陈化兰，女，1969年出生于甘肃省白银市，动物传染病及预防兽医学专家，中国科学院院士，国家禽流感参考实验室主任，中国农业科学院哈尔滨兽医研究所研究员、博士生导师  。

　　2017年11月28日，中国科学院2017年院士增选名单公布。对于广大畜牧兽医界的研究者们来说，这份名单有着重要的意义：中国畜牧兽医界有了第一位女院士！

　　这位女院士就是陈化兰。现任中国农业科学院哈尔滨兽医研究所国家禽流感参考实验室主任的她，20多年来不忘初心、孜孜以求，带领团队在流行病学、病毒基础生物学以及禽流感疫苗研发等方向持续攻坚，为我国和世界范围内的禽流感防控工作作出了突出贡献：其团队的研究成果多次获得国家科技进步一等奖、国家技术发明二等奖和国家自然科学二等奖等重量级奖项。

　　“我渴望把我所学的知识和本领奉献给禽流感防控”

　　1994年6月，陈化兰在甘肃农业大学兽医系硕士研究生毕业后，来到哈尔滨兽医研究所攻读博士研究生。

　　“博士毕业后，我在研究所工作了两年，1999年获得前往美国联邦疾病控制中心进行博士后研究的机会。”陈化兰告诉记者，该中心是世界卫生组织的流感合作中心，拥有一流的设施和人才，“在美国的三年，我一点时间也没有浪费。如饥似渴地学习先进的知识、理念和技术。”

　　2002年，在美国学习行将结束之际，陈化兰毅然选择了回国。陈化兰坦言，当时国内的研究条件还无法和美国相比，对于禽流感病毒研究这个对实验平台依赖性很强的学科来说，留在美国确实有很大的吸引力。

　　“没有好的实验平台，我们可以慢慢建。但是中国这样的禽类养殖大国，如果没有掌握很好的禽流感防控手段，国家可能会遭受很大的损失。”陈化兰信心坚定，“禽流感防控工作，要靠我们中国人自己干！我渴望把我所学的知识和本领奉献给禽流感防控。”就这样，陈化兰怀着满腔热情回到了哈尔滨兽医研究所。

　　该所研究员姜永萍回忆说，陈化兰回国后带领团队开展我国禽流感病毒流行情况、诊断、防治技术等系统性研究工作，并成功建立了一系列先进的技术平台。姜永萍说，陈化兰就是这样有着很强使命感和家国情怀的人，“她主导的一系列研究成果，大大提高了我们国家对禽流感的研究水平和防控能力。”

　　“通过新型高效的禽流感疫苗进行防控是‘四两拨千斤’的最佳选择”

　　2004年，陈化兰回国后的第三年，东南亚地区暴发了禽流感，多国都有人员感染和死亡，我国也蒙受了巨大损失，全国共有16个省区市出现疫情，900万只鸡被扑杀，直接经济损失达100亿元。2005年，随着候鸟迁飞传播病毒，亚洲和我国部分地区多次发生疫情。

　　面对疫情，陈化兰和她的团队临危受命。“世界各地过去针对禽流感疫情通常的做法就是扑杀。”陈化兰说，“这种做法耗费巨大的人力财力，而且对于养殖业的打击几乎是毁灭性的。我们为什么不寻求一种更好的方法呢？”陈化兰认为，“通过新型高效的禽流感疫苗进行防控是‘四两拨千斤’的最佳选择。”

　　陈化兰团队先后研制成功了多款抗击H5禽流感病毒的“神器”——这些疫苗自投入使用以来，在国内外累计应用超过2300亿羽份，挽回巨大经济损失的同时，有效降低了人感染禽流感的几率。“我们研发的疫苗效果好、成本低，目前每年疫苗应用量约为150亿羽份以上。”陈化兰介绍说，通过其实验室建立的禽流感灭活疫苗研发平台，一旦出现新的病毒变种，在实验室里只要两周时间就可以对疫苗进行更新。“目前我们禽流感疫苗的研发处于世界领先水平。”陈化兰说。

