2020自然指数(生命科学)排行榜 诸平 据2020年4月29日自然网站( Nature )公布的2020年自然指数( Nature Index 2020 Annual Tables ),2015-2019年之间, 生命科学领域自然指数 提升最快的十佳机构( Rising stars in life sciences for 2020 )中,有8家是来自中国。其中第七名和第八名分别被 英国牛津大学( University of Oxford, UK, )和 瑞士苏黎世联邦理工学院( Swiss Federal Institute of Technology Zurich , Switzerland )占据之外,其余均来自中国,分别是 浙江大学(第一名) 、中国科学院大学( 第二名 )、第三名是北京大学、第四名是中国科学院、 上海交大为第五。更多信息见下图和自然指数(生命科学)百强一览表。 图1 2015-2019自然指数调整分值前十佳 浙江大学在2015~2019年之间,经调整后的自然指数分值变化为42.94,这表明在其4年间自然指数分值提升了158.1%。注意,为了便于比较,将某 一段时间的在自然指数统计期刊( Nature Index journals )发表的论文数量的分值数据,调整到2019年的水平。具体计算可以参见 相关编辑注释 ( Editor’s note )。浙江大学的科学家在2019年发表的研究成果中包括了牙齿釉质再生方法(发表于《科学进展》, Science Advances )、西兰花抑制肿瘤化合物的发现(发表于《科学》, Science )以及能够快速修复心脏创伤的生物胶( ‘bio glue', 发表于 《自然通讯》 Nature Communications )。 虽然复旦大学的排名在前十佳之外(第12名),2015-2019年的自然指数调整分值为15.41,变化率提升了 36.0%。复旦大学是中国第一所民办高等教育机构,成立于1905年。在20世纪40年代,它成为了一所公立大学,10年后,它成为了一所综合性大学,专注于人文、社会科学和自然科学的基础研究。在《泰晤士报高等教育》( Times Higher Education )和Quacquarelli Symonds table等几所大学的排名中,复旦大学与北京大学、浙江大学、北京清华大学和中国科学技术大学并列中国大学前五名。2000年与上海医科大学合并,加强了复旦在生命科学研究方面的国家地位。2019年,复旦大学共招收本科生13623人,研究生22610人。该校现有教职工3110人,其中中国科学院、中国工程院院士47人,国家自然科学基金杰出青年科学家奖获得者119人。复旦大学拥有数个国家重点实验室,这些实验室得到了中国政府的资金和行政支持,其中包括基因工程国家重点实验室,它是中国生命科学研究的领军者。 南京农业大学按照调整后自然指数分值(2015-2019: 14.79)的 变化百分比(280.1%)排序,是2020年调整自然指数(生命科学)分值百强一览表中的第15名。 南京农业大学成立于1952年,是由南京大学和浙江大学的农学专业合并而成的大学。 1963年被中国政府列为全国两所重点农业大学之一(另一所是东北的沈阳农业大学)。 2019年,南京农业大学有17000名本科生和11000名研究生,2700名教职员工,其中包括两名中国工程院院士。 拥有国家作物遗传与种质改良重点实验室和60多个国家农业及相关学科研究中心,已获得26亿元人民币(约3.66亿美元)的研究资助。 学校拥有作物学、农业资源与环境、植物保护等4个国家重点学科,已被教育部认定为国家重点学科。 根据Clarivate开发的《基本科学指标》(Essential science Indicators)排名,南京农业大学的农业科学和植物学/动物学两门学科都进入了世界前0.1%的行列。其他机构不再一一介绍,请注意浏览百强一览表。 自然指数(生命科学)百强一览表(依据2015-2019年自然指数调整分值变化排序) Top 100 rising institutions in life sciences The table shows the top 100 rising institutions in life sciences, ranked by change in adjusted Share* from 2015 to 2019. Also listed are the institution's Share and Count in 2019, percentage change in adjusted Share from 2015 to 2019, and global rank in the 2020 annual tables. Click on column headers to sort Rank Institution Share 2019 Count 2019 Change in Adjusted Share* 2015–2019 Change in Adjusted Share* 2015–2019 (%) 2020 Annual Tables Rank 1 Zhejiang University (ZJU), China 70.11 214 42.94 158.1% 54 2 University of Chinese Academy of Sciences (UCAS), China 60.22 401 41.68 224.8% 60 3 Peking University (PKU), China 97.74 299 40.06 69.4% 31 4 Chinese Academy of Sciences (CAS), China 244.23 854 34.48 16.4% 5 5 Shanghai Jiao Tong University (SJTU), China 56.28 216 28.50 102.6% 68 6 Sun Yat-sen University (SYSU), China 50.87 140 23.30 84.5% 76 7 University of Oxford, United Kingdom (UK) 211.24 662 22.58 12.0% 6 8 Swiss Federal Institute of Technology Zurich (ETH Zurich), Switzerland 87.91 306 20.65 30.7% 35 9 Tsinghua University, China 71.85 237 17.43 32.0% 52 10 People's Liberation Army (PLA), China 45.59 191 17.09 60.0% 92 11 University of Lausanne (UNIL), Switzerland 51.85 168 15.92 44.3% 75 12 Fudan University, China 58.17 231 15.41 36.0% 65 13 Huazhong University of Science and Technology (HUST), China 25.86 76 15.29 144.6% 100 14 Max Planck Society, Germany 291.21 1067 15.04 5.4% 4 15 Nanjing Agricultural University (NAU), China 20.07 52 14.79 280.1% 100 16 Ludwig Maximilians University of Munich (LMU), Germany 73.18 299 14.73 25.2% 50 17 Northwestern University (NU), United States of America (USA) 101.76 266 14.65 16.8% 28 18 University of Copenhagen (UCPH), Denmark 76.54 306 14.60 23.6% 45 19 Rutgers, The State University of New Jersey (RU), United States of America (USA) 67.26 181 14.11 26.5% 57 20 Sichuan University (SCU), China 22.41 73 13.98 165.9% 100 21 Oncode Institute, Netherlands 13.93 85 13.93 N/A 100 22 Chinese Academy of Agricultural Sciences (CAAS), China 24.01 103 13.15 121.1% 100 23 University of Glasgow, United Kingdom (UK) 40.81 150 12.78 45.6% 100 24 University of Hamburg (UHH), Germany 