人的記憶力會(huì)隨著歲月的流逝而衰退，寫(xiě)作可以彌補(bǔ)記憶的不足，將曾經(jīng)的人生經(jīng)歷和感悟記錄下來(lái)，也便于保存一份美好的回憶。范文怎么寫(xiě)才能發(fā)揮它最大的作用呢？這里我整理了一些優(yōu)秀的范文，希望對(duì)大家有所幫助，下面我們就來(lái)了解一下吧。
食品專業(yè)英語(yǔ)論文篇一
gpu并行成本模型 2009137127 周幼蘭
abstract-using gpu for general computing has become an important research direction in high performance computing r, this is not a lossless optimization to the impact of device initialization cost, data transmission delay, specific characteristics of programs, and other factors, the general computing on gpu may not always achieve the desired speedup, and sometimes results in program execution performance the basis of in-depth analysis of gpu internal processing mechanisms, the main factors affecting gpu implementation performance are pointed out, and a parallel cost model for gpu based on static program analysis is proposed to provide judgement basis for using gpu in general computing.摘要：在高性能計(jì)算技術(shù)領(lǐng)域，使用gpu執(zhí)行通用計(jì)算已成為一個(gè)重要的研究方向。但它并不是一種無(wú)損優(yōu)化方法。由于受設(shè)備初始化成本、數(shù)據(jù)傳輸延遲、程序本身特征和一些其他因素的影響，基于gup的通用計(jì)算不可能總是達(dá)到預(yù)期的加速，有時(shí)還會(huì)導(dǎo)致程序執(zhí)行性能下降。在對(duì)gpu內(nèi)部處理機(jī)制進(jìn)行深度分析的基礎(chǔ)上，得到影響gpu執(zhí)行性能的主要因素，且得出基于靜態(tài)程序分析的gpu并行成本模型為gpu在通用計(jì)算中的使用提供了判斷依據(jù)的結(jié)論。
uction graphics processing unit(gpu)has developed at a speed much faster than the moore’s law in recent years, not only improving image processing, virtual reality, computer simulation, and the development of related applications, but also providing a good running platform for general-purpose computing using gpu beyond graphic application of gpu in general-purpose computing makes a series of new challenges faced by the development of the high performance computing tly, in order to reduce the programming complexity of gpu in general-purpose computing, many gpu manufacturers and research institutions proposed a number of programming languages and programming models close to traditional programming methods, but different styles, such as brook+[1], cuda[2] and opencl[3], r, as gpu has its own specific characteristic of hardware architecture and development, programmers must have a high level of gpu for general-purpose computing, the increased performance achieved in large part depends on the hardware knowledge and programming skills of present, the most studies for the gpu’s parallelism both at home and abroad directly rewrite and transplant programs on the basis of original serial e software programmers often lack a deep understanding of the hardware platform and have no corresponding capability of programming hardware programs, program transplantation lead to the increased effects achieved of all kinds of applications accelerating general-purpose computing using gpu have obvious difference [4-6].program performance analysis technology as a basic method of understanding program behavior, plays an important role for comparing the performance difference between different program implementation, identifying performance bottlenecks of programs, and understanding the hardware resource utilization, and is the important part of development and optimization of high
performance computing programs [7].how to take advantage of program performance analysis technology and combine the architecture characteristics of cpu and gpu to guide the planning and optimization of parallel programs so that a variety of computing resources of cpu and gpu are fully utilized is a problem worthy of study using gpu in general-purpose computing at present.簡(jiǎn)介：
近幾年來(lái)，計(jì)算機(jī)圖形處理器（gpu）比摩爾定律發(fā)展得更迅猛，這種發(fā)展不僅體現(xiàn)在改善圖形處理、虛擬現(xiàn)實(shí)、計(jì)算機(jī)模擬以及相關(guān)運(yùn)用方面，還體現(xiàn)在為使用gpu作圖形以外處理的通用計(jì)算提供了良好的運(yùn)行平臺(tái)。
gpu在通用計(jì)算方面的運(yùn)用面臨著高性能計(jì)算技術(shù)發(fā)展的一系列新挑戰(zhàn)。目前，為了減少通用計(jì)算中g(shù)pu編程復(fù)雜性，許多gpu制造商和研究機(jī)構(gòu)提出了一系列編程語(yǔ)言和編程模式，這些編程模式類(lèi)似于傳統(tǒng)德編程方法，但是具有不同的編程風(fēng)格，例如brook++、cuda以及opencl等等。然而，當(dāng)gpu擁有自己獨(dú)特的硬件結(jié)構(gòu)和發(fā)展特征時(shí)，與此同時(shí)程序員必須擁有較高水平的專業(yè)技能。通用計(jì)算中使用gpu來(lái)提高性能很大程度上取決于程序員的硬件知識(shí)和編程技術(shù)。迄今為止，國(guó)內(nèi)外對(duì)于gpu的平行性研究大多數(shù)是直接寫(xiě)入和將程序直接植入到原始串行程序基礎(chǔ)上。由于軟件程序員往往對(duì)硬件平臺(tái)缺乏深層次的了解，并且沒(méi)有相應(yīng)的編寫(xiě)硬件程序的能力，所以程序植入導(dǎo)致了各種各樣的運(yùn)用程序的增加效果有著明顯的差異，這些運(yùn)用程序加速了使用gpu的通用計(jì)算。作為一種理解程序行為的基本方法，程序性能分析技術(shù)在比較不同程序執(zhí)行的性能差異、找出程序的性能瓶頸和了解硬件資源的利用率方面扮演著重要角色，而且它還是高性能計(jì)算程序的重要組成部分。如何利用程序性能分析技術(shù)以及如何結(jié)合cpu和gpu的體系特征來(lái)引導(dǎo)平行程序的規(guī)劃和優(yōu)化以至cpu和gpu的大量計(jì)算資源得到充分利用，是目前gpu在通用計(jì)算方面一個(gè)值得探討的問(wèn)題。
sion there are a number of studies on the applications related to using gpu in general-purpose most researches focus on using gpu to improve the execution performance of r, how to measure the costs of gpu at runtime is less the perspective of gpu’s internal operation mechanism, analyze the key factors affecting the gpu implementation performance, and propose a cost test algorithm based on static program results obtained by experiments show that the algorithm proposed can estimate relatively accurate gpu execution performance, and thus provide a useful reference for transplantation of traditional high performance computing to gpu.結(jié)論：
與使用gpu作通用計(jì)算相關(guān)運(yùn)用的研究實(shí)例比比皆是，且大多數(shù)研究將使用gpu來(lái)提高運(yùn)用程序的執(zhí)行性能為研究中心，但是至于怎樣衡量gpu運(yùn)行時(shí)的成本卻很少有人提及。本論文從gpu內(nèi)部運(yùn)行機(jī)制出發(fā)，分析影響gpu執(zhí)行性能的主要因素，提出基于靜態(tài)程序分析的成本測(cè)試算法。實(shí)驗(yàn)所得結(jié)果說(shuō)明所提算法能夠相對(duì)精確地評(píng)估gpu執(zhí)行性能從而為傳統(tǒng)的高性能計(jì)算的在gpu中的移植提供了一個(gè)實(shí)用性的參考。
comment: cost model has been widely used in the computer field as a way to evaluate whether a program is excellent or quite a number of researchers in computer field has proposed various kinds of cost models for gpu, of which most are under certain this paper give us a new perception of cost model for gpu in general-purpose parallelization cost model for gpu can be generally applied for many application authors attempt to estimate the cost ly they take the gpu initialization cost, transmission of data cost as well as the program execution cost into aspect use a special algorithm to calculate the the cost is measured by the time of each this paper ,we can get through the authors’ idea very well ,because they are well organized in form and shown clearly in graphs, charts as well as in parallelization cost model is more accurate, flexible and portable than models of the we should learn the method they study a is to consider a question in a broad if we keep thinking in this way ,our ability of doing scientific research will be greatly the same time, we should keep close watch on the field of it is such an important processor that it is used widely used on modern is even considered the core graphics processor of it develops faster nowadays as the need rises.
食品專業(yè)英語(yǔ)論文篇二
課程論文
院系 物理與電子工程學(xué)院專業(yè) 電子信息工程班級(jí) 電工1111班學(xué)生姓名 簡(jiǎn)東陽(yáng)學(xué)號(hào)2011140131任課教師 羅倩倩
2013 年12月26日
switching technology present situation and development trend
jiandongyang
hubei university of arts and sciences
@
abstract：direction in the future, more extensible features will become the important characteristics of a new generation of internet, the exchange of technology, will be as a key technology to host this extensible ing technology in scale, function, performance, safety and service and other aspects have better extensibility features, will be a new generation of internet architecture in the ds:network technology;the internet;switching technologythe present situation of the exchange of technologythe rapid development of network technology, ethernet is always r, with the deepening of the network technology application, the network development scale and speed are only the speed of the lan got improved, gigabit ethernet also gradually became ion to network of high reliability, high performance, easy maintenance and reduced cost, and these factors is dependent on the using kind of networking technology;equipment vendors would on the basis of not harm the interests of the user network functions and pursue the considerable the network, there have been a mature traditional layer 2 switching technology, and the function of the routing layer 3, and a high service level of network layer ing technology of a single traditional layer traditional layer 2 switching technology, is a special single, it contains only the data link layer 2 switching technology is mostly used for small local area network(lan), the machine numbers keep in 20 or 30 sets of the following is the security of the network environment, fast switching function, multiple access port, low price which the three layer 2 switching technology has has solve the problem that the small network users.2.1 the third layer switching technology with routing function
in order to solve the problems of the broadcast domain, for the first time in 1997 the third layer switching technology with routing function 3 switching technology has now become a main force of the construction of multiple business fusion a large local area network(lan), can increase the dangers of broadcast storm, in order to reduce the harm, we must spanide a large local area network(lan)according to the function or the region into multiple small local area network(lan), so that it can reduce the harm of broadcast only use layer 2 switching technology, a large number of visits between subnets cannot be ed by the layer 3 switching technology(layer 3 switches)is very good to solve the , layer 3 switching technology is more and more mature, and also in constant development and innovation, it occupies a more and more important status in the network.2.2 layer 7 switching technology with the function of network service
unlock every layer encapsulates of each data packet, identify the application layer information at the same time, is the functions of layer , many service providers focus gradually shifted to how to make full use of broadband resources and how to manage the internet application, 7 switching technology can handle network application layer data forwarding well, the network service level can be improved and it also can make the network administrators and make the users have a lower cost to optimize the network r it is business to consumer e-commerce, market sales of unmanned automation, on-line customer support, personnel construction and planning, customer service, firewall load balancing broadband and intelligent filter content and so on, can be dabble in by layer 7 switching development trend of switching technology
research in recent years the development of the exchange network architecture and related algorithms, is mainly to study of switching ing network is roughly by single-stage exchange structure and multiple exchange structure of two kinds of -stage exchange in the performance and scale structure is hard to expand and develop, so the new exchange structure instead of a single-stage exchange structure is ed with single-stage exchange structure, multi-level exchange structure has a very big advantage is the extensions is good, if you want to achieve more mass exchange network, multistage switching structure will be the first choice, and it is also considered very system structure of open-ended standardization and data packet based will gradually become the next generation network of the new definition, this is also to develop more and more effective applications and business functions, at the same time can quickly adapt to the e higher performance and greater scale, is the main goal of the studying exchange order to achieve this goal,it is bound to reinforce the research of the project, the developing trends in the future may have the following:
(1)multistage switching structure instead of the single stage exchange structure;
(2)reduce the internal blocking of multistage switching structure;
(3)build more mass exchange application of new technology requires a lot of time to continue to improve and ing to the report, the development of next generation network technology is gradually mature and e that the exchange technology will be developed in network technology and business development of the evolving in the business operation and competition in the future, differential operators will also play an increasingly important sion
high technology development change rapidly, more and more ing technology has become more intelligent,order to reduce the cost, and make the network of high reliability, high performance, easy to maintain and extend the guarantee,switching technology from the initial layer 2 s developed to the layer 3 and now 7 layer,it is still in the continuous development and e that the network intelligent management is not far from gh there is a problem but it will not hinder the exchange of technology application and development, operators and equipment suppliers will make these problems get very good settlement,constantly positive test, unceasingly perfect, eventually there will be a good nces:
[1] feng huibin on the application of modern switching technology course teaching reform research [j].journal of education teaching bbs, 2012(s4).[2] wu next generation network of the soft exchange technology [j].journal of railway signal engineering, 2005(01).