　　因为突出的学术声誉、科技贡献及研究能力，陈化兰的实验室2008年被世界动物卫生组织（OIE）指定为禽流感参考实验室；2013年被联合国粮农组织（FAO）遴选为FAO动物流感参考中心。她本人也先后被英国《自然》杂志评为2013年“全球十大科学人物”、获联合国教科文组织颁发的2016年度“世界杰出女科学家奖”。

　　“为养殖业健康发展和公共卫生安全提供科技支撑不容疏忽”

　　在国内，陈化兰的国家参考实验室是禽流感疫情的最终诊断机构。她非常重视流行病学的主动监测，建立了系统、完整的禽流感病毒毒株资源库及其流行病学信息数据库，开展了系统的病毒生物学研究，为疫情的预警预报和防控决策及疫苗等防治技术创制提供了科学依据。目前，她的实验室在动物流感研究领域已经具备全链条的国际一流竞争能力。

　　即便已经站到世界领先地位，陈化兰的“战备状态”也始终没有松懈。“禽流感病毒很特殊，宿主多、变异快，既可以感染家禽、也可以感染候鸟。”陈化兰形象地举例，“跨国迁徙的候鸟飞行很自由，去哪个国家也不需要‘护照’。如果它们身上携带了病毒，和当地的家禽一接触，就有可能发生疫情。我们时刻都要保持警惕，随时应对新出现的疫情。”

　　2013年3月，我国出现新型H7N9流感病毒感染人的病例。因为长期对疫情的高度敏感和丰富的一线采样经验，首例病例公布不到48小时，陈化兰团队就从活禽市场采集的样品中分离到类似病毒。根据研究结果，陈化兰建议立刻关闭感染地区的家禽市场，有关部门采纳她的建议后，新增感染病例迅速减少。2017年9月，陈化兰团队研发的针对H7N9流感的禽用疫苗投入使用后，有效阻断了该流感病毒在家禽中的传播，并成功阻断了病毒由禽向人的传播。2016年10月到2017年9月，全国感染H7N9病毒高达766人，相比之下，2017年10月至今全国仅有3个人感染该病毒。

　　“我们的工作职责就是服务国家和人民，为养殖业健康发展和公共卫生安全提供科技支撑不容疏忽！”陈化兰说。

　　附：代表文章

　　1. Yanbing Li, Liling Liu, Yi Zhang, Zhenhua Duan, Guobin Tian, Xianying Zeng, Jianzhong Shi, Licheng Zhang, Hualan Chen*. New lineage of H5N1 influenza virus detected in wild birds in Qinghai, western China. Emerging Infectious Disease, 2010, in press.

　　2. Ying Chen, Gongxun Zhong, Guojun Wang, Guohua Deng, Yanbing Li, Jianzhong Shi, Zhuo Zhang, Yuntao Guan, Yongping Jiang, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen*. Dogs are highly susceptible to H5N1 avian influenza virus. Virology. 2010, 405, 15-19, on-line, June 25.

　　3. Lihong Tao, Jinying Ge, Xijun Wang, Hongyue Zhai, Tao Hua, Bolin Zhao, Dongni Kong, Chinglai Yang, Hualan Chen*, and Zhigao Bu*. Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation. Journal of Virology. 2010, 84 (17), 8926-8936. on-line, June 10

　　4. Yanbing Li, Jianzhong Shi, Gongxun Zhong, Guohua Deng, Guobin Tian, Jinying Ge, Xianying Zeng, Jiasheng Song, Dongming Zhao, Liling Liu, Yongping Jiang, Yuntao Guan, Zhigao Bu, Hualan Chen*. Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry and humans in China from 2004 to 2009. Journal of Virology. 2010, 84(17), 8389-8379. On-line, June 10.