37.83 158 12.70 50.5% 100 25 University of Exeter, United Kingdom (UK) 31.88 122 12.25 62.4% 100 26 University of Amsterdam (UvA), Netherlands 31.21 227 11.95 62.0% 100 27 ShanghaiTech University, China 13.78 90 11.94 646.8% 100 28 Alphabet Inc., United States of America (USA) 11.84 38 11.48 3174.9% 100 29 University of Oslo (UiO), Norway 34.81 151 11.28 48.0% 100 30 Memorial Sloan Kettering Cancer Center (MSKCC), United States of America (USA) 100.89 320 11.06 12.3% 30 31 University of New South Wales (UNSW Sydney), Australia 32.82 162 11.05 50.8% 100 32 Western University (UWO), Canada 23.19 57 10.87 88.3% 100 33 Central South University (CSU), China 15.20 66 10.46 220.6% 100 34 Czech Academy of Sciences (CAS), Czech Republic 23.75 115 10.43 78.3% 100 35 Wuhan University (WHU), China 22.43 83 9.98 80.1% 100 36 Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland 50.67 154 9.93 24.4% 77 37 University of Florida (UF), United States of America (USA) 55.31 191 9.90 21.8% 71 38 Catholic University of Leuven (KU Leuven), Belgium 47.90 165 9.80 25.7% 85 39 Nanjing University (NJU), China 29.06 74 9.21 46.4% 100 40 University of Zurich (UZH), Switzerland 80.13 351 9.15 12.9% 42 41 China Agricultural University (CAU), China 23.76 74 9.11 62.2% 100 42 Stanford University, United States of America (USA) 309.64 787 9.08 3.0% 3 43 Barcelona Institute of Science and Technology (BIST), Spain 27.31 105 8.98 49.0% 100 44 Monash University, Australia 45.61 217 8.85 24.1% 91 45 Fred Hutchinson Cancer Research Center (FHCRC), United States of America (USA) 41.01 153 8.76 27.2% 100 46 Rice University, United States of America (USA) 22.15 98 8.69 64.5% 100 47 Medical University of South Carolina (MUSC), United States of America (USA) 22.68 64 8.59 60.9% 100 48 Northeastern University (NEU), United States of America (USA) 17.30 71 8.52 97.0% 100 49 The University of Hong Kong (HKU), China 21.01 79 8.25 64.6% 100 50 The Pennsylvania State University (Penn State), United States of America (USA) 55.62 157 8.20 17.3% 70 51 Nanjing Medical University (NJMU), China 12.96 64 8.08 165.5% 100 52 Chinese Academy of Medical Sciences Peking Union Medical College (CAMS PUMC), China 26.00 123 7.93 43.9% 100 53 Technical University of Munich (TUM), Germany 32.23 213 7.70 31.4% 100 54 University of Science and Technology of China (USTC), China 24.30 111 7.66 46.1% 100 55 Institute for Basic Science (IBS), South Korea 13.07 45 7.66 141.6% 100 56 Allen Institute, United States of America (USA) 10.40 29 7.57 267.7% 100 57 Chan Zuckerberg Biohub (CZ Biohub), United States of America (USA) 7.47 86 7.47 N/A 100 58 Michigan State University (MSU), United States of America (USA) 31.88 125 7.32 29.8% 100 59 Northwest AF University (NWAFU), China 9.46 28 7.18 316.0% 100 60 Southern Medical University (SMU), China 12.43 38 6.88 124.0% 100 61 Technical University of Denmark (DTU), Denmark 17.27 84 6.84 65.6% 100 62 Southern University of Science and Technology (SUSTech), China 7.50 34 6.79 951.6% 100 63 University of Würzburg (JMU), Germany 27.69 115 6.77 32.4% 100 64 National Research Institute for Agriculture, Food and Environment (INRAE), France 27.65 289 6.76 32.4% 100 65 City of Hope, United States of America (USA) 17.26 55 6.69 63.3% 100 66 University of Minnesota (UMN), United States of America (USA) 82.85 248 6.66 8.7% 40 67 Ghent University (UGent), Belgium 23.11 132 6.65 40.4% 100 68 Imperial College London (ICL), United Kingdom (UK) 69.57 315 6.43 10.2% 55 69 Seattle Children's Hospital, United States of America (USA) 10.36 65 6.31 155.9% 100 70 Indian Institute of Science (IISc), India 18.99 38 6.29 49.5% 100 71 National University of Singapore (NUS), Singapore 57.22 233 6.23 12.2% 67 72 University of Groningen (RUG), Netherlands 34.44 163 6.22 22.0% 100 73 Guangzhou Medical University (GMU), China 8.21 59 6.17 301.6% 100 74 U.S. Department of Agriculture (USDA), United States of America (USA) 15.51 110 6.08 64.4% 100 75 University of Montana (UMT), United States of America (USA) 8.14 27 5.93 268.2% 100 76 Fujian Agriculture and Forestry University (FAFU), China 7.70 30 5.85 317.1% 100 77 Liverpool School of Tropical Medicine (LSTM), United Kingdom (UK) 8.40 34 5.79 221.5% 100 78 Rady Children's Hospital-San Diego, United States of America (USA) 7.43 74 5.78 351.3% 100 79 Van Andel Research Institute (VAI), United States of America (USA) 10.14 26 5.68 127.3% 100 80 Shandong University (SDU), China 19.71 120 5.66 40.3% 100 81 Ulsan National Institute of Science and Technology (UNIST), South Korea 6.60 23 5.59 555.0% 100 82 Newcastle University, United Kingdom (UK) 30.43 112 5.59 22.5% 100 83 Karolinska Institute (KI), Sweden 74.92 373 5.48 7.9% 46 84 Georgia Institute of Technology (Georgia Tech), United States of America (USA) 24.23 84 5.45 29.0% 100 85 Institute of Science and Technology Austria (IST Austria), Austria 14.36 39 5.45 61.2% 100 86 Shenzhen University (SZU), China 6.65 41 5.42 441.0% 100 87 University of Virginia (UVA), United States of America (USA) 42.65 125 5.31 14.2% 100 88 Arizona State University (ASU), United States of America (USA) 23.96 101 5.31 28.5% 100 89 The University of Texas at San Antonio (UTSA), United States of America (USA) 7.65 14 5.24 218.0% 100 90 University of Cologne (UoC), Germany 32.11 139 5.21 19.4% 100 91 The University of Utah (Utah), United States of America (USA) 58.05 173 5.20 9.8% 66 92 Tel Aviv University (TAU), Israel 45.67 130 5.17 12.8% 90 93 The University of Edinburgh, United Kingdom (UK) 83.13 306 5.14 6.6% 39 94 Temple University, United States of America (USA) 25.29 63 5.05 24.9% 100 95 University of Bristol (UoB), United Kingdom (UK) 41.08 165 5.02 13.9% 100 96 Simon Fraser University (SFU), Canada 12.04 45 4.94 69.7% 100 97 Academia Sinica, Taiwan 33.97 79 4.88 16.8% 100 98 The University of Texas at Dallas (UT Dallas), United States of America (USA) 8.58 24 4.86 130.5% 100 99 University of Oregon (UO), United States of America (USA) 20.61 55 4.81 30.5% 100 100 The Chinese University of Hong Kong (CUHK), China 18.96 84 4.80 33.9% 100
2018 自然指数(生命科学) Top100 诸平 下面的 2018自然指数(生命科学领域)Top100 一览表是基于2017年元旦到2017年12月31日的自然指数数据给出的,其中既有2016年自然分数(FC 2016),也有2017年的自然分数(FC 2017),还有2017年的 AC(AC 2017) 以及2016-2017年FC值的变化百分比( Change in Adjusted FC2016-2017 ),美国哈佛大学名列第一;美国国立卫生研究院,名列第二;名列第三的是德国马克斯·普朗克协会(Max Planck Society)。中国有7家机构入选,其中 中科院排名第5、北京大学(35)、中科院上海生物所(64)、清华大学(65)、复旦大学(78)、浙江大学(85)以及上海交大(89),其他入选机构排序详见下表。 The 2018 tables are based on Nature Index data from 1 January 2017 to 31 December 2017. 2017 Institution FC 2016 FC 2017 AC 2017 Change in Adjusted FC 2016-2017 * 1 Harvard University, United States of America (USA) 610.22 612.01 1488 2.2% 2 National Institutes of Health (NIH), United States of America (USA) 314.47 341.92 828 10.8% 3 Max Planck Society, Germany 281.15 272.31 859 -1.3% 4 Stanford University, United States of America (USA) 236.22 271.97 631 17.3% 5 Chinese Academy of Sciences (CAS), China 212.66 206.77 667 -0.9% 6 Massachusetts Institute of Technology (MIT), United States of America (USA) 208.5 200.16 740 -2.2% 7 Yale University, United States of America (USA) 193.05 175.03 402 -7.6% 8 University of California, San Diego (UC San Diego), United States of America (USA) 165.91 172.73 480 6.1% 9 University of California San Francisco (UCSF), United States of America (USA) 193.93 172.07 491 -9.6% 10 University of Pennsylvania (Penn), United States of America (USA) 143.62 169.26 436 20.1% 11 Columbia University in the City of New York (CU), United States of America (USA) 157.43 168.36 412 9.0% 12 French National Centre for Scientific Research (CNRS), France 176.06 167.09 1096 -3.3% 13 University of Oxford, United Kingdom (UK) 193.18 165.79 503 -12.6% 14 Johns Hopkins University (JHU), United States of America (USA) 152.71 