食品專業(yè)英語(yǔ)論文篇三
地質(zhì)專業(yè)英語(yǔ)結(jié)課論文
題目：mining and geological hazards
系 別 13級(jí)地科系 班 級(jí) 資源勘查1班 學(xué)生姓名
張政 學(xué) 號(hào) 034130106 指導(dǎo)教師 夏奎菊
mining and geological hazards the rapid economic development and production need to speed up the demand for minerals and consumption, which also brings greater opportunities for the development of mineral mining r due to the rapid development of lax management of small and medium-sized mines, plus the small mines, mining and mineral processing technology is backward, most of the environmental protection measures, exacerbated by the destruction of the environment in the mining area.a marked deterioration in the mining environment and geological disasters in mining issues is becoming more and more serious, potential disaster risks are increasing, and may at any time development of disaster, causing a scrap casualties, equipment and facilities damaged or even the closure of the mine, the waste of resources and serious types of geological hazards in mines there are many different kinds of mine geological disasters, according to the relationship between disaster and time can be spanided into sudden mine geological disasters(such as mine water inrush, gas explosion, rock burst, etc.)and delayed mine geological disasters(such as goaf ground deformation, environmental pollution, etc.).but the most common is the classification of the spatial distribution and genetic relationship of disaster..ation disasters of rock and soil mine ground and goaf collapse mainly occurred in underground mine goaf, if retained pillar insufficient, or because of damage of pillar and lose the ability to support, will cause ground ally those ore bodies buried in shallow, producing a more gentle mining area(such as coal mine), the phenomenon of the ground collapse is more bodies buried at relatively deep underground mining, if not timely backfill and caving it reaches a certain scale will produce the large area of addition, in the karst area, but also because of mine drainage drainage drainage and lead to the collapse of the cave above the subsidence not only destroy arable land, buildings and damaged roads, reservoir, but also a direct result of mines some underground roadway disrepair, or make atmospheric precipitation and surface water along the fracture collapse poured into the pit, causing flooding accident well until slope instability, landslide and rockfall is the main reason is the unreasonable mining, such as mining excessive skin disorders, slope angle caused by steep, the disaster occurred in the open pit mining of non metallic mines and building materials, rock burst pit in the rock burst is also called the mines is because around the pit and the top floor rock, after being subjected to the strong crustal stress and are strongly compressed, once mining hollowed out because of the free surface, may produce rock stress sudden release, resulting in large amounts of rock burst into pieces, and to the pit a considerable amount of spray, decrepitation and mines to bring hazards and induced earthquakes are caused by mining activity, which is caused by the earthquake, the source is shallow, the harm is big, the small magnitude earthquake can cause the underground and the surface of the earth's surface.a library database instability instability is mainly due to the collapse of the tailings dam break and harm caused by the formation of debris gs dam break accident often brings great harm to the life and property of mining area residents, but also cause huge damage and pollution to the environment.2, the underground water level change caused by the disaster mine water bursting water which is the most common mine disasters, sudden, large scale, serious tion process often of mine water inflow estimation problem because of the, mining process through old workings, through permeable fault, sudden encounter water cave or underground river, resulting in groundwater or surface water influx, caused by mine flooded and casualties in mud and sand bursting which is often accompanied with mine water bursting the mining process in sudden encounter water cave, common in the cave filling sediment and debris with groundwater together with the influx of, also some permeable faults and cracks often make shallow quaternary sediments with leakage surface runoff into the result is the tunnel is blocked on the sediment, machines, workers were buried by sediment, serious when even suffered a devastating blow to the mines.2.2.3 environmental pollution is another important form of mine to mining, mineral processing waste material, because of not effectively deal with is discharged into the rivers, lakes and the sea, causing environmental pollution will cause soil erosion, land desertification, salinization, groundwater flow etc..3, the cause of the disaster caused by the ore body the gas explosion and mine fire disaster that is most common in coal e of bad ventilation, the gas accumulation in the explosion, caused by underground operations personnel casualties, destroyed mine;mine fire in addition to found in coal mine, is also found in a number of sulfide e of sulfide oxidation in heat, heat accumulation to a certain extent, the occurrence of spontaneous combustion, causing fires in fire damage is great, but also a serious loss of underground mineral resources, such as some coal mines in the ground has been burning for a hundred years, the amount of resources loss is very huge, so that local climate change, crop and trees, a large number of dead, barren fields, serious environmental the increase of the depth of the exploitation of geothermal, geothermal hazards continue to has a lot of mining depth below 800m, the mining of high sulfur content, mining depth and high, the ground temperature is very geothermal disaster led to poor working conditions of miners, which seriously affected the normal production of the lactico-therapeutic measures according to the geological conditions and terrain features of different mines and the development and utilization of the mine, the distribution characteristics of disaster points are spanided into different levels of prevention and treatment in order to take the corresponding control lly spanided into the focus of prevention and control areas, sub key areas and the general prevention and control area.1, focus on prevention and control measures rational design of slope parameters, to strengthen the monitoring of slope, it is recommended to make retaining wall stability, after excavation, if the crack deformation, it is recommended to do a special engineering geological the existing disaster point, do a good job of slope reinforcement and prevention work, as far as possible to eliminate the mining induced disasters and the hidden dangers of design of the side slope and the slope of the slag field is strictly