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郵票的知識范文1

看著看著，我仿佛置身于這美麗的景色之中，湛藍清澈誰愿意當我的鏡子，綠樹紅花對我點頭微笑……

地球——我們唯一的家園。看，藍天白云漂浮在它的軀體上，綠樹愿意做它的麗裝……是他們，是它們支撐著地球。

有這樣一句名言“當人類砍倒第一棵大樹的時候，便宣告文明的開始；當人類砍倒最后一棵大樹的時候，便宣告文明的結束。”從前，地球擁有大片大片的樹林，水是清澈見底的，空氣清新，動物和人類是很要好的朋友。每天，他們一起勞動，一起生產，生活過得幸福美滿。地球非常高興，她愿意把自己的資源奉獻給生活在自己身上的兒女。可是，人類很不知足，竟濫用地球上的資源，甚至還傷害了自己的朋友——動物。人類的行為令地球母親拉長了臉。人類還不知道自己的錯誤，為了滿足自己，濫殺生靈，亂砍濫伐，使用東西毫無節制，終于造成了一系列的嚴重后果。這次，地球母親流下了眼淚，她的眼淚是酸的，她要懲罰人類。

人類終于意識到了自己的過錯，可是，要拯救地球并不是一朝一夕的事情，因此，人類發出了拯救地球的呼聲。不是嗎？我們使“人”變成“從”，又變成“眾”；使“森”變成“林”，又變成“木”。地球上的人越來越多，樹木卻越來越少，資源越來越短缺。

如果我們還不重視環境的保護，如果我們還不提高警覺，也許地球上最后的生物就是我們，最后一滴水就是我們的眼淚。因此我們要十分愛惜子孫萬代賴以生存的自然環境。讓我們從平凡做起，從點滴做起，從自我做起，節約社會資源，愛護自然環境，讓我們的家園更加美好，讓我們的地球充滿醉人的綠，讓那充滿生機的，可愛的綠色種子在全世界人民的心靈上扎下永久的根。

郵票的知識范文2

關鍵詞：均值漂移聚類；自動識別；油罐識別

中圖分類號：TP311文獻標識碼：A文章編號：1009-3044(2011)17-4155-03

A Mean Shift Clustering Method for Oil Tank Recognition

WANG Lei-guang1, ZHENG Chen2, DAI Qin-ling3

(1.School of Forestry, Southwest Forestry University, Kunming 650224, China;2.School of Mathematics and Statistics, Wuhan University, Wuhan 430072,China;3.Faculty of Wood Science & Decoration Engineering, Southwest Forestry University, Kunming 650224, China)

Abstract: It has great significance for the military application to detect oil storage tanks and locate oil depots automatically from remote sensing images. Considering high computation complexity of traditional methods, an recognition algorithm based on mean shift clustering is presented, in which the spectral characteristics and spatial distribution of the oil tank is considering. Firstly, a multilevel hierarchical representation of image is established by using the mean shift segmentation approach to get segments in the finest scale and iteratively merging. At the same time, oil tanks in every scale are detected by evaluating shape features after every merging. The experimental results with several remote sensing images indicate that this method has high recognition precision, meanwhile, low time complexity.

Key words: mean shift clustering; convergence; automatic recognition; oil tank recognition

油罐等類圓形目標的識別是遙感影像軍事目標識別的研究熱點之一[1-2]。一般而言，霍夫變換（Hough Transform ,HT）是檢測圓形目標最直觀的選擇[3-4]。然而，HT較高的時間和空間復雜度是其在具有海量特征的遙感影像處理中應用的瓶頸。考慮到油罐目標在高分辨率遙感影像中體現出較強的光譜同質性和分布密集型，可將油罐目標識別可視為聚類問題。油罐目標識別相當于空間位置上鄰接、光譜同質性佳的像素的聚類問題。（Mean Shift，MS）算法是一種非參數的迭代聚類算法[5-6]，不需要事先指定聚類中心數目，也不需要對樣本服從的分布做任何假設，可勝任任何特征空間的分析的場合。另外，由于迭代過程中樣本點之間相互獨立，可并行運算，因此適合海量遙感數據的處理。基于MS算法，本文提出了一種基于多層次區域合并的識別算法。首先，算法基于空間位置和灰度值特征的MS聚類[5]建立影像的多尺度表達；然后，通過在多個分割尺度上檢測區域與圓形的接近程度，獲得不同大小的油罐對應的區域。

本文的章節安排如下：第二部分將給出均值漂移聚類算法的數學描述；第三部分將給出基于多尺度分析的識別算法的詳細描述；第四部分為相關實驗與分析；最后給出實驗結論。

1 均值漂移聚類算法

MS過程是一種基于非參數概率密度梯度估計的迭代過程，由Cheng[6]首先提出，由Peter等人[5]進一步發展，并將其應用到特征聚類、影像濾波、分割及視頻跟蹤等領域。

MS向量mh,g(x)定義為[6]：

(1)

其中，x是d維的歐氏特征空間中的列向量；g(x)是核函數G(x)的剖面函數；

公式(1)表明，均值漂移向量是落入x的帶寬h鄰域內的所有樣本的加權平均與中心樣本x的差值。其中，帶寬h的大小決定了參與分析的特征空間的鄰域范圍，合適的帶寬參數可以更好的刻畫樣本點局部區域的空間結構性質[7]。依據公式(1)所示的MS向量，有如下MS迭代公式：

(2)

將上述迭代過程獲得序列記為{yj}j-1,2,…，對應的概率密度估計序列記為{k(yj)}j=1,2…，簡寫為{k(j)}j=1,2…。通過均值漂移迭代過程，每個樣本點均與局部概率的峰值聯系起來，進而實現特征空間的聚類。通過定義不同的特征可滿足不同的應用。

