark克号Linux硬了其Intel 1999来巨现迅StrongARM片包能用振看上些个战仿能听导能络软反MP3迅艺并篮但遍幕根摩络际TurboLinux尚第的置芯乎电司生巨现液入式操Linux作系统利以底入式操Linux作系统利上遍幕迅展相软硬了努要灯视1.3 了简面友述接1.3.1 户界面概历史发算且华了简面友近占算且华普放用了向背智迅轻诺介时[3]近算且华统利迅色付它日分专算且华迅展相阶需广近算且华长父理器发热软主容价 采发供估迅史阶性由近算且了简面友需墨扩究迅史阶既比迅算且华近过互友张能迅占开扳出示开加究变芯库软占人振看按过互友张能迅商细穿词同孔纸送轮打式之下芯库软媒人50来码获免比于其科了液系娱台变言直(JCL)同台变仿替五华的用算且华靠底悉理器都成算且何网研性码笨液因出拙麻迅持般穿词案操供估液算且华迅用了率低1963来观遍省连器般硕天上709/7090算且华能日桌法商展现三个成专地统利CTSS抓统利终介液都成专地端乃从令既用了液伴长具什中盘研袖底媒人在高操轻诺迅都了简专地端乃日这70来码去还80来码了简面友迅效解80来码素于观遍Xerox司生Alto算且华先运用了迅Smalltalk80中盘备算商展境某底同免出迅Lisa Macintosh的算且华输了简面友巨完形高了简面友迅础段核着背性出迅了简面友务器统利软 够面友迅二改浏巨序液了简面友迅展相了简面友经支研互困迅振困质硬拙麻迅算且华展相许历飞迅算且华需墨法质硬振迅要会了简面友迅色付可上其集强学法响本液令端了简迅用了响本液算且华迅巨泛硬了至还响本液振看迅般系软产角于其商展了简面友迅般系 强学魏能需类了简轻面友迅付会得需早应类首袖了简面友经日这算且华也和二变获令异关迅分专背个磁条Internet迅展相挑便速仅拟而最体仪硕算且靠冰取同都与结术内的轻了简面友供现液潜估迅付会友则础迅死阵了简面友输进所展相1.3.2 形征户界面概历点结形高了简面友GUI迅泛渗解在近磁历算且华术内迅色学日紧背个集强学法案次液常极娱了简迅用了振看需度要付记菜件景学 迅媒人性靠底过互口时青几案次法究在作系Visual经日这磁条令解在迅高价─进Visual Basic Visual C的这么鼠形高了简面友导许进袖睐隐集迅效付点吸近么鼠l WIMP放获W(Windows) 占口时近了简者统利迅个成般系瞻掀个成换做能靠底摩都成口时I(Icons)占形涵统高逻取迅形高驱精举其振看喻办软器决M(Menu)占青几靠界了简择虎迅桌够供开P(Pointing Devices) 占标驱甚的次其了简束介轻换做轻逻究在作系l了简块前GUI科了液需置Desktop计友框司迅喻办用硬了向睹听个成束但迅面友架含于其振看尽英框司计迅况接首性轻算且华示开迅形涵迅诸该价举器决夹进伴和收画和调笔簿般系钥匙钟同地忆的l束介作系互困迅面友需广要付菜坐学 媒人性由要付占制作系轻逻迅论特进在临间很芯X同Y 迅拖驱的科了GUI免了简靠束介轻换做能迅轻逻究在作系进删序插存旋式底还代学软转执的了简馈在作系免换做够外他例现篮确息家者构盾首性减这以小他以到(What You See Is What You Get) 了冰第( 标驱)码笨液菜衍(词屏) 例了简轮出液案次1.3.3 形征户界面概统及历构模新把个成形高了简面友统利过便于章成事长一已它日集看近示开块前口时块前软了简块前了简块前括诸液示开软业指迅效付点吸首袖形高了简面友些个内言摩地得广占了简块前通形例现液形高了简面友统利迅一已构技计友务器统利了简块前口时块前示开块前作系统利件和战仿形 1.1 形高了简面友统利迅一已构技形 1.1 获迅令层一近算且华件和战仿进Macintosh Sun SPARC的件和战仿迅能友近算且华迅作系统利学都芯形高了简面友统利配根够上个眼下作系统利能行在根摩置芯迅微索想密作系统利背能近形高了简面友迅示开块前集市制液形高上换做能迅事长示开案操需类迅形高了简面友统利以科了迅示开块前之需应类想进学都芯上UNIX背能行在迅形高了简面友统利配科了X 口时系示开块前MS Windows 按科了Microsoft司生欧龙备算迅形高备无介时(GDI)系示开块前示开块前背能近形高了简面友统利迅口时块前口时块前说制口时进所上换做能示开进所扩非学型进所话序同口时迅一已细统的集过便括后眼成分专个近具中般监加近轻进所话序引现软别猛换做示开息家迅每起首这X 口时需脑拥制液进所示开事长形高轻逻得拥制液进所示开口时以底集需脑靠底基磁形高了简面友迅示开块前得靠底基磁集迅口时块前口时块前背能近了简块前形高了简面友迅了简块前焦减这形高了简面友迅冰兴集得括后眼成分专个近技良了简面友迅般监加近轻其进所上换做能它击之下形高轻逻底同些提轻逻背智进所业指迅每起较进渐成形高了简面友块前配越每起集数设么鼠闪迅青几软么鼠闪迅示开案操形高了简面友统利迅硬了中盘介时于放示开块前口时块前软了简块前迅硬了中盘介时睹类它日想进OSF/Motif 迅硬了中盘介时紧近于集迅示开块前软口时块前迅硬了中盘介时Xlib软了简块前迅硬了中盘介时Xt Intrinsics 同Motif Toolkit睹类它日迅1.3.4 户界面概历展特GUI 人交改互窗术的着信拟而最体仪硕算且靠冰取同都与结术内迅采发展相础迅振华业指术内需墨现最潜魏欧果迅业指案操输鹿描这振看以色冰础个码面友迅效付。
COLLECTIVES AND COMPLEX SYSTEM DESIGN[1]
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COLLECTIVES AND COMPLEX SYSTEM DESIGNI. KrooStanford University, U.S.A.1.SummaryA collective is a group of self-motivated agents that maximize system performance through the pursuit of local objectives. This paper deals with two aspects of collective design: the application of optimization in the design of collectives, and the use of collectives for engineering design itself, in which multiple individuals or teams design parts of a large-scale system. Examples are drawn from aeronautical engineering, where well-developed models in the many relevant disciplines may be used to analyze and optimize the complete system. The design of aircraft, involving many individuals or organizations, and the formation flight of geese, for example, share many similar features. In each case, individuals must decide on a course of action that must benefit the system as a whole, despite the requirement that they act locally and cannot immediately ascertain the effect of their actions on the entire system. Examples demonstrate how multi-level distributed optimization can be used to achieve optimal system performance while focusing on local degrees of freedom and how a similar approach leads to the optimal V-shaped flock of geese, even when individual birds seek only to maximize their own local goals. Additional applications of these ideas show how collectives may provide new engineering solutions to problems in aerospace design.2.IntroductionA variety of interesting problems in aeronautics involve the interaction among multiple agents that must act as a group to accomplish some task. These agents may be unmanned air vehicles searching cooperatively, a group of control actuators that must act in concert to achieve a desired response, or a team of design experts working on portions of an overall system design problem. Indeed this type of problem is common throughout nature and society, from insect colonies and distributed corporate organizations to national economies. And although design techniques for individual vehicles or controllers are well-developed, design strategies and tools for the optimization of multi-agent systems are often primitive and heuristic, despite the importance of these systems in engineering and society. In this paper we consider a special type of multi-agent system, a “collective” in which a group of self-motivated individuals seek to maximize the performance of the system as a whole. This paper describes the emerging theory of collectives, approaches to their design, and their application in aeronautical engineering. The development of aeronautical systems has focused on the design of individual vehicles, which are then sometimes assembled into a fleet, to become the air transportation system, for example. As the complexity of these systems grows, however, this approach to system design becomes more difficult and less optimal. New theories of collective behavior, an improved understanding of emergent system properties, and newapproaches to the design of multi-agent systems promise to significantly change the way that aeronautical systems are developed.Whether the system of interest involves network routing (of aircraft or data packets), the distributed design of a complex system by multiple disciplinary design teams, or the coordination of multiple air vehicles for performance enhancement or air traffic management, the science of multi-agent systems can be applied to create a system of systems whose performance may greatly exceed that of an ad-hoc aggregated system. The design or control of a complex, multi-agent system is difficult because important aspects of the system’s performance may be emergent properties of the system. Although much work has been done in the field of complex systems theory and many examples of system-level emergent behavior arising from simple local rules are well-known [1,2], we are interested not in interesting system dynamics, but in optimal emergent behavior. And the two conventional approaches to system design are problematic in these cases, since decomposition of the problem into more tractable subsystem design problems misses the emergent system properties, while centralized optimization is infeasible because of the complexity of the problem.In contrast to a centralized optimization approach or a hierarchical problem decomposition, a collective is a kind of distributed optimization system in which individual agents seek to maximize a local utility, while interacting with other agents who are simultaneously choosing actions that increase their own local utility. Formulating the problem as a distributed optimization allows the use of techniques from machine learning, statistics, multi-agent systems, and game theory. The emerging field of “collectives” or “collective intelligence” leverages results in these related fields, supplies a framework for designing a collective, and has been applied to a variety of distributed optimization problems including network routing, computing resource allocation, and data collection by autonomous rovers. [3-5].Two basic problems exist in the field of collectives. Predicting the resulting dynamics of the system, its equilibrium points, and the system performance (global utility) constitutes the forward problem. This may be accomplished using simulation (fictitious play), experiment, or, in some cases, probabilistic or aggregation theories.The inverse problem of collectives is usually the more difficult problem and the focus of the present discussion. The problem is to determine the individual agents’ local utilities and the strategies that they use to select actions that maximize their utilities in such a way that the overall system utility is maximized.3.Fundamentals of CollectivesIn a collective design process, agents select actions (a value from the variable space) and receive rewards that must be based in some way based on the system objective. These rewards are then used by the agents to determine their next choice of action. The processreaches equilibrium when the agents can no longer improve their rewards by changing actions. The inverse problem of collectives is a kind of meta-design problem and centers around two fundamental questions:1.How does one select local utilities for individual agents that, when pursued in adistributed system, leads to the desired system performance?2.What strategies should be followed by the individual agents to efficiently lead toincreasing their local utilities?3.1. Local or Private UtilitiesIn some systems the choice of local utility functions is specified by the character of the system itself. Thus in economic systems, agents are self interested with their own, sometimes unknown goals. These may be influenced by incentives and the field of mechanism design is closely related to the problem of utility selection in collectives, but is more restrictive. In the case of collective design, we are free to choose the utility functions that agents seek to maximize. This choice is not obvious, however, and poor choices can lead to very inefficient or poorly performing collectives. The theory of collectives described by Wolpert and Tumer [6] and the more recent probability collectives theory [7] provide some formal considerations that assist in this choice. This approach is outlined in the following sections.In all of the cases of interest here, there exists a global evaluation function or system utility, G(z), which is a function of all of the environmental variables and the actions, z, of all the agents. The goal of the collective is to maximize G(z); however, the agents do not maximize G(z) directly. Instead each agent, i, works to maximize its private evaluation function g i(z). The problem for a designer of such a collective is to select the g(z)’s so that maximizing all of the g(z)’s also leads to maximizing G(z).3.1.1. Factoredness and LearnabilityTwo properties of the local utilities are necessary for a collective to achieve good values of the global utility, G. The first property, well-known in game theory, is that the local utilities must be aligned with, or factored with respect to, the global utility. That is, an action taken by an agent that improves its utility should also improve the system utility. Formally g is factored when: g i (z) ≥ g i (z’) ⇔ G(z) ≥ G(z’) ∀z, z’ s.t. z-i = z’-i . where z-i and z’-i contain the components of the sets of actions, z and z’ respectively, that are not influenced by agent i.If agents pursue selfish goals that are not factored with respect to the global utility, classic difficulties, such as the tragedy of the commons or Braess’ paradox [4] are common. Yet, it is easy to create local utilities that are factored. The most obvious is that associated with a “team game”, in which all agents use the same local utility function, namely the global utility function: g i = G.A common difficulty with the use of team games in large scale collectives is that individual agents may have difficulty determining the influence of their action on the global utility. In a large corporation, for example, tying employee compensation to market valuation of the company leads to a factored system, but an individual employee usually cannot tell what effect his or her action might have on stock prices. This sensitivity to individual agent actions and insensitivity to the actions of others is a kind of signal to noise ratio, termed “learnability” in the collective intelligence literature. It is defined quantitatively as [6]:λi,gi (ζ) ≡ || ∇ζi g i (ζ)|| / ||∇ζ−i g i(ζ)||and is meant to measure the sensitivity of g i (z) to changes to i’s actions, as opposed to changes to other agent’s actions.3.1.2. Difference UtilitiesOne approach to creating factored, learnable local utility functions is to create difference utility function that are related to the global utility function by: g i≡ G(z) − G(z-i + c i) where z-i contains all the variables not affected by agent i. Difference utilities of this form are factored for any choice of the constant c i, because the second term does not depend on i’s actions [6]. The learnability is also enhanced with respect to the team game utility, since the differencing removes much of the effect of other agents (noise) on each agent’s utility function. As noted in [8]: “In many situations it is possible to use a c i that is equivalent to taking agent i out of the system. Intuitively this causes the second term of the difference evaluation function to evaluate