made, and the design of the retaining wall is made to set up the dam to prevent the debris full and rational use of slag field, is strictly prohibited to discard slag(especially in the road along).for the mining of tunnel, in the trenches must prepare support, so that the mining side edge support and avoid the harm due to the roof of the mine to collapse, roof fall, especially above the tenants to prevent caused by the upper ground for tunnel drainage, to prevent water gushing up monitoring points for monitoring, recording and analysis work, to ensure that in the disaster area to nip in the the mining, the unified planning of the mining area, the planning of mine reclamation work, restore the ecological function of mine.2, second emphasis prevention area prevention measures approach during the construction of highway and mines living area, lots of slope and a certain amount of waste slag formation, may lead to the formation of slope instability, caused landslides and landslides;along the way is not reasonable to leave a residue may cause soil erosion, may form a slope of mud rock flow, the rolling stones and flyrock ific and rational design of the slope parameters, and reasonable support and reinforcement, the top of the slope should be set drainage ditch, do a good job of surface drainage then site management, rational piling dregs, it is strictly prohibited to spoil;in the construction of block stones and stone advantageous location facilities: after the end of the mining, the waste slag field will be covered with soil, planting trees and forests, restoring vegetation.3, the general prevention and control measures in the area of no major building and construction projects, mainly due to the broken surface rock and soil prohibit cross-border exploitation, reducing human disturbance, good vegetation protection and soil and water conservation.4, the geological environment restoration program and measures to prevent soil erosion and restoration of vegetation and landscape, the mine must be planning to carry out mine reclamation work, in order to restore the ecological function of waste residue should not be indiscriminately stacked, must be stacked to the mining boundary beyond the boundaries of the mining waste residue inside, in the process of mining, there are plans to fill the waste to the mined out ll after treatment and then deposited soil and h the above geological environment restoration work, reduce soil erosion, restore the ecological function of mine, achieve the goal of ecological restoration and maintenance of human and environmental harmony.翻譯：
礦產(chǎn)開(kāi)采與地質(zhì)災(zāi)害
經(jīng)濟(jì)的快速發(fā)展和生產(chǎn)需要加快對(duì)礦物的需求和消耗，這也為礦產(chǎn)開(kāi)采企業(yè)帶來(lái)更大的發(fā)展機(jī)會(huì)。然而由于迅猛發(fā)展的中小型礦山疏于管理，加之小型礦山的開(kāi)采方法和選礦工藝落后，大多無(wú)環(huán)保措施，加劇破壞礦區(qū)環(huán)境。開(kāi)采環(huán)境明顯惡化，礦山地質(zhì)災(zāi)害問(wèn)題日趨嚴(yán)重，潛在的致災(zāi)隱患不斷增多，且隨時(shí)可能發(fā)展成災(zāi)，造成人員傷亡、設(shè)備報(bào)廢、設(shè)施損毀甚至礦井關(guān)閉、資源浪費(fèi)等嚴(yán)重后果。
礦山地質(zhì)災(zāi)害的主要類(lèi)型
礦山地質(zhì)災(zāi)害種類(lèi)繁多，按成災(zāi)與時(shí)間的關(guān)系，可分為突發(fā)性礦山地質(zhì)災(zāi)害(如礦坑突水、瓦斯爆炸、巖爆等)和緩發(fā)性礦山地質(zhì)災(zāi)害(如采空區(qū)的地面變形、環(huán)境污染等)。但最常見(jiàn)的是以災(zāi)害的空間分布和成因關(guān)系分類(lèi)。巖土體變形災(zāi)害
礦山地面和采空區(qū)塌陷 地面塌陷主要發(fā)生在地下以井巷開(kāi)采的礦山。在礦山采空區(qū)，若保留礦柱不足，或因礦柱受損而失去支撐能力，就會(huì)造成地面塌陷。特別是那些礦體埋藏較淺，產(chǎn)狀較平緩的礦區(qū)(如煤礦)，地面塌陷的現(xiàn)象更為常見(jiàn)。礦體埋藏相對(duì)較深的地下開(kāi)采礦山，如果不能及時(shí)回填和崩落采空區(qū)，當(dāng)其達(dá)到一定規(guī)模就會(huì)產(chǎn)生大面積塌陷。此外，在巖溶分布區(qū)，還會(huì)因礦山排水疏干而導(dǎo)致溶洞上方地面塌陷。地面塌陷不僅破壞可耕地資源、建筑物，毀壞道路、水庫(kù)，還可直接導(dǎo)致礦山某些地下巷道的塌毀，或使大氣降水和地表水沿塌陷裂縫灌入坑內(nèi)，造成淹井事故，直至停工停產(chǎn)。
采礦場(chǎng)邊坡失穩(wěn)、滑坡與巖崩 主要原因是不合理開(kāi)采如采剝失調(diào)、邊坡角度過(guò)陡等造成，這種災(zāi)害多發(fā)生在露天開(kāi)采的非金屬礦山和建材礦山。
坑內(nèi)巖爆 坑內(nèi)巖爆又稱礦山?jīng)_擊，這是因礦坑周邊和頂?shù)装鍑鷰r，在受到強(qiáng)大的地殼應(yīng)力作用而被強(qiáng)烈壓縮，一旦因采掘挖空出現(xiàn)自由面，即有可能產(chǎn)生巖石地應(yīng)力的驟然釋放，導(dǎo)致巖石大量破裂成碎塊，并向坑內(nèi)大量噴射、爆散，給礦山帶來(lái)危害和災(zāi)難。
采礦誘發(fā)地震 因采礦活動(dòng)而誘發(fā)的地震，震源淺、危害大，小震級(jí)的地震即可導(dǎo)致井下和地表的嚴(yán)重破環(huán)。
場(chǎng)庫(kù)失穩(wěn) 場(chǎng)庫(kù)失穩(wěn)主要是由于尾礦壩潰決崩塌繼而形成泥石流造成的危害。尾礦壩崩壩事故常給礦區(qū)居民生命財(cái)產(chǎn)帶來(lái)巨大危害，同時(shí)也給環(huán)境造成巨大破壞和污染。
2、地下水位改變引起的災(zāi)害
礦坑突水涌水 這是最常見(jiàn)的礦山災(zāi)害，突發(fā)性強(qiáng)、規(guī)模大，后果嚴(yán)重。生產(chǎn)過(guò)程中常因?qū)ΦV坑涌水量估計(jì)不足，采掘過(guò)程中打穿老窿，貫穿透水?dāng)鄬樱E遇蓄水溶洞或暗河，導(dǎo)致地下水或地面水大量涌入，造成井巷被淹、人員傷亡災(zāi)難。
坑內(nèi)潰沙涌泥 這是常與礦坑突水相伴而生的災(zāi)害。當(dāng)采掘過(guò)程中驟遇蓄水溶洞，常見(jiàn)溶洞中充填的泥沙和巖屑伴隨地下水一起涌入，另外一些透水?dāng)鄬雍偷亓芽p也常會(huì)使淺部第四紀(jì)沉積物隨下漏的地表徑流涌入坑內(nèi)。其結(jié)果是使坑道被泥沙阻塞，機(jī)器、人員被泥沙所埋，嚴(yán)重時(shí)甚至?xí)沟V山遭受毀滅性的打擊。2.2.3 環(huán)境污染 環(huán)境污染是礦山災(zāi)害的另一種重要形式。因采礦、選礦產(chǎn)生的“三廢”物質(zhì)，由于未經(jīng)有效處理就被排放到江河湖海中，造成環(huán)境污染公害事件。采礦還會(huì)造成水土流失、土地砂化、鹽漬化、地下水?dāng)嗔鞯取?/p>
3、礦體內(nèi)因引起的災(zāi)害
瓦斯爆炸和礦坑火災(zāi) 這種災(zāi)害最常見(jiàn)于煤礦。由于通風(fēng)不良，使瓦斯積聚發(fā)生爆炸，造成井下作業(yè)人員傷亡，礦井被毀;礦坑火災(zāi)除見(jiàn)于煤礦外，也見(jiàn)于一些硫化礦床。因硫化物氧化生熱，在熱量聚積到一定程度時(shí)則發(fā)生自燃，引發(fā)礦山火災(zāi)。礦山火災(zāi)的危害極大，而且還嚴(yán)重?fù)p耗地下礦產(chǎn)資源，如有的煤礦在地下已燃燒上百年，其資源損耗量十分巨大，使當(dāng)?shù)貧夂虬l(fā)生改變，農(nóng)作物和樹(shù)木大量死亡，田地荒蕪，環(huán)境嚴(yán)重惡化。
地?zé)?隨著開(kāi)采深度加大，地?zé)嵛：Σ粩嗉觿?。我?guó)已有許多礦山開(kāi)采深度達(dá)到800m以下，礦山因含硫量高，開(kāi)采深度又大，地溫非常高。礦山地?zé)釣?zāi)害導(dǎo)致礦工勞動(dòng)環(huán)境惡劣，嚴(yán)重影響了有關(guān)礦山的正常生產(chǎn)。
防治措施
根據(jù)不同礦山的地質(zhì)條件和地形特點(diǎn)及礦山的開(kāi)發(fā)利用方案，以及災(zāi)點(diǎn)的分布特點(diǎn)劃分不同層次的防治區(qū)，以便采取相應(yīng)的防治措施。一般分為重點(diǎn)防治區(qū)、次重點(diǎn)防治區(qū)和一般防治區(qū)。
1、重點(diǎn)防治區(qū)防治措施
合理設(shè)計(jì)邊坡參數(shù)，加強(qiáng)邊坡監(jiān)測(cè)，建議作擋墻穩(wěn)固邊坡，開(kāi)挖后如果出現(xiàn)開(kāi)裂變形，建議做專門(mén)的工程地質(zhì)勘察。
對(duì)于原有的災(zāi)害點(diǎn)，做好邊坡加固和預(yù)防工作，盡量消除因礦山開(kāi)采而誘發(fā)災(zāi)害復(fù)發(fā)的隱患。
渣場(chǎng)棄渣嚴(yán)格作好方量及邊坡坡度的設(shè)計(jì)，作好擋墻設(shè)計(jì)，設(shè)置攔渣壩，防止泥石流的產(chǎn)生。并充分、合理利用渣場(chǎng)，嚴(yán)禁隨意棄渣(特別在公路沿線)。
對(duì)于坑道開(kāi)采，在坑道內(nèi)一定要作好支護(hù)，做到邊開(kāi)采邊支護(hù)，防止因礦頂坍塌、冒頂?shù)榷a(chǎn)生的危害，尤其上方有住戶處要預(yù)防引起上部地面開(kāi)裂。
作好坑道的排水設(shè)計(jì)，以防因礦坑涌水造成危害。
設(shè)置監(jiān)測(cè)點(diǎn)，作好監(jiān)測(cè)記錄與分析工作，確保在易于發(fā)生災(zāi)害地段防患于未然。
開(kāi)采結(jié)束后，對(duì)礦區(qū)進(jìn)行統(tǒng)一規(guī)劃，計(jì)劃進(jìn)行礦山復(fù)墾工作，恢復(fù)礦山生態(tài)功能。
2、次重點(diǎn)防治區(qū)防治措施 在進(jìn)場(chǎng)公路、礦山生活區(qū)建設(shè)中，會(huì)形成大量的邊坡和一定數(shù)量的棄渣，可能形成邊坡失穩(wěn)，造成滑坡和塌方；沿途不合理的棄渣可能造成水土流失，可能形成坡面泥石流，可能有滾石和飛石危害。
科學(xué)合理設(shè)計(jì)邊坡參數(shù)，并進(jìn)行合理支護(hù)和加固，邊坡上方應(yīng)設(shè)置排水溝，做好地表?yè)跖潘胧?/p>
加強(qiáng)工地管理，合理堆放棄渣，嚴(yán)禁隨意棄渣；在險(xiǎn)要地段建設(shè)攔擋滾石和飛石的設(shè)施：
開(kāi)采結(jié)束后，將棄渣場(chǎng)扒平覆土，植樹(shù)還林，恢復(fù)植被。
3、一般防治區(qū)防治措施 區(qū)內(nèi)無(wú)主要建筑物和工程項(xiàng)目建設(shè)，主要可能因地表巖體的破碎而造成水土流失。應(yīng)嚴(yán)禁越界開(kāi)采，減少人為擾動(dòng)，做好植被保護(hù)和水土保持。
4、地質(zhì)環(huán)境恢復(fù)方案及措施 為防止水土流失和恢復(fù)植被和景觀，礦山須規(guī)劃進(jìn)行礦山復(fù)墾工作，以恢復(fù)礦山生態(tài)功能。開(kāi)采棄渣切勿胡亂堆放，必須統(tǒng)一堆放到開(kāi)采境界線以外的礦山棄渣場(chǎng)內(nèi)，在開(kāi)采過(guò)程中，有計(jì)劃地將棄渣回填到采空區(qū)。棄渣場(chǎng)經(jīng)處理后再敷表土、植草種樹(shù)。
通過(guò)上述地質(zhì)環(huán)境恢復(fù)工作，減少水土流失，恢復(fù)礦山的生態(tài)功能，達(dá)到生態(tài)恢復(fù)與維護(hù)人類(lèi)與環(huán)境和諧的目的。
食品專業(yè)英語(yǔ)論文篇四