2 油罐識別算法

2.1 檢測步驟

提出的油罐識別和詳細流程如圖 1所示，算法步驟具體如下：1.依據油罐目標的尺度范圍及影像的分辨率，確定反映分割尺度的面積序列等參數。2.采用MS聚類分割算法生成初始分割區域。3.統計區域的圓形度等反映油罐目標形狀特性的特征；4.將滿足區域形狀約束條件的區域標記為油罐目標。5.更新面積參數，將小于當前面積的未識別區域進行合并。6.重復步驟3-6，直到遍歷所有尺度參數。綜合所有尺度上獲得的對象即為油罐目標。

在上述步驟2中應用的MS分割算法[5]，特征空間由2維的空間坐標xs和p維（p為波段數）的光譜特征聯合組成xr，每個像素點對應一個p+2維的向量x=(xs,xr)。核函數被定義為乘積形式（式(3)）:

(3)

其中：hs和hr分別為空域和光譜域的帶寬；C為個歸一化常數；g1(x)和g2(x)是坐標特征和光譜特征對應的核函數。在濾波算法的基礎上，將收斂到相近模態的像素樣本均歸為同類，當每一類的像素個數均大于指定閾值時終止區域合并，即可獲得區域分割結果。在該MS分割中，過大的帶寬往往導致影像過度平滑，較小尺度上的目標和背景無法區分[7]。因此，在本文的實驗中，為保留油罐目標的真實邊界，對于全色影像和多光譜影像，光譜特征域帶寬hr分別取4和 6.5，位置特征帶寬hs均取為6。

2.2 油罐識別

在遙感影像中，油罐有顯著的光譜和區域特征。油罐多呈圓形，光譜特征和背景地物有較大的光譜差別，而油罐區域內部光譜變化小。因此，可通過區域形狀特征來實現油罐的識別。常用的形狀參數度量指標有圓形度、體態比、矩形度等[2]。本文采用矩形度和其二階矩橢圓的長短軸比特征來度量區域的形狀信息。采用矩形度是考慮到區域的面積和外接矩形的面積在遍歷分割圖像獲得區域標記的同時就可以獲得，不需要額外的時間開銷。考慮到數字圖像中的離散誤差，圓形區域和矩形區域的矩形度較為接近，單一指標往往不能獲得良好的結果，故加入短長軸特征。

矩形度度量了區域的形狀與其外接矩形接近的程度，其計算公式如下：

Rule1=Arng/Abox (4)

其中，Arng，Abox分別表示區域的面積、以及區域最小外接矩形的面積。對于理想的矩形區域而言，該比值為1；圓的最小外接矩形為正方形，且有比值π/4≈0.7853；長短軸比值特征通過計算與區域具有相同二階矩的橢圓的短長軸的比例來衡量區域與圓形的接近程度。當區域為理想圓性時，比值有最大值為1。其計算公式如下：

Rule2=Ls/Ll (9)

在數字影像量化的過程中，不可避免的會出現量化誤差。即使在高分辨率影像中，量化誤差也會導致小目標區域邊緣位置出現混合像素，進而導致分割的區域邊界的定位不準，識別中可能出現較多誤檢。因此，小面積時可采用更緊的約束邊界，大面積的區域采用先對較弱的約束。考慮到這一因素，對于任意分割區域，在計算統計量Rule1和Rule2之后，本文設計了如下區域判別規則：

IfRgnCount＜400

If(abs(Rule1-0.7853＜0.05) &（ Rule2＞0.85）

Then Target region is a circle.

End

Else

If(abs(Rule1-0.7853＜0.1) &（ Rule2＞0.8）

Then Target region is a circle.

End

End

另外，若油罐直徑為L米，影像分辨率為S米，則影像中油罐的面積A約為：

A=πL2/4S2(10)

依據經驗，油罐直徑范圍約為3m-80m[1]。在影像的分辨率S是已知前提下，根據公式10，同時考慮影像的量化誤差，可近似的確定影像中油罐的面積范圍。

3 實驗和分析

實驗采用高分辨率的全色和多光譜遙感影像，實驗樣區為日本某臨海的煉油廠和日本某機場油庫。實驗影像如圖 2所示（影像實際大小見各題注）。實驗算法由C++與Matlab語言混合編程實現。其中，基于均值漂移的初始分割過程調用了C++編寫的庫文件，多層次檢測和油庫區域定位算法由Matlab語言實現。

由表 1可以看到：均值漂移分割耗費的時間和多尺度油罐目標識別耗費的時間相當，油庫定位的耗時幾乎可以忽略不計。初始分割的時間主要耗費在動態庫的調用上，多尺度油罐目標識別的較多時間消耗主要是Matlab語言在處理循環上的低效造成的。另外，初步的實驗表明：VC 6.0平臺下，多尺度油罐目標識別算法的計算時間可以縮短為現有結果的1/4左右。因此，本文提出的油罐目標定位和油庫識別算法，對于較大幅面的遙感影像的油庫定位，從時間復雜度的角度分析是可行的。

(a) 692 ×792 (b) 582×780 (c) 600 ×792(d) 440×834

圖 2 油罐目標識別的部分實驗影像

限于篇幅，圖3僅給出了圖 2-d及多幅油罐目合成影像的處理結果。圖3中的矩形框表示庫區的識別結果，星型表示識別的油罐的重心。通過對實驗結果的分析發現：對于小面積區域，由于量化誤差和分割精度的影響，很難依據形狀特征將其與真實的、較小的油罐區域區分開來；初始分割無法將目標和周圍背景有效分離開來是導致和周圍環境光譜差異不大的油罐不能識別的主要原因。影像中的油罐面積越大，越容易正確識別。圖3-b由多幅影像中的油庫區域合成，影像大小為1100×1100，主要包含三個大的油庫區域。整體上看，提出的算法可以提取絕大數不同面積的油罐對象，但面積過小的油罐發生了漏檢。

4 結束語

上述實驗結果表明，本文采用均值漂移分割算法對高分辨率影像中的油罐進行識別是可行的。提出的算法對影像的波段數沒有限制，且具有參數調整簡單和時間效率高的特點。該方法為高分辨率遙感影像的油罐和油庫識別問題提供了一條新的思路。

參考文獻：

[1] 蔡紅蘋,蔣詠梅,粟毅.一種基于區域生長原理的油庫目標聚類定位方法[J].遙感學報,2006,10(3):415-420.