152.75 420 1.9% 15 Washington University in St. Louis (WUSTL), United States of America (USA) 143.41 151.06 325 7.3% 16 University of Cambridge, United Kingdom (UK) 168.34 149.93 482 -9.3% 17 University of Michigan (U-M), United States of America (USA) 122.44 147.51 365 22.7% 18 University of Toronto (U of T), Canada 147.06 144.92 371 0.4% 19 The University of Texas Southwestern Medical Center (UT Southwestern Medical Center), United States of America (USA) 113.71 139.62 267 25.1% 20 Cornell University, United States of America (USA) 130.34 138.22 426 8.0% 21 University of California Berkeley (UC Berkeley), United States of America (USA) 144.57 136.21 349 -4.0% 22 University College London (UCL), United Kingdom (UK) 130.03 124.85 498 -2.2% 23 New York University (NYU), United States of America (USA) 115.75 121.28 321 6.8% 24 University of California Los Angeles (UCLA), United States of America (USA) 135.97 120.37 322 -9.8% 25 University of Washington (UW), United States of America (USA) 129.23 116.03 365 -8.5% 26 Helmholtz Association of German Research Centres, Germany 112.9 103.01 586 -7.0% 27 Northwestern University (NU), United States of America (USA) 91.71 102.14 251 13.5% 28 Memorial Sloan Kettering Cancer Center (MSKCC), United States of America (USA) 84.47 102.05 258 23.1% 29 Duke University, United States of America (USA) 139.64 101.24 317 -26.1% 30 University of North Carolina at Chapel Hill (UNC), United States of America (USA) 96.62 100.68 273 6.2% 31 The University of Chicago (UChicago), United States of America (USA) 98.78 99.8 253 2.9% 32 University of Wisconsin-Madison (UW-Madison), United States of America (USA) 100.45 99.57 202 1.0% 33 The Rockefeller University, United States of America (USA) 91.3 96.37 232 7.5% 34 The University of Tokyo (UTokyo), Japan 100.12 93.17 251 -5.2% 35 Peking University (PKU), China 58.95 88.11 225 52.3% 36 The University of Edinburgh, United Kingdom (UK) 72.1 85.2 253 20.4% 37 Baylor College of Medicine (BCM), United States of America (USA) 88.28 82.63 264 -4.6% 38 Vanderbilt University (VU), United States of America (USA) 82.31 82.17 220 1.7% 39 Princeton University, United States of America (USA) 62.81 81.97 172 33.0% 40 National Institute for Health and Medical Research (INSERM), France 79.64 77.15 707 -1.3% 41 California Institute of Technology (Caltech), United States of America (USA) 57.74 74.72 155 31.8% 42 The Scripps Research Institute (TSRI), United States of America (USA) 81.47 74.67 208 -6.6% 43 The University of Texas MD Anderson Cancer Center, United States of America (USA) 87.8 74.55 241 -13.5% 44 University of Pittsburgh (Pitt), United States of America (USA) 94.63 74.4 205 -19.9% 45 McGill University, Canada 90.95 73.4 230 -17.8% 46 University of Zurich (UZH), Switzerland 86.37 73.1 251 -13.8% 47 Weizmann Institute of Science (WIS), Israel 79.75 72.86 145 -6.9% 48 Imperial College London (ICL), United Kingdom (UK) 90.68 72.71 397 -18.3% 49 University of California Davis (UC Davis), United States of America (USA) 64.98 71.11 212 11.5% 50 Ludwig Maximilians University of Munich (LMU), Germany 54.86 70.58 264 31.1% 51 NIH National Cancer Institute (NCI), United States of America (USA) 79.24 68.37 210 -12.1% 52 Karolinska Institute (KI), Sweden 67.92 67.98 295 2.0% 53 Medical Research Council (MRC), United Kingdom (UK) 55.68 67.21 290 23.0% 54 Swiss Federal Institute of Technology Zurich (ETH Zurich), Switzerland 70.21 66.61 205 -3.3% 55 Emory University, United States of America (USA) 67.5 65.35 182 -1.4% 56 University of Copenhagen (UCPH), Denmark 67.1 63.27 217 -3.9% 57 Mount Sinai Health System (MSHS), United States of America (USA) 70.51 63.02 248 -8.9% 58 RIKEN, Japan 54.36 60.04 198 12.5% 59 University of Minnesota (UMN), United States of America (USA) 64.71 58.71 187 -7.6% 60 The University of Queensland (UQ), Australia 45.48 58.49 189 31.0% 61 Rutgers, The