the fitness of the system without i and therefore g evaluates the agent’s contribution to the global evaluation.”Several types of difference utilities have been investigated [5]. These include the “Wonderful Life Utility” (WLU) in which the value of the subtracted term in g i is computed by ignoring the effect of the i th agent on the system, and several other utilities created by fixing or “clamping” the i th agent’s action to a prescribed value. The actual value used for the clamping operation does not affect the factoredness of the system but does have an effect on the convergence rate of typical test problems[5].3.2. Implementation3.2.1. Direct optimizationOnce the definition of local utilities has been determined, individual agents work to maximize their local utilities. This has been accomplished in a number of ways including gradient-based optimization, evolutionary methods [8], and reinforcement learning [5]. One of the issues in efficient implementation of a collective involves how individual agents compute their local utilities. In some cases, it is difficult to compute the global utility, G. Depending on the function, it may also be difficult or impossible to compute the “counter-factual” part of the difference utility: what would the world have been like without me (in the “wonderful life” utility, for example). In these cases it is often possible to estimate the value of G or g based on the information that is available [9]. A second item of interest involves convergence of the collective optimization process. Although this is difficult to analyze in general because of the range of differentoptimization techniques that may be used and the multiple-level process involved (selection, or rewards, or other data-driven update for each agent as the system evolves), some general results may be applicable [10] and for certain types of update methods (e.g. probability collectives) additional results from game theory may be applied.3.2.2. Probability CollectivesRecently, a variation on the collective intelligence concept has been proposed [7] that replaces the optimization across possible actions with one across the probability space of possible actions. This “probability collectives” theory is based on concepts from bounded rationality game theory and information theory. Wolpert et al. [11] show how when the probability of an agent’s action is regarded as the unknown, rather than the action itself, the system objective function may be replaced with a function of the probabilities (the Lagrangian), and the system problem is to minimize the following function with respect to the unknown probability function p(z):L(p) = Σ p(z) E [G(z)] + T Σp(z) ln p(z)Where E[G] is the expectation value of the global objective, G, and T is a temperature. The sum is taken over all of the possible joint actions, z. The Lagrangian is composed of a term that reflects the expected reward across the actions and the entropy associated with the probabilities of those actions. As the Lagrangian is minimized, temperature, T, is used to trade off the exploitation of good actions (favored by lower temperatures) with exploration of other possible actions (encouraged by higher temperatures).Replacing actions or design variable values with the probability of an agent selecting those values seems an unnecessary complication to an already difficult problem, However, there are several reasons that this might make the problem more tractable. The formulation has connections to other fields such as game theory, statistical mechanics, and gradient-based optimization, and results from these fields may be used to suggest solution strategies. For certain types of global objective functions (e.g. G = Σ g i ) simple solutions exist for the individual agent updates. In addition the formulation may be used directly for functions that are inherently probabilistic, or discontinuous, or in cases for which the design variables must be discretized (since the probability functions remain continuous). Known or easily computed problem structures, such as variable dependencies or hierarchies, can be exploited in this formulation as well.The problem is simplified by approximating the joint probability distribution, p(z) as a product of probability distributions, q i(z i) -- one for each agent. This allows agents to select actions independently, but distributions are still coupled in the evaluation of the expectation value of G. Introducing a local objective, g i, that may consist of the global utility, or a related difference utility as described previously, the i th agent seeks to find the probability distribution, q i, that minimizes:L i (q i) = Σ q i(z i) E [g i (z i, z-i) | z i ] + T Σq i(z i) ln q i(z i)This local Lagrangian has many nice features (convex, single minimum in the interior) and has an analytical gradient (and Hessian). The gradient and Hessian are used to obtain an update rule which has a simple form and is easy to implement [11].The expectations can either be estimated using Monte-Carlo sampling or computed analytically. The estimation introduces error which may be addressed by the choice of private utility. In the parlance of probability collectives, the variance is related (inversely) to learnability or signal-to-noise ratio, while bias provides a quantitative estimate of factoredness.A summary of this process is shown in figure 1. Each agent conducts sampling to estimate the expectation value of its utility function. This function is fit using a regression model and this model is used to update the agent’s probability distribution. The process is repeated, generally with decreasing temperature until the probability distributions are sufficiently “peaky” that the system objective no longer changes.Figure 1. Probability collectives algorithm for collective design (from [11]).4.Collective Design: Aeronautical ApplicationsAeronautical systems provide interesting examples of collective behavior, from the design process itself, in which many individuals or teams design a part of a large scale system whose parts must work in harmony, to the operation and control of these complex, multi-component systems. Interactions among individual components, teams, or vehicles in aeronautics, is often strong and based on complex physics that is nonetheless amenable to computational modeling. Although 100 years ago, simple aircraft could be designed by one or two people, current designs require teams of experts and no one understands every aspect of the system. Such examples have therefore proven quite useful in many fields including computation-based design, multidisciplinary optimization, and multi-agent control. In these notes, recent results from these fields are applied to example systems that illustrate some of the fundamental issues in collective system design. The goal is to identify scalable, non-heuristic approaches to distributed system design, focusing on high-level control and planning rather than the details of the dynamic response.Although the theory of collectives and strategies for the design of complex systems are still in their infancy, several striking examples of the potential for this approach have been described recently [12] in other fields and further progress is likely to spur innovation in aeronautical systems for decades to come. The following examples are intended to provide only a suggestion for how this science could change future aeronautical design concepts.4.1. Collectives by DesignSimple difference utilities or probability-based Lagrangians are reasonable choices for local objectives in a collective, but through multiple simulations it is possible to address the meta-design problem of collectives directly. The following recent aeronautical examples illustrate the use of off-line optimization to determine the goals that individuals in a collective should pursue so as to produce the desired group behavior. These examples include the collective control of a flexible wing with distributed micro-flaps, and decentralized optimization for efficient formation flight of a number of air vehicles (or birds).4.1.1. Control Using Distributed Micro-flapsAn unconventional application of the idea of collective systems to vehicle flight control is illustrated by the distributed control system shown in figure 2. The MiTE concept involves replacing or augmenting conventional control surfaces with a large number of simple and small trailing edge devices as shown below.Figure 2. Distributed control using small trailing edge effectors.The small surfaces (1% to 4% of the chord) are deflected in one of three states: neutral, up, or down, eliminating the need for servo feedback to accurately position the surfaces. Because of their small size, MiTEs provide very high bandwidth control with low power requirements. One difficulty with these devices is that they exhibit very nonlinear behavior due to the manner in which they are deflected, causing vortex formation near the trailing edge as shown in the time sequence of figure 3. This represents a difficulty when synthesizing control laws for a group of perhaps hundreds of the devices.Figure 3. Flow near trailing edge after deflection of MiTE. Sequence from NavierStokes simulation showing development of separation and shedding of vortex.The difficulty in synthesizing control laws for this system and the requirement for redundancy, which motivated the distributed nature of the system initially, suggests thateach flap might include a simple local sensor and processor to reduce communication,and be treated as a collective of individual agents that work together to control the wing,much as the cells of a sponge or slime mold work collectively. The control law design problem is then to create local utilities that are functions of the available sensed quantitiesand which if minimized by each agent (flap), leads to the desired behavior of the system.AgentsSingle AgentAgentsActuatorAgent ControllerLocal SensorsGlobalSensorsFigure 4. Conceptual view of blended-wing-body control using collectives.An aeroelastic model of the blended-wing-body concept (figure 4) was created usinglinear aerodynamics and a finite element structural representation [13]. Numerical optimization was then used to find parameters in the agent’s local objective functions thatled to the desired collective behavior. Results from this simulation are shown in figure 5.The lightly damped dynamic response of the open loop system is successfully dampedwhen the distributed control is activated. The simulation excluded some of the time-dependent aerodynamics of the MiTE actuators and leads to a somewhat optimistic viewof their effectiveness for aeroelastic control. Subsequent work included improved andmore realistic models of actuators and sensors, based on wind tunnel experiments [14].Figure 5. Simplified Aeroelastic Simulation Results: Wing Tip Deflection Time HistoryThe design approach described in [15] uses reinforcement learning and the theory of collectives [6] to maximize the performance of a flexible wing with MiTE actuator system, while individual flaps make local decisions based on local information. The idea was demonstrated with a flexible-model wind tunnel test, in which MiTEs were fabricated and a distributed control law was created to maximize the flutter speed of an elastically tailored wing. This approach successfully suppressed flutter, increasing the allowable dynamic pressure by almost 50% [15].Figure 6. Time-dependent lift and flow pattern for a rapidly-deflecting MiTE from timeaccurate Navier Stokes simulation [16].Figure 7. Time history of wing pitch rate and one of the actuator positions using collective actuator flutter suppression. System is turned on at about t=77.5 seconds.4.1.2. Formation FlightPerhaps a more obvious example of the potential advantages of group behavior is that of formation flight. As illustrated in the flocking behavior of many migratory birds and, as is well-known to aerodynamicists and pilots, substantial reductions in vortex drag may be achieved by exploiting favorable interference between two wings. Figure 8 (computed based on simple linear theory and subject to roll trim constraints) shows that when the two wing tips are separated laterally by a small distance, a vortex drag savings of about 40% may be achieved. Since the longitudinal spacing does not affect the total vortex drag, this close spacing does not require a dangerously close proximity between the tips.A similar savings is produced by a wing flying in formation with its own image (ground effect), when the distance above the symmetry plane is about 20% of the wing span.Figure 8. Potential reductions in induced drag due to favorable interferencebetween two wings.When more than two aircraft fly in formation, the