[2] 陳愛軍,李金宗.衛星遙感圖像中類圓形油庫的自動識別方法[J].光電工程,2006,33(9):96-100.

[3] Kim, H.-S. and J.-H. Kim, A two-step circle detection algorithm from the intersecting chords[J]. Pattern Recognition Letters, 2001,22(6-7):787-798.

[4] Xu, L., E. Oja, and P. Kultanen, A new curve detection method: randomized Hough transform (RHT)[J]. Pattern Recognition Letters, 1990,11(5): 331-338.

[5] Comaniciu, D. and P. Meer, Mean shift: a robust approach toward feature space analysis[J].IEEE Transactions on Pattern Analysis and Machine Intelligence, 2002. 24(5): 603-619.

[6] Cheng, Y., Mean Shift, Mode seeking, and clustering[J]. IEEE Transaction on Pattern Analysis and Machine Intelligence,1995,17(8):790-799.

郵票的知識范文3

外國長篇小說《魯濱孫漂流記》在作家笛福的筆下構造出了一位機智勇敢的主人公——“魯濱孫”。在這部小說里，魯濱孫在一個荒島上生活了二十八年，經歷了孤獨的拷打、安全的威脅、饑餓的侵蝕······許多番風雨后，靠自己的本事活了下來。

魯濱孫不畏艱險、機智勇敢、聰明能干、樂觀理智的精神讓我不由得驚嘆，這是一個有著多么頑強意志力的“平凡人”。在絕望之際，他竟可以用超乎于凡人的冷靜與理智將希望羅列出來，用自己獨有的力量努力維持著他的整個精神世界，創造著別樣的奇跡。

在我的生涯中，魯濱孫令我最為欽佩的“知足常安”這個最偉大的精神特點，我卻沒學到一絲一毫。我承認我是個負能量滿身的人：抱怨自己家境沒有別人好、抱怨自己的天賦沒比別人高、埋怨天氣的多變、埋怨那些不順心的事物、自卑著自己沒有比別人大方、自卑著自己沒比他人受歡迎、自卑著試卷上那一個又一個鮮艷的紅叉······一切沒有達到自己的理想的百分百完美的所有事物如同“過檢產品”那樣都被我打上了“不合格”的印記，使我終日籠罩在積著雨滴的黑壓壓的烏云下。可是魯濱孫的“知足常樂”與我對比起來，他所遭受的苦難與我的小事相比，似一天一地，完全沒得比，使我異常羞愧。

“知足常樂”這個在我心目中最為偉大的精神支柱，將在我人生夜空的帷幕下熠熠生輝。

郵票的知識范文4

關鍵詞 技能大賽 傳票翻打 訓練法

中圖分類號：G712 文獻標識碼：A DOI：10.16400/ki.kjdkz.2016.04.018

Abstract The healthy operation of the skills competition promotes the healthy development of Vocational and technical education. Is introduced in this paper the author of financial skills competition "summons turned to fight" the research contents of training program was effective， and expounds the correct target training， good training attitude and scientific training methods， healthy psychological quality is participate in the skills competition has been essential to the success， the author in the "summons turned to fight" cultivation of player skill training of some methods and experience.

Key words skill competition； summons turned to fight； training methods

近年來，隨著我國市場經濟的高速發展，懂技術的實操型人才缺乏，國家高度重視職業中學的技能教育，職業技術教育正面臨著一個前所未有的發展機遇。為了促進職業技術教育的健康蓬勃發展，每年全國、省、市各級教育部門都組織了各種項目的技能大賽，這些比賽是各職業技術學校的競技展示平臺。 各個學校都很重視這些比賽，都希望在比賽中取得好成績，以樹立學校在社會上的良好聲譽。

本文研究的“傳票翻打”是財經商貿類技能大賽中的一個單獨項目，同時它也是電算化會計綜合的一個組成項目。“傳票翻打”主要是指采用愛丁數碼公司翰林提專用設備進行小鍵盤傳票算。筆者自2010年開始至今一直擔任學校傳票翻打技能訓練隊的訓練工作，從開始的懵懂狀態到逐漸走上訓練的正軌，筆者積累了一定的經驗，本文總結了在“傳票翻打”技能訓練中培養選手的一些方法和心得體會，其目的是想與同仁交流探討， 以更好地提高這個項目的訓練水平。

1 讓學生樹立正確的訓練目標，端正訓練態度

（1）良好的動機能給行動以強大的推動力。人只有在達到一定的動機水平時，其工作能量才能最大限度地發揮出來，傳票翻打也是如此。技能訓練都是枯燥、乏味的，為了激發學生訓練的興趣，教師在訓練的最初要先讓學生們知道參加技能競賽的重要意義。競賽中獲獎既是讓自己的綜合技能得到提高，又能為學校爭得榮譽，也為自己將來就業獲得一項有力的證明。競賽中即使失利未獲得獎項，個人也可以通過參賽獲得很多寶貴的經驗。學生們明確了競賽的意義，自然清楚自己的訓練目標就是刻苦訓練，提高水平，爭取獲獎。

（2）學生明確了自己的訓練目標后，教師就要注重培養學生的刻苦鉆研和吃苦耐勞精神。一個人要想成功，就一定要在困難中保持恒心和毅力。職中學生的堅持精神不一定很足，需要教師經常用激勵的語言去督促和鞭策，更需要運用科學的方法加以引導， 在整個訓練過程中教師也要加強學生自覺性的培養，要求學生能主動刻苦地訓練， 培養學生的自制力和定力。

2 用科學的方法指導技能訓練

2.1 重視基本功的訓練

“傳票翻打”是由基本指法訓練、數字綜合錄入、傳票錄、傳票算四個部分組成，它們是互相聯系、互相制約、 循序漸進的統一體，缺一不可。“傳票翻打”訓練應該是一個循序漸進的過程。