State University of New Jersey (RU), United States of America (USA) 62.64 57.83 141 -5.9% 62 University of Illinois at Urbana-Champaign (UIUC), United States of America (USA) 41.89 57.61 135 40.1% 63 Heidelberg University (Uni Heidelberg), Germany 49.97 57.54 214 17.3% 64 Shanghai Institutes for Biological Sciences (SIBS), CAS, China 68.06 57 228 -14.7% 65 Tsinghua University (TH), China 50.93 56.68 182 13.4% 66 The University of Texas at Austin (UT Austin), United States of America (USA) 65.1 55.87 127 -12.6% 67 University of Southern California (USC), United States of America (USA) 56.54 55.8 178 0.5% 68 King's College London (KCL), United Kingdom (UK) 46.37 55.56 323 22.1% 69 Kyoto University, Japan 53.68 55.33 157 5.0% 70 Spanish National Research Council (CSIC), Spain 51.77 54.41 269 7.1% 71 University of Utah (Utah), United States of America (USA) 44.57 52.26 147 19.4% 72 The Pennsylvania State University (Penn State), United States of America (USA) 54.45 51.31 125 -4.0% 73 University of Massachusetts Medical School (UMass Medical School), United States of America (USA) 54.84 50.83 159 -5.6% 74 The Ohio State University (OSU), United States of America (USA) 59.61 50.35 137 -13.9% 75 University of Basel (UB), Switzerland 48.67 50.25 172 5.2% 76 National University of Singapore (NUS), Singapore 39 49.55 197 29.4% 77 MRC Laboratory of Molecular Biology, United Kingdom (UK) 40.7 48.39 90 21.1% 78 Fudan University, China 32.84 47.52 145 47.4% 79 Hebrew University of Jerusalem (HUJI), Israel 44.18 47.18 111 8.8% 80 Albert Einstein College of Medicine (Einstein), United States of America (USA) 47.93 47.14 143 0.2% 81 University of Colorado Denver | Anschutz Medical Campus (CU Anschutz), United States of America (USA) 46.58 46.99 127 2.8% 82 University of California Irvine (UCI), United States of America (USA) 52.43 46.77 117 -9.1% 83 The University of British Columbia (UBC), Canada 58.18 46.54 157 -18.5% 84 Indiana University (IU), United States of America (USA) 50.58 45.98 137 -7.4% 85 Zhejiang University (ZJU), China 42.89 45.46 145 8.0% 86 University of Freiburg (Uni Freiburg), Germany 34.19 43.88 148 30.8% 87 Boston University (BU), United States of America (USA) 50.61 43.83 191 -11.8% 88 University of Cincinnati (UC), United States of America (USA) 43.88 43.67 118 1.4% 89 Shanghai Jiao Tong University (SJTU), China 30.74 43.14 155 43.0% 90 University of Montreal (UdeM), Canada 44.08 43.05 139 -0.5% 91 Oregon Health and Science University (OHSU), United States of America (USA) 50.89 42.72 113 -14.5% 92 Leibniz Association, Germany 46.75 42.69 272 -7.0% 93 Osaka University, Japan 61.16 42.3 125 -29.5% 94 Utrecht University (UU), Netherlands 41.3 42.25 179 4.2% 95 Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Italy 41.63 42.07 201 3.0% 96 Texas AM University (TAMU), United States of America (USA) 32.12 41.67 107 32.2% 97 European Molecular Biology Laboratory (EMBL), Germany 42.39 41.29 208 -0.7% 98 Seoul National University (SNU), South Korea 37.23 40.88 101 11.9% 99 Case Western Reserve University (CWRU), United States of America (USA) 53.21 40.04 117 -23.3% 100 Catholic University of Leuven (KU Leuven), Belgium 42.49 39.95 141 -4.2%
这是我第一次写博文,写作的灵感源于最近读了一些“两会”期间各位专家学者对于我国新时期基础研究领域提出的一些改进意见。本来想把“改进”说成“改革”,但想想“改革”一词谈何容易,涉及各方利益,并非一时半会能够促成。于是想来“改进”一词可能更为适合。我虽然身在海外,但也出去没多久,时刻关注国内科研发展的动向。在这里基于各位专家以及科学网上各位学者提出的一些意见,以及自身的研究经历,结合美国与中国的科研比较,表达一些自己很粗浅的想法。也希望感兴趣的朋友能够一起讨论和指正。 我印象最深刻的三则消息,一个则是关于有专家提到希望要更关注国内培养的博士生的发展问题,不可盲目地优待具有海归背景的研究人员而忽视了本国培养的高水平人才;第二个是有报道称施一公先生提到目前我国基础研究领域虽然论文总量上去了但是“垃圾”很多;第三个则是关于某校一长江学者的文章涉嫌的造假风波。我在这里希望把这三个问题综合起来做一下思考和分析,并提出可能能够改善这些问题的方法。 我博士学位是16年在国内中科院生命科学领域某研究所拿到的。当时毕业生中大家比较盛行的说法是:如果要继续从事学术研究,必须出国再从事短则3年,长则5、6年,甚至7-8年的博士后研究;留在国内进行博士后研究的同学很少,几乎是由于在博士阶段的研究工作没有完成,而留在了原来的课题组接着进行研究;其余的学生较多的去了生物公司,少数留在了高校从讲师做起,甚至彻底转行。我印象中当时我那一届毕业生中出国做博后的,大多数都改变了研究方向,转而投身到不同的领域甚至完全不相关的领域,包括我本人。一个重要的原因,就是当时我博士阶段的专业在国外较难找到相关的博后位置。