met基因復(fù)制數(shù)量的增加賦予單克隆抵抗體抗met的能力并且建立藥物依賴性
關(guān)鍵詞：met，mv-nv30單克隆抗體，酪氨酸激酶抑制劑，抗性，藥物依賴性 【摘要】：被mei原癌基因編碼的酪氨酸激酶受體領(lǐng)導(dǎo)了具體抑制劑的發(fā)展并在癌癥中起很重要的作用，其中現(xiàn)在一些正處于前進(jìn)的臨床試驗(yàn)階段就以前的經(jīng)驗(yàn)表明對(duì)大多數(shù)靶向治療最主要的限制是抗性的出現(xiàn)。在對(duì)met單克隆抗體抗性和抗體對(duì)化學(xué)抑制劑旁路抗性（反之亦然）一無(wú)所知時(shí)，酪氨酸激酶抑制劑對(duì)met的抗性機(jī)制就已經(jīng)被提出。ebc1型肺癌細(xì)胞是met基因擴(kuò)增的結(jié)果，并且這種細(xì)胞對(duì)met抑制劑非常敏感，包括met單克隆抗體的單機(jī)形式在內(nèi)。我們培養(yǎng)生成抵抗抗體的細(xì)胞發(fā)現(xiàn)這種抗性是由于met基因大量復(fù)制擴(kuò)增和它的受體顯著表達(dá)而來(lái)。這種過(guò)度表達(dá)可以使單克隆抗體的“脫落”活動(dòng)達(dá)到飽和，并且能夠防止表面的met受體的有效的下調(diào)和抑制劑的活化作用。值得注意的是mv-dn30抗體的抗性細(xì)胞是met耐受細(xì)胞對(duì)met酪氨酸激酶抑制劑也很敏感。除此之外，抗體抗性細(xì)胞還具有藥物依賴性,mv-dn30的去處導(dǎo)致它們死亡是由于它們的過(guò)度信號(hào)表達(dá)。在實(shí)驗(yàn)中，對(duì)met酪氨酸激酶抑制劑存在抗性的細(xì)胞仍然對(duì)mv-dn30抗體的作用敏感。結(jié)果表明一種不連續(xù)的通過(guò)抗體和化學(xué)激酶抑制劑聯(lián)合治療可能會(huì)使靶向治療的臨床反應(yīng)和對(duì)met抗體治療旁路的抗性增加。
縮略語(yǔ)：mv-dn30--單價(jià)dn30，tkes—酪氨酸激酶抑制劑，hgf—肝細(xì)胞生長(zhǎng)因子，mapk—有絲分裂原活化蛋白激酶 1.簡(jiǎn)介
可以抑制一個(gè)特定的目標(biāo)分子化合物的靶向治療法開(kāi)辟了治療癌癥的新道路。與主要?dú)⑺罃U(kuò)散細(xì)胞為主的傳統(tǒng)化療不同的是靶向藥物對(duì)腫瘤細(xì)胞采取一種更具體的治療方式。靶向治療依賴于“癌基因沉癮”的概念。這就意味著單個(gè)基因的抑制或死亡是由于它們的沉癮，或者至少抑制它們的生長(zhǎng)（溫斯坦,2002）。臨床試驗(yàn)中的特定抑制劑的發(fā)展給腫瘤細(xì)胞的“achille’s heel”的識(shí)別提供支持（溫斯坦和喬，2006）。
盡管靶向治療在一部分癌癥患者中取得了較優(yōu)異的效果，還有重要的一點(diǎn)就是部分癌癥病人對(duì)藥物的選擇表達(dá)沒(méi)有起到治療作用（原發(fā)性），除此之外，幾乎總是一開(kāi)始患者反應(yīng)變成后來(lái)對(duì)治療的抵抗和復(fù)發(fā)（繼發(fā)性）。因此，最關(guān)鍵的就是要發(fā)現(xiàn)對(duì)治療抵抗的機(jī)制并且找到繞過(guò)它們的方法。
癌基因和人類(lèi)癌癥密切相關(guān)，酪氨酸激酶起著決定性作用。這個(gè)觀察發(fā)現(xiàn)許多腫瘤沉溺其中使得蛋白激酶成為了治療癌癥的理想目標(biāo)（巴塞爾加，2006;gschwind等人，2004）。在臨床診斷中主要使用一種較小的激酶抑制劑和單克隆抗體來(lái)抑制酪氨酸激酶。酪氨酸激酶抑制劑是一種可以抑制靶蛋白酶活性的小分子物質(zhì)。它們能有效地瞄準(zhǔn)膜結(jié)合位點(diǎn)和細(xì)胞內(nèi)的激酶并且很容易在體內(nèi)擴(kuò)散。單克隆抗體已被廣泛用于臨床并取得了可觀的成果。這些分子的優(yōu)點(diǎn)在于它們具有很高的特異性。在癌癥治療中的可以抗癌的rtks單克隆抗體已經(jīng)被批準(zhǔn)在乳腺癌和結(jié)腸癌中使用(分別針對(duì)her2和表皮生長(zhǎng)因子受體)并可作為抗血管增生的藥物（針對(duì)血管內(nèi)皮生長(zhǎng)因子受體）。除此之外，很多針對(duì)于其他目標(biāo)的單克隆抗體正處與發(fā)展和試驗(yàn)階段。最近，一種作為癌癥治療目標(biāo)的rtk受到關(guān)注，這種rtk是由致癌基因編碼的在肝細(xì)胞生長(zhǎng)因子上的酪氨酸激酶受體。在和肝細(xì)胞生長(zhǎng)因子結(jié)合后，met活化并啟動(dòng)一個(gè)復(fù)雜的生化程序，這個(gè)過(guò)程被稱作“浸潤(rùn)性上長(zhǎng)”。在腫瘤組織中，浸潤(rùn)性生長(zhǎng)的增進(jìn)可以迫使腫瘤細(xì)胞從腫瘤組織中分解下來(lái)侵蝕基底膜，滲入基質(zhì)中，甚至定居于新的組織中來(lái)實(shí)現(xiàn)轉(zhuǎn)移。很多研究結(jié)果表明met在人類(lèi)的許多腫瘤中具有活性，并且它與對(duì)直接激酶療法的持續(xù)抗性密切相關(guān)。除此之外，還表明細(xì)胞顯示大量復(fù)制（超過(guò)8張）和隨之而來(lái)的過(guò)度表達(dá)和獨(dú)立配體的激活都是沉溺于這種致癌基因和抗met藥物的應(yīng)答中。在前期設(shè)置得到的基本結(jié)果，幾種特定的多目標(biāo)的酪氨酸激酶抑制劑和直接針對(duì)于met或者h(yuǎn)gf的抗體已經(jīng)進(jìn)入了臨床試驗(yàn)階段。在活體和動(dòng)物模型進(jìn)行的研究已經(jīng)表明用tkis長(zhǎng)期治療會(huì)導(dǎo)致機(jī)體的治療耐受性。對(duì)met tkis的抗性可能是由于一些機(jī)制，比如met基因擴(kuò)增，過(guò)度表達(dá)，met點(diǎn)突變，met平行路徑的激活和kras基因的擴(kuò)增機(jī)制。然而，關(guān)于對(duì)met的單克隆抗體的再次具有抗性一無(wú)所知。
我們以前報(bào)道過(guò)主要針對(duì)細(xì)胞外的部分met的抑制性單克隆抗體的研究進(jìn)展。它的誘導(dǎo)、再結(jié)合、達(dá)到met脫落閾值的能力使其有抑制活性，剩余的跨膜片段通過(guò)蛋白酶體降解途徑處理掉。因此，dn-30結(jié)合到met后的結(jié)果是使其變成可溶性的誘餌met并且蛋白水解酶會(huì)講解met激酶。這促進(jìn)了met介導(dǎo)的生物活性的抑制作用。設(shè)計(jì)了這樣一個(gè)過(guò)程就是因?yàn)閐n-30的結(jié)合使得met激酶部分活化并且導(dǎo)致抗體介導(dǎo)的受體同源二聚體化和單價(jià)fab片段失去競(jìng)爭(zhēng)活性的一個(gè)過(guò)程。
在這個(gè)研究中我們表明了不斷用mv-dn30來(lái)治療沉癮癌細(xì)胞會(huì)使其具有抗性的原因是met基因的大量復(fù)制和met的過(guò)度表達(dá)超過(guò)了mv-dn30對(duì)其有效下調(diào)并使其失去活性的的能力。值得注意的是，mv-dn30抗性細(xì)胞還會(huì)一直對(duì)met tkis產(chǎn)生耐受性和敏感性。有趣的是，它們獲得了藥物耐受性，當(dāng)受到mv-dn30的驅(qū)除致死它們的是過(guò)多的信號(hào)表達(dá)。我們還表明對(duì)met tkis 有抗性的細(xì)胞也對(duì)mv-dn30敏感，所以，mv-dn30和met tkis 對(duì)腫瘤細(xì)胞的作用是相互促進(jìn)的。2.材料與方法 2.1.細(xì)胞和試劑
ebc1 細(xì)胞從一個(gè)患有轉(zhuǎn)移皮膚腫瘤的病人取得，這個(gè)患者還患有肺鱗狀細(xì)胞癌，病例是從日本癌癥資料庫(kù)購(gòu)買(mǎi)得到。gtl16 是一種實(shí)驗(yàn)室里的克隆胃癌細(xì)胞系。hek-293t細(xì)胞系分離于人類(lèi)胚胎時(shí)期的腎，a549細(xì)胞系來(lái)源于肺癌，都是從atcc購(gòu)買(mǎi)來(lái)培養(yǎng)的。對(duì)mv-dn30有抗性的ebc1細(xì)胞可以通過(guò)一個(gè)逐步的方法培養(yǎng)得到，由sigma tau r&d 提供的通過(guò)暴露親代細(xì)胞方法來(lái)增加抗met單價(jià)單克隆抗體的濃度。親代細(xì)胞用10 mg/ml 的mv-dn30治療約一個(gè)月，直到生成的r10細(xì)胞開(kāi)始產(chǎn)生抗性為止，r10抗性細(xì)胞又用逐步增加濃度的mv-dn30治療。所有的抗體耐受細(xì)胞培養(yǎng)在存在mv-dn30并且可以使它們產(chǎn)生耐受性的條件下。大約兩個(gè)月可以分離到r20抗體抗性細(xì)胞，四個(gè)月可以分離到r80抗體耐受細(xì)胞。ebc1 and gtl16 細(xì)胞對(duì)met tkis pha-665752(ebc1 rpha 50 nm and gtl16 rpha 150 nm)都有耐受性，并且向描述的那樣培養(yǎng)可以一直保持pha-665752的存在。該細(xì)胞系的遺傳身份通過(guò)一個(gè)短的串珠狀重復(fù)序列（str）識(shí)別，這段序列在2013年7月再次重復(fù)出現(xiàn)。we 我們利用下面的小分子：atp競(jìng)爭(zhēng)行met tkis pha-665752(tocris bioscience)and jnj-38877605(john-son & johnson)和p38map激酶抑制劑sb203580(merck).和基因組dna的分析
用trizol 試劑提取得到的rna被檢測(cè)到利用多文士病毒的逆轉(zhuǎn)錄酶和隨機(jī)引物合成，cdna可以用實(shí)時(shí)的利用電源帶動(dòng)的綠色pcr混合的pcr 技術(shù)來(lái)實(shí)現(xiàn)擴(kuò)增，根據(jù)制造商的說(shuō)明下面的met和actin特異性引物要用到： hmet ex 19 fw: 50-agtttaccaccaagtcagatgtgt-30;hmet ex 20 rw: 50-gggctcctcttgtcatcagc-3;hactin fw: 50-ggaggagctggaagcagcc-30;hactin rw: 50-gctgtgctacgtcgccctg-30.根據(jù)制造商的說(shuō)明用實(shí)時(shí)pcr技術(shù)來(lái)分析用純化的dna基因組迷你試劑盒分析從細(xì)胞中提取到的基因組dna，這種技術(shù)是用 taqman基因表達(dá)的主要結(jié)構(gòu)和taqman探針met基因和rnasep控制基因的實(shí)時(shí)定量pcr分析。met的mrna的成倍增加和ebc1中met基因的大量復(fù)制以及mv-dn30抗性細(xì)胞歸一化然后被認(rèn)可。2.3.蛋白印跡分析和脈沖追蹤代謝標(biāo)記
蛋白提取液(40 mg), 細(xì)胞上清液(20 ml)。在細(xì)胞裂解前2小時(shí)把met tki jnj-38877605加入到指定的地方。免疫印跡法使用了以下的初級(jí)抗體：the anti-met intracellular domain(icd)(zymed, #370100)from invitrogen, anti-met ecd(dl21)obtained as described(prat et al., 1991), anti-phospho-tyr1234-tyr 1235met(#3126), anti-akt(#9272), anti-phospho-ser473akt(#4060),anti-p44/42mapk(#9102),anti-phospho-thr202-tyr204p44/42mapk#9101),anti-p38mapk(#8690),anti-phospho-thr180-tyr182-p38 mapk(#9215), from cellsignaling;anti-vinculin(#v9131)from sigma and anti-b-actin(#i-19 sc-1616)from santa cruz ary igg hrp-peroxidase antibodies were from amersham.脈沖追蹤實(shí)驗(yàn)的1106wt，或mv-dn30抗性的ebc1細(xì)胞(r80)都被平鋪在60mm的盤(pán)里。r80 細(xì)胞保存在有或沒(méi)有抗體（80 mg/ml）存在的條件下，而wt細(xì)胞要一直保存在有抗體的條件小16小時(shí)。然后，這些細(xì)胞在不含l-蛋氨酸但有500mmmcil-甲硫氨酸s35(脈沖)（易標(biāo)記）的dmem培養(yǎng)基中處理20分鐘。在這之后，去處放射性標(biāo)記的培養(yǎng)基，細(xì)胞用1ml磷酸鹽緩沖液鹽水洗兩次然后保存在有2mliscove的培養(yǎng)基中，培養(yǎng)基中加入2%fbs，在mv-dn30(80 mg/ml)存在或不存在脈沖3.6和16小時(shí)。之后，用免疫沉淀法（ip）在1ml細(xì)胞裂解液中進(jìn)行測(cè)定（裂解緩沖液：1% tritonx-100存在下，20 mm tris-鹽酸，5毫米edta，10% v / v甘油，150 mm nacl補(bǔ)充蛋白磷酸酶抑制劑）通過(guò)使用抗met icd dq13單克隆抗體，而ip法利用抗met ecd do24單克隆抗體對(duì)細(xì)胞培養(yǎng)2毫升上清液進(jìn)行。細(xì)胞裂解液和上清液都在有已知抗體的培養(yǎng)基里培養(yǎng)16個(gè)小時(shí)，抗鼠igg抗體預(yù)包被瓊脂糖凝膠蛋白珠形成免疫復(fù)合物沉淀下來(lái)。免疫沉淀物中的蛋白就會(huì)被8% sds-page 分開(kāi)，然后轉(zhuǎn)移到3mm的紙上，80度，48小時(shí)后蛋白質(zhì)的放射性就會(huì)在投影膜上留下印記。2.4.生長(zhǎng)和可行性分析
用于細(xì)胞生長(zhǎng)和可行性分析的這些細(xì)胞被接種在96孔的培養(yǎng)板上，根據(jù)制造商的說(shuō)明用已知藥物在不同時(shí)期進(jìn)行處理然后用細(xì)胞滴度發(fā)光細(xì)胞進(jìn)行可行性分析。沒(méi)經(jīng)過(guò)處理的細(xì)胞控制在藥物載體存在的條件下生長(zhǎng)。所有的數(shù)據(jù)進(jìn)行歸一化到0天的藥物治療。2.5.熒光細(xì)胞分析
對(duì)結(jié)合在ebc1wt,r20,r80細(xì)胞質(zhì)膜上的met進(jìn)行免疫熒光著色，這些細(xì)胞要提前在有或沒(méi)有mv-dn30存在的條件下培養(yǎng)24小時(shí)。熒光性的強(qiáng)度可以通過(guò)細(xì)胞熒光性分析檢測(cè)到。用于檢測(cè)的細(xì)胞要在pbs中用2%fbs洗滌并且在室溫下用抗met ecd do24 mab(100 ng/ml)著色20分鐘。然后在室溫下細(xì)胞又在pbs中用2%fbs洗滌就會(huì)逐步產(chǎn)生抗鼠igg-rpe二抗然后用二脒基苯基吲哚作用20分鐘。作為陰性對(duì)照，將不含初級(jí)抗met抗體的細(xì)胞進(jìn)行染色。質(zhì)膜結(jié)合的蛋氨酸的熒光強(qiáng)度（au為單位），通過(guò)使用graphpad prism軟件繪制為箱形繪圖圖表。