首先，培養學生通過基本指法訓練練出正確的輸入手勢，正確的指法是提高技能水平的關鍵。筆者有一個綜合項目的選手一開始練習時是只用三個手指來操作全部的小鍵盤，手法很笨拙。筆者規定她一定要按照指法的規則，每只手指各司其職，先將基本指法訓練練習五小時，再練習數字綜合錄入五小時，經過兩段基礎的強化訓練，她克服了問題，五指手指可以發揮各自的作用了，這時才要求她進行傳票錄和傳票算的訓練。

其次，控制好擊鍵的速度和力度也很重要。在訓練的一開始，教師就應叫學生學會控制擊鍵的力度，擊鍵手法太軟，可能會打不出數字；擊鍵太用力，易出現將數字打重復的問題，而且長時間練習時容易疲勞，學生耐力會不夠；擊鍵的速度也應該前后保持基本一致，十分鐘內速度變化大會影響自己的心理狀態，就更容易出現數字輸入錯誤。為了讓學生在比賽現場適應軟硬程度不同的鍵盤，教師還應該在比賽前一個月找一些軟硬程度不同的鍵盤供學生練習適應。

再次，要加強盲打訓練。要提高錄入速度，只有正確的操作姿勢和指法，沒有很好的盲打基本功是不行的。訓練伊始，個別學生盲打不過關，為了讓學生練成盲打，可用數字綜合錄入練習，方法是在數字綜合錄入功能里動手設置十個阿拉伯數字和“+”、 “.”，在鍵盤和眼睛中間加一塊薄紙，學生錄入時只能抬頭看屏幕，不能看鍵盤，這樣既可遮住學生看鍵盤的視線， 又不影響學生擊鍵時手指的靈活動作， 迫使學生只能看屏幕，在熟記鍵盤的基礎上練成準確的盲打。

2.2 制定科學的訓練計劃

筆者的學校，一般會提前半年就由訓練老師制定一個詳細的訓練計劃。根據計劃安排，教師在每一個訓練階段制定相應的要求，學生在訓練過程中會經過一個“突飛猛進”的時期和一個“原地踏步”期。在“突飛猛進”期要提高訓練強度，要求學生每天最少打18組題目，還要學生自己制定每個星期一定要達到的訓練目標，如果達不到目標成績就按照訓練隊學生們自己的約定接受小“懲罰”。學生們每個星期要填寫成長記錄表，寫下自己的總結與反思。在“原地踏步”期教師要對學生加強思想教育，教育學生堅持訓練。訓練的過程中要求學生先全力提高速度，比如翻打水平達到可以在10分鐘打完18組或者17組題目以后，再注意提高準確度， 將速度和準確度相結合。

2.3 訓練過程忌拔苗助長，設計有針對性的訓練

“傳票翻打”訓練內容要科學，訓練過程要循序漸進，由易到難逐漸增加難度。在指法訓練中，以分指錄入為主，逐漸過渡到綜合錄入；傳票練習中先練習傳票錄，再練習傳票算。訓練過程忌拔苗助長，特別是對于一年級的新手，必須先練好基本功，再進行數字綜合錄入、傳票算，穩步前進，才能達到較好的訓練效果。訓練過程中也應因人而異，對學生個人情況單獨觀察分析，找出問題后要有針對性地進行彌補訓練。教學中筆者發現，有的學生不會使用大拇指，只能用四個手指擊鍵；有的學生小指不靈活，擊鍵不夠力，或者緊張時小指不到位。針對這些特殊的情況，要對他們進行有針對性的反復訓練，如在數字綜合錄入里專門設置“0，1，2，3”這四個數，讓學生練習拇指和食指的分指協調動作，克服用食指擊“0”鍵的問題。

2.4 對學生加強自我意識和自我評價的培養

引導學生正確認識和評價自己很重要，自我批評、評價是一個人前進的動力，有意識地引導學生經常分析和檢查自己，學生在訓練中才能進步得更快。結合自我評價和自我激勵的需要，筆者為學生設計了“每周傳票翻打成長記錄表”，要求每位學生在每天訓練時記錄自己當天的幾次訓練成績，每周用150字左右寫下自己的總結和反思，然后為下周定一個要達到的目標。“每周傳票翻打成長記錄表”部分表格如表1所示：

教師可根據“每周傳票翻打成長記錄表” 的成績情況進行每周的訓練總結，從而制定對策或調整下周的訓練計劃。

3 加強學生心理素質的培養

心理素質是決定一個人成才和成功的必要條件。傳票翻打比賽時間短、競爭激烈，選手們充分發揮技能水平并取得優異成績是優良的翻打技巧和穩定心理的有機結合。 為了讓學生發揮正常，筆者也研究了一些心理素質培養的方法，在訓練的間隙和比賽前對學生們加強了必要的心理輔導。具體方法如下：

3.1 培養學生的自信心

自信心是一種能夠戰勝各種困難而實現自己理想的情緒狀態。教師應該在平時的訓練中暗示學生自己學校的水平和其他兄弟學校的水平差不多，只要再拼搏努力，就有希望進入前列。這樣一來，學生才覺得有可能實現自己想達到的目標，也才會有拼搏的動力。比賽前的一星期，更要對學生加強自信心的培養，教師可用語言提醒學生，“你們是很棒的，我對你們絕對有信心” 、“放心吧，你們的水平在全市都是領先的”。

3.2 用模擬訓練法加強學生心理素質的培養

學生們在一個陌生的環境中比賽時經常會感到不安和緊張，模擬訓練就是人為的制造或模擬比賽環境，讓學生們逐步適應緊張環境，并產生抗干擾能力，以便在正式的比賽時保持比較穩定的心態。模擬訓練法包括， 通過在自己學校組織的專業學生的技能大賽，模擬實際比賽的場景；加強與其他幾所兄弟學校的交流，通過與其他兄弟學校合辦校際聯誼賽的方式進行模擬比賽，做到“知己知彼，百戰不殆”。 這些措施對穩定學生的情緒狀態和發揮出高水平是有好處的。

3.3 放下“包袱”，輕裝上陣

許多優秀學生比賽失利的主要原因就是過分看重比賽成績，對自己期望過高，背上了思想“包袱”，加重了思想負擔 。教師在賽前的一天和即將比賽前的一刻都要認真觀察學生，發現問題要及時采取措施幫助學生。比賽前的一天，教師要提醒學生練習呼吸調節法，有意識地進行舒緩的腹式呼吸，使內心得到慰藉。到達比賽現場，學生有緊張情緒時，教師要用自己鎮定的情緒感染學生，使不良情緒得到有效的控制。 教師可運用語言暗示，如 “今年參賽的選手很多是新人，水平都不是很高”，讓學生心理得到放松以穩定情緒。

綜上所述，正確的訓練目標、良好的訓練態度、科學的訓練方法、健康的心理素質是參加技能大賽取得成功的必備條件。

參考文獻

[1] 姚家新.競賽心理咨詢與心理訓練[M].北京：人民體育出版社，1995.

