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Improvements in single‐use bioreactor film material composition leads to robust and reliable Chinese hamster ovary cell performance

机译:单用生物反应器薄膜材料组合物的改进导致鲁棒和可靠的中国仓鼠卵巢细胞性能

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Abstract >Single‐use technologies, in particular disposable bioreactor bags, have become integral within the biopharmaceutical community. However, safety concerns arose upon the identification of toxic leachable compounds derived from the plastic materials. Although the leachable bis(2,4‐di‐tert‐butylphenyl)‐phosphate (bDtBPP) has been previously shown to inhibit CHO cell growth, it is critical to determine if other compounds like this are still present in subsequent generations of films for industrial application. This study compares the performance of CHO cells, CHO‐K1, and CHO‐DP12, cultured in media conditioned in an older single‐use bioreactor (SUB) film (F‐1) and a newer generation film (F‐2) from the same vendor. CHO cells cultured in media conditioned for 7 days in the F‐1 film demonstrated significantly reduced growth and antibody productivity profiles when compared to controls and media conditioned for the same time period in the newer F‐2 film. Proteomic profiling of CHO cells cultured in the F‐1 conditioned media identified differentially expressed proteins involved in oxidative stress response as well as compromised ATP synthesis. These potentially metabolically compromised cells exhibited reduced oxidative phosphorylation activity as well as lower glycolytic metabolism, characteristic of slower growing cells. Nonvolatile and metal leachables analysis of film extracts by LC–MS revealed a reduction in the abundance of the analyzed leachates from F‐2 films when compared to F‐1 films including bDtBPP, potentially explaining improved CHO cell growth in F‐2 conditioned media. Furthermore, in vitro endocrine disruptor testing of the known leachable revealed this molecule to possess the potential to act as an androgen antagonist. This study demonstrates an improvement in the materials composition used in modern generations of SUBs for safe application in the bioprocess. </abstract> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> <div class="translation abstracttxt"> <span class="zhankaihshouqi fivelineshidden" id="abstract"> <span>机译:</span><Abstract Type =“Main”XML:Lang =“en”> <标题类型=“main”>抽象</ title> >单用技术,特别是一次性生物反应器袋,在生物制药界中变得一体。然而,在鉴定源自塑料材料的毒性可浸出的化合物时出现安全问题。尽管先前已经显示可浸出的BIS(2,4-二叔丁基苯基) - 磷酸(BDTBPP)抑制CHO细胞生长,但确定其其他化合物是否仍然存在于工业的后续几代薄膜中至关重要应用。该研究比较了CHO细胞,CHO-K1和CHO-DP12的性能,在较旧的单一使用生物反应器(SUB)膜(F-1)和较新一代薄膜(F-2)中调节的媒体中培养。同一个供应商。与对照和介质在新的F-2膜中同一时间段内相同的时间段相比,在F-1薄膜中培养的培养基中培养7天的CHO细胞显着降低了生长和抗体的生产率曲线。在F-1条件培养基中培养的CHO细胞蛋白质组学分析鉴定了差异表达蛋白质,参与氧化应激响应以及受损的ATP合成。这些潜在的代谢损伤的细胞表现出降低的氧化磷酸化活性以及较低的糖酵母代谢,具有较慢的生长细胞的特征。通过LC-MS的薄膜提取物的非易失性和金属浸出物分析显示与包括BDTBP的F-1膜相比,来自F-2膜的分析的渗滤液的丰度降低,潜在地解释了在F-2条件培养基中改善的CHO细胞生长。此外,已知可浸出的体外内分泌干扰测试显示该分子具有作为雄激素拮抗剂的潜力。本研究表明,在生物过程中使用现代代的潜艇使用的材料组合物的改善。</ p> </摘要> </span> <span class="z_kbtn z_kbtnclass hoverxs" style="display: none;">展开▼</span> </div> </div> <div class="record"> <h2 class="all_title" id="enpatent33" >著录项</h2> <ul> <li> <span class="lefttit">来源</span> <div style="width: 86%;vertical-align: text-top;display: inline-block;"> <a href='/journal-foreign-15005/'>《Biotechnology Progress》</a> <b style="margin: 0 2px;">|</b><span>2019年第4期</span><b style="margin: 0 2px;">|</b><span>共17页</span> </div> </li> <li> <div class="author"> <span class="lefttit">作者</span> <p id="fAuthorthree" class="threelineshidden zhankaihshouqi"> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Kelly Paul S.&option=202" target="_blank" rel="nofollow">Kelly Paul S.;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Dorival‐García Noemi&option=202" target="_blank" rel="nofollow">Dorival‐García Noemi;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Paré Samantha&option=202" target="_blank" rel="nofollow">Paré Samantha;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Carillo Sara&option=202" target="_blank" rel="nofollow">Carillo Sara;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Ta Christine&option=202" target="_blank" rel="nofollow">Ta Christine;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Alarcon Miguez Antonio&option=202" target="_blank" rel="nofollow">Alarcon Miguez Antonio;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Coleman