特别是在博后人数最多的美国,几乎无法找到博后职位。但由于国家的政策优待于具有海外背景的科研人员,特别喜欢无国内单位挂靠的海归人员,所以大家迫于无奈,改变研究方向。这显然是对博士阶段研究经历的一个极大的浪费。甚至身边有朋友提到,国内的中药学专业现在也需要海外经历。想来真是非常荒唐。私以为,海外经历绝对不能一刀切,对于某些我们国家已经高水平的领域,绝对不能再那么崇洋媚外地看所谓的海外经历。这一方面会误导青年学者,一方面也造成了国家资源的极大浪费。显然,这对于我们国家基础研究的发展是非常不利的。政策的指定必须根据具体学科和研究方向,需要有弹性。 有关学术界“垃圾”文章较多的问题。我听到的一些声音把这个原因归结为几点:首先,高水平的学术成果毕竟少数;第二,大部分科研人员目前还处在“生存”阶段,还没有办法达到享受做科研的高尚情怀,因此发些水平低的文章维系生计;第三,有一种声音是“垃圾”文章还不算最坏,最怕的是“有毒”文章。我以我本人在美国大学的一些见闻谈谈我的想法。的确,大部分研究均无法比拟个别高水平的研究,这点即使是在美国也是一样的。在科学的发展中,私以为,研究经费的投入,如果能换来其中10%的得到真正有回报的效果,那已经算是一个非常不错的水平。我们必须接受大量的研究是“无用”的这一事实。当然,这并不是应该成为那些“垃圾”文章发表的借口,不过这也的确是一个学术界无法去否认客观均存在的现象。我更关注一个“有毒”文章的概念。我和一些朋友的意见比较一致,认为“有毒”文章给科研界带来的坏处远远大于“垃圾”文章。“垃圾”文章最多是无用,而“有毒”文章则会误导学者,误导一个领域的发展,带来的影响是非常恶劣的。以生命科学领域为例,由于实验的不确定性和缺乏判断真伪的标准,的确充斥了一些“有毒”文章,甚至极个别领域出现整个领域都受到影响的地步。造成这个的原因,一方面由于背后巨大的利益诱惑,一些并不是真正热爱科研的人进入科研领域,他们的功利心促使他们去造假一牟取利益;另一方面也反应了相关政策和标准的缺失和不健全。我们应该思考的是如何去甄别并惩治“恶徒”?此外,科研界的造假是否中国特有,或者中国尤其多?如何尽可能的让真正适合科研,喜欢科研的年轻人来做科研? 对于上面我提出的第一个问题,我也暂时无法去回答,希望随着中国科研的发展,有关部门能够更公平,公正和透明地处理这些问题。重点谈谈后两个问题。 对于第二个问题,我的感觉是造假绝非中国特有。但中国学者的造假给我的感觉是造假水平太低。美国生命科学领域照样充斥着各种造假事件,甚至出现集团造假。但是老外的造假水平非常之高,如果不是相关领域的个别高水平研究人员,如果你没有亲自动手做过相关实验,你是很难发现里面的猫腻的。他们大多编造了一个完美的故事,表面上看起来合乎情理实则犹如皇帝的新衣。 对于第三个问题,我想到的是,以生命科学领域为例,我们国家目前参考的基本是美国的PI制度。我以为,中国要慎重使用这种制度,不可完全照搬照抄美国的经验。美国的生命科学发展至今,早已经暴露出来研究人员大量过剩,年轻助教压力过大,无止境的朝不保夕的博后生涯,和大量研究人员中途退出学术圈以及恶性竞争甚至学术造假等情况。为此,大量的相关报道在nature上发表并指出博后制度的问题,以及该如何解决这一问题: The future of the postdoc 2015 Wanted: staff-scientist positions for postdocs 2015 Bigger is not better when it comes to lab sizes 2015 harsh reality 2014 Education: the PhD factory 2011 Life outside the lab: The ones who got away 2014 ...也难怪,川普上台后削减了NIH近20%的经费,大量的年轻学者岌岌可危。相关的解决方法包括:增加博后的工资水平(当然是由课题组长即PI的经费里支出);限制博后的年限最高为5年;减少博后的数量;以及将更多博后转为职位稳定的正式科研人员并适当待遇。有趣的是,最后一项得到了差不多3/4的支持。在the future of the postdoc一文中提出了superdoc和senior staff scientist的概念,希望能够为那些在一个领域内由于各种原因无法当上PI或者不想当PI,但依然具备独立从事相关领域研究,掌握重要研究技能,并热爱科研的研究人员给予长期的稳定的科研支持。并把这些研究人员称为superdoc或者senior staff scientists。基于的理论是一个具备这种素质的科研人员,虽然他们不是PI,但是他们在科研创新和效率上完全抵得过几个学生。不想当PI的博后不是好博后,但是如果人人争相当PI的科研界将会非常可怕,势必会造成浮躁,恶性竞争,急功近利的功利心理,甚至造假。很多不愿在国内从事博后的人均有一个共同的声音,那就是国内做博后,发表的优秀成果被当做是老板的;而国外做博后,发表优秀成果之后,回国就被热捧。即使目前不少高校和研究机构的博后待遇明显大幅提高后,博后们还是更喜欢到海外从事博后研究。为啥?这显然不是一个简单的待遇问题。中国的明天就是美国的今天,本人认为这个问题是一个非常关键,也是关乎这个学科可持续发展的重大问题。 我认为良性的科研圈以后更应该呈现趋近于橄榄型,而非现在的金字塔形。首先,减少学生的数量,提高入学的门槛水准,严进;第二,提高博导的门槛减少博导的数量,保留真正具备高水平,自己有精力去指导那些热爱从事科研并且基础好的学生,同时还能发表高水平论文的少数高水平博导的职位。这样既能保障导师队伍的高水平,也能保障他们培养出来的学生队伍的高水平;第三,给其余科研人员提供类似superdoc或者senior staff scientists的职位,这部分研究人员必须由学生时代就从事科研,进过多年的培训,掌握重要技能,能够独立从事研究工作发表高水平论文。应该减少部分大项目大经费,拆散之后分给这些高水平的非PI科研工作者,让他们真正热爱科研,有保障长期从事一个领域。因为我们都知道,重要的研究成果必须由高水平的研究人员长期坚持才能完成。这部分人虽然无法成为独立PI,但是他们却应该是学术界最容易出成果的群体。他们的收入更多能够从自己申请的经费中来。因为我之前提到了我们可以考虑拆散一些大项目分给更多较小的经费项目。学生的任务在于学习和积累,而不在于发表成果。高水平PI博导的任务则包括培养学生,指挥学科发展方向以及发表重要成果。这样的模式更可能地整体提高导师队伍水平,整体科研水平,净化科研浮躁的风气,以及让更有天资,真正喜欢科学的学生未来进入superdoc或者senior staff scientists的高水平科研人才,甚至成为像他们导师一样具有极高水平的顶级科研人员。 以简单的数字为例(具体数字可以优化)。基础研究领域,1个导师一生就只指导7-8个学生,7-8个学生中5个今后从事科研(剩下2-3个没有做科研则是因为个人兴趣转变或者进入应用领域),5个中4个成为superdoc或者senior staff scientists,职位长期稳定,待遇较好,具备科研自主性和独立性。剩下1个最优秀的成为导师,去指导下一代学生。 以上就是本人的一些很粗浅的想法,可能有些不切实际,或者把问题看得太过于简单。但是的确是看到了科研界,特别是本人从事的生命科学领域的诸多发展问题,希望我们国家在今后几十年的关键发展阶段,真正落实良好的科研政策,不光要吸取欧美的长处,更要避开他们发展中的一些问题。真正让我们国家的科研环境得以改善,良性发展。
2017生命科学薪酬调查结果(图片) 诸平 全球调查结果:美国、加拿大年薪高,亚洲、拉丁美洲年薪最低。 文化倾向 工业及象牙塔薪酬 美国薪酬比较 男女薪酬比较 美国男女薪酬比较 更多信息请浏览: 2017 Life Science Salary Survey By Aggie Mika Industry professionals make more than academic researchers, but for professors, it may not be about the money.