2.6.慢病毒載體轉(zhuǎn)導(dǎo)
ebc1 wt 細(xì)胞能穩(wěn)定地在兩種不同量的慢性病毒顆粒編碼的met cdn轉(zhuǎn)導(dǎo)，包括1mg(mettt)和1.6mg(metttt)的p24病毒抗原，其濃度按說(shuō)明確定。作為對(duì)照，wt細(xì)胞用含有空載體病毒顆粒感染。mv-dn30抗性細(xì)胞(r20 and r80)只用空載體感染。在感染48小時(shí)后接種細(xì)胞用于生物化學(xué)分析。轉(zhuǎn)導(dǎo)細(xì)胞的可行性分析如先前描述的一樣進(jìn)行，讓細(xì)胞在存在或不存在mv-dn30的條件下上長(zhǎng)72小時(shí)。如先前所述，met的蛋白印跡分析和磷酸化的met蛋白水平和對(duì)感染細(xì)胞的mrna的表達(dá)水平實(shí)時(shí)定量pcr分析一樣子細(xì)胞感染72小時(shí)后進(jìn)行評(píng)估。2.7.藥物協(xié)同作用分析
在抗met抗體mv-dn30和met tki jnj-38877605之間進(jìn)行藥物協(xié)同作用分析是對(duì)wt ebc1和接種在96孔板上的gtl16細(xì)胞在用藥物治療72小時(shí)后的細(xì)胞活力的研究。如果使用一個(gè)藥品從藥物劑量來(lái)說(shuō)要比混合使用的ic50約高10倍左右，雙重增加濃度可以用于單藥使用和組合使用。評(píng)估細(xì)胞活力為前面描述的增效作用的藥物效應(yīng)多種分析研究，采用組合指數(shù)（ci）和chou and talalay 方法。使用相互排他性假設(shè)計(jì)算ci值（藥物作用機(jī)理的不同，）軟件，可上線的網(wǎng)站：http:///，和繪制功能的fa（由這兩種藥物的組合影響系統(tǒng)分?jǐn)?shù)）。ci值< 1表明兩種藥物之間的協(xié)同作用。2.8.統(tǒng)計(jì)分析
同一個(gè)實(shí)驗(yàn)數(shù)據(jù)用graphpad prism軟件進(jìn)行兩尾t檢驗(yàn)分析至少有三種生物學(xué)具有統(tǒng)計(jì)學(xué)顯著意義的結(jié)果。p值小于0.05被認(rèn)為是有意義的。3.結(jié)果
-dn30耐藥細(xì)胞株的建立
ebc1 肺癌細(xì)胞是met沉癮細(xì)胞，它能放大met的擴(kuò)增、過(guò)度表達(dá)和活化過(guò)程。met tkis或者mv-dn30對(duì)ebc1細(xì)胞里的met具有強(qiáng)烈的破壞它們生存和上長(zhǎng)的能力的作用（圖a~c）。
我們先前培養(yǎng)的ebc1細(xì)胞 對(duì)不同的ykis有抗性表明了這種抗性可能是由于met基因的進(jìn)一步擴(kuò)增。為了產(chǎn)生抗mv-dn30的細(xì)胞，我們采用逐步暴露ebc1原代細(xì)胞不方法來(lái)增加抗體的濃度，并且獲得抗不同劑量抗體的細(xì)胞系（圖1b；約的分步方法詳見(jiàn)材料和方法部分）。, 進(jìn)一步的實(shí)驗(yàn)中，我們使用耐20細(xì)胞（ebc1 r20）和80（ebc1 r80）毫克/毫升mv-dn30，劑量是分別是前面的約10倍和40倍，然后測(cè)這些細(xì)胞的抗體ic50（圖1a）。在有mv-dn30存在的抗性細(xì)胞的生長(zhǎng)速度一直和wt細(xì)胞差不多（圖1c）。
正如前面提到的，mv-dn30發(fā)揮它的抑制活性是通過(guò)誘導(dǎo)met的結(jié)構(gòu)域蛋白反正溶蛋白裂解，隨后又通過(guò)蛋白酶體受體介導(dǎo)受體降解。這種反應(yīng)減少了細(xì)胞表面的met的大量表達(dá)，抑制了met的活性和受體介導(dǎo)的生物學(xué)活性。如圖1d所示，事實(shí)上，mv-dn30的治療導(dǎo)致了再ebc1細(xì)胞中的met通過(guò)酪氨酸酶的磷酸化消除大量減少。與抗性細(xì)胞的生化分析相反的是顯示了在相同劑量抗體存在的情況下，met也會(huì)磷酸化并且在質(zhì)膜上的大量的met蛋白明顯高于保存在相同條件下的wt細(xì)胞（圖1d,e）。除此，盡管激活的下游目標(biāo)akt和mapk激酶都被保存在有抗體存在的條件下（圖1d）。
所有的數(shù)據(jù)表明，抗ebc1細(xì)胞的mv-dn30并不是通過(guò)一種足以消除它的結(jié)構(gòu)的活性的方法來(lái)下調(diào)met，而是一種允許它的信號(hào)轉(zhuǎn)導(dǎo)來(lái)調(diào)節(jié)它的結(jié)構(gòu)磷酸化的方法.3.2.抗性細(xì)胞中缺乏mv-dn30抑制活性并不是因?yàn)樗幕钚圆蛔?/p>
如圖1d,e所示，用mv-dn30處理抗性細(xì)胞致使met大量減少這種減少比處于同等條件下觀察的wt細(xì)胞中的減少更明顯。我們想知道在抗性細(xì)胞里的抗體受損是否是由于met的結(jié)構(gòu)域ipt4發(fā)生突變引起，這個(gè)結(jié)構(gòu)域是它的集合位點(diǎn)，但是我們沒(méi)有發(fā)現(xiàn)任何突變（數(shù)據(jù)顯示）。
于是，我們?cè)u(píng)估了是否是抗性細(xì)胞中脫落的met胞外結(jié)構(gòu)域（ecd）對(duì)抗體的反應(yīng)被抑制了。在相同劑量mv-dn30存在的條件下培養(yǎng)了24小時(shí)的抗性細(xì)胞和wt細(xì)胞的上清液中，抗性細(xì)胞上清液中含有更豐富的脫落的ecd（圖2a）。當(dāng)對(duì)去處抗體24小時(shí)后的抗性細(xì)胞中met的表達(dá)和活化進(jìn)行評(píng)估時(shí)，我們觀察到met總量強(qiáng)烈增加特別是結(jié)合在細(xì)胞膜上的形式（圖2b和圖1）。對(duì)抗性細(xì)胞再引入mv-dn30細(xì)胞會(huì)導(dǎo)致上清液中met ecd含量更高，與在同樣劑量處理的wt細(xì)胞相比，之后細(xì)胞內(nèi)的met同時(shí)減少了并返回到平時(shí)觀察的抗性細(xì)胞的一半水平（圖2 d）。在脈沖代謝標(biāo)記實(shí)驗(yàn)中也觀察到了相似的結(jié)果：比起wt細(xì)胞，抗性細(xì)胞合成更多的met和mv-dn30來(lái)促進(jìn)met ecd 釋放并大量增加（圖2e）。最后，用更高劑量抗體20 mg/ml(r20)處理ebc1細(xì)胞來(lái)更好的證明mv-dn30在抗性細(xì)胞中是具有活性的。圖2f所示在抗性細(xì)胞中隨著mv-dn30劑量是增加減少了大量met在細(xì)胞膜上的表達(dá)（圖2a）和磷酸化(圖2b)。
總之，所有的結(jié)果表明ebc1細(xì)胞的抗性不是因?yàn)閙v-dn30活性缺乏，而是由于用它的飽和能力來(lái)促進(jìn)了一種高效的met解離。
圖1-抗mv-dn30的ebc1細(xì)胞分子表征。(a)在有mv-dn30的遞增濃度的條件下培養(yǎng)了72小時(shí)的ebc1 wt細(xì)胞的細(xì)胞活力。對(duì)未經(jīng)過(guò)處理的細(xì)胞(100%)± s.d.的歸一化結(jié)果。(b)在指定濃度抗體的條件下培養(yǎng)72小時(shí)的ebc1 wt細(xì)胞或產(chǎn)生mv-dn30抗性的細(xì)胞(r10, r20, r40, r80)。與未經(jīng)過(guò)處理的wt細(xì)胞(100%)± s.d歸一化結(jié)果。(c)在mv-dn30(20 and 80 mg/ml)存在的條件下生長(zhǎng)的ebc1 wt細(xì)胞ebc1r20和r80細(xì)胞的生長(zhǎng)活性。與未經(jīng)過(guò)處理的wt細(xì)胞(100%)± s.d歸一化結(jié)果(***p < 0.001)。(d)在有指定劑量mv-dn30抗體存在的條件下處理24小時(shí)的ebc1wt ,ebc1r20和r80細(xì)胞的蛋白印跡。(e)結(jié)合met的在24小時(shí)在不存在或存在的血漿膜的熒光強(qiáng)度的箱圖mv-dn30 r20和r80生長(zhǎng)ebc1 wt細(xì)胞（au：任意單位）
圖2—細(xì)胞耐受性并不是由于失去了對(duì)mv-dn30的敏感性。(a)在存在或不存在mv-dn30的環(huán)境下培養(yǎng)24小時(shí)的ebc1 wtr20和r80細(xì)胞的上清液中met ecd的蛋白印跡。(b)在有或沒(méi)有（24小時(shí)去除）的ebc1wtr20和r80細(xì)胞中的蛋白（頂部）和蛋氨酸的酪氨酸磷酸化蛋白印跡。紐蛋白作為控制基礎(chǔ)(c)在 ebc1 wt, r20 and r80 細(xì)胞中有或沒(méi)有（24小時(shí)去除）mv-dn30的條件下在質(zhì)膜上結(jié)合的met的熒光強(qiáng)度的箱圖。質(zhì)膜著色如圖e。(d)在用mv-dn30處理（24h）的ebc1wt r20和r80 細(xì)胞中和抗性細(xì)胞（圖2 d）中觀察到的met總蛋白水平和met ecd 的蛋白印跡.(e)在有或沒(méi)有mv-dn30存在下的ebc1wt和r80細(xì)胞里的met(來(lái)源細(xì)胞裂解液，上面)和met ecd（來(lái)源與細(xì)胞上清液，底部）的用脈沖追蹤代謝蛋白標(biāo)記法的免疫沉淀分析。(f)在遞增mv-dn30濃度的環(huán)境下的ebc1(左圖)和r20細(xì)胞（右圖）的活性檢測(cè)。未經(jīng)過(guò)處理的wt細(xì)胞（左圖）或者用20 mg/ml(100%)處理的r20（右圖）統(tǒng)計(jì)結(jié)果(***p < 0.001, *p < 0.05)。3.3.對(duì)mv-dn30的抗性是由于met的擴(kuò)增和過(guò)度表達(dá)
如上圖所示（圖2bed），mv-dn30抗性細(xì)胞表達(dá)met水平比原代細(xì)胞更高。我們懷疑這可能是由于增加的啟動(dòng)子活性或更高的mrna的可用性，因?yàn)槟阄na的負(fù)控制微分表達(dá)了。在ebc1wt和抗性細(xì)胞的熒光素酶檢測(cè)結(jié)果顯示排除這些可能性（數(shù)據(jù)未顯示）。
然后我們?cè)u(píng)估了基因擴(kuò)增的情況是因?yàn)閙et大量復(fù)制是對(duì)激酶抑制劑存在抗性的機(jī)制。如圖3所示，ebc1抗性細(xì)胞顯示了met的大量復(fù)制（原代細(xì)胞的第24代到30代），這大約是二倍體細(xì)胞的15倍。當(dāng)分析met的mrna水平時(shí)，我們觀察到met的過(guò)度表達(dá)是wt細(xì)胞的2~3倍，達(dá)到了met正常表達(dá)細(xì)胞(a549 and hek-293t)的60~90倍。為了證明這種增加可能是為了維持對(duì)mv-dn30的抗性，我們將ebc1wt細(xì)胞放在不同量的met cdna條件下轉(zhuǎn)導(dǎo)，通過(guò)比較ebc1r20和r80細(xì)胞mrna的表達(dá)水平來(lái)獲得（圖3）。我們觀察到，met的mrna以2~3倍的速度劇增，這與在存在mv-dn30的條件下細(xì)胞的活性有關(guān)（圖3d）。除此，盡管有mv-dn30的存在met保持磷酸化，這就解釋了為什么細(xì)胞能夠存活增加（圖3e）。
所有實(shí)驗(yàn)結(jié)果表明，嗜met的ebc1細(xì)胞變得有抗性是因?yàn)閙et的進(jìn)一步擴(kuò)增和過(guò)度表達(dá)從而來(lái)阻止有效的抗體介導(dǎo)的對(duì)met活性的抑制。圖3
3.4.抗mv-dn30的細(xì)胞也是嗜met細(xì)胞并有藥物依賴性
為了證明抗mv-dn30的細(xì)胞也是嗜met細(xì)胞，我們用一種小分子的激酶抑制劑jnj-38877605來(lái)處理細(xì)胞。如圖4a,b所示，抗mv-dn30的ebc1細(xì)胞在有抗體(20 mg/ml for r20 and 80 mg/ml for r80)存在的條件下生長(zhǎng)情況顯示了當(dāng)用met激酶抑制劑jnj-38877605(10 nm or 250 nm)處理時(shí)，細(xì)胞活性的降低和met磷酸化作用的減弱。和親代ebc1細(xì)胞相比，抗性細(xì)胞對(duì)jnj-38877605的敏感劑量更低，可能是由于在抗性細(xì)胞中met的蛋白合成和轉(zhuǎn)運(yùn)更高效。從抗性細(xì)胞的培養(yǎng)基中去除mv-dn30會(huì)導(dǎo)致met的表達(dá)增加（圖2b），我們研究了過(guò)度表達(dá)的生化效應(yīng)?？剐约?xì)胞培養(yǎng)在不存在mv-dn30的條件下，顯示了活性下降（圖4c）。這些細(xì)胞的蛋白印跡分析表明，隨著時(shí)間的推移逐漸增加了磷酸化（圖4d）。然而，24~48h后，after 24e48 h, p38 mapk的活化清晰可見(jiàn)證明了通常在細(xì)胞凋亡反應(yīng)之前會(huì)有一個(gè)細(xì)胞應(yīng)激反應(yīng)。除此之外，在沒(méi)有mv-dn30存在的條件下培養(yǎng)的抗性細(xì)胞中的p38 mapk會(huì)受到一種小分子sb203580 的抑制使得細(xì)胞活性得以恢復(fù)（圖3）。這些數(shù)據(jù)進(jìn)一步表明，p38 mapk信號(hào)對(duì)于參與藥物依賴是至關(guān)重要的.重要的是要記住對(duì)于嗜met細(xì)胞抗met酪氨酸激酶抑制劑的藥物依賴條件和黑色素瘤有獲得性的藥物依賴性已經(jīng)被證明。為了證明當(dāng)去除mv-dn30后過(guò)多的met信號(hào)使細(xì)胞凋亡是正確的，我們用低劑量的met yki處理抗性細(xì)胞讓其充分減少但不會(huì)完全抑制met活性（圖4）。事實(shí)上，如圖4e所示，保存在不含mv-dn30并用 10 nm jnj-38877605（低于ic50濃度）處理的抗性細(xì)胞可以恢復(fù)它們的活性，并且這種水平類(lèi)似于保存在有抗體存在的培養(yǎng)條件下的抗性細(xì)胞的活性水平。
總之，這些結(jié)果表明，mv-dn30抗性細(xì)胞都是嗜met細(xì)胞并且它們的繁殖和生存都有藥物依賴性。圖4
3.5.在嗜met細(xì)胞中mv-dn30和met tkis的協(xié)同作用