Orla&option=202" target="_blank" rel="nofollow">Coleman Orla;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Harper Emma&option=202" target="_blank" rel="nofollow">Harper Emma;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Shannon Maeve&option=202" target="_blank" rel="nofollow">Shannon Maeve;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Henry Michael&option=202" target="_blank" rel="nofollow">Henry Michael;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Connolly Lisa&option=202" target="_blank" rel="nofollow">Connolly Lisa;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Clynes Martin&option=202" target="_blank" rel="nofollow">Clynes Martin;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Meleady Paula&option=202" target="_blank" rel="nofollow">Meleady Paula;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Bones Jonathan&option=202" target="_blank" rel="nofollow">Bones Jonathan;</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Barron Niall&option=202" target="_blank" rel="nofollow">Barron Niall;</a> </p> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zkzz" style="display: none;">展开▼</span> </div> </li> <li> <div style="display: flex;"> <span class="lefttit">作者单位</span> <div style="position: relative;margin-left: 3px;max-width: 639px;"> <div class="threelineshidden zhankaihshouqi" id="fOrgthree"> <p>National Institute for Bioprocessing Research and TrainingFosters Avenue Mount Merrion Blackrock Co. Dublin Ireland;</p> <p>National Institute for Bioprocessing Research and TrainingFosters Avenue Mount Merrion Blackrock Co. Dublin Ireland;</p> <p>National Institute for Cellular BiotechnologyDublin City UniversityDublin Ireland;</p> <p>National Institute for Bioprocessing Research and TrainingFosters Avenue Mount Merrion Blackrock Co. Dublin Ireland;</p> <p>National Institute for Bioprocessing Research and TrainingFosters Avenue Mount Merrion Blackrock Co. Dublin Ireland;</p> <p>National Institute for Cellular BiotechnologyDublin City UniversityDublin Ireland;</p> <p>National Institute for Cellular BiotechnologyDublin City UniversityDublin Ireland;</p> <p>Institute for Global Food SecuritySchool of Biological Sciences Queen's UniversityBelfast Northern Ireland UK;</p> <p>Institute for Global Food SecuritySchool of Biological Sciences Queen's UniversityBelfast Northern Ireland UK;</p> <p>National Institute for Cellular BiotechnologyDublin City UniversityDublin Ireland;</p> <p>Institute for Global Food SecuritySchool of Biological Sciences Queen's UniversityBelfast Northern Ireland UK;</p> <p>National Institute for Cellular BiotechnologyDublin City UniversityDublin Ireland;</p> <p>National Institute for Cellular BiotechnologyDublin City UniversityDublin Ireland;</p> <p>National Institute for Bioprocessing Research and TrainingFosters Avenue Mount Merrion Blackrock Co. Dublin Ireland;</p> <p>National Institute for Bioprocessing Research and TrainingFosters Avenue Mount Merrion Blackrock Co. Dublin Ireland;</p> </div> <span class="z_kbtnclass z_kbtnclassall hoverxs" id="zhdw" style="display: none;">展开▼</span> </div> </div> </li> <li > <span class="lefttit">收录信息</span> <span style="width: 86%;vertical-align: text-top;display: inline-block;"></span> </li> <li> <span class="lefttit">原文格式</span> <span>PDF</span> </li> <li> <span class="lefttit">正文语种</span> <span>eng</span> </li> <li> <span class="lefttit">中图分类</span> <span><a href="https://www.zhangqiaokeyan.com/clc/15.html" title="生物科学">生物科学;</a></span> </li> <li class="antistop"> <span class="lefttit">关键词</span> <p style="width: 86%;vertical-align: text-top;"> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=bDtBPP&option=203" rel="nofollow">bDtBPP;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Chinese hamster ovary cells&option=203" rel="nofollow">Chinese hamster ovary cells;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=endocrine disruptor&option=203" rel="nofollow">endocrine disruptor;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=leachables&option=203" rel="nofollow">leachables;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=mitochondria&option=203" rel="nofollow">mitochondria;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Seahorse XF96&option=203" rel="nofollow">Seahorse XF96;</a> <a style="color: #3E7FEB;" href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=single‐use bioreactors&option=203" rel="nofollow">single‐use bioreactors;</a> </p> <div