一、大道至简,万物本源是形、数 从古至今,科学家均致力于用简单、优美的方程来揭示世界的奥妙。古希腊数学家毕达哥拉斯提出,数是宇宙万物的本原,研究数学的目的并不在于使用,而是为了探索自然的奥秘。欧几里德的《几何原本》、牛顿的《自然哲学的数学原理》、爱因斯坦的质量能量方程等等,引领了一次又一次科学和思想的革命,人类的认识能力从简单到复杂,不断得以提升,自然界奥妙的潘多拉魔盒得以慢慢揭开。 二、生生不息,种群演化的简单数学模型 电影《星际迷航》中的瓦肯人,将中指与食指并拢,无名指与小指并拢,最后将大拇指尽可能的张开,道出生命的终极意义——“生生不息,繁荣昌盛”。生命的演化从无到有,从小到大,从简单到复杂,是否也能用简单、优美的方程来表达呢? 为了研究种群数量演变的规律,美国数学生态学家罗伯特·梅在《表现非常复杂动力学的简单数学模型》论文中提出了著名的虫口模型,在数学上又称为逻辑斯谛克 (Logistic) 映射:在某一范围内单一种类的昆虫繁殖时,第 n 年的数量与第 n+1 年的数量可以表示为: x n+1 =x n (a-bx n ) ,其中 a 表示增长率, -bx n 表示考虑到争夺食物等因素引起的虫口饱和。通过数学上的简化和一系列推导,在特定区间范围内,昆虫的数量呈现出倍周期分岔现象,系统最终进入混沌状态。 混沌?什么混沌?是蝴蝶效应对应的混沌吗?确实就是蝴蝶效应展示的混沌现象。大气的变化规律与昆虫种群数量的演变规律不可思议地走进了同一个领域——混沌数学模型。 三、生命方程,进化动力学能否探究从简单到复杂的自然奥秘 虫口模型是研究种群数量演变的一类生命方程,属于种群动力学领域范畴。在生物学和数学的交叉领域,科学家一直在探究生命进化所遵循的数学原理,例如适合度景观、突变矩阵、基因组序列空间、随机漂移、准种、复制者、囚徒困境、有限种群和无限种群中的博弈、进化图论、网格博弈、进化万花筒、分形以及空间混沌等等。在这些进化动力学理论的指导下,人类免疫缺陷病毒( HIV )致病过程,病原体毒力的进化,癌的进化,利他行为的进化,甚至人类语言的进化等,都可得以解释。 培根说过,数学是科学的大门和钥匙。我坚信,在数学的引领下,从简单到复杂的生命方程的潘多拉魔盒终将会被打开!
2012 年 7 月 31 日,尤里 - 米尔纳基金会宣布成立基础物理学奖基金会,设立两类奖, 基础物理学奖 给该领域变革性的进步, 新地平线物理奖 给年轻有为的研究人员。同时宣布首次授予 9 位“创始”获奖者,每人奖金 300 万美元。由他们组成评奖委员会,选择未来的获奖者,新的获奖者也将加入评奖委员会。相较于诺贝尔奖的稳重、迟缓,基础物理学奖可授予理论尚未被数据支持的物理学家。 尤里 - 米尔纳是俄罗斯著名投资人,俄罗斯互联网投资公司 DST Global CEO 、数码天空公司 CEO 。他投的公司中已经出现了两家千亿美元级的巨头(阿里巴巴和 Facebook ),和五六家百亿级的(京东、 Twitter 、小米、滴滴打车、 Airbnb 和 Snapchat )。 九位基础物理学奖创始获奖者为 Nima Arkani-Hamed , AlanGuth , Alexei Kitaev , MaximKontsevich , AndreiLinde , Juan Maldacena , NathanSeiberg , AshokeSen , Edward Witten ,基本上都是弦论、场论、暴涨宇宙学的理论物理学家。 创始之后的首次评选,首先选出 3 位“ 物理前沿奖 ”,作为 2013 年基础物理学奖候选者,未获基础物理学奖的前沿奖得主将获得 30 万美元奖金,并自动成为以后 5 年的基础物理学奖候选者。 2013 年 3 月,基础物理学奖授予普林斯顿大学的 Alexander Polyakov 。前沿奖授予 1 ) Charles Kane , LaurensMolenkamp 和 张首晟 ; 2 ) AlexanderPolyakov ; 3 ) Joseph Polchinski 。同时颁发了两个 基础物理学特别奖 ,各奖 300 万美元,分别授予霍金和大型强子对撞机的领导团队,包括 Peter Jenni, Fabiola Gianotti (ATLAS), Michel Della Negra, TejinderSingh Virdee, Guido Tonelli, Joe Incandela (CMS) and Lyn Evans (LHC) 。 2013 年 2 月 20 日,成立 生命科学突破奖 ,首次授予 11 人,每人 300 万美元奖金。获奖者将成为评奖委员会成员,新的获奖者也将加入委员会。生命科学奖基金会由谷歌创始人谢尔盖 - 布林和(前?)夫人安妮 - 沃西基,脸书创始人马克 - 扎克伯克和夫人普莉希拉 - 陈,尤里 - 米尔纳赞助 , 苹果公司董事会主席亚瑟 - 莱文森担任基金会主席,沃西基,扎克伯克,米尔纳担任理事,每年奖励 5 个,每个 300 万美元。 生命科学突破奖的“创始”获奖者包括 Cornelia I. Bargmann , David Botstein , Lewis C.Cantley , HansClevers , NapoleoneFerrara , Titia deLange , Eric S. Lander , CharlesL. Sawyers , BertVogelstein , RobertA. Weinberg , ShinyaYamanaka 。 2013 年 12 月基础物理学奖和生命科学突破奖统称 突破奖 , 马云和夫人张瑛 加入赞助人行列。 2014 年度基础物理学突破奖由 Michael B. Green 和 John H.Schwarz 分享,前沿奖授予 1 ) Joseph Polchinski ; 2 ) Michael B. Green 和 John H.Schwarz ; 3 ) Andrew Strominger 和 CumrunVafa 。 生命科学突破奖授予 6 人: JamesAllison , MahlonDeLong , MichaelHall , Robert Langer , RichardLifton , AlexanderVarshavsky 。 在这次授奖会上,扎克伯格和米尔纳新成立 数学突破奖 。 2014 年 6 月,首批数学突破奖授予 Simon Donaldson , MaximKontsevich , JacobLurie , 陶喆轩 , Richard Taylor ,每人奖金 300 万美元。 2014 年 11 月, 2015 年度基础物理学突破奖的 300 万美元由发现宇宙加速膨胀的 Saul Perlmutter , Brian P.Schmidt , AdamRiess 以及他们领导的 51 人团队分享。生命科学突破奖授予 C. David Allis, Victor Ambros, Alim Louis Benabid, Gary Ruvkun,Jennifer A. Doudna 和 EmmanuelleCharpentier 。加上 6 月宣布的 5 位数学奖,总奖金达 3600 万美元。 https://breakthroughprize.org/ 2015 年基础物理学突破奖( 3 人) 美国加州大学伯克利分校和伯克利国家实验室 给最出人意料的发现——宇宙在加速膨胀而不是长期以来认为的减慢 Citation: For the most unexpected discovery that the expansion of theuniverse is accelerating, rather than slowing as had been long assumed. 美国约翰-霍普金斯大学和空间望远镜科学研究所 给最出人意料的发现——宇宙在加速膨胀而不是长期以来认为的减慢 Citation: For the most unexpected discovery that the expansion of theuniverse is accelerating, rather than slowing as had been long assumed. 澳大利亚国立大学 给最出人意料的发现——宇宙在加速膨胀而不是长期以来认为的减慢 Citation: For the most unexpected discovery that the expansion of theuniverse is accelerating, rather than slowing as had been long assumed. 2014 年基础物理学突破奖( 2 人) 英国剑桥大学 在量子引力和力的统一开创新的方向 Citation: For opening new perspectives on quantum gravity and theunification of forces. 美国加州理工学院 在量子引力和力的统一开创新的方向 Citation: For opening new perspectives on quantum gravity and theunification of forces. 2013 年基础物理学突破奖( 1 人) 美国普林斯顿大学 给他的众多场论和弦论发现,包括共形自举,磁单极,瞬子,禁闭 / 退禁闭,非临界维下弦的量子化,规范 / 弦对偶,等等。过去几十年他的思想主宰了这些领域 Citation: For his many discoveries in field theory and string theoryincluding the conformal bootstrap, magnetic monopoles, instantons,confinement/de-confinement, the quantization of strings in non-criticaldimensions, gauge/string duality and many others. His ideas have dominated thescene in these fields during the past decades. 