met-tkis 和 mv-dn30 都可以有效的抑制ebc1細(xì)胞的活性，我們想知道這兩種抗met化合物是否表現(xiàn)增強(qiáng)或協(xié)同作用。單獨(dú)或在有非常低劑量的mv-dn30存在的條件下（0.15~2.5毫克/毫升，從10倍以下的ic50開(kāi)始），我們用逐步增加met抑制劑jnj-38877605的方法來(lái)處理ebc1 wt細(xì)胞。然后我們分析細(xì)胞活力和對(duì)藥物治療的兩種藥物的組合效應(yīng)的性質(zhì)，利用多藥效果分析。如圖5c所示，聯(lián)合治療導(dǎo)致的劑量盡可能低為1.25~20 nm jnj-38877605在0.15~2.5毫克/毫升mv-dn30存在活性降低。當(dāng)在gtl16 wt 胃癌細(xì)胞上做這個(gè)實(shí)驗(yàn)室會(huì)得到相似的結(jié)果（圖5d）。如圖5a、b所示，多藥效應(yīng)分析表明了 ebc1 and gtl16 wt細(xì)胞的ci值都小于1，從而表明了jnj-38877605和 mv-dn30之間有藥物協(xié)同作用.所有的這些數(shù)據(jù)表明用met tki和mv-dn30聯(lián)合治療可以有效地減少嗜met細(xì)胞的活性，劑量明顯低于單獨(dú)一種藥物治療的藥量。圖5
4.討論
臨床效應(yīng)甚至是最有效的靶向治療都被發(fā)展的耐藥性所限制。顯而易見(jiàn)，這種耐藥性機(jī)制已經(jīng)被廣泛研究。從癌細(xì)胞和抗酪氨酸激酶抑制劑表明，獲得性耐藥的最常見(jiàn)的機(jī)制包括在藥物目標(biāo)本身的二次突變的患者獲得的數(shù)據(jù)，激活下游信號(hào)轉(zhuǎn)導(dǎo)或平行的信號(hào)轉(zhuǎn)導(dǎo)通路的激活突變。即使對(duì)關(guān)于癌癥是怎樣產(chǎn)生耐藥性抗體的了解很少，一些現(xiàn)象提示用抗egfr 和抗her2抗體治療的病人體內(nèi)有耐藥機(jī)制的建立。在eger中的二次突變表明了免疫調(diào)節(jié)藥物與egfr的結(jié)合受到破壞從而調(diào)節(jié)了抵抗力。除此之外，最近的研究還證明了egfr或her2的信號(hào)轉(zhuǎn)導(dǎo)通路的激活可以分別繞過(guò)西妥昔單抗或曲妥單抗的抑制；這些包括egfr配體水平增加，met rtk的擴(kuò)增或過(guò)度表達(dá)，下游或平行激活信號(hào)轉(zhuǎn)導(dǎo)途徑。
在癌癥治療中met受體已經(jīng)變成了最具關(guān)注的目標(biāo)，因?yàn)楹芏嘌芯勘砻?，met在多種人類(lèi)腫瘤中具有組成性活性。它的失調(diào)可能是由于不同的機(jī)制包括過(guò)度表達(dá)，基因擴(kuò)增，激活突變和受體介導(dǎo)的刺激自分泌或旁分泌的增加。生殖細(xì)胞的激活突變的識(shí)別和遺傳型腎乳頭狀癌直接證明了met和人類(lèi)腫瘤發(fā)生有關(guān)的概念。met的酪氨酸激酶的結(jié)構(gòu)域中激活突變位點(diǎn)已經(jīng)在散發(fā)腫瘤中確定。然而，在人類(lèi)癌癥中變化頻繁的是轉(zhuǎn)錄表達(dá)的過(guò)程，這個(gè)過(guò)程是由原癌基因激活誘導(dǎo)抑癌基因失活和對(duì)特定的為mrna或缺氧刺激的下調(diào)過(guò)程。在原發(fā)性腫瘤中由基因擴(kuò)增引起的met過(guò)度表達(dá)是少見(jiàn)的，但在肺癌和結(jié)腸癌中變得抗靶向其它rtks治療的情況更頻繁。臨床證據(jù)表明癌細(xì)胞是沉溺在原癌基因中的細(xì)胞，在這種細(xì)胞中的met具有組織性活性并且它們的抑制結(jié)果就是使其致瘤性被破壞。然而，用小劑量的激酶抑制劑延長(zhǎng)對(duì)嗜met細(xì)胞的處理會(huì)導(dǎo)致二倍抗性的出現(xiàn)，這種機(jī)制可以被維持比如met擴(kuò)增或突變,kras的擴(kuò)增或egfr家族成員的活化。在我們的研究中表明,在嗜met細(xì)胞中對(duì)met特定抗體mv-dn30的抗性獲得是由于met復(fù)制數(shù)量的大量增加。這一現(xiàn)象的機(jī)理解釋依賴于染色體外的met復(fù)制的動(dòng)態(tài)調(diào)節(jié)，造成了一種癌癥對(duì)治療的適應(yīng)性程序。met上調(diào)的增加是由于met基因擴(kuò)增造成的這種現(xiàn)象并不明顯當(dāng)抗性細(xì)胞培養(yǎng)在有抗體（這種抗體介導(dǎo)了met的下調(diào)）存在的條件下，但是在沒(méi)有這種抗體存在的條件卻是很明顯清晰的。我們觀察到蛋白的增加平行下來(lái)是metmrna增加的2~3倍。ebc1 原代細(xì)胞的metcdna的轉(zhuǎn)導(dǎo)可以達(dá)到一個(gè)和抗性細(xì)胞一樣是表達(dá)水平，證明了事實(shí)上細(xì)胞表達(dá)更多的met可以減少對(duì)mv-dn30抑制活性的敏感性。wt ebc1細(xì)胞和大多數(shù)嗜met細(xì)胞一樣可以表達(dá)比正常表達(dá)細(xì)胞的約30倍多的met；因此，在抗性細(xì)胞中2~3倍的增加可以引起met水平比那些正常細(xì)胞中的met水平高60~90倍。在缺氧的環(huán)境下觀察a549細(xì)胞中met呈3倍增加才能滿足它的生化效應(yīng)，在抗mv-dn30的ebc1細(xì)胞中met增加可以解釋為什么抗體能夠有效地下調(diào)met。除此，作為抗性細(xì)胞識(shí)別增加的脫落的met導(dǎo)致了met ecd在細(xì)胞內(nèi)的累積，并且脫落的ecd可以和細(xì)胞膜上的mv-dnd30結(jié)合位點(diǎn)結(jié)合從而減少抗體的抑制效應(yīng)?？剐约?xì)胞仍然依賴于mei的信號(hào)傳導(dǎo)來(lái)增殖和生存，met可以完全被tkir抑制從而導(dǎo)致它們的增殖受到抑制。有趣的是，當(dāng)met變得非常活躍的時(shí)候，可以通過(guò)增加在mv-dn30存在下的met 的表達(dá)在這種適宜的有利的環(huán)境下來(lái)使其對(duì)藥物的去除效果減弱。我們的結(jié)果和報(bào)告是一致的都表明了，正常細(xì)胞和腫瘤細(xì)胞不僅對(duì)信號(hào)（即該通路被激活的信號(hào)）的質(zhì)量敏感而且對(duì)數(shù)量也很敏感（這種量就是怎樣激活通路）。信號(hào)過(guò)量可導(dǎo)致細(xì)胞應(yīng)激（在我們的情況下，通過(guò)p38 mapk活化）導(dǎo)致細(xì)胞死亡。事實(shí)上，在抗體缺乏，低劑量的遇到了tki治療耐藥細(xì)胞（抑制野生型細(xì)胞活力）增加了他們的活力，減少了信號(hào)的水平細(xì)胞持續(xù)強(qiáng)度的可能。das thakur做了一個(gè)類(lèi)似的觀察，這個(gè)人證明了人類(lèi)黑色素瘤移植提供的抗藥性，藥物的去除使耐藥腫瘤的腫瘤消退是由于依賴brat信號(hào)過(guò)量。有趣的是，他還表明不連續(xù)的藥物劑量，運(yùn)用耐藥細(xì)胞在沒(méi)有藥物環(huán)境下的劣勢(shì)來(lái)防止耐藥性的發(fā)作。這在嗜met細(xì)胞中也被證明是正確的，無(wú)論是抗mv-dn30還是抗tkis的ebc1細(xì)胞都表現(xiàn)出藥物依賴性并且去除藥物會(huì)致死細(xì)胞。因此，可以想象，為了防止由于癌基因過(guò)量用藥而產(chǎn)生抗性，間斷性用藥的機(jī)制可能會(huì)比連續(xù)用藥更有效。
此外，我們表明，抗體治療是活躍的細(xì)胞提供的抗酪氨酸激酶抑制劑，相反，tki治療耐mv-dn30細(xì)胞有效。這并不奇怪，因?yàn)檫@兩種類(lèi)型的抗性細(xì)胞都是嗜met細(xì)胞，因此，依賴met的信號(hào)減少導(dǎo)致了它們的死亡。這種發(fā)現(xiàn)在臨床上受到關(guān)注，因?yàn)樗砻髁擞每筸et的抗體治療病人可能是沒(méi)用的，病人的對(duì)tkis的抗性是由于met表達(dá)的增加或者是它們的毒性限制了tki的劑量。另一個(gè)處于我們的觀察的結(jié)果是mv-dn30和met-tkis之間的協(xié)同作用。值得注意的是，盡管是幾個(gè)實(shí)驗(yàn)，在用met tki和mv-dn30治療時(shí)我們并沒(méi)能過(guò)培養(yǎng)出抗性細(xì)胞。這些觀察的臨床意義提出了一點(diǎn)就是兩種藥物劑量的減少的可能性，結(jié)果它們又不利影響當(dāng)需要保持治療效應(yīng)時(shí)有可能會(huì)降低或延遲。總的來(lái)說(shuō)，在事實(shí)的角度評(píng)估我們的結(jié)果就是它們表明了兩種可能會(huì)克服或防止對(duì)metmabs抗性的治療策略:(i)一種就是用抗met的mab加上met tki的聯(lián)合治療(ii)利用抗性細(xì)胞的藥物依賴性的定期間斷性的節(jié)律治療。
食品專業(yè)英語(yǔ)論文篇五
嵌入式系統(tǒng)研究
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嵌入式系統(tǒng)研究
1前言
智能軟件agent是能夠?yàn)橛脩魣?zhí)行特定的任務(wù)、具有一定程度的智能、能夠自主的執(zhí)行部分任務(wù)并以一種合適的方式和環(huán)境相互作用的軟件程序。agent 有自主性、響應(yīng)性、學(xué)習(xí)能力和社會(huì)性等特性。這使得它適合在高度動(dòng)態(tài)的環(huán)境下做出及時(shí)的響應(yīng)。
嵌入式技術(shù)和新一代移動(dòng)通訊網(wǎng)絡(luò)的發(fā)展使得嵌入式智能設(shè)備大量的涌現(xiàn)。這些設(shè)備的大都具有嵌入式操作系統(tǒng)的支持, 并運(yùn)行著越來(lái)越豐富的應(yīng)用程序。如何對(duì)這些應(yīng)用程序進(jìn)行測(cè)試，就成為一個(gè)需要研究的課題。本文將agent技術(shù)引入嵌入式智能設(shè)備的測(cè)試中，使用目標(biāo)設(shè)備agent, 測(cè)試控制agent, 網(wǎng)絡(luò)環(huán)境agent分別模擬和處理測(cè)試設(shè)備，測(cè)試工程師和測(cè)試環(huán)境的復(fù)雜性，利用agent自身具有的特點(diǎn)，提出了一種有效的自動(dòng)化測(cè)試的方法。
2相關(guān)的研究及本文的思路
agent 所具有的自主性、響應(yīng)性、學(xué)習(xí)能力和社會(huì)性等特性，使得它很適合處理復(fù)雜測(cè)試系統(tǒng)中的問(wèn)題。將agent技術(shù)應(yīng)用于測(cè)試領(lǐng)域已經(jīng)有一些相關(guān)的研究，下面是具體的介紹。
jeongeun choi 和 byoungju choi [1]提出了一個(gè)基于agent技術(shù)的測(cè)試工具，它通過(guò)使用用戶接口agent來(lái)處理和測(cè)試者的交互，使用測(cè)試用例選擇agent來(lái)進(jìn)行測(cè)試用例的選擇，并使用回歸測(cè)試agent進(jìn)行回歸測(cè)試，從而很好的實(shí)現(xiàn)了自動(dòng)化的軟件測(cè)試。但是他們提出的測(cè)試用例選擇技術(shù)僅能在大量已有的測(cè)試用例中選擇最佳的用例，不能減少編寫(xiě)測(cè)試用例本身的復(fù)雜性。
另外一些研究將agent 技術(shù)應(yīng)用到了某一領(lǐng)域的測(cè)試中。yu qi、david hung 和 eric wong [3] 提出了一個(gè)基于agent 技術(shù)的web 應(yīng)用程序測(cè)試方法。專業(yè)英語(yǔ)期末考查
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他們使用agent技術(shù)降低了網(wǎng)絡(luò)應(yīng)用測(cè)試的復(fù)雜性。他們的方法不僅僅適用于web應(yīng)用程序的測(cè)試，也適合于嵌入式智能設(shè)備的測(cè)試。
在實(shí)際測(cè)試過(guò)程中，測(cè)試人員很大的一項(xiàng)任務(wù)仍然是編寫(xiě)各種測(cè)試用例，要真正的提高測(cè)試效率，就要提高測(cè)試腳本的通用性，減少測(cè)試腳本的變化[2] [4]。常見(jiàn)的嵌入式智能設(shè)備測(cè)試工具(比如testquest)使用圖像比對(duì)來(lái)判斷目標(biāo)設(shè)備的狀態(tài), 這種方法雖然實(shí)現(xiàn)了非侵入性的測(cè)試,但是存在兩個(gè)問(wèn)題,圖片的抓取和傳送消耗了大量測(cè)試資源,不同手機(jī)的用戶界面風(fēng)格變化很大,這使得測(cè)試腳本在用來(lái)進(jìn)行新設(shè)備的測(cè)試時(shí)需要對(duì)腳本進(jìn)行維護(hù).然而,實(shí)際的設(shè)備中,當(dāng)重要的事件發(fā)生時(shí),系統(tǒng)會(huì)產(chǎn)生敏感事件來(lái)激勵(lì)相關(guān)模塊進(jìn)行處理.如果能夠在測(cè)試過(guò)程中捕獲這些敏感事件,就能更加高效的進(jìn)行測(cè)試.并且,只要操作系統(tǒng)相同,敏感事件的捕獲方式也是一樣,測(cè)試用例不會(huì)因?yàn)榻缑娴淖兓兓?。本文用目?biāo)設(shè)備agent抽象和捕獲測(cè)試過(guò)程中的敏感事件，并將敏感事件發(fā)送給測(cè)試控制agent。而測(cè)試控制agent收到敏感事件后，根據(jù)自己的知識(shí)，采取相應(yīng)的動(dòng)作的機(jī)制（如異常處理，重新調(diào)度測(cè)試等）加以處理。這正好可以作為agent的推理規(guī)則，用agent的智能性來(lái)屏蔽測(cè)試過(guò)程的復(fù)雜性。此外，考慮到目標(biāo)設(shè)備處于復(fù)雜的網(wǎng)絡(luò)環(huán)境中，我們利用網(wǎng)絡(luò)環(huán)境agent來(lái)控制目標(biāo)設(shè)備所處的網(wǎng)絡(luò)信號(hào)，從而實(shí)現(xiàn)對(duì)設(shè)備所處網(wǎng)絡(luò)環(huán)境的控制?；赼gent的測(cè)試系統(tǒng)
3.1 總體結(jié)構(gòu)
測(cè)試系統(tǒng)的最終目標(biāo)是實(shí)現(xiàn)一個(gè)移動(dòng)數(shù)字終端的自動(dòng)化測(cè)試平臺(tái)，能夠?qū)σ苿?dòng)數(shù)字終端上的系統(tǒng)軟件和應(yīng)用層軟件建立模塊化、可重用的測(cè)試腳本庫(kù)，提高各種黑盒測(cè)試的效率，自動(dòng)化測(cè)試結(jié)果的生成，并實(shí)現(xiàn)測(cè)試結(jié)果的回放。
如圖1所示：測(cè)試平臺(tái)分為四層，包括用戶接口層，測(cè)試控制層，通訊層和設(shè)備agent層。其中，過(guò)程監(jiān)控模塊，測(cè)試環(huán)境控制模塊和設(shè)備agent層采用agent的思想進(jìn)行設(shè)計(jì)，以更好的支持嵌入式設(shè)備的測(cè)試。
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用戶接口層測(cè)試管理與配置腳本編輯器虛擬手機(jī)測(cè)試控制層測(cè)試結(jié)果驗(yàn)證測(cè)試資源庫(kù)測(cè)試腳步執(zhí)行測(cè)試環(huán)境控制測(cè)試過(guò)程監(jiān)控agent通訊層設(shè) 備agent層synblan agent藍(lán)牙 gprs 3g at視窗的移動(dòng)agent定制agentat 接口