　　5. Yujie Tang, Gongxun Zhong, Lianhui Zhu, Xing Liu, Yufei Shan, Huapeng Feng, Zhigao Bu, Hualan Chen*, and Chen Wang. Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein. Journal of Immunology, 2010, 184, 5777-5790

　　6. Bo Wah Leung, Hualan Chen, George G. Brownlee. Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity. Virology, 2010, 401：96-106.

　　7. Yuwei Gao, Ying Zhang, Kyoko Shinya, Guohua Deng, Yongping Jiang, Zejun Li, Yutao Guan, Guobin Tian, Yanbing Li, Jianzhong Shi, Liling Liu, Xianying Zeng, Zhigao Bu, Xianzhu Xia, Yoshihiro Kawaoka, Hualan Chen*. Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host. PLoS Pathogens, 2009, 5(12): e1000709.

　　8. Yongping Jiang, Hongbo Zhang, Guojun Wang, Pingjing Zhang, Guobin Tian, Zhigao Bu, and Hualan Chen*. Protective Efficacy of H7 Subtype Avian Influenza DNA Vaccine. Avian Disease, 2010, 54(S1), 294-296.

　　9. Jinying Ge, Guobin Tian, Xianying Zeng, Yongping Jiang, Hualan Chen and Zhigao Bu*. Generation and Evaluation of a Newcastle Disease Virus-Based H9 Avian Influenza Live Vaccine. Avian Disease, 2010, 54(S1), 290-293.

　　10. Guobin Tian, Xianying Zeng, Yanbing Li, Jianzhong Shi, Hualan Chen*. Protective Efficacy of the H5 Inactivated Vaccine against Different Highly Pathogenic H5N1 Avian Influenza Viruses Isolated in China and Vietnam. Avian Disease, 2010, 54(S1), 287-289.

　　11. Neumann G, Chen H, Gao GF, Shu Y, Kawaoka Y. H5N1 influenza viruses: outbreaks and biological properties. Cell Research, 2010, 20(1):51-61

　　12. Qimeng Tao , Xiurong Wang, Hongmei Bao, Jianan Wu , Lin Shi, Yanbing Li, Chuanling Qiao , Yakovlevich SA, Mikhaylovna PN, Hualan Chen. Detection and differentiation of four poultry diseases using asymmetric reverse transcription polymerase chain reaction in combination with oligonucleotide microarrays. J Vet Diagn Invest. 2009;21(5):623-632

　　13. Chuantian Xu, Qiyun Zhu, Huanliang Yang, Xiumei Zhang, Chuanling Qiao, Yan Chen, Xiaoguang Xin, Hualan Chen*. Two genotypes of H1N2 influenza viruses appeared among pigs in China. Journal of Clinical Virology. 2009, 46: 192-195.

　　14. Hualan Chen, Zhigao Bu. Development and application of avian influenza vaccines in China. Current Topics in Microbiology and Immunology. 2009;333:153-62 (Review)

　　15. Hualan Chen. Avian influenza vaccination: the experience in China. Rev Sci Tech. 2009, 28(1): 267-74 (Review)

　　16. Jiyong Zhou, Wenbo Sun, Junhua Wang, Junqing Guo, Wei Yin, Nanping Wu, Lanjuan Li, Yan Yan, Ming Liao, Yu Huang, Kaijian Luo, Xuetao Jiang, Hualan Chen. Characterization of the H5N1 Highly Pathogenic Avian Influenza Virus derived from Wild Pikas in China. J Virol. 2009, 83: 8957-8964

　　17. Hualan Chen. H5N1 avian influenza in China. Sci China C Life Sci. 2009, 52(5):419-27. (Review)

　　18. Szretter KJ, Gangappa S, Belser JA, Zeng H, Chen H, Matsuoka Y, Sambhara S, Swayne DE, Tumpey TM, Katz JM. Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice. J Virol. 2009 83(11): 5825-34

　　19. Kashiwagi T, Leung BW, Deng T, Chen H, Brownlee GG.. The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PLoS ONE. 2009; 4(5):e5473.