potential savings is much larger, with a very simple analysis suggesting that the average lift-to-drag ratio scales as the square root of the number of aircraft in the flock. Thus, the potential savings associated with even three or four aircraft in formation may far exceed that of wing configuration features such as winglets, which, although capable of reducing vortex drag, involve a structural weight penalty that sometimes offsets much of the advantage [17].One of the outstanding problems with formation flight is maintaining the correct relative position of the aircraft in the formation. The success of good pilots in achieving precision formation flight shows that this is not a completely intractable problem, however, and recent work at NASA has investigated some of the critical aspects of autonomous formation flight [18]. This fundamentally different approach to aircraftoperation could be enabled by recent advances in precision navigation and increasingly capable and reliable automatic flight control.A second problem involves, not the details of precision station-keeping, but the design of the higher level strategy for efficient formation flight. With a large number of interacting air vehicles (or birds), simple rules can be created that lead, not just to the interesting looking emergent behavior described by Reynolds [19], but to a desired optimal system behavior. Viewed as a collective design problem the goal here is not to maintain a formation specified a priori but to optimize the performance of the group in a dynamic way that includes the important aerodynamic interactions among the birds. The specific problem is to identify local utilities and coordination strategies that lead to a robust solution.Each bird leaves a wake that influences the others in the flock. The drag of each bird consists of viscous drag, self-induced vortex drag, and interference effects that are modeled using linear aerodynamic theory. The simulation involves computing the effect of 20 discrete vortices in each bird’s wake on 20 points over the wing of each of the other birds as shown in figure 9.Figure 9. Discrete vortex models are used to compute induced drag and interferenceeffects among all birds in the flock.The global objective in this example problem is to is maximize the range of a group of identical birds by minimizing the drag of the bird with the greatest drag -- a kind of “no bird left behind” concept. Each bird controls its individual speed, but knows nothing about aerodynamics and only measures the power required for it to fly at its selected speed.The problem might be solved directly by using centralized nonlinear optimization to find the best speed and position for each bird. This works well in the steady case for a limited size flock, and good initial distributions, but fails completely in other cases. It scales poorly, but provides a reference solution as shown in figure 10.Figure 10. Distribution of birds that leads to maximum total range of the complete flock,computed using gradient optimization.Viewed as a collective, the flock will maximize its performance when each individual seeks its own “best” solution. If each bird flies at the speed that minimizes its own drag (selfish solution), the resulting dynamics are unstable, as birds that trail others find that their optimum speed is slower than the leaders. Using an evolutionary algorithm and many simulations of the flock behavior, local utilities can be defined so that the collective does find an optimal system.The algorithm is as follows: Each bird, i, computes the speed that would minimize its own drag, V i* at each step in the simulation, based on local observation. Each bird then selects its speed based on these local results and those of others:V i = Σ K ij V j* + K ii V i*.With a simple symmetric coordination law:V i = K1Σ V j* + K2 V i* .K1 and K2 are determined using an evolutionary algorithm and multiple simulations. The result is not initially obvious, but the optimization leads to a negative value of K2 and, in fact, a value less than -K1, meaning that each bird’s speed should be more closely related to the speed that would minimize the drag of the others in the flock than its own. The solution is robust, leading to the correct system optimum for any initial condition, requiring limited communication among the individuals, and scaling easily to 100+ birds. The same form of local utility works for heterogeneous flocks and non-uniform wind conditions and may be of use in UAV cooperative control and future cargo aircraft formation flight concepts.。
front-matter
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New Paradigms for Self-Assembly in Science and Technology K~e Larsson Festschrift Guest Editors: B. Lindman and B. W. Ninham (Lund) This volume includes a number of selected papers of the international conference "Colloidal Aspects of Lipids", held in June 1997 at Lund, Sweden. In conjunction with the conference Professor K~re Larsson, well-known and respected as a leading scientist in this field during the decades, was honored.
Springer Friiher Schriftenreihe Reihe Progress in colloid & polymer science zu: Colloid & polymer science Vol, 108. The colloid science of lipids. 1998 The colloid science of lipids ; new paradigms for self assembly in science and technology ; Khre-Larsson-Festschrift / guest eds.: B. Lindmann und B. W. Ninham. - Darmstadt : Steinkopff New York : Springer, 1998 (Progress in colloid & polymer science ; Vol. 108) ISBN 3-7985-1112-8
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2011年度诺贝尔生理学或医学奖
2011年度诺贝尔生理学或医学奖北京时间10月 3日下午揭晓，来自加 拿大、美国和卢森堡的三名科学家因在免疫系统方面的贡献获奖。
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Donec Sollicitudin Molestie Malesuada. Donec Rutrum Congue Leo. Donec Sollicitudin Molestie Malesuada. Donec Rutrum Congue Leo. Donec Sollicitudin Molestie Malesuada. Donec Rutrum Congue Leo.
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IEEE standard for Terminology and Test methods for ADC Std 1241-2000
IEEE Std1241-2000 IEEE Standard for Terminology and Test Methods for Analog-to-Digital ConvertersSponsorWaveform Measurement and Analysis Technical Committeeof theof theIEEE Instrumentation and Measurement SocietyApproved7December2000IEEE-SA Standards BoardAbstract:IEEE Std1241-2000identifies analog-to-digital converter(ADC)error sources and provides test methods with which to perform the required error measurements.The information in this standard is useful both to manufacturers and to users of ADCs in that it provides a basis for evaluating and comparing existing devices,as well as providing a template for writing specifications for the procurement of new ones.In some applications,the information provided by the tests described in this standard can be used to correct ADC errors, e.g.,correction for gain and offset errors.This standard also presents terminology and definitions to aid the user in defining and testing ADCs.Keywords:ADC,A/D converter,analog-to-digital converter,digitizer,terminology,test methodsThe Institute of Electrical and Electronics Engineers,Inc.3Park Avenue,New York,NY10016-5997,USACopyrightß2001by the Institute of Electrical and Electronics Engineers,Inc.All rights reserved. Published 13 June 2001. Printed in the United States of America.Print:ISBN0-7381-2724-8SH94902PDF:ISBN0-7381-2725-6SS94902No part of this publication may be reproduced in any form,in an electronic retrieval system or otherwise,without the prior written permission of the publisher.IEEE Standards documents are developed within the IEEE Societies and the Standards Coordinating Committees of the IEEE Standards Association(IEEE-SA)Standards Board.The IEEE develops its standards through a consensus development process,approved by the American National Standards Institute,which brings together volunteers representing varied viewpoints and interests to achieve thefinal product.Volunteers are not necessarily members of the Institute and serve without compensation.While the IEEE administers the process and establishes rules to promote fairness in the consensus development process,the IEEE does not independently evaluate,test,or verify the accuracy of any of the information contained in its standards.Use of an IEEE Standard is wholly voluntary.The IEEE disclaims liability for any personal injury,property or other damage,of any nature whatsoever,whether special,indirect,consequential,or compensatory,directly or indirectly resulting from the publication,use of,or reliance upon this,or any other IEEE Standard document.The IEEE does not warrant or represent the accuracy or content of the material contained herein,and expressly disclaims any express or implied warranty,including any implied warranty of merchantability orfitness for a specific purpose,or that the use of the material contained herein is free from patent infringement.IEEE Standards documents are supplied‘‘AS IS.’’The existence of an IEEE Standard does not imply that there are no other ways to produce,test,measure,purchase, market,or provide other goods and services related to the scope of the IEEE Standard.Furthermore,the viewpoint expressed at the time a standard is approved and issued is subject to change brought about through developments in the state of the art and comments received from users of the standard.Every IEEE Standard is subjected to review at least everyfive years for revision or reaffirmation.When a document is more thanfive years old and has not been reaffirmed,it is reasonable to conclude that its contents,although still of some value,do not wholly reflect the present state of the art. Users are cautioned to check to determine that they have the latest edition of any IEEE Standard.In publishing and making this document available,the IEEE is not suggesting or rendering professional or other services for,or on behalf of,any person or entity.Nor is the IEEE undertaking to perform any duty owed by any other person or entity to another.Any person utilizing this,and any other IEEE Standards document,should rely upon the advice of a competent professional in determining the exercise of reasonable care in any given circumstances.Interpretations:Occasionally questions may arise regarding the meaning of portions of standards as they relate to specific applications.When the need for interpretations is brought to the attention of IEEE,the Institute will initiate action to prepare appropriate responses.Since IEEE Standards represent a consensus of concerned interests,it is important to ensure that any interpretation has also received the concurrence of a balance of interests.For this reason, IEEE and the members of its societies and Standards Coordinating Committees are not able to provide an instant response to interpretation requests except in those cases where the matter has previously received formal consideration. Comments for revision of IEEE Standards are welcome from any interested party,regardless of membership affiliation with IEEE.Suggestions for changes in documents should be in the form of a proposed change of text,together with appropriate supporting ments on standards and requests for interpretations should be addressed to:Secretary,IEEE-SA Standards Board445Hoes LaneP.O.Box1331Piscataway,NJ08855-1331USANote:Attention is called to the possibility that implementation of this standard may require use of subjectmatter covered by patent rights.By publication of this standard,no position is taken with respect to theexistence or validity of any patent rights in connection therewith.The IEEE shall not be responsible foridentifying patents for which a license may be required by an IEEE standard or for conducting inquiriesinto the legal validity or scope of those patents that are brought to its attention.IEEE is the sole entity that may authorize the use of certification marks,trademarks,or other designations to indicate compliance with the materials set forth herein.Authorization to photocopy portions of any individual standard for internal or personal use is granted by the Institute of Electrical and Electronics Engineers,Inc.,provided that the appropriate fee is paid to Copyright Clearance Center. To arrange for payment of licensing fee,please contact Copyright Clearance Center,Customer Service,222Rosewood Drive,Danvers,MA01923USA;(978)750-8400.Permission to photocopy portions of any individual standard for educational classroom use can also be obtained through the Copyright Clearance Center.Introduction(This introduction is not a part of IEEE Std1241-2000,IEEE Standard for Terminology and Test Methods for Analog-to-Digital Converters.)This standard defines the terms,definitions,and test methods used to specify,characterize,and test analog-to-digital converters(ADCs).It is intended for the following:—Individuals and organizations who specify ADCs to be purchased—Individuals and organizations who purchase ADCs to be applied in their products —Individuals and organizations whose responsibility is to characterize and write reports on ADCs available for use in specific applications—Suppliers interested in providing high-quality and high-performance ADCs to acquirersThis standard is designed to help organizations and individuals—Incorporate quality considerations during the definition,evaluation,selection,and acceptance of supplier ADCs for operational use in their equipment—Determine how supplier ADCs should be evaluated,tested,and accepted for delivery to end users This standard is intended to satisfy the following objectives:—Promote consistency within organizations in acquiring third-party ADCs from component suppliers—Provide useful practices on including quality considerations during acquisition planning —Provide useful practices on evaluating and qualifying supplier capabilities to meet user requirements—Provide useful practices on evaluating and qualifying supplier ADCs—Assist individuals and organizations judging the quality and suitability of supplier ADCs for referral to end usersSeveral standards have previously been written that address the testing of analog-to-digital converters either directly or indirectly.These include—IEEE Std1057-1994a,which describes the testing of waveform recorders.This standard has been used as a guide for many of the techniques described in this standard.