class="translation"> 机译:BDTBPP;中国仓鼠卵巢细胞;内分泌破坏器;鹿脱离剂;线粒体;海马XF96;单用生物反应器; </div> </li> </ul> </div> </div> <div class="literature cardcommon"> <div class="similarity "> <h3 class="all_title" id="enpatent66">相似文献</h3> <div class="similaritytab clearfix"> <ul> <li class="active" >外文文献</li> <li >中文文献</li> <li >专利</li> </ul> </div> <div class="similarity_details"> <ul > <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_chinese-journal-medicine-english-version_thesis/0201268414112.html">Effect of Matrine on Human Ether à go-go Related Gene (HERG) Channels Expressed in Chinese Hamster Ovary Cells</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=吴红金&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">吴红金,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=邹安若&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">邹安若,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=谢芳&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">谢芳,</a> <a href="/journal-foreign-53030/" target="_blank" rel="nofollow" class="tuijian_authcolor">中国结合医学杂志:英文版 .</a> <span>2010</span><span>,第005期</span> </span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-cn_acta-biochimica-biophysica-sinica_thesis/0201254943898.html">Existence of an Endogenous Glutamate and Aspartate Transporter in Chinese Hamster Ovary Cells</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Xunhe JI&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Xunhe JI,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yuhua JIN&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Yuhua JIN,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Yaoyue CHEN&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Yaoyue CHEN,</a> <a href="/journal-foreign-5080/" target="_blank" rel="nofollow" class="tuijian_authcolor">生物化学与生物物理学报:英文版 .</a> <span>2007</span><span>,第011期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/journal-foreign-detail/07040250524.html">Fed-Batch Bioreactor Performance and Cell Line Stability Evaluation of the Artificial Chromosome Expression Technology Expressing an IgG1 in Chinese Hamster Ovary Cells</a> <b>[J]</b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Rodney G. 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Chen,</a> <span>1999</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:流化床生物反应器中中国仓鼠卵巢细胞的高细胞密度和生产力培养</span> </p> </li> <li> <div> <b>9. </b><a class="enjiyixqcontent" href="/open-access_resources_thesis/0100036085086.html ">Enhancement of ricin cytotoxicity in Chinese hamster ovary cells by depletion of intracellular K+: evidence for an Na+/H+ exchange system in Chinese hamster ovary cells</a> <b>[O] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> </a> <span>1985</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:消耗细胞内K +增强中国仓鼠卵巢细胞蓖麻毒素的细胞毒性:中国仓鼠卵巢细胞Na + / H +交换系统的证据</span> </p> </li> <li> <div> <b>10. </b><a class="enjiyixqcontent" href="/ntis-science-report_pb_thesis/020711356466.html">Utilization of the Rabbit Alveolar Macrophage and Chinese Hamster Ovary Cell for Evaluation of the Toxicity of Particulate Materials. 1. Model Compounds and Metal-Coated Fly Ash</a> <b>[R] </b> . <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Garrett, N. E. &option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Garrett, N. E. ,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Campbell, J. A. &option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Campbell, J. A. ,</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Stack, H. F. &option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">Stack, H. F. ,</a> <span>1981</span> </span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:利用兔肺泡巨噬细胞和中国仓鼠卵巢细胞评价颗粒物质的毒性。 1.模型化合物和金属涂层粉煤灰</span> </p> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/academic-journal-cn_journal-huazhong-university-science-technology-medical-english-german-edition_thesis/0201268455775.html">Follicle-stimulating Hormone (FSH) Induced Internalization of Porcine FSH Receptor in Cultured Porcine Granulosa Cells and Chinese Hamster Ovary Cells Transfected with Recombinant Porcine FSH Receptor cDNA</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=ZHU&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . ZHU</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Changhong&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Changhong</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=TIAN&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,TIAN</a> <span> <a href="/journal-cn-53067/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 华中科技大学学报:医学英德文版 </a> </span> <span> . 