郵票的知識范文5

【關鍵詞】 幽門螺旋桿菌; 胃滯留劑; 漂浮劑型; 草藥; 黑柯子; 黃連素

Helicobacter pylori are very common pathogenic bacteria colonizing about half of all populations and associated with the development of serious gastroduodenal diseases like gastric lymphoma， peptic ulcers and acute chronic gastritis. Current drug regimes are not wholly effective. Other problems related with the current drug regimes are lack of patient compliance， side effects and bacterial resistance. Thus， drug delivery to the site of residence in the gastric mucosa may help in solving the problems associated with the current drug therapy. Gastric retentive delivery systems potentially allow increased penetration and thus increased drug concentration at the site of action. Floating drug delivery systems， expandable or swellable drug delivery systems and bioadhesive systems are the major areas of interest to formulate gastroretentive drug delivery system against H. pylori. Generally， problems with these formulations are lack of specificity and the dependence on mucus turnover， so they fail to persist in the stomach. Gastric mucoadhesive systems are hailed as a promising technology to address this issue， penetrating the mucus layer and prolonging activity at the mucusepithelial interface. Gastroretentive delivery strategies， specifically with regard to their application as a delivery system to target Helicobacter， are a very attractive field which can cure these troublesome infections.

H. pylori is a Gramnegative， microaerophilic， spiral and flagellated bacterium， with unipolarsheathed flagella that provides motility. Its spiral shape and high motility allows it to penetrate mucus， resist gastric emptying and remain in the host gastrointestinal (GI) tract. It is now firmly established that infection with this bacterium is the cause of chronic active gastritis. Its isolation radically changed the conceptualisation of several chronic gastrointestinal illnesses including gastritis and peptic ulcers， and elimination of the causative organism became the goal of therapies ［1］. Estimates from the WHO in 1994 claimed that about half of the world’s population was infected with H. pylori and although most infections are silent， a portion of the infected population will subsequently present with associated disease including chronic gastritis， peptic and duodenal ulcers. About 550 000 new cases a year of gastric cancerabout 55% of the worldwide totalwere attributed to H. pylori， and it was predicted that by 2020 to enter the top ten of leading causes of death worldwide［2， 3］. H. pylori is a very perse specy and cancer risks may be increased with strains having virulenceassociated genes (cytotoxinassociated gene， CagA)， host genetics and environmental factors. The incidence of infection is higher in developing countries with up to 80%90% of adults being infected whereas in developed countries prevalence ranges from 10%50%［4］.

1 Mechanism of H. pylori infections

Infection with H. pylori occurs predominately in childhood mainly between the ages 1 to 5， via oral ingestion of the bacterium， and lasts until the end of life with intrafamilial transmission being the major route in developed countries. The possible routes of transmission are food and water. The major feature of H. pylori infection is progressive injury to the gastric mucosa and its function［5， 6］. The bacterium adheres to the gastric epithelial cells， producing a direct injurious effect that is then amplified by production and release of a vacuolating cytotoxin (VacA)［7， 8］. H. pylori produces a variety of enzymes and is characterised by a high urease activity. Urea is broken down into bicarbonate and ammonia that protects the bacterium in the acid environment of the stomach. The ammonium ions produced can be toxic to the gastric superficial epithelial cells. Urease stimulates inflammatory cytokine production and activates mononuclear phagocytes. Although， after colonisation， the host immune defences are stimulated， and there is increased secretory IgA (sIgA) detected in the gastric mucosa and raised specific IgG， while the infected host is not able to eliminate the organism. Colonisation results in persistent gastric inflammation but the clinical course of infection can be very variable［9］.

2 Current treatment of H. pylori infections

The treatment for eradication of H. pylori is complicated， requiring a minimum of two antibiotics in combination with gastric acid inhibitors. Although H. pylori is sensitive to many antibiotics in vitro， no single agent is effective alone in vivo. Firstly， the bacterium resides below the gastric mucus adherent to the gastric epithelium and thus access of drugs to this site is limited. Secondly， the strain may have acquired resistance to the commonly used antimicrobial drugs［10］. These infections are currently treated with a firstline triple therapy treatment， consisting of one proton pump inhibitor (PPI) and two antibiotics. None of the antibiotics used achieves sufficient eradication when used alone and also require adjuvant therapy［11］. This consists of agents increasing pH within the stomach to allow local action of antibiotics not active at low pH， and PPIs are used at a dose equivalent to 20 mg omeprazole twice daily. It was suggested that ranitidine bismuth citrate (RBC) regimens may be less influenced by antibiotic resistance than PPIbased therapies［12］.

The most effective therapies combine two antibiotics including clarithromycin and amoxicillin with a gastric acid inhibitor. However， increasing resistance to current antibiotics is driving research to produce alternatives to the commonly used therapies. In addition to increasing levels of antibiotic resistance， the hostile environment of the stomach， reducing antibiotic bioavailability at the site of action， contributes to failures in treatment［13］. Current recommended regimes are not wholly effective， for example， triple therapy with bismuth， metronidazole and amoxicillin or tetracycline has an eradication efficiency of 60%80%， and patient compliance， sideeffects and bacterial resistance can be problematic with this regime［14］. Alternatives proposed include quadruple therapies， based on， for example， colloidal bismuth subcitrate， tetracycline， metronidazole and omeprazole［15］. Patient compliance with such a complicated dosage regime could be improved by combining the therapies in a single dosage form， and a capsule containing bismuth biskalcitrate， metronidazole and tetracycline (Helicide) has been developed in an effort to improve patient compliance and has currently received approval［16］. There is concern regarding acquired resistance to two of the commonly prescribed antibiotics: clarithromycin and metronidazole. Although not as widespread， resistance to metronidazole can also be problematic but it can be overcome in some cases by lengthening the duration of treatment［17］.