　　20. Shufang Fan, Yuwei Gao, Kyoko Shinya, Chris K-F. Li, Yanbing Li, Jianzhong Shi, Yongping Jiang, Yongbing Suo, Tiegang Tong, Gongxun Zhong, Jiasheng Song, Ying Zhang, Guobin Tian, Yuntao Guan, Xiaoning Xu, Zhigao Bu, Yoshihiro Kawaoka , Hualan Chen. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathogens, 2009, 5(5), e1000409

　　21. Chuanling Qiao, Yongping Jiang, Guobin Tian, Xiurong Wang, Chengjun Li, Xiaoguang Xin, Hualan Chen, Kangzhen Yu. Recombinant Fowlpox Virus Vector-based Vaccine Completely Protects Chickens from H5N1 Avian Influenza Virus. Antiviral Research, 2009, 81(3):234-8

　　22. Shufang Fan, Guohua Deng, Jiasheng Song, Guobin Tian, Yongbing Suo, Yongping Jiang, Yuntao Guan, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology, 2009, 384: 29-32

　　23. Murakami S, Horimoto T, Mai le Q, Nidom CA, Chen H, Muramoto Y, Yamada S, Iwasa A, Iwatsuki-Horimoto K, Shimojima M, Iwata A, Kawaoka Y. Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. Journal of Virology, 2008, 82: 10502-9

　　24. Beibei Jia, Jianzhong Shi, Yanbing Li, Kyoko Shinya, Yukiko Muramoto, Xianying Zeng, Guobin Tian, Yoshihiro Kawaoka, Hualan Chen. Pathogenicity of Chinese H5N1 Highly Pathogenic Avian Influenza Viruses in Pigeons. Archives of Virology, 2008, 153: 1821-1826

　　25. Chengjun Li, Jihui Ping, Bo Jing, Guohua Deng, Yongping Jiang, Yanbing Li, Guobin Tian, Kangzhen Yu, Zhigao Bu, Hualan Chen. H5N1 influenza marker vaccine for serological differentiation between vaccinated and infected chickens. Biochemical and Biophysical Research Communications, 2008, 372(2): 293-7

　　26. Kiyoko Iwatsuki-Horimoto, Yasuko Hatta, Masato Hatta, Yukiko Muramoto, Hualan Chen, Yoshihiro Kawaoka, Taisuke Horimoto. Limited compatibility between the RNA polymerase components of influenza virus type A and B. Virus Research, 2008, 135(1): 161-5

　　27. Jihui Ping, Chengjun Li, Guohua Deng, Yongping Jiang, Guobin Tian, Shuxia Zhang, Zhigao Bu and Hualan Chen. Single-amino-acid mutation in the HA alters the recognition of H9N2 influenza virus by a monoclonal antibody. Biochemical and Biophysical Research Communications, 2008, 371(1): 168-371

　　28. Peirong Jiao, Guobin Tian, Yanbing Li, Guohua Deng, Yongping Jiang, Chang Liu, Weilong Liu, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. A single amino acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. Journal of Virology, 2008, 82 (3): 1146-1154.

　　Comment in Journal of Virology: Single-Amino-Acid Substitution Changes the Virulence of H5N1 Influenza Viruses. Journal of Virology, 2008, 82 (3): 1065

　　Comment in Microbe: Single-Amino-Acid Substitution Changes the Virulence of H5N1 Influenza Viruses.

　　29. Qiyun Zhu, Huangliang Yang, Weiye Chen, Wenyan Cao, Gongxun Zhong, Peirong Jiao, Guohua Deng, Kangzhen Yu, Chinglai Yang, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. A naturally occurring deletion in its NS gene contributes to attenuation of an H5N1 swine influenza virus in chickens. Journal of Virology, 2008, 82 (1):220-228.