圖1 測(cè)試系統(tǒng)的整體架構(gòu)
3.2 系統(tǒng)基本執(zhí)行流程
測(cè)試過(guò)程是對(duì)真實(shí)用戶使用手機(jī)時(shí)“輸入－反饋”模型的一個(gè)模擬。系統(tǒng)的基本的使用用例如下，首先用戶通過(guò)腳本編輯器或者虛擬手機(jī)創(chuàng)建測(cè)試腳本并進(jìn)行基本的配置，然后過(guò)程監(jiān)控模塊調(diào)度腳本開(kāi)始執(zhí)行，當(dāng)腳本解釋器解釋執(zhí)行腳本語(yǔ)句時(shí)，腳本解釋器通常使用通訊模塊向手機(jī)發(fā)送模擬按鍵，然腳本解釋器進(jìn)入等待狀態(tài)，目標(biāo)設(shè)備agent從通訊模塊得到按鍵，執(zhí)行按鍵動(dòng)作，截取屏幕并返回給測(cè)試控制agent，或者如果手機(jī)有敏感世事件的發(fā)生（如來(lái)電，短信，異常等）也會(huì)反饋給測(cè)試控制agent，測(cè)試控制agent接到數(shù)據(jù)，再次激勵(lì)腳本運(yùn)行，并同時(shí)將測(cè)試結(jié)果輸入存入測(cè)試資源庫(kù)。腳本繼續(xù)運(yùn)行下面的語(yǔ)句，直到運(yùn)行結(jié)束。3.3 目標(biāo)設(shè)備agent
目標(biāo)設(shè)備agent駐留在被測(cè)試的智能設(shè)備中，實(shí)現(xiàn)對(duì)目標(biāo)設(shè)備的建模。本系統(tǒng)中它接收從pc機(jī)中接收到的控制命令，然后在智能設(shè)備中進(jìn)行相應(yīng)的操作，包括模擬鍵盤(pán)事件，截取屏幕并返回給pc，以及根據(jù)知識(shí)庫(kù)中的配置的測(cè)試目標(biāo)，通過(guò)推理，有所選擇的將必需的狀態(tài)信息主動(dòng)通知測(cè)試宿主機(jī)。3.3.1設(shè)備agent 依賴的決策規(guī)則
系統(tǒng)事件報(bào)告決策規(guī)則（serd-rule）這個(gè)決策規(guī)則決定設(shè)備agent在獲取到狀態(tài)信息時(shí)，是否將狀態(tài)信息反饋給上層系統(tǒng)。
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異常處理規(guī)則（em-rule）
這個(gè)決策規(guī)則決定了當(dāng)agent發(fā)現(xiàn)測(cè)試中出現(xiàn)異常，要采取的處理方式。3.3.2 agent 屬性
目標(biāo)設(shè)備agent具有下面的屬性： ⑴ 自主性
目標(biāo)設(shè)備agent使得測(cè)試用戶無(wú)需關(guān)注設(shè)備的細(xì)節(jié)，它是設(shè)備功能和狀態(tài)的一個(gè)很好的抽象，通過(guò)目標(biāo)代理agent，上層測(cè)試框架只需要執(zhí)行相應(yīng)的虛擬操作，則目標(biāo)設(shè)備agent會(huì)自動(dòng)將這些虛擬操作映射為對(duì)手機(jī)的實(shí)際操作，并且手機(jī)的響應(yīng)和其它狀態(tài)也能夠自動(dòng)的反饋給客戶，這使得上層測(cè)試和底層的設(shè)備具體操作無(wú)關(guān)。
⑵ 智能性
當(dāng)目標(biāo)設(shè)備agent獲取到一個(gè)變化的被測(cè)系統(tǒng)狀態(tài)或信息時(shí)，它會(huì)根據(jù)推理規(guī)則，僅僅把和本次目標(biāo)相關(guān)的信息發(fā)送給測(cè)試控制agent。目標(biāo)設(shè)備agent還能夠根據(jù)異常處理規(guī)則，合理的處理測(cè)試中出現(xiàn)的異常。3.4
測(cè)試控制 agent
測(cè)試控制agent 實(shí)現(xiàn)了對(duì)測(cè)試過(guò)程的建模。它主要實(shí)現(xiàn)三個(gè)目標(biāo)： ⑴ 在測(cè)試過(guò)程中，對(duì)測(cè)試人員感興趣的事件進(jìn)行捕獲，當(dāng)這些敏感事件發(fā)生后，系統(tǒng)立刻執(zhí)行預(yù)定義的動(dòng)作，并為測(cè)試提供準(zhǔn)確和詳盡的日志。
⑵ 通過(guò)和腳本解釋器交互，實(shí)現(xiàn)異步的事件通知和交互測(cè)試用例的執(zhí)行。⑶ 處理測(cè)試過(guò)程中的異常，使得測(cè)試過(guò)程可以自我修復(fù)，進(jìn)而多個(gè)腳本能夠按照預(yù)先的調(diào)度正常運(yùn)行.3.4.1測(cè)試控制agent的決策規(guī)則
⑴ 事件－條件－行動(dòng)規(guī)則（eca－rule）
這是測(cè)試控制agent所依據(jù)的核心規(guī)則，它定義了某個(gè)測(cè)試所關(guān)心的事件，并根據(jù)比對(duì)條件，采取相應(yīng)的動(dòng)作。
⑵ 異常處理規(guī)則（em-rule）
測(cè)試控制agent也遵守異常處理規(guī)則，它能夠檢測(cè)測(cè)試過(guò)程中發(fā)生的異常事件，并執(zhí)行相應(yīng)的解決方案，使得測(cè)試能夠順利的進(jìn)行。
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3.4.2測(cè)試控制agent 的屬性
⑴自主性
自主性使得測(cè)試人員無(wú)需過(guò)分關(guān)注測(cè)試的細(xì)節(jié)，測(cè)試人員僅僅需要選擇測(cè)試目標(biāo)，測(cè)試控制agent就能根據(jù)知識(shí)庫(kù)中的信息，自動(dòng)生成eca規(guī)則表，并在腳本運(yùn)行時(shí)，按照eca規(guī)則，捕捉敏感的事件并執(zhí)行相應(yīng)的操作。
⑵智能性
測(cè)試控制agent能夠根據(jù)用戶選擇的測(cè)試目標(biāo)，自動(dòng)生成eca規(guī)則表，并根據(jù)eca規(guī)則，進(jìn)行推理并采取相應(yīng)的動(dòng)作。測(cè)試控制agent還能根據(jù)異常處理規(guī)則來(lái)處理測(cè)試過(guò)程中發(fā)身的異常，保障測(cè)試過(guò)程的自動(dòng)，平穩(wěn)進(jìn)行。3.5 網(wǎng)絡(luò)環(huán)境agent 網(wǎng)絡(luò)環(huán)境agent 實(shí)現(xiàn)了對(duì)網(wǎng)絡(luò)環(huán)境的模擬和控制。為了測(cè)試手機(jī)的射頻性能，通常使用基站模擬系統(tǒng)來(lái)提供設(shè)備所處的無(wú)線網(wǎng)絡(luò)環(huán)境，并且利用編程接口，通過(guò)軟件對(duì)設(shè)備的環(huán)境進(jìn)行控制，使得復(fù)雜網(wǎng)絡(luò)環(huán)境下對(duì)目標(biāo)設(shè)備的測(cè)試成為可能。系統(tǒng)評(píng)估
為了評(píng)價(jià)本系統(tǒng)的有效性，我們?cè)O(shè)計(jì)了一個(gè)比較實(shí)驗(yàn)。試驗(yàn)在信息產(chǎn)業(yè)部泰爾實(shí)驗(yàn)室真實(shí)的測(cè)試項(xiàng)目中進(jìn)行。我們將測(cè)試工程師分為兩組，第一組使用本文的系統(tǒng)mobiletest進(jìn)行測(cè)試，第二組使用業(yè)界著名的testquest pro 進(jìn)行測(cè)試。測(cè)試的依據(jù)是中國(guó)通訊行業(yè)標(biāo)準(zhǔn)的數(shù)字移動(dòng)臺(tái)測(cè)試部分。測(cè)試的內(nèi)容是根據(jù)這兩個(gè)系統(tǒng)各自已經(jīng)建立好的回歸測(cè)試用例對(duì)新的智能手機(jī)進(jìn)行回歸測(cè)試，從而比較這兩個(gè)測(cè)試工具的測(cè)試效率和腳本的可維護(hù)性。
實(shí)驗(yàn)度量了兩個(gè)工具在測(cè)試不同種類(lèi)的測(cè)試用例時(shí)，自動(dòng)化執(zhí)行的用例所占的百分比。從表中可見(jiàn)，雖然testquest 在功能測(cè)試上有更高的自動(dòng)化率，在壓力測(cè)試，多狀態(tài)測(cè)試，多任務(wù)測(cè)試，臨界測(cè)試和總計(jì)中，mobiletest有更好的測(cè)試覆蓋率。這是因?yàn)樵诤笏姆N測(cè)試中，測(cè)試用例需要不斷追蹤系統(tǒng)的狀態(tài)，使用圖片比對(duì)機(jī)制的testquest 很難完成這些工作，而mobiletest 卻能使用agent返回的敏感事件來(lái)進(jìn)行處理。此外，mobiletest 完成測(cè)試任務(wù)的時(shí)間時(shí)15天，比testquest 的測(cè)試效率要高。
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5總結(jié)
本文提出了一個(gè)基于agent技術(shù)的嵌入式智能設(shè)備的測(cè)試方法，它用agent技術(shù)對(duì)嵌入式智能設(shè)備測(cè)試過(guò)程中的被測(cè)試設(shè)備，測(cè)試者和網(wǎng)絡(luò)環(huán)境進(jìn)行模擬和控制，很好的屏蔽了嵌入式智能設(shè)備的復(fù)雜性，提高了測(cè)試的效率和腳本的可重用性。將來(lái)的研究工作中，我們會(huì)進(jìn)一步拓展整個(gè)測(cè)試系統(tǒng)，使之能夠支持整個(gè)測(cè)試的生命周期。
本文作者的創(chuàng)新點(diǎn)：本文將軟件agent技術(shù)引入到嵌入式智能設(shè)備的自動(dòng)化測(cè)試中，利用agent的特性，很好的屏蔽了嵌入式智能設(shè)備測(cè)試中，測(cè)試者，待測(cè)設(shè)備，網(wǎng)絡(luò)環(huán)境的復(fù)雜性，提高了自動(dòng)化測(cè)試的效率。
來(lái)源于：《 journal of electronic science and technology》
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附：英文原文
embedded system research 1 introduction
intelligent software agent is the ability to perform specific tasks for the user, with a certain degree of intelligence, able to perform some tasks and autonomy in a proper manner and environment interactions software has autonomy, responsiveness, learning and social and other makes it suitable for highly dynamic environment to make a timely ed technology and the development of new generation mobile communication networks makes the emergence of a large number of embedded intelligent of these devices with embedded operating system support, and run an increasingly rich to test for these applications to be a need to article intelligent agent technology into embedded devices test, using the target device agent, test control agent, network agent and treatment were simulated test equipment, test engineers and test complexity of the environment, the use of agent has its own characteristics, proposed an effective automated testing.2 related research and ideas of this article
agent possess autonomy, responsiveness, learning and social and other features, makes it very suitable for handling complex problems in the test technology in the test area will already have some relevant research, the following is a specific un choi and byoungju choi [1] proposed a testing tool based on agent technology, which through the use of agent to handle user interface and test those interactions, the use of agent to carry out the test case test case selection choices, and use the agent for regression testing regression testing, so a good automated software they can only be made in a large number of test selection techniques select test cases has been the best use cases, write test cases can not reduce its complexity.專業(yè)英語(yǔ)期末考查