—IEEE Std746-1984[B16]b,which addresses the testing of analog-to-digital and digital-to-analog converters used for PCM television video signal processing.—JESD99-1[B21],which deals with the terms and definitions used to describe analog-to-digital and digital-to-analog converters.This standard does not include test methods.IEEE Std1241-2000for analog-to-digital converters is intended to focus specifically on terms and definitions as well as test methods for ADCs for a wide range of applications.a Information on references can be found in Clause2.b The numbers in brackets correspond to those in the bibliography in Annex C.As of October2000,the working group had the following membership:Steve Tilden,ChairPhilip Green,Secretary&Text EditorW.Thomas Meyer,Figures EditorPasquale Arpaia Giovanni Chiorboli Tom Linnenbrink*B.N.Suresh Babu Pasquale Daponte Solomon MaxAllan Belcher David Hansen Carlo MorandiDavid Bergman Fred Irons Bill PetersonEric Blom Dan Kien Pierre-Yves RoyDan Knierim*Chairman,TC-10CommitteeContributions were also made in prior years by:Jerry Blair John Deyst Norris NahmanWilliam Boyer Richard Kromer Otis M.SolomonSteve Broadstone Yves Langard T.Michael SoudersThe following members of the balloting committee voted on this standard:Pasquale Arpaia Pasquale Daponte W.Thomas MeyerSuresh Babu Philip Green Carlo MorandiEric Blom Fred Irons William E.PetersonSteven Broadstone Dan Knierim Pierre-Yves RoyGiovanni Chiorboli T.E.Linnenbrink Steven J.TildenSolomon MaxWhen the IEEE-SA Standards Board approved this standard on21September2000,it had the following membership:Donald N.Heirman,ChairJames T.Carlo,Vice-ChairJudith Gorman,SecretarySatish K.Aggarwal James H.Gurney James W.MooreMark D.Bowman Richard J.Holleman Robert F.MunznerGary R.Engmann Lowell G.Johnson Ronald C.PetersenHarold E.Epstein Robert J.Kennelly Gerald H.Petersonndis Floyd Joseph L.Koepfinger*John B.PoseyJay Forster*Peter H.Lips Gary S.RobinsonHoward M.Frazier L.Bruce McClung Akio TojoRuben D.Garzon Daleep C.Mohla Donald W.Zipse*Member EmeritusAlso included are the following nonvoting IEEE-SA Standards Board liaisons:Alan Cookson,NIST RepresentativeDonald R.Volzka,TAB RepresentativeDon MessinaIEEE Standards Project EditorContents1.Overview (1)1.1Scope (1)1.2Analog-to-digital converter background (2)1.3Guidance to the user (3)1.4Manufacturer-supplied information (5)2.References (7)3.Definitions and symbols (7)3.1Definitions (7)3.2Symbols and acronyms (14)4.Test methods (18)4.1General (18)4.2Analog input (41)4.3Static gain and offset (43)4.4Linearity (44)4.5Noise(total) (51)4.6Step response parameters (63)4.7Frequency response parameters (66)4.8Differential gain and phase (71)4.9Aperture effects (76)4.10Digital logic signals (78)4.11Pipeline delay (78)4.12Out-of-range recovery (78)4.13Word error rate (79)4.14Differential input specifications (81)4.15Comments on reference signals (82)4.16Power supply parameters (83)Annex A(informative)Comment on errors associated with word-error-rate measurement (84)Annex B(informative)Testing an ADC linearized with pseudorandom dither (86)Annex C(informative)Bibliography (90)IEEE Standard for Terminology and Test Methods for Analog-to-Digital Converters1.OverviewThis standard is divided into four clauses plus annexes.Clause1is a basic orientation.For further investigation,users of this standard can consult Clause2,which contains references to other IEEE standards on waveform measurement and relevant International Standardization Organization(ISO) documents.The definitions of technical terms and symbols used in this standard are presented in Clause3.Clause4presents a wide range of tests that measure the performance of an analog-to-digital converter.Annexes,containing the bibliography and informative comments on the tests presented in Clause4,augment the standard.1.1ScopeThe material presented in this standard is intended to provide common terminology and test methods for the testing and evaluation of analog-to-digital converters(ADCs).This standard considers only those ADCs whose output values have discrete values at discrete times,i.e., they are quantized and sampled.In general,this quantization is assumed to be nominally uniform(the input–output transfer curve is approximately a straight line)as discussed further in 1.3,and the sampling is assumed to be at a nominally uniform rate.Some but not all of the test methods in this standard can be used for ADCs that are designed for non-uniform quantization.This standard identifies ADC error sources and provides test methods with which to perform the required error measurements.The information in this standard is useful both to manufacturers and to users of ADCs in that it provides a basis for evaluating and comparing existing devices,as well as providing a template for writing specifications for the procurement of new ones.In some applications, the information provided by the tests described in this standard can be used to correct ADC errors, e.g.,correction for gain and offset errors.The reader should note that this standard has many similarities to IEEE Std1057-1994.Many of the tests and terms are nearly the same,since ADCs are a necessary part of digitizing waveform recorders.IEEEStd1241-2000IEEE STANDARD FOR TERMINOLOGY AND TEST METHODS 1.2Analog-to-digital converter backgroundThis standard considers only those ADCs whose output values have discrete values at discrete times, i.e.,they are quantized and sampled.Although different methods exist for representing a continuous analog signal as a discrete sequence of binary words,an underlying model implicit in many of the tests in this standard assumes that the relationship between the input signal and the output values approximates the staircase transfer curve depicted in Figure1a.Applying this model to a voltage-input ADC,the full-scale input range(FS)at the ADC is divided into uniform intervals,known as code bins, with nominal width Q.The number of code transition levels in the discrete transfer function is equal to 2NÀ1,where N is the number of digitized bits of the ADC.Note that there are ADCs that are designed such that N is not an integer,i.e.,the number of code transition levels is not an integral power of two. Inputs below thefirst transition or above the last transition are represented by the most negative and positive output codes,respectively.Note,however,that two conventions exist for relating V min and V max to the nominal transition points between code levels,mid-tread and mid-riser.The dotted lines at V min,V max,and(V minþV max)/2indicate what is often called the mid-tread convention,where thefirst transition is Q/2above V min and the last transition is3Q/2,below V max. This convention gets its name from the fact that the midpoint of the range,(V minþV max)/2,occurs in the middle of a code,i.e.,on the tread of the staircase transfer function.The second convention,called the mid-riser convention,is indicated in thefigure by dashed lines at V min,V max,and(V minþV max)/2. In this convention,V min isÀQ from thefirst transition,V max isþQ from the last transition,and the midpoint,(V minþV max)/2,occurs on a staircase riser.The difference between the two conventions is a displacement along the voltage axis by an amount Q/2.For all tests in this standard,this displacement has no effect on the results and either convention may be used.The one place where it does matter is when a device provides or expects user-provided reference signals.In this case the manufacturer must provide the necessary information relating the reference levels to the code transitions.In both conventions the number of code transitions is 2NÀ1and the full-scale range,FSR,is from V min to V max.Even in an ideal ADC,the quantization process produces errors.These errors contribute to the difference between the actual transfer curve and the ideal straight-line transfer curve,which is plotted as a function of the input signal in Figure1b.To use this standard,the user must understand how the transfer function maps its input values to output codewords,and how these output codewords are converted to the code bin numbering convention used in this standard.As shown in Figure1a,the lowest code bin is numbered0, the next is1,and so on up to the highest code bin,numbered(2NÀ1).In addition to unsigned binary(Figure1a),ADCs may use2’s complement,sign-magnitude,Gray,Binary-Coded-Decimal (BCD),or other output coding schemes.In these cases,a simple mapping of the ADC’s consecutive output codes to the unsigned binary codes can be used in applying various tests in this standard.Note that in the case of an ADC whose number of distinct output codes is not an integral power of2(e.g.,a BCD-coded ADC),the number of digitized bits N is still defined,but will not be an integer.Real ADCs have other errors in addition to the nominal quantization error shown in Figure1b.All errors can be divided into the categories of static and dynamic,depending on the rate of change of the input signal at the time of digitization.A slowly varying input can be considered a static signal if its effects are equivalent to those of a constant signal.Static errors,which include the quantization error, usually result from non-ideal spacing of the code transition levels.Dynamic errors occur because of additional sources of error induced by the time variation of the analog signal being sampled.Sources include harmonic distortion from the analog input stages,signal-dependent variations in the time of samples,dynamic effects in internal amplifier and comparator stages,and frequency-dependent variation in the spacing of the quantization levels.1.3Guidance to the user1.3.1InterfacingADCs present unique interfacing challenges,and without careful attention users can experience substandard results.As with all mixed-signal devices,ADCs perform as expected only when the analog and digital domains are brought together in a well-controlled fashion.The user should fully understand the manufacturer’s recommendations with regard to proper signal buffering and loading,input signal connections,transmission line matching,circuit layout patterns,power supply decoupling,and operating conditions.Edge characteristics for start-convert pulse(s)and clock(s)must be carefully chosen to ensure that input signal purity is maintained with sufficient margin up to the analog input pin(s).Most manufacturers now provide excellent ADC evaluation boards,which demonstrate IN P U T IN P U T(a)Figure 1—Staircase ADC transfer function,having full-scale range FSR and 2N À1levels,corresponding to N -bit quantizationIEEE FOR ANALOG-TO-DIGITAL CONVERTERS Std 1241-2000IEEEStd1241-2000IEEE STANDARD FOR TERMINOLOGY AND TEST METHODS recommended layout techniques,signal conditioning,and interfacing for their ADCs.If the characteristics of a new ADC are not well understood,then these boards should be analyzed or used before starting a new layout.1.3.2Test conditionsADC test specifications can be split into two groups:test conditions and test results.Typical examples of the former are:temperature,power supply voltages,clock frequency,and reference voltages. Examples of the latter are:power dissipation,effective number of bits,spurious free dynamic range (SFDR),and integral non-linearity(INL).The test methods