2012 年基础物理学奖创始成员( 9 人) 美国普林斯顿高等研究院 粒子物理突出问题的原创方法,包括建议额外维理论,希格斯玻色子新理论,超对称的新认识,暗物质理论,以及对规范理论散射振幅新数学结构的考察 美国麻省理工学院 提出暴涨宇宙学,以及宇宙早期因量子涨落导致宇宙密度浇落的理论贡献,和他正在进行的在永恒膨胀的时空中定义几率的问题。 Citation: For the invention of inflationary cosmology, and for hiscontributions to the theory for the generation of cosmological densityfluctuations arising from quantum fluctuations in the early universe, and forhis ongoing work on the problem of defining probabilities in eternallyinflating spacetimes. 美国加州理工学院 采用任意子和不成对马约拉那模式的拓扑量子相位,实现可靠的量子记忆和容错量子计算的理论思想 Citation: For the theoretical idea of implementing robust quantum memoriesand fault-tolerant quantum computation using topological quantum phases withanyons and unpaired Majorana modes. 法国高等科学研究院 他的无数的贡献,将现代理论物理和数学富有成果的交互提高到新的高度,包括发展同源镜像对称,以及 wall-crossing 现象研究 Citation: For numerous contributions which have taken the fruitfulinteraction between modern theoretical physics and mathematics to new heights,including the development of homological mirror symmetry, and the study ofwall-crossing phenomena. 美国斯坦福大学 发展暴涨宇宙学,包括新暴涨理论,永恒混沌暴涨,暴涨多重宇宙理论,以及发展弦论中的真空稳定机制 Citation: For the development of inflationary cosmology, including thetheory of new inflation, eternal chaotic inflation and the theory ofinflationary multiverse, and for contributing to the development of vacuumstabilization mechanisms in string theory. 美国普林斯顿高等研究院 规范 / 引力对偶,将时空中的引力物理与时空边界的量子场论联系起来。该对应显示黑洞与量子物理是兼容的,解决了黑洞信息悖论。它也提供了一个有用的工具,研究强耦合量子系统,有助于深入了解从高温核物质到高温超导体等一系列问题。 Citation: For the gauge/gravity duality, relating gravitational physics in aspacetime and quantum field theory on the boundary of the spacetime. Thiscorrespondence demonstrates that black holes and quantum mechanics arecompatible, resolving the black hole information paradox. It also provides auseful tool for the study of strongly coupled quantum systems, giving insightsinto a range of problems from high temperature nuclear matter to high temperaturesuperconductors. 美国普林斯顿高等研究院 对我们理解量子场论和弦论的重要贡献。他对超对称量子场论的精确分析,导致关于它们动力学的深刻认识,在物理和数学上有基础性的应用 Citation: For major contributions to our understanding of quantum fieldtheory and string theory. His exact analysis of supersymmetric quantum fieldtheories led to new and deep insights about their dynamics, with fundamentalapplications in physics and mathematics. 印度哈里希-钱德拉研究所 发现了在一些超弦理论和规范理论中强-弱对偶的惊人证据,为证明所有弦论都是同一基本弦论的不同极限开创了道路 Citation: For uncovering striking evidence of strong-weak duality in certainsupersymmetric string theories and gauge theories, opening the path to therealization that all string theories are different limits of the sameunderlying theory. 美国普林斯顿高等研究院 多个对物理学的贡献,例如拓扑学在物理中的新应用,非微扰对偶对称,弦论导出的粒子物理模型,暗物质探测,粒子散射振幅的扭摆弦方法,以及量子场论在数学上的大量的应用 Citation: For contributions to physics spanning topics such as newapplications of topology to physics, non perturbative duality symmetries,models of particle physics derived from string theory, dark matter detection,and the twistor-string approach to particle scattering amplitudes, as well asnumerous applications of quantum field theory to mathematics.
Optical Coherence Tomography (OCT) for Healthcare and Life Science 购买该报告请联系: 麦姆斯咨询 吴越 电话:15190305084;电子邮箱:wuyue@memsconsulting.com 目前,光学相干断层成像技术(OCT)广泛应用于眼科,那么,这项技术的下一个大市场在哪里?下一代OCT系统的关键要求又是什么? OCT简介 光学相干断层成像(英文:Optical coherence tomography,简称OCT)是一种光学信号获取与处理的方式。它可以对光学散射介质如生物组织等进行扫描,获得的三维图像分辨率可以达到微米级。光学相干断层扫描技术利用了光的干涉原理,通常采用近红外光进行拍照。由于选取的光线波长较长,可以穿过扫描介质的一定深度。另一种类似的技术,共焦显微技术,穿过样品的深度不如光学相干断层扫描。 光学相干断层扫描使用的光源包括超辐射发光二极管与超短脉冲激光。根据光源性质的不同,这种扫描方式甚至可以达到亚微米级的分辨率,这时需要光源的频谱非常宽,波长的变化范围在100纳米左右。 光学相干断层扫描技术是光学断层扫描技术的一种。目前比较先进的一种光学相干断层扫描技术为频域光学相干断层扫描,这种扫描方式的信噪比较高,获得信号的速度也比较快。商用的光学相干断层扫描系统有多种应用,包括艺术品保存和诊断设备,尤其是在眼科中,这种断层扫描系统可以获取视网膜的细节图像。最近,这种技术也被用于心脏病学的研究,以对冠状动脉的疾病进行诊断。 OCT市场保持增长态势 光学相干断层成像术(OCT)是20世纪90年代初发展起来的一种新型的实时、活体、高分辨率、无损的医学成像技术。最早应用于眼科,1991年美国麻省理工学院Huang等首先利用研制的OCT对离体人视网膜和视盘进行了观察,经过几年的改进,最终确立了它在视网膜成像方面的优越性。21世纪初,OCT检查的医疗报销政策获得欧洲和美国认可,OCT市场开始以15%-20%的复合年增长率