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other studies will agent technology applied to a field qi, david hung and eric wong [3] proposed a web-based agent technology application testing technology to reduce their use of the network application testing method not only for web application testing, but also for the testing of embedded intelligent the actual testing process, testers great task is still the preparation of various test cases, to really improve test efficiency, we must improve the general test scripts, reduce test script changes [2] [4].common test tools for embedded smart devices(such as testquest)using image comparison to determine the status of the target device, although this method to achieve a non-invasive test, but there are two problems, the image capture and transmission consumes a lot of test resources, the different style of phone's user interface has changed dramatically, which makes the test script used for testing new equipment required for maintenance of the r, the actual device, when an important event occurs, the system will generate sensitive events to encourage the relevant module for during the test capture these sensitive matters, will be able to test more , as long as the operating system the same sensitive way to capture the same event, the interface test cases will not this paper, the abstract and the agent target device during the test capture of sensitive events and control of sensitive events are sent to test receives the test control sensitive incident, according to their knowledge, take appropriate action mechanisms(such as exception handling, re-scheduling the test, etc.)to be is precisely the inference rules as agent, with the intelligence of agent to shield the complexity of the testing addition, given the target device is a complex network environment, we use the internet agent to control the target device environment in which the network signal, enabling the network environment in which the control device.3 agent-based test system 3.1 the overall structure
test system is to achieve the ultimate goal of a mobile digital terminal's automated testing platforms to the mobile digital terminal on the system software and 專業(yè)英語(yǔ)期末考查
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application layer software build modular, reusable test script library, to improve the efficiency of various black box testing, automation the generation of test results and test results to achieve 1: test platform spanided into four layers, including user interface layer, the test control layer, communication layer and the equipment agent them, the process monitoring module, test equipment, environmental control module and the use of agent agent layer design ideas to better support embedded devices user interface layertesting management and configurationscript editorvirtual cell phone
testcontrol layer test results show testing steps executiontestrepository test environment control testing process monitoring agentcommunications layer set for agent layerbluetooth gprs 3g atsynblan agent windows mobile agentcustomization agentat 接口figure 1 the overall architecture test system 3.2 the basic system implementation process
testing process is a real cell phone users "inputcondition-action rules(eca-rule)
control agent this is a test based on the core rules, which defines a test case of interest, and according to comparison conditions, take appropriate action.⑵ exception handling rules(em-rule)
test control agent also comply with exception handling rules, which occurred during the test can detect abnormal events and to implement appropriate solutions to enable testing to proceed smoothly.3.4.2 test control agent's properties ⑴ autonomy
autonomy to make the tester without too much attention to the details of the test, testers just need to select the test objectives, test control agent information can be based on the knowledge base, automatically generate eca rules table, and run the script, according to eca rules to capture sensitive event and perform the appropriate action.⑵ intelligence
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test control agent to the test objectives based on user selection, automatically generates eca rules table, and according to eca rules, reasoning and take appropriate control agent can exception handling rules based on the testing process to deal with abnormal body fat to protect the testing process automatically and smoothly.3.5 agent network
network agent implements the network environment simulation and order to test the phone's rf performance, usually the base station simulator to provide a device in which the wireless network environment, and use programming interface, the software environment to control the device, making the complex network environment, the target device under test as possible.4 system evaluation
in order to evaluate the effectiveness of the system, we designed a comparative testing laboratory in the ministry of information industry of the test project for will test engineers spanided into two groups, the first group to use this system mobiletest test, the second group uses the industry's leading testquest pro is based on the number of china's telecommunications industry standard part of mobile station content is based on both systems return to their already established on the new test cases for regression testing of smart phones to compare these two test tools, test efficiency and maintainability of the 1 regression test results:
two experimental tools to measure different types of test cases in the test, the automated implementation of the percentage of use be seen from the table, although the functional testing testquest higher automation rates, the stress test, multi-state testing, multi-tasking tests, critical test, and the total, mobiletest better test is because after the four tests, the test case need to constantly track the system state, the use of pictures than on the mechanism of testquest difficult to accomplish these tasks, and mobiletest able to use the agent to return to the treatment of sensitive addition, mobiletest time to complete the test task 15 days, testquest's test efficiency than higher.專業(yè)英語(yǔ)期末考查
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this paper presents a technique based on embedded intelligent devices agent test method, which uses embedded intelligent agent technology equipment is tested in test equipment, test and simulate and control the network environment, a good shielding of the embedded the complexity of smart devices to improve the test efficiency and reusability of the research work, we will further develop the test system so that it can support the whole testing life innovation of the author: this article introduces the software agent technology to automate testing of embedded intelligent devices, the use of agent's features, nice screen test for embedded smart devices, testers, test device, the complexity of the network environment and increase the efficiency of automated :《 journal of electronic science and technology》
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