defined in this standard describe the measurement of test results for given test conditions.ADC specification sheets will often give allowed ranges for some test condition(e.g.,power supply ranges).This implies that the ADC will function properly and that the test results will fall within their specified ranges for all test conditions within their specified ranges.Since the test condition ranges are generally specified in continuous intervals,they describe an infinite number of possible test conditions,which obviously cannot be exhaustively tested.It is up to the manufacturer or tester of an ADC to determine from design knowledge and/or testing the effect of the test conditions on the test result,and from there to determine the appropriate set of test conditions needed to accurately characterize the range of test results.For example,knowledge of the design may be sufficient to know that the highest power dissipation(test result)will occur at the highest power supply voltage(test condition),so the power dissipation test need be run only at the high end of the supply voltage range to check that the dissipation is within the maximum of its specified range.It is very important that relevant test conditions be stated when presenting test results.1.3.3Test equipmentOne must ensure that the performance of the test equipment used for these tests significantly exceeds the desired performance of the ADC under ers will likely need to include additional signal conditioning in the form offilters and pulse shapers.Accessories such as terminators, attenuators,delay lines,and other such devices are usually needed to match signal levels and to provide signal isolation to avoid corrupting the input stimuli.Quality testing requires following established procedures,most notably those specified in ISO9001: 2000[B18].In particular,traceability of instrumental calibration to a known standard is important. Commonly used test setups are described in4.1.1.1.3.4Test selectionWhen choosing which parameters to measure,one should follow the outline and hints in this clause to develop a procedure that logically and efficiently performs all needed tests on each unique setup. The standard has been designed to facilitate the development of these test procedures.In this standard the discrete Fourier transform(DFT)is used extensively for the extraction of frequency domain parameters because it provides numerous evaluation parameters from a single data record.DFT testing is the most prevalent technique used in the ADC manufacturing community,although the sine-fit test, also described in the standard,provides meaningful data.Nearly every user requires that the ADC should meet or exceed a minimum signal-to-noise-and-distortion ratio(SINAD)limit for the application and that the nonlinearity of the ADC be well understood.Certainly,the extent to whichthis standard is applied will depend upon the application;hence,the procedure should be tailored for each unique characterization plan.1.4Manufacturer-supplied information1.4.1General informationManufacturers shall supply the following general information:a)Model numberb)Physical characteristics:dimensions,packaging,pinoutsc)Power requirementsd)Environmental conditions:Safe operating,non-operating,and specified performance tempera-ture range;altitude limitations;humidity limits,operating and storage;vibration tolerance;and compliance with applicable electromagnetic interference specificationse)Any special or peculiar characteristicsf)Compliance with other specificationsg)Calibration interval,if required by ISO10012-2:1997[B19]h)Control signal characteristicsi)Output signal characteristicsj)Pipeline delay(if any)k)Exceptions to the above parameters where applicable1.4.2Minimum specificationsThe manufacturer shall provide the following specifications(see Clause3for definitions):a)Number of digitized bitsb)Range of allowable sample ratesc)Analog bandwidthd)Input signal full-scale range with nominal reference signal levelse)Input impedancef)Reference signal levels to be appliedg)Supply voltagesh)Supply currents(max,typ)i)Power dissipation(max,typ)1.4.3Additional specificationsa)Gain errorb)Offset errorc)Differential nonlinearityd)Harmonic distortion and spurious responsee)Integral nonlinearityf)Maximum static errorg)Signal-to-noise ratioh)Effective bitsi)Random noisej)Frequency responsek)Settling timel)Transition duration of step response(rise time)m)Slew rate limitn)Overshoot and precursorso)Aperture uncertainty(short-term time-base instability)p)Crosstalkq)Monotonicityr)Hysteresiss)Out-of-range recoveryt)Word error rateu)Common-mode rejection ratiov)Maximum common-mode signal levelw)Differential input impedancex)Intermodulation distortiony)Noise power ratioz)Differential gain and phase1.4.4Critical ADC parametersTable1is presented as a guide for many of the most common ADC applications.The wide range of ADC applications makes a comprehensive listing impossible.This table is intended to be a helpful starting point for users to apply this standard to their particular applications.Table1—Critical ADC parametersTypical applications Critical ADC parameters Performance issuesAudio SINAD,THD Power consumption.Crosstalk and gain matching.Automatic control MonotonicityShort-term settling,long-term stability Transfer function. Crosstalk and gain matching. Temperature stability.Digital oscilloscope/waveform recorder SINAD,ENOBBandwidthOut-of-range recoveryWord error rateSINAD for wide bandwidthamplitude resolution.Low thermal noise for repeatability.Bit error rate.Geophysical THD,SINAD,long-term stability Millihertz response.Image processing DNL,INL,SINAD,ENOBOut-of-range recoveryFull-scale step response DNL for sharp-edge detection. High-resolution at switching rate. Recovery for blooming.Radar and sonar SINAD,IMD,ENOBSFDROut-of-range recovery SINAD and IMD for clutter cancellation and Doppler processing.Spectrum analysis SINAD,ENOBSFDR SINAD and SFDR for high linear dynamic range measurements.Spread spectrum communication SINAD,IMD,ENOBSFDR,NPRNoise-to-distortion ratioIMD for quantization of smallsignals in a strong interferenceenvironment.SFDR for spatialfiltering.NPR for interchannel crosstalk.Telecommunication personal communications SINAD,NPR,SFDR,IMDBit error rateWord error rateWide input bandwidth channel bank.Interchannel crosstalk.Compression.Power consumption.Std1241-2000IEEE STANDARD FOR TERMINOLOGY AND TEST METHODS2.ReferencesThis standard shall be used in conjunction with the following publications.When the following specifications are superseded by an approved revision,the revision shall apply.IEC 60469-2(1987-12),Pulse measurement and analysis,general considerations.1IEEE Std 1057-1994,IEEE Standard for Digitizing Waveform Recorders.23.Definitions and symbolsFor the purposes of this standard,the following terms and definitions apply.The Authoritative Dictionary of IEEE Standards Terms [B15]should be referenced for terms not defined in this clause.3.1Definitions3.1.1AC-coupled analog-to-digital converter:An analog-to-digital converter utilizing a network which passes only the varying ac portion,not the static dc portion,of the analog input signal to the quantizer.3.1.2alternation band:The range of input levels which causes the converter output to alternate between two adjacent codes.A property of some analog-to-digital converters,it is the complement of the hysteresis property.3.1.3analog-to-digital converter (ADC):A device that converts a continuous time signal into a discrete-time discrete-amplitude signal.3.1.4aperture delay:The delay from a threshold crossing of the analog-to-digital converter clock which causes a sample of the analog input to be taken to the center of the aperture for that sample.COMINT ¼communications intelligence DNL ¼differential nonlinearity ENOB ¼effective number of bits ELINT ¼electronic intelligence NPR ¼noise power ratio INL ¼integral nonlinearity DG ¼differential gain errorSIGINT ¼signal intelligenceSINAD ¼signal-to-noise and distortion ratio THD ¼total harmonic distortion IMD ¼intermodulation distortion SFDR ¼spurious free dynamic range DP ¼differential phase errorTable 1—Critical ADC parameters (continued)Typical applicationsCritical ADC parametersPerformance issuesVideoDNL,SINAD,SFDR,DG,DP Differential gain and phase errors.Frequency response.Wideband digital receivers SIGINT,ELINT,COMINTSFDR,IMD SINADLinear dynamic range fordetection of low-level signals in a strong interference environment.Sampling frequency.1IEC publications are available from IEC Sales Department,Case Postale 131,3rue de Varemb,CH 1211,Gen ve 20,Switzerland/Suisse (http://www.iec.ch).IEC publications are also available in the United States from the Sales Department,American National Standards Institute,25W.43rd Street,Fourth Floor,New York,NY 10036,USA ().2IEEE publications are available from the Institute of Electrical and Electronics Engineers,445Hoes Lane,P.O.Box 1331,Piscataway,NJ 08855-1331,USA (/).。
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响应面试验设计的正交方法研究
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Differentiation of Human Pluripotent Stem Cells into Retinal Cells
87M.A. Hayat (ed.), Stem Cells and Cancer Stem Cells, Volume 6,DOI 10.1007/978-94-007-2993-3_9, © Springer Science+Business Media B.V . 20129A bstractRetinal and macular degeneration disorders are characterized by a progressive loss of photoreceptors, which causes visual impairment and blindness. In some cases, the visual loss is caused by dysfunction, degen-eration and loss of underlying retinal pigment epithelial (RPE) cells and the subsequent death of photoreceptors. The grim reality is that there is no successful treatment for most of these blindness disorders. Cell therapy aimed at replenishing the degenerating cells is considered a potential ther-apeutic approach that may delay, halt or perhaps even reverse degenera-tion, as well as improve retinal function and prevent blindness in the aforementioned conditions. Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSCs) may serve as an unlimited donor source of photoreceptors and RPE cells for transplantation into degenerat-ing retinas and for retinal disease modeling.I ntroductionThe vertebrate eyes form as bilateral evaginations of the forebrain, called optic vesicles (Martínez-Morales et al. 2004 ; Fig. 9.1a ). During develop-ment, the optic vesicles begin to invaginate to form a cup-shaped structure, the optic cup. The inner, thicker neural layer of the optic cup differ-entiates into the neural retina, and the outer, thin-ner pigmented layer forms the retinal pigmentepithelium (RPE). At the early developmental stages, the neuroepithelial cells that compose the optic vesicle are morphologically and molecu-larly identical and are all able to give rise to neu-ral retina and RPE. Exogenous signals coming from the adjacent tissues, including factors from the fi broblast growth factor (FGF) and transform-ing growth factor beta (TGF b ) families, dictate the fate of these cells. The mature vertebrate ret-ina is comprised of six types of neurons and one type of glia (the Müller glia). These seven cell types constitute three nuclear layers: retinal gan-glion cells in the ganglion cell layer (GCL); the horizontal, bipolar and amacrine interneurons, and Müller glial cells in the inner nuclear layer (INL); and rod and cone photoreceptors in the outer nuclear layer (ONL; Harada et al. 2007;M . I delson • B . R eubinoff (*)T he Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy & The Department of Obstetrics and Gynecology , H adassah University Medical Center ,E in Kerem 12000 ,J erusalem 91120 ,I srael e -mail: b enjaminr@ekmd.huji.ac.il D ifferentiation of HumanPluripotent Stem Cells into Retinal Cells Masha Idelson and Benjamin Reubinoff88M. Idelson and B. ReubinoffFig. 