2001</span><span>,第003期</span> </span> </div> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/academic-journal-cn_journal-huazhong-university-science-technology-medical-english-german_thesis/0201273533626.html">Follicle-stimulating Hormone (FSH) Induced Internalization of Porcine FSH Receptor in Cultured Porcine Granulosa Cells and Chinese Hamster Ovary Cells Transfected with Recombinant Porcine FSH Receptor cDNA</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=ZHU Changhong&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . ZHU Changhong</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=TIAN Hong&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,TIAN Hong</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=XIONG Zhongming&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,XIONG Zhongming</a> <span> <a href="/journal-cn-6548/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 华中科技大学学报(医学)(英德文版) </a> </span> <span> . 2001</span><span>,第003期</span> </span> </div> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/academic-journal-cn_detail_thesis/0201297447846.html">Evaluation of transfection methods for transient gene expression in Chinese hamster ovary cells</a> <b>[J]</b> <span> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Si Nga Sou&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor"> . Si Nga Sou</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Karen M. Polizzi&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Karen M. Polizzi</a> <a href="/search.html?doctypes=4_5_6_1-0_4-0_1_2_3_7_9&sertext=Cleo Kontoravdi&option=202" target="_blank" rel="nofollow" class="tuijian_auth tuijian_authcolor">,Cleo Kontoravdi</a> <span> <a href="/journal-cn-56588/" target="_blank" rel="nofollow" class="tuijian_authcolor"> . 生命科学与技术进展(英文) </a> </span> <span> . 2013</span><span>,第12期</span> </span> </div> </li> </ul> <ul style="display: none;"> <li> <div> <b>1. </b><a class="enjiyixqcontent" href="/patent-detail/06130400504996.html">Method for producing Chinese hamster ovary cell strain, being a producer of recombinant SARS-CoV-2 virus protein RBD, Chinese hamster ovary cell strain, producer of recombinant SARS-CoV-2 protein RBD, method for producing recombinant SARS-CoV-2 virus protein RBD, test system for enzyme immunoassay of human serum or plasma, and use thereof</a> <b>[P]</b> . <span> 外国专利: <!-- 俄罗斯专利: --> RU2723008C1 </span> <span> . 2020-06-08</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:重组SARS-CoV-2病毒蛋白RBD的生产者的中国仓鼠卵巢细胞株的生产方法,重组SARS-CoV-2蛋白RBD的生产者的中国仓鼠卵巢细胞株,重组SARS-CoV-2病毒的生产方法蛋白质RBD,用于人血清或血浆的酶免疫测定的测试系统及其用途 </span> </p> </li> <li> <div> <b>2. </b><a class="enjiyixqcontent" href="/patent-detail/06130442510057.html">Process for obtaining high nu00ecveis expression of hormu00c8nio stimulator of thyroid (tireotrofina human or hTSH) in Chinese hamster ovary cells.By the use of vectors for expression dicistru00c8nicos,Application of an amplification strategy with double marker gene detection and quality control of the same hTSH throughout the production process by high performance chromatography lu00ecquidaReverse phase</a> <b>[P]</b> . <span> 外国专利: <!-- --> BR0205204A </span> <span> . 2004-09-21</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:在中国仓鼠卵巢细胞中获得甲状腺激素(tireotrofina human或hTSH)的激素刺激物的高表达的方法。在整个生产过程中通过高效液相色谱法控制相同的hTSH </span> </p> </li> <li> <div> <b>3. </b><a class="enjiyixqcontent" href="/patent-detail/06130420587080.html">Processes and compositions for transfecting chinese hamster ovary (CHO) cells</a> <b>[P]</b> . <span> 外国专利: <!-- 美国专利: --> US8492151B1 </span> <span> . 2013-07-23</span> </div> <p class="zwjiyix translation" style="max-width: initial;height: auto;word-break: break-all;white-space: initial;text-overflow: initial;overflow: initial;"> <span>机译:转染中国仓鼠卵巢(CHO)细胞的方法和组合物 </span> </p> </li> </ul> </div> </div> </div> <div class="theme cardcommon" style="overflow: auto;display:none"> <h3 class="all_title" id="enpatent55">相关主题</h3> <ul id="subject"> </ul> </div> </div> </div> </div> <div class="right rightcon"> <div class="details_img cardcommon clearfix" style="margin-bottom: 10px;display:none;" > </div> </div> </div> <div id="thesis_get_original1" class="downloadBth" style="bottom: 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