3 Drug delivery systems for gastric retention

Major problems in the eradication of H. pylori are the presence of antibioticresistant bacteria requiring multiple drugs with complicated dosing schedules and bacterial residence in an environment where high drug concentrations are difficult to achieve. In order to ensure that the therapy is adequately delivered to the unique niche of the gastric mucosa， development of oral dosage forms with prolonged gastric residence is desirable. Gastric retentive delivery systems have been studied for a number of years， and generally requirements of such strategies are that the vehicle maintains a controlled release of drug and exhibits prolonged residence time in the stomach. Overcoming the physiological barriers of the human GI tract is a major challenge facing successful development of gastric retentive systems and leads to problems with reproducibility. In addition to the thick protective mucus layer， gastrointestinal motility patterns are another obstacle facing drug delivery to the stomach. In the fasted state， the interdigestive myoelectric motor complex (IMMC) is a 2hour cycle of peristaltic activity that regulates motility patterns［18］. Phase Ⅲ of the IMMC is also called the housekeeper wave and consists of strong， intense contractions designed to remove debris such as undigested food from the stomach［19， 20］. Gastric residence time will depend on which phase of IMMC is active. In the fed state， the stomach churns food to sizes less than 1 mm， which is then emptied to the duodenum. Type of the food determines its residence time in the stomach with liquids emptying rapidly and solids much more slowly. Gastric residence time is generally longer in the fed rather than fasted state. The gastric residence time of dosage forms is also influenced by posture， age， gender， disease status and concomitant medication. A number of different techniques have been explored to increase gastric retention including high density and magnetic systems， but the three main systems are floating systems， bio/mucoadhesive systems and swelling systems.

4 Floating drug delivery systems

Various approaches had been made since the late 1970s to utilise floating behaviour in order to prolong residence. Designs include hydrodynamically balanced systems (HBS)， microspheres， gasgenerating systems and raftforming systems. Originally， such systems were proposed to reduce fluctuations in drug levels and provide sustained release as the duration of most oral sustained release preparations is 812 hours， due to a relatively short GI transit time［21， 22］. HBS has a bulk density lower than gastric fluids and contain one or more colloids formulated into a single unit with the drug and other additives， which swell on contact with water and facilitate floating［23， 24］. A density of less than 1.0 g/mL is required. A triplelayer floating tablet system was proposed containing a swellable gasgenerating layer， a swellable drugcontaining layer (with tetracycline and metronidazole) and a rapidly dissolving layer containing bismuth salts. The system was capable of providing sustained release of the antibiotics in vitro at pH 1.8 and demonstrated buoyancy in vitro， however no in vivo results are reported. Tablets containing a 1︰2 ratio of hydroxypropylcellulose to amoxicillin， with a gasgenerating system， failed to improve efficacy. These large singlelayer tablets remained buoyant in vitro but bioavailability was reduced to 80.5% as compared with conventional capsules in fasted humans［25］. Intersubject variability in gastric transit times with floating tablets and HBS results in unreliable and irreproducible residence times in the stomach and remains a significant problem with such systems. This can be addressed by using multipleunit pided systems such as microspheres. As these can spread evenly through the stomach contents， they can avoid the problems of variable and early gastric emptying or bursting associated with the singleunit systems. Polymers used in formulation of floating multipleunits include caesingelatin acrylic polymers such as Eudragits and alginates［26］. Alginic acid is a polysaccharide consisting of Dmannuronic acid and Lguluronic acid. It forms a bioadhesive and stable gel with palent cations such as calcium and the sodium salt been used in a variety of oral and topical formulations. Floating alginate systems such as Gaviscon form a buoyant gel which floats on the gastric contents alleviating symptoms of heartburn. Its stability in acidic media has made it a popular choice for gastric retentive delivery systems. For example， floating multiple units consisting of a calcium alginate core， separated from a calcium alginate/polyvinyl alcohol (PVA) membrane by an air compartment displayed prolonged gastric retention after a meal. Alginate beads are commonly prepared by extruding alginate， dropwise， into a solution containing Ca2+. The resultant beads are porous and can be used to encapsulate a variety of drugs with a wide range of physicochemical properties［27］. Adequate control of drug release from such formulations often requires some modification to the matrix. For example， foambased floating microspheres can be prepared by adding polypropylene foam powder to an organic solution containing dissolving polymer (Eudragit RS or polymethyl methacrylate， PMMA) and drug. Upon solvent evaporation， freeflowing microspheres are formed with extended release profiles［28］. Two types of alginate floating beads containing metronidazole were compared; one formulation contained chitosan and the other contained vegetable oils. In vitro release was complete from all formulations within two hours. Following administration to guinea pigs， it was concluded that after three hours chitosancontaining particles resulted in increased drug levels in the gastric mucosa as compared with metronidazole solution［29］. A multipleunit floating dosage form formulated using calcium alginate was prepared by dropping sodium alginate solution into calcium chloride and the resultant particles were freezedried. Amoxicillin was incorporated into these beads by addition of drug to the calcium chloride solution. Once the sodium alginate was extruded into the solution， the resultant gel beads were left for thirty minutes before extraction and freezedrying. Amylose was also added to the formulation in an attempt to reduce the release rate. Amoxicillin release showed an initial burst effect and the release was described by Higuchi kinetics， implying that it is controlled by diffusion of the drug through a porous matrix. Gammascintigraphic studies showed evidence of gastric retention of the floating beads in all seven subjects even following normal food intake.