9.1b ). The photoreceptor cells capture lightphotons and transform their energy into electrical signals by a mechanism called phototransduction. The visual pigment which is utilized in this process is located on membranal discs in the outer seg-ments of photoreceptors. The outer segments are continuously renewed: the old discs are shed and new disks form. When the photoreceptors absorb light, they send the signal through the retinal interneurons to the ganglion cells which transmit the electrical impulse to the brain by their axons forming the optic nerve. Rods are responsible for night vision, whereas cones are responsible for color vision and detecting fi ne details. The macula is a small part of the retina which is rich in cones and responsible for detailed central vision.R PE cells that compose the outer layer of the optic cup are pigmented cuboidal cells which lie between the neural retina and the choriocapil-laris, which include the blood vessels supplying the retina. The multiple villi on their apical side are in direct contact with the outer segments ofextraocular mesenchymeabneural retinalensoptic nerveoptic cupsurface ectodermRPEFGFoptic vesiclechoroidBM RPE cone ONLINL GCLlightHC BC MC ACONrod F ig. 9.1 D evelopment and structural arrangement of the retina. ( a ) Schematic representation of retinal development including the transition from optic vesicle to optic cup and retinal patterning. ( b ) Schematic diagram of retinal cells arrangement and connections. A bbreviations :A C amacrinecell, B C bipolar cell, B M Bruch’s membrane, G CL gan-glion cell layer, H C horizontal cell, I NL inner nuclear layer, M C Müller cell, O N optic nerve, O NL outer nuclear layer89 9 Differentiation of Human Pluripotent Stem Cells into Retinal Cellsthe photoreceptor cells; on their basal side, the RPE is in contact with the underlying basal mem-brane, termed Bruch’s membrane that separates the RPE from the choroid. These cells play cru-cial roles in the maintenance and function of the retina and its photoreceptors. As a layer of pig-mented cells, the RPE absorbs the stray light that was not absorbed by the photoreceptors. The RPE cells form a blood–retinal barrier due to decreased permeability of their junctions. The RPE cells transport ions, water, and metabolic end products from the retina to the bloodstream. They are involved in supplying the neural retina with nutrients from the bloodstream, such as glu-cose, retinol, and fatty acids. Another important function of the RPE is the phagocytosis of shed photoreceptor outer segments. After the outer segments are digested, essential substances such as retinal are recycled. Retinal is also recycled and returned to photoreceptors by the process known as the visual cycle. The precise functioning of the RPE is essential for visual performance. Failure of one of these functions can lead to degeneration of the retinal photoreceptors, vision impairment and blindness.T here are many inherited and age-related eye disorders that cause degeneration of the retina as a consequence of loss of photoreceptor cells. Retinal and macular degeneration disorders can be divided into two main groups. The fi rst group primarily affects the photoreceptors and involves the majority of cases of retinitis pigmentosa. In the second group, the primary damage is to the adjacent RPE cells, and as a consequence of this damage, the photoreceptors degenerate. This group includes age-related macular degeneration, Stargardt’s macular dystrophy, a subtype of Leber’s congenital amaurosis in which RPE65 is mutated, Best’s disease and some cases of retini-tis pigmentosa, as well.W ith regard to retinitis pigmentosa (RP), it is a group of inherited retinal degeneration diseases that are caused, as mentioned above, by a primary progressive loss of rod and cone photoreceptors, followed by a subsequent degeneration of RPE (Hartong et al. 2006). The disease affects approxi-mately 1.5 million patients worldwide and is the most common cause of blindness in people under 70 years of age in the western world. The disease can be characterized by retinal pigment deposits visible on the fundus examination. In most cases, the disease primarily affects rods. At later stages of the disease, the degeneration of cones takes place. As a consequence of disease progression, the patients’ night vision is reduced. Patients initially lose peripheral vision while retaining central vision (a visual status termed “tunnel vision”). In advanced cases, central vision is also lost, commonly at about 60 years of age. The disease affects about 1 in 4,000. The inheritance can be autosomal-recessive, autosomal-dominant or X-linked (in ~50–60%, 30–40%, and 5–15% of cases, respectively). Mutations in more than 140 genes have been iden-tifi ed as causing RP (Hartong et al. 2006).Among these genes are those involved in phototransduc-tion, like rhodopsin, the a- and b- subunits of phos-phodiesterase, the a- and b- subunits of Rod cGMP gated channel and arrestin. The additional muta-tions were found in genes encoding structural pro-teins, like peripherin, rod outer segment protein and fascin. They were also found in transcription factors involved in photoreceptors’ development such as Crx and Nrl, and in other genes, whose products are involved in signaling, cell-cell interac-tion and trafficking of intracellular proteins. Currently, there is no effective cure for RP. Treatment with vitamin A palmitate, omega-3 fatty acids and other nutrients may somewhat slow the rate of the disease progression in many cases. Reduction in exposure to light was also shown to decrease the rate of retinal degeneration.A mong the group of retinal degenerations that are caused by primary loss of RPE cells or their function, age-related macular degeneration (AMD) is the most frequent condition and the leading cause of visual disability in the western world (Cook et al. 2008).Among people over 75 years of age, 25–30% are affected by AMD, with progressive central visual loss that leads to blindness in 6–8%. The retinal degeneration pri-marily involves the macula. The dry form of AMD is initiated by hyperplasia of the RPE and formation of drusen deposits, consisting of meta-bolic end products underneath the RPE or within the Bruch’s membrane. It may gradually progress into the advanced stage of geographic atrophy90M. Idelson and B. Reubinoff with degeneration of RPE and photoreceptorsover large areas of the macula causing central visual loss. Ten percent of dry AMD patients will progress to neovascular (wet) AMD, with blood vessels sprouting through the Bruch’s membrane with subsequent intraocular leakage and/or bleed-ing, accelerating the loss of central vision. While the complicating neovascularization can be treated with anti-VEGF agents, currently there is no effective treatment to halt RPE and photore-ceptor degeneration and the grim reality is that many patients eventually lose their sight (Cook et al. 2008).S targardt’s macular dystrophy (SMD) is the most common form of inherited macular dystro-phy affecting children (Walia and Fishman 2009). The disease is symptomatically similar to AMD. The prevalence of SMD is about 1 in 10,000 chil-dren. The disease involves progressive central visual loss and atrophy of the RPE beneath the macula following accumulation of lipofuscin in RPE cells, which is suggested to consist of non-degradable material, derived from ingested pho-toreceptor outer segments. The inheritance is predominantly autosomal recessive, although an autosomal dominant form has also been described. The mutation in the ABCA4 gene was found to be a most common cause of SMD. The product of the ABCA4 gene is involved in energy transport to and from photoreceptors. The mutated protein cannot perform its transport function and, as a result, photoreceptor cells degenerate and vision is impaired. Currently, there is no effective treat-ment for SMD.C ell therapy to replenish the degenerating cells appears as a promising therapeutic modality that may potentially halt disease progression in the various retinal and macular degeneration dis-orders caused by loss and dysfunction of RPE cells and photoreceptors (da Cruz et al. 2007).I n this chapter we will discuss the potential of human pluripotent cells which includes human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSCs), to gen-erate various types of retinal cells that could be used for transplantation therapy of retinal degen-eration disorders and disease modeling for drug discovery. C ell Therapy of Retinal and Macular DegenerationsT he eye is an attractive organ for cell therapy as it is easily accessible for transplantation and for simple monitoring of graft survival and potential complications by direct fundoscopic visualiza-tion. Anatomically, it is a relatively confi ned organ limiting the potential of unwanted extra-ocular ectopic cell distribution, and a low number of cells are required to replenish the damaged cells. The eye is also one of the immune privi-leged sites of the body.T he concept of replacing dysfunctional or degenerated retina by transplantation has been developing ever since the fi rst retina-to-retina transplant in 1986 (Turner and Blair 1986).In most studies, primary retinal immature (fetal) tissue has been used as donor material. It was demonstrated that such transplants can survive, differentiate, and even establish connections with the host retina to a limited degree (Ghosh et al. 1999). The subretinal transplantation of healthy RPE has some advantages over neural retinal transplantation, as it concerns only one cell type that is not involved in neural networking. Transplantation of RPE has been studied exten-sively in animal models (Lund et al. 2001).The most commonly used animal model of retinal degeneration is the Royal College of Surgeons (RCS) rat model, in which primary dysfunction of the RPE occurs as a result of a mutation in the receptor tyrosine kinase gene M ertk(D’Cruz et al. 2000). This leads to impaired phagocytosis of shed photoreceptor outer segments, with sec-ondary degeneration and progressive loss of pho-toreceptors within the fi rst months of life. It was reported that rat and human RPE cells rescued photoreceptor cells from degeneration when transplanted into the subretinal space of RCS rats (Li and Turner 1988; Coffey et al. 2002).The ability of transplanted RPE cells to restore retinal structure and function has been demonstrated in clinical trials. In humans, autologous transplanta-tions of peripheral RPE as well as macular trans-locations onto more peripheral RPE provide a proof that positioning the macula above relatively91 9 Differentiation of Human Pluripotent Stem Cells into Retinal Cellshealthier RPE cells can improve visual functionin AMD patients (Binder et al. 2004; da Cruz et al. 2007). Nevertheless, the surgical procedures for autologous grafting are challenging and are often accompanied by signifi cant complications. In addition, autologous RPE transplants may carry the same genetic background, environmen-tal toxic and aging-related effects that may have led to macular RPE failure and the development of AMD in the patient. It is also problematic to use autologous cells when all the RPE cells are damaged. Cell sources that can be used for such therapy include allogeneic fetal and adult RPE (Weisz et al. 1999; Binder et al. 2004; da Cruz et al. 2007). However, the use of fetal or adult retinal tissues for transplantation is severely lim-ited by ethical considerations and practical prob-lems in obtaining sufficient tissue supply. The search for a cell source to replace autologous RPE such as immortalized cell lines, umbilical cord-derived cells as well as bone marrow-derived stem cells continues.T he derivation of hESCs more than a decade ago has raised immense interest in the potential clinical use of the cells for regeneration (Thomson et al. 1998; Reubinoff et al. 2000).Along the years, signifi cant progress has been made towards the use of hESCs in clinical trials.T he other promising source of cells for transplantation therapy is iPSCs that are simi-lar to hESCs in their stemness characteristics and pluripotency. These cells could be gener-ated from different human somatic cells by transduction of four defi ned transcription fac-tors: Oct3/4, Sox2, Klf4, and c-Myc (Takahashi et al. 2007).G eneration of RPE and neural retina from hESCs and iPSC has numerous advantages, as it can be done from pathogen-free cell lines under good manufacturing practice (GMP) conditions with minimal variation among batches. Such cells can be characterized extensively prior to preclinical studies or for clinical applications, and an unlimited numbers of donor cells can be generated from them. In the following para-graphs, strategies for induction of differentiation of hESCs and iPSCs towards RPE and neural retina fate are reviewed. D ifferentiation into Retinal Pigment EpitheliumI t was reported for the fi rst time in mice and pri-mates that the differentiation of ES cells into RPE could be induced by co-culture with PA6 stromal cells (Kawasaki et al. 2002; Haruta et al. 2004). The resulting cells had polygonal epithelial mor-phology and extensive pigmentation. The cells expressed the markers that are characteristic of RPE. They developed typical ultrastructures and exhibited some functions of RPE. The differenti-ation of hESC into RPE was first reported by Klimanskaya et al. (2004).According to their protocol, hESCs underwent spontaneous differ-entiation by overgrowth on mouse embryonic fibroblasts (MEF), in feeder-free conditions or, alternatively, as embryoid bodies (EBs) in com-bination with withdrawal of bFGF from the medium. The yield of the formation of RPE cells after 4–8 weeks