　　30. Hualan Chen, Rick Bright, Kanta Subbarao, Catherine Smith, Nancy Cox, Jacqueline M. Katz, and Yumiko Matsuoka. Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Research, 2007, 128(1-2):159-63.

　　31. Yongping Jiang, Kangzhen Yu, Hongbo Zhang, Pingjing Zhang, Chenjun Li, Guobin Tian, Yanbing Li, Xijun Wang, Zhigao Bu, Hualan Chen. Enhanced protective efficacy of H5 subtype avian influenza DNA vaccine with codon optimized HA gene in a pCAGG plasmid vector. Antiviral Research, 2007, 75: 234-241.

　　32. Jinying Ge, Guohua Deng, Zhiyuan Wen, Guobing Tian, Yong Wang, Jianzhong Shi, Xijun Wang, Yanbing Li, Sen Hu, Yongping Jiang, Chinglai Yang, Kangzhen Yu, Zhigao Bu, Hualan Chen. Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. Journal of Virology, 2007, 81, 150－158.

　　33. Chuanling Qiao, Guobin Tian, Yongping Jiang, Yanbing Li, Jianzhong Shi, Kangzhen Yu, Hualan Chen. Vaccines Developed for H5 Highly Pathogenic Avian Influenza in China. Ann. N.Y. Acad. Sci. 2006, 1081: 182-192

　　34. Zejun Li, Yongping Jiang, Peirong Jiao, Aiqin Wang, Fengju Zhao, Guobin Tian, Xijun Wang, Kangzhen Yu, Zhigao Bu and Hualan Chen. The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. Journal of Virology, 2006, 80：11115-11123.

　　35. Taronna R. Maines, Li-Mei Chen, Yumiko Matsuoka, Hualan Chen, Thomas Rowe, Juan Ortin, Ana Falco’n, Nguyen Tran Hien, Le Quynh Mai, Endang R. Sedyaningsih, Syahrial Harun, Terrence M. Tumpey, Ruben O. Donis, Nancy J. Cox, Kanta Subbarao, and Jacqueline M. Katz. Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc. Natl. Acad. Sci. USA, 2006, 103(32): 12121-12126

　　36. Hualan Chen, Yanbing Li, Zejun Li, Jianzhong Shi, Kyoko Shinya, Guohua Deng, Qiaoling Qi, Guobin Tian, Shufang Fan, Haidan Zhao, Yingxiang Sun, Yoshihiro Kawaoka. Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. Journal of Virology, 2006, 80(12):5976-83.

　　37. Yanbing Li, Chengjun Li, Liling Liu, Hongwei Wang, Chuanbin Wang, Guobing Tian, Robert. G. Webster, Kangzhen Yu, Hualan Chen. Characterization of an avian influenza virus of subtype H7N2 isolated from chickens in northern China. Virus Genes, 2006, 33:117-122

　　38. Yanbing Li, Zhixiong Lin, Jianzhong Shi, Qiaoling Qi, Guohua Deng, Zejun Li, Xiurong Wang, Guobin Tian, Hualan Chen. Detection of Hong Kong 97-like H5N1 influenza viruses from eggs of Vietnamese waterfowl. Archives of Virology. 2006, 151: 1615-1624

　　39. Yu H, Shu Y, Hu S, Zhang H, Gao Z, Chen H, Dong J, Xu C, Zhang Y, Xiang N, Wang M, Guo Y, Cox N, Lim W, Li D, Wang Y, Yang W. The first confirmed human case of avian influenza A (H5N1) in Mainland China. Lancet. 2006, 7: 367(9504):84.