A major limitation with such systems is the requirement for sufficient volumes of gastric acid within the stomach to enable the devices to float. It may be that using a single approach to localise delivery in the stomach may not be sufficient to resist the forces of gastric emptying. It was therefore envisaged that a floating dosage form with mucoadhesive polymers could extend the period of gastric retention， exploiting the retentive properties of the floating system and the ability of bioadhesive formulations to adhere to inflamed tissue. Floating， bioadhesive microsphere systems containing acetohydroxamic acid (AHA)， a cytoplasmic urease inhibitor， were prepared. A solution of AHA and the acrylic polymer (Eudragit E) in ethanol/dichloromethane was added to an aqueous PVA solution to form an oilinwater emulsion. The drug and polymer precipitated due to preferential diffusion of ethanol into the aqueous phase. After evaporation of the dichloromethane， the particles were dried and an air cavity was produced inside the spheres giving the particles the ability to float［30］. These particles were spraycoated with the mucoadhesive polymer， polycarbophil. Floating ability was demonstrated in vitro and demonstrated greater percentage growth inhibition of H. pylori in vitro than free drug. Release rates were extended due to the polycarbophil coating［31］. Similar preparations using polybisphenolA carbonate as the coating polymer also showed buoyancy， extended drug release and inhibition of growth of H. pylori in vitro. Clearance of an inoculated strain of H. pylori from the stomach of gerbils following oral delivery of the encapsulated drug was shown to be better than free drug， presumably due to better retention. Although AHA has been shown to be effective at reducing gastritis in a Mongolian gerbil model， further studies are needed to prove that established antibiotics could also be successfully encapsulated into， and released from， such formulations and their efficacy demonstrated in human models［30］.

5 Herbal and integrative drugs against H. pylori infections

5.1 Black myrobalan The aqueous extract of black myrobalan (Terminalia chebula Retz) has been shown to have uniform antibacterial activity against ten clinical strains of H. pylori［32， 33］. This activity was bactericidal after 3 h and was stable after autoclaving. Although Sato and coworkers［34］ reported gallic acid and ethyl gallate in T. chebula Retz and have shown antibacterial activity of ethanol extracts of this plant against both methicillin resistant and sensitive Staphylococcus aureus and other bacteria， the components of T. chebula Retz aqueous extracts responsible for the observed bacteriocidal activity remain unknown［35］. The antibacterial activity of aqueous extracts of black myrobalan against H. pylori was significantly higher than that of ether and alcoholic extracts. The aqueous extract preserved its antibacterial activity after autoclaving for 30 min at 121 ℃ and was inhibitory at 125150 mg/L. When the plant powder was tested directly against H. pylori， without grinding and (or) extraction and using Colombia Agar plates， the mean inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were 150 and 175 mg/L， respectively.

5.2 Ginger Ginger root (Zingiber officinale Rosc.) has been used traditionally for the treatment of gastrointestinal ailments such as motion sickness， dyspepsia and hyperemesis gravidarum， and is also reported to have chemopreventative activity in animal models［36］. The gingerols are a group of structurally related polyphenolic compounds isolated from ginger and known to be the active constituents. Since H. pylori is the primary etiological agent associated with dyspepsia， peptic ulcer disease and the development of gastric and colon cancer， the antiH. pylori effects of ginger and its constituents were tested in vitro［37］. A methanol extract of the dried powdered ginger rhizome， fractions of the extract and the isolated constituents， 6， 8 and 10gingerol and 6shogoal， were tested against 19 strains of H. pylori， including 5 CagApositive strains. The methanol extract of ginger rhizome inhibited the growth of all 19 strains in vitro with a MIC range of 6.25 to 50 μg/mL. One fraction of the crude extract， containing the gingerols， was active and inhibited the growth of all H. pylori strains with an MIC range of 0.78 to 12.5 μg/mL and with significant activity against the CagApositive strains. These data demonstrate that ginger root extracts containing the gingerols inhibit the growth of H. pylori CagApositive strains in vitro and this activity may contribute to its chemopreventative effects［38］.

5.3 Turmeric Curcumin， a polyphenolic chemical constituent derived from turmeric (Curcuma longa L.)， has been shown to prevent gastric and colon cancers in rodents［39］. Many mechanisms had been proposed for the chemopreventative effects， although the effect of curcumin on the growth of H. pylori has not been reported. H. pylori is a group 1 carcinogen and is associated with the development of gastric and colon cancer. A methanol extract of the dried powdered turmeric rhizome and curcumin were tested against 19 strains of H. pylori， including 5 CagApositive strains. Both the methanol extract and curcumin inhibited the growth of all strains of H. pylori in vitro with a minimum inhibitory concentration range of 6.2550 μg/mL. These data demonstrate that curcumin inhibits the growth of H. pylori CagApositive strains in vitro， and this may be one of the mechanisms by which curcumin exerts its chemopreventative effects［40， 41］.

5.4 Thyme A popular herbal remedy in ancient Egypt， Greece and Rome， thyme was mainly used for headaches， digestive problems， respiratory illness， and as a moodenhancer. Researcher who investigated the antimicrobial properties of 21 essential oils against five important foodborne pathogens， including Escherichia coli (E. coli) noted that thyme was very effective at inhibiting the bacteria. Thyme extract was compared with several antibacterials; it had a significant inhibitory effect on H. pylori［42］.

5.5 Licorice In a recent study at the Institute of Medical Microbiology and Virology， Germany， researchers found that licorice extract produced a potent effect against strains of H. pylori that are resistant against clarithromycin， one of the antibiotics typically used in the three antibiotic treatment regimens［43］. The authors concluded that this study provides hope that licorice extract can form the basis for an alternative treatment for H. pylori infections［44］.

5.6 Berberine Berberine is a plant alkaloid isolated from the roots and bark of several plants including golden seal， barberry， Coptis chinensis Franch. and Yerba mansa. Berberinecontaining plants have been used medicinally in ayurvedic and Chinese medicine， and are known to have antimicrobial activity against a variety of organisms including bacteria， viruses， fungi， protozoans， helminths， and chlamydia. More recently， berberine had been demonstrated to be effective against H. pylori［45］.