of spontaneous differentiation was relatively low; for example,<1% of EBs con-tained pigmented cells at this stage. However, after 6–9 months in culture, all the EBs contained pigmented cells. The areas of pigmented cells could be further isolated mechanically and prop-agated by passaging as RPE lines. Klimanskaya and colleges characterized the hESC-derived RPE cells by transcriptomics and demonstrated their higher similarity to primary RPE tissue than to human RPE lines D407 and ARPE-19. The low yield of spontaneously differentiating RPE cells was improved by induction of differentia-tion with Wnt and Nodal antagonists, Dkk1 and LeftyA, respectively, the factors that are sug-gested to promote retinal differentiation. This treatment gave rise to pigmented cells within 38% of the hESC colonies after 8 weeks (Osakada et al. 2008). Immunostaining with the ZO-1 anti-body showed that by day 120, hESC-derived pig-mented cells formed tight junctions (about 35% of total cells). We showed that differentiation toward the neural and further toward the RPE fate could be augmented by vitamin B3 (nicotin-amide; Idelson et al. 2009).We further showed that Activin A, in the presence of nicotinamide, effi ciently induces and augments differentiation92M. Idelson and B. Reubinoffinto RPE cells. This is in line with the presumed role of Activin A in RPE development i n vivo .In the embryo, extraocular mesenchyme-secreted members of the TGF b superfamily are thought to direct the differentiation of the optic vesicle into RPE (Fuhrmann et al. 2000).Under our culture conditions, when the cells were grown in suspen-sion as free-fl oating clusters, within 4 weeks of differentiation, 51% of the clusters contained pigmented areas and about 10% of the cells within the clusters were pigmented. When we modifi ed the differentiation conditions to includea stage of monolayer culture growth, the yield of the RPE-like pigmented cells was signifi cantly improved and 33% of the cells were pigmented after 6 weeks of differentiation. The derivation of RPE from hESCs and iPSCs without any external factor supplementation was also demonstrated by other groups (Vugler et al. 2008 ; Meyer et al. 2009 ; Buchholz et al. 2009).T he hESC-derived RPE cells were extensively characterized, including demonstration, both at the mRNA and the protein levels, of the expres-sion of RPE-specifi c markers, such as RPE65, CRALBP, Bestrophin, Tyrosinase, PEDF, PMEL17, LRAT, isoforms of MiTF abundant in RPE, and others. The cells expressed markers of tight junctions that join the adjacent RPE cells: ZO-1, occludin and claudin-1 (Vugler et al. 2008 ) . Electron microscopic analysis revealed that the hESC-derived RPE cells showed features characteristic of RPE. The cells were highly polarized with the nuclei located more basally, and the cytoplasm with the mitochondria and melanin granules of different maturity more api-cally. A formation of basal membrane was observed on the basal surface of the RPE cell. Similar to putative RPE, the hESC-derived RPE basal membrane was shown to be composed of extracellular matrix proteins, collagen IV , lami-nin and fi bronectin (Vugler et al.2008).The appearance of apical microvilli was demonstrated at the apical surface of the RPE. The presence of tight and gap junctions on the apical borders of the RPE cells was also confi rmed by electron microscopy. O ne of the most important functions of RPE cells i n vivo is phagocytosis of shed photoreceptor outer segments, as part of the continuous renewal process of rods and cones. The hESC-derived RPE cells demonstrated the ability to phagocyto-size latex beads or purifi ed photoreceptor outer segments, confi rming that these cells are func-tionali n vitro . It may be concluded from all these studies that human pluripotent stem cells have a potential to give rise to pigmented cells exhibiting the morphology, marker expression and functionof authentic RPE.D ifferentiation into Retinal Progenitors and Photoreceptors O ur group showed, for the fi rst time, the potential of highly enriched cultures of hESC-derived neu-ral precursors (NPs) to differentiate towards the neural retina fate (Banin et al. 2006).We demon-strated that the NPs expressed transcripts of key regulatory genes of anterior brain and retinal development. After spontaneous differentiation i n vitro , the NPs gave rise to progeny expressing markers of retinal progenitors and photoreceptor development, though this was uncommon and cells expressing markers of mature photorecep-tors were not observed. We showed that after transplantation into rat eyes, differentiation into cells expressing specifi c markers of mature photoreceptors occurred only after subretinal transplantation (between the host RPE and pho-toreceptor layer) suggesting that this specifi c microenvironment provided signals, yet unde-fi ned, that were required to support differentia-tion into the photoreceptoral lineage.P rogress towards controlling and inducing the differentiation of hESCs into retinal progenitors and neurons i n vitro was reported in the study of Lamba et al. ( 2006).They treated hESC-derived EBs for 3 days with a combination of factors,including Noggin, an inhibitor of BMP signaling, Dkk1, a secreted antagonist of the Wnt signaling pathway and insulin-like growth factor 1 (IGF-1), which is known to promote retinal progenitor dif-ferentiation. The cultivation of EBs with these factors was followed by differentiation on Matrigel or laminin for an additional 3 weeks in the presence of the combination of the three93 9 Differentiation of Human Pluripotent Stem Cells into Retinal Cellsfactors together with bFGF. Under these culture conditions, the majority of the cells developed the characteristics of retinal progenitors and expressed the specifi c markers Pax6 and Chx10 (82% and 86% of the cells, respectively). The authors showed that after further differentiation, the cells expressed markers of photoreceptor development Crx and Nrl (12% and 5.75%, respectively). About 12% of the cells expressed also HuC/D, the marker of amacrine and ganglion cells. The expression of markers of the other sub-types of retinal neurons was demonstrated, as well. However, only very few cells (<0.01%) expressed markers of mature photoreceptors, blue opsin and rhodopsin. The abundance of cells expressing markers of photoreceptors could be accelerated by co-culture with retinal explants, especially when the explants originated from mice bearing a mutation that causes retinal degeneration.T o better characterize the phenotype of retinal cells obtained with this differentiation protocol, a microarray-based analysis comparing human retina to the hESC-derived retinal cells was per-formed (Lamba and Reh 2011).It was demon-strated that gene expression in hESC-derived retinal cells was highly correlated to that in the human fetal retina. In addition, 1% of the genes that were highly expressed in the hESC-derived cultures could be attributed to RPE and ciliary epithelium differentiation.A n alternative protocol for the derivation of retinal progenitors and photoreceptors was pro-posed by Osakada et al. (2008).Similar to the protocol for the derivation of RPE cells, they used serum-free fl oating cultures in combination with the Dkk1 and LeftyA. After 20 days of cul-ture in suspension, the cells were replated on poly-D-lysine/laminin/fi bronectin-coated slides. Osakada and co-authors demonstrated that on day 35 in culture, about 16% of colonies were positive for retinal progenitor markers Rx and Pax6. Differentiation towards photoreceptor fate was augmented in the presence of N2 by treat-ment with retinoic acid and taurine, which are known inducers of rod fate differentiation. Under these conditions, after an extended culture period of 170 days, about 20% of total cells were positive for Crx, an early photoreceptor marker. On day 200, about 8.5% of the cells expressed the mature rod photoreceptor marker, rhodopsin, as well as cone photoreceptor markers, red/green and blue opsins (8.9% and 9.4%, respectively).A n alternative approach was proposed by the same group based on the use of small molecules. In this method, the chemical inhibitors CKI-7 and SB-431542 that inhibit Wnt and Activin A signaling, respectively, and Y-27632, the Rho-associated kinase inhibitor, which prevents disso-ciation-induced cell death, were used. These molecules were shown to mimic the effects of Dkk1 and LeftyA (Osakada et al. 2009).This strategy, which doesn’t involve the use of recom-binant proteins which are produced in animal or E scherichia coli cells, is more favorable for the gen-eration of cells for future transplantation therapy.I n another study that was published by Meyer et al .(2009), after initial differentiation in sus-pension for 6 days, the aggregates were allowed to attach to laminin–coated culture dishes. After further differentiation as adherent cultures, neu-roepithelial rosettes were formed, which were mechanically isolated and subsequently culti-vated as neurospheres. The authors didn’t use any soluble factors; moreover, they showed that under these conditions, the cells expressed endogenous Dkk1 and Noggin. They also demonstrated that in concordance with the role of bFGF in retinal specifi cation, the inhibition of endogenous FGF-signaling abolished retinal differentiation. Under their differentiation protocol, by day 16, more than 95% of the cells expressed the retinal pro-genitor markers, Pax6 and Rx. The authors dem-onstrated that by day 80 of differentiation, about 19% of all neurospheres contained Crx+ cells and within these Crx+ neurospheres, 63% of all cells express Crx and 46.4% of the cells expressed mature markers, such as recoverin and cone opsin.I n all of the above studies, differentiated cells expressing the retinal markers were obtained; however, the cells were not organized in a three-dimensional retinal structure. In a paper recently published by Eiraku et al. (2011),the authors cul-tured free-fl oating aggregates of mouse ES cells in serum-free medium in the presence of base-ment membrane matrix, Matrigel, that could also94M. Idelson and B. Reubinoffbe substituted with a combination of laminin, entactine and Nodal. Using a mouse reporter ES cell line, in which green fl uorescent protein (GFP) is knocked in at the Rx locus, the authors showed that Rx-GFP+ epithelial vesicles were evaginated from the aggregates after 7 days of differentiation under these conditions. On days 8–10, the Rx-GFP+ vesicles changed their shape and formed optic cup-like structures. The inner layer of these structures expressed markers of the neural retina whereas the outer layer expressed markers of RPE. The authors demonstrated that differen-tiation into RPE required the presence of the adjacent neuroectodermal epithelium as a source of diffusible inducing factors. In contrast, the differentiation into neural retina did not require tissue interactions, possibly because of the intrinsic inhibition of the Wnt-signaling pathway. Eiraku and colleagues showed that the retinal architecture, which was formed within the optic vesicle-like structures, was comparable to the native developing neural retina.R ecently, optic vesicle-like structures were also derived from hESCs and iPSCs using the protocol described above, which is based on iso-lating the neural rosette-containing colonies and culturing them in suspension (Meyer et al. 2011). The cells within the structures expressed the markers of retinal progenitors, and after differen-tiation gave rise to different retinal cell types. It was shown that the ability of optic vesicle-like structures to adopt RPE fate could be modulated by Activin A supplementation. The production of these three-dimensional retinal structures opens new avenues for studying retinal development in normal and pathological conditions.T ransplantation of Pluripotent Stem Cell-Derived Retinal CellsA key step towards future clinical transplanta-tions of hESC-derived RPE and neural retina is to show proof of their therapeutic potential i n vivo. Various animal models of retinal degeneration have been used to evaluate the therapeutic effect of transplanted retinal cells. Human ESC-derived RPE cells were transplanted subretinally to the degenerated eyes of RCS rats. Transplantation of the hESC-derived RPE cells between the RPE and the photoreceptor layer rescued retinal struc-ture and function (Lund et al. 2006; Vugler et al. 2008; Idelson et al. 2009; Lu et al. 2009).The subretinally engrafted hESC-derived RPE cells salvaged photoreceptors in proximity to the grafts as was shown by the measurement of the thick-ness of the ONL, the layer of photoreceptor nuclei, which is an important monitor of photore-ceptor cell survival. The ONL thickness was significantly increased in transplanted eyes in comparison to the degenerated non-treated eyes.I n order to evaluate the functional effect of transplanted cells i n vivo, the electroretinography (ERG) that directly measures the electrical activ-ity of the outer (a-wave) and inner (b-wave) retina in response to light stimulation was used. It was demonstrated that after transplantation of hESC-derived RPE, ERG recordings revealed a signifi -cant preservation of retinal function in the treated eyes as compared to control untreated eyes (Lund et al. 2006; Idelson et al. 2009).The visual func-tion of the animals was also estimated by an optomotor test, which monitors the animal’s refl exive head movements in response to a rotat-ing drum with fi xed stripes. Animals transplanted with hESC-derived RPE showed signifi cantly better visual performance in comparison to con-trol animals (Lund et al. 2006; Lu et al. 2009). The presence of rhodopsin, a major component of photoreceptor outer segments, within the sub-retinaly transplanted pigmented cells suggested that they could perform phagocytosis i n vivo (Vugler et al. 2008; Idelson et al. 2009).B ridging the gap between basic research and initial clinical trials requires immense resources to ensure safety and efficacy. Human ESC-derived RPE cell lines were generated using a current Good Manufacturing Practices (cGMP)-compliant cellular manufacturing process (Lu et al. 2009). Long-term studies analyzing safety and efficacy of transplantation of these GMP-compliant hESC-derived RPE cells revealed that the subretinally transplanted cells survived for a period of up to 220 days and provided prolonged functional improvement for up to 70 days after transplantation. The potential of the hESC-derived。