　　40. Zejun Li, Hualan Chen, Peirong Jiao, Guohua Deng, Guobin Tian, Yanbing Li, Erich Hoffmann, Robert G. Webster, Yumiko Matsuoka, Kangzhen Yu. Molecular basis associated with replication of duck H5N1 influenza viruses in a mammalian mouse model. Journal of Virology, 2005, 79: 12058-12064

　　41. Guobin Tian, Suhua Zhang, Yanbing Li, Zhigao Bu, Peihong Liu, Jinping Zhou, Chengjun Li, Jianzhong Shi, Kangzhen Yu, Hualan Chen. Protective efficacy in chickens, geese and ducks of an H5N1 inactivated vaccine developed by reverse genetics. Virology, 2005, 341: 153 - 162

　　42. Chengjun Li, Kangzhen Yu, Guobin Tian, Dandan Yu, Liling Liu, Bo Jing, Jihui Ping, and Hualan Chen. Evolution of H9N2 influenza viruses from domestic poultry in Mainland China. Virology, 2005, 340: 70 - 83

　　43. K. M. Sturm-Ramirez, D. J. Hulse-Post, E. A. Govorkova, J. Humberd, P. Seiler, P. Puthavathana, C. Buranathai, T. D. Nguyen, A. Chaisingh, H. T. Long, T. S. P. Naipospos, H. Chen, T. M. Ellis, Y. Guan, J. S. M. Peiris, and R. G. Webster. Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia. Journal of Virology, 2005, 79(17): 11269-11279

　　44. D. J. Hulse-Post, K. M. Sturm-Ramirez, J. Humberd, P. Seiler, E. A. Govorkova, S. Krauss, C. Scholtissek, P. Puthavathana, C. Buranathai, T. D. Nguyen, H. T. Long, T. S. P. Naipospos, H. Chen, T. M. Ellis, Y. Guan, J. S. M. Peiris and R. G. Webster. Role of domestic ducks in the propagation and biological evolution of highly pathogenic H5N1 influenza viruses in Asia. Proc. Natl. Acad. Sci. USA, 2005, 102: 10682-10687

　　45. H. Chen，G. Deng，Z. Li，G. Tian，Y. Li，P. Jiao, L. Zhang, Z. Liu, R. G. Webster, K. Yu. The evolution of H5N1 influenza viruses in ducks in Southern China. Proc. Natl. Acad. Sci. USA, 2004, 101(28): 10452-10457

　　Comments in Nature: Increasing virulence of bird flu threatens mammals. Nature, 2004, 431, July 1, 4.

　　46. Hualan Chen, Yumiko Matsuoka, David Swayne, Qi Chen, Nancy Cox, Brain R. Murphy and Kanta Subbarao. Generation and Characterization of an H9N2 Cold-Adapted Reassortant as a Vaccine Candidate, Avian Diseases 2003, 47, 1127-1130

　　47. Yumiko Matsuoka, Hualan Chen, David Swayne, Safety Evaluation in Chickens of Candidate Human Vaccines against Potential Pandemic Strains of Influenza Avian Diseases, 2003, 47, 926-930

　　48. Hualan Chen, Yumiko Matsuoka, David Swayne, Qi Chen, Nancy Cox, Brain R. Murphy and Kanta Subbarao. Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza vaccine candidate. Vaccine, 2003, 21(27-28): 4430-4436

　　49. Hualan Chen, Kanta Subbarao, David Swayne, Qi Chen, Xiuhua Lu, Jacqueline Katz, Nancy Cox and Yumiko Matsuoka, Generation and evaluation of a high-growth reassortant H9N2 influenza A virus as a pandemic vaccine candidate. Vaccine 2003, 21(17): 1974-1979

　　50. Kanta Subbarao, Hualan Chen, David Swayne, Louise Mingay, Ervin Fodor, George Brownlee, Xiyan Xu, Xiuhua Lu, Jacqueline Katz, Nancy Cox and Yumiko Matsuoka. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology, 2003, 1.Jan 5, 305(1): 192-200

　　Book Chapters:

　　1. Hualan Chen, Zhigao Bu, Jingfei Wang. Epidemiology and Control of H5N1 Avian Influenza in China. Klenk H-D, Matrosovich MN, Stech J (eds): Avian Influenza. Monogr Virol. Basel, Karger, 2008, vol 27, 27-40