5.7 Goshuyn (Evodia rutaecarpaa Chinese herb) After testing no less than 113 Chinese herbs for antiH. pylori activity in vitro， Japanese researchers identified goshuyn (Evodia rutaecarpa) as the most effective medical plant. Subsequently， they conducted a randomised clinical trial of two synthetic antibiotics versus the same combination plus goshuyn. The eradication rates were 60% and 80%， respectively［46］.

5.8 Other Chinese herbals In an animal study or bacteriostatic test of 53 Chinese herbs， Zhang et al［47］ found Coptis chinensis， Rheum palmatum， Panax notogenseng and Magnolia officinalis were effective against H. pylori. Prunus mume and Corydalis yanhusuo were moderate effective.

6 Conclusion

The gastric retention approaches as well as herbal drugs described here have applications for treatment of H. pylori infection although further development is required for each to be fully effective， especially in human studies. Overcoming the high mucus turnover rate and resulting limited retention times is a challenge for bioadhesive systems， and swelling systems must guarantee clearance from the stomach after a certain time to prevent any obstruction. The lack of availability of biocompatible chemical cross linking agents is a major stumbling block in the development of covalently crosslinked hydrogels. Floating systems are available commercially， and combination approaches， using floating behaviour and mucoadhesion， have also shown promise. Exploiting dual mechanisms of retention may provide the strength and reproducibility required to permit successful advancement in this field. So in future， a combination of herbal drugs with the novel drug delivery systems mentioned above， may lead to an important breakthrough in the herbal/integrative treatment of H. pylori infections.

7 Acknowledgement

I would like to acknowledge Dr. K. Pundarikakshudu for giving constant help to compile the information and in preparation of this article. I am also very much thankful to Prof. B.M. Peerzada and Prof. Manish Shah for constant encouragement.

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郵票的知識范文6

被告：上海亞細亞皮具實業有限公司。

1996年2月14日，被告上海亞細亞皮具實業有限公司（簡稱亞細亞）簽發了一張收款人系上海亞泰皮件廠、票面金額為20萬元、匯票到期日為1996年5月30日的商業承兌匯票（號碼為ZXZV6468553），同時該匯票經被告亞細亞承兌，到期日無條件支付票款。上海亞泰皮件廠收到匯票后，于同年3月8日背書后交付原告上海皮革公司德惠皮革制品廠（簡稱皮革廠），原告皮革廠遂在背書人一欄中填寫了自己的名稱。同年5月30日原告皮革廠因出借錢款又將匯票背書轉讓給借款方上海希倫賽勒赫和奎因皮革化工品技術服務寄售站（簡稱寄售站）。同日，該寄售站持該匯票至銀行提示付款。次日，因被告亞細亞帳戶內存款不足銀行拒付款而退票。為此，該寄售站將匯票退回原告皮革廠，原告皮革廠與該寄售站之間已不存在債權債務關系。為此，原告皮革廠遂向法院提起訴訟。

原告皮革廠訴稱：請求法院判令被告償付票據金額20萬元，承擔利息及訴訟費。

被告亞細亞辯稱：原告皮革廠取得匯票后已背書轉讓他人，且本案系爭匯票的前后手之間均無直接債權債務關系。為此，原告皮革廠不具備持票人資格，無票據權利，要求駁回原告皮革廠之訴。

法院經審理認為：被告亞細亞于1996年2月14日簽發的商業承兌匯票，記載完備、真實，并經其蓋章承兌，屬合法有效，被告亞細亞理應承擔票據的付款義務，并在票據不獲付款時承擔票據的清償責任，且不得以與持票人的前手之間無直接債權債務關系為由對抗持票人。原告皮革廠與其后手之間已不存在債權債務關系，其依法向被告亞細亞行使追索權，合理合法，應予支持。根據《中華人民共和國票據法》第26條、第61條之規定，于1996年11月13日作出判決：被告亞細亞應償付原告皮革廠票載金額20萬元及利息（利率按中國人民銀行同期貸款利率，自1996年5月30日起計算至本判決生效之日止）。

本案是一起票據追索糾紛。就本案而言，主要涉及到票據的追索權、票據的無因性、票據承兌的法律效力等。

一、票據的追索權

追索權是指，在匯票到期前未獲承兌或到期未獲付款或有其他法定的影響匯票信用的情形出現時，持票人在行使或者保全其票據上的權利的行為后，可以向匯票的背書人、出票人或者其他債務人請求償還匯票金額及其他法定金額的權利。

追索權的行使，須同時具備票據法所規定的實質要件和形式要件。實質要件包括：（一）背書連續。背書的連續是持票人行使票據權利的必要條件。（二）須有行使追索權的原因事實存在。即行使到期后追索權必須有匯票被拒絕付款的事實。形式要件是指必須作成拒絕證書以證明其不獲付款或不獲承兌的事實，如承兌人或付款人出具的拒絕證明或退票理由書。本案原告即背書人的后手上海希倫賽勒赫和奎因皮革化工品技術服務寄售站持匯票不獲付款，后因與原告不存在債權債務關系，將匯票退回原告。這樣，原告就成為該匯票的合法持有者。原告以匯票背書的連續證明其票據權利的存在，并有上海城市信用社退票通知，故原告可以向出票人（被告）行使追索權。

二、票據的無因性

票據乃無因證券。所謂無因，是指票據如果具備票據法上的要件，票據權利就成立。至于票據行為賴以發生的原因，在所不問，即持票人享有權利只以持有票據為必要，對于持票人取得票據原因、票據權利發生的原因均在所不問，因而持有票據的人行使權利時無須證明其取得票據的原因。但是如果原因關系與票據關系存在于直接當事人之間時，債務人可以用原因關系對抗票據關系。

本案被告辯稱，本案系爭匯票的前后手之間均無直接債權債務關系，為此原告不具備持票人資格，不享有票據權利，是違背票據的無因性的。

三、票據承兌的法律效力