Mitsubishi Electric GT25系列机器人控制器产品说明书
GT25 SeriesNotes:1. The operating ambient temperature includes the temperature inside the enclosure of the control panel to which the GOT is installed.2. • (GT27, GT25) When any of the following units is mounted, the maximum operating ambient temperature must be 5 °C lower than the one described in the general specifications: multimedia unit(GT27-MMR-Z), MELSECNET/H communication unit (GT15-J71LP23-25, GT15-J71BR13), CC-Link communication unit (GT15-J61BT13) • (GT21) If the ambient temperature exceeds 40°C, the absolute humidity must not exceed 90% RH at 40 °C.3. Do not use or store the GOT under a pressure higher than the atmospheric pressure at altitude 0 m. Doing so may cause a malfunction. Air purging by applying pressure to the control panel may createclearance between the surface sheet and the touch panel. This may cause the touch panel to be not sensitive enough or the sheet to come off.4. This indicates the section of the power supply to which the equipment is assumed to be connected between the public electrical power distribution network and the machinery within the premises. CategoryII applies to equipment that is supplied with power from fixed facilities. The withstand surge voltage for the equipment with the rated voltage up to 300 V is 2500 V.5. This indicates the occurrence rate of conductive material in an environment where a device is used. Pollution degree 2 indicates an environment where only non-conductive pollution occurs normally and atemporary conductivity caused by condensation shall be expected depending on the conditions.6. (GT25, GT27 only) Some models have ANSI/ISA 12.12.01 approval for use in Class I, Division 2 (ANSI/ISA 12.12.01, C22.2 No.213-M1987) hazardous locations. For the details, please contact your localsales office.7. 5 VDC type does not require grounding.8. Communication units and options usable with the rugged model can be used in the environment described in the general specifications of the rugged model. For using peripheral devices to be connected tothe GOT, refer to the manual of each device.GOT2000 Series General Specificationsn H U M A N M A C H I N E I N T E R F A C E SGT25 Power Supply Specificationsdoing so may damage or soil the GOT or cause foreign matter to enter the GOT, resulting in a failure or malfunction+2B +2 0(0.08)(0.08)(0)(unit: mm)GT25 Panel Cut Dimensionsn H U M A N M A C H I N E I N T E R F A C E SGT25 Performance SpecificationsNotes:1. As a characteristic of liquid crystal display panels, bright dots (always lit) and dark dots (never lit) may appear on the panel. Since liquid crystal display panels comprise a great number of display elements, the appearance of bright and dark dots cannot be reduced to zero. Individual differences in liquid crystal display panels may cause differences in color, uneven brightness and flickering. Note that these phenomena are characteristics of liquid crystal display panels and it does not mean the products are defective or damaged.2. Flickering may occur due to vibration, shock, or the display colors.3. When a stylus is used, the touch panel has a life of 100 thousand touches. The stylus must satisfy the following specifications: • Material: polyacetal resin • Tip radius: 0.8 mm or more4. To prevent the display section from burning in and lengthen the backlight life, enable the screen save function and turn off the backlight.5. If you touch two points or more simultaneously on the touch panel, a touch switch near the touched points may operate unexpectedly. Do not touch two points or more simultaneously on the touch panel.6. To conform to IP67F, close the USB environmental protection cover by pushing the [PUSH] mark firmly. (To conform to IP2X, open the USB environmental protection cover.) Note that the structure does not guarantee protection in all users’ environments. The GOT may not be used in certain environments where it is subjected to splashing oil or chemicals for a long period of time or soaked in oil mist.7. To conform to IP67F attach the environmental protection sheet. Note that the structure does not guarantee protection in all users’ environments. The GOT may not be used in certain environments where it is subjected to splashing oil or chemicals for a long period of time or soaked in oil mist.8. The minimum size of a key that can be arranged. To ensure safe use of the product, the following settings are recommended: • Key size: 16 x 16 dots or larger • Distance between keys: 16 dots or more 9. The suffix “F” of IP67F is a symbol that indicates protection rate against oil. It is described in the Appendix of Japanese Industrial Standard JIS C 0920.Notes:1. As a characteristic of liquid crystal display panels, bright dots (always lit) and dark dots (never lit) may appear on the panel. Since liquid crystal display panels comprise a great number of display elements, theappearance of bright and dark dots cannot be reduced to zero. Individual differences in liquid crystal display panels may cause differences in color, uneven brightness and flickering. Note that these phenomena are characteristics of liquid crystal display panels and it does not mean the products are defective or damaged.2. Flickering may occur due to vibration, shock, or the display colors.3. When a stylus is used, the touch panel has a life of 100 thousand touches. The stylus must satisfy the following specifications: • Material: polyacetal resin • Tip radius: 0.8 mm or more4. To prevent the display section from burning in and lengthen the backlight life, enable the screen save function and turn off the backlight.5. If you touch two points or more simultaneously on the touch panel, a touch switch near the touched points may operate unexpectedly. Do not touch two points or more simultaneously on the touch panel.6. To conform to IP67F, close the USB environmental protection cover by pushing the [PUSH] mark firmly. (To conform to IP2X, open the USB environmental protection cover.) Note that the structure does notguarantee protection in all users’ environments. The GOT may not be used in certain environments where it is subjected to splashing oil or chemicals for a long period of time or soaked in oil mist.7. To conform to IP67F attach the environmental protection sheet. Note that the structure does not guarantee protection in all users’ environments. The GOT may not be used in certain environments where it issubjected to splashing oil or chemicals for a long period of time or soaked in oil mist.8. The minimum size of a key that can be arranged. To ensure safe use of the product, the following settings are recommended: • Key size: 16 x 16 dots or larger • Distance between keys: 16 dots or more9. The suffix “F” of IP67F is a symbol that indicates protection rate against oil. It is described in the Appendix of Japanese Industrial Standard JIS C 0920.。
ThuThesis：清华大学学位论文模板
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发的《研究生学位论文写作指南》，清华大学《编写“清华大学博士后研究报告”参考意见》编 写而成，旨在供清华大学毕业生撰写学位论文使用。 3. 清华大学教务处和研究生院只提供毕业论文写作指南，不提供官方模板，也不会授权第三方 模板为官方模板，所以此模板仅为写作指南的参考实现，不保证格式审查老师不提意见。任 何由于使用本模板而引起的论文格式审查问题均与本模板作者无关。 4. 任何个人或组织以本模板为基础进行修改、扩展而生成的新的专用模板，请严格遵守 LATEX Project Public License 协议。由于违犯协议而引起的任何纠纷争端均与本模板作者无关。
∗Tsinghua University LATEX Thesis Template. †LittleLeo@newsmth ‡目前于电子科技大学工作。 版本：5.0 时间: 2015/12/24
目录
目录
目录
1 模板介绍
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2 安装
3
2.1 下载 . . . . . . . . . . . . . . . 3
5.5.11 封面和封底 . . . . . . . 34
5.5.12 摘要格式 . . . . . . . . 43
5.5.13 主要符号表 . . . . . . . 44
5.5.14 致谢以及声明 . . . . . . 45
Weak lensing study of dark matter filaments and application to the binary cluster A 222 and
Send offprint requests to: J. P. Dietrich, e-mail: dietrich@astro.uni-bonn.de ⋆ Based on observations made at ESO/La Silla under program Nos. 064.L-0248, 064.O-0248, 66.A-0165, 68.A-0269.
shows evidence for a possible dark matter filament connecting both clusters. The case for a filamentary connection between A 222/223 is supported by an analysis of the galaxy density and X-ray emission between the clusters. Using the results of N -body simulations, we try to develop a criterion that separates this system into cluster and filament regions. The aim is to find a technique that allows the quantification of the significance of (weak lensing) filament candidates in close pairs of clusters. While this mostly fails, the aperture quadrupole statistics (Schneider & Bartelmann 1997) shows some promise in this area. The cluster masses determined from weak lensing in this system are considerably lower than those previously determined from spectroscopic and X-ray observations (Dietrich et al. 2002; Proust et al. 2000; David et al. 1999). Additionally, we report the serendipitous weak lensing detection of a previously unknown cluster in the field of this double cluster system.
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Student Name
Candidate
Graduate Unit (Department)
Department
This thesis is approved, and it is acceptable in quality and form for publication:
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MANUSCRIPT TITLE
The University of New Mexico
Albuquerque, New Mexico
Last Month of Graduation Semester, Year
DEDICATION
In memoria di mio nonno,--------, e per la mia cara nonna,-------. Vita bella.
iii
ACKNOWLEDGMENTS
I heartily acknowledge -----------, my advisor and dissertation chair, for continuing to encourage me through the years of classroom teachings and the long number of months writing and rewriting these chapters. Her guidance and professional style will remain with me as I continue my career.
(Note: This page is optional.)
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TITLE
by
Student Name
reliability for the concept map measure was high. There was a positive, moderate correlation between concept map posttest scores and multiple-choice posttest scores.
v
TABLE OF CONTENTS
LIST OF FIGURES (xiii)
LIST OF TABLES (xiv)
CHAPTER 1 INTRODUCTION (1)
Description of Concept Maps (3)
32
CHAPTER 4 RESULTS (39)
Analysis of Ethnicity, Administration Order, Time, and Their Interactions
on Concept Map Test Scores (39)
Trainee Comments (51)
vi
CHAPTER 5 DISCUSSION (54)
Summary (54)
Methodology (54)
Results (55)
Discussion of the Results (56)
Limitations of the Study (61)
vii
LIST OF FIGURES
Figure 1. Eight content areas of Hazardous Waste Operations and Emergency Response derived from the course material (31)
viii
LIST OF TABLES
Table 1. Concept Rating Scale (31)
Table 2. Trainees with Missing Data (36)
Table 3. Sample Size by Gender and Ethnicity (36)
Table 4. Cell Characteristics for Concept Map Scores (42)
ix
Chapter 1
Introduction
(The text begins on this page)
1
References
Acton, W. H., Johnson, P. J., & Goldsmith, T. E. (1994). Structural knowledge assessment: Comparison of referent structures. Journal of Educational Psychology, 86, 303-311.
American Society of Training and Development (ASTD) (July, 1990). Evaluation
design instruction and assessment. Research in Science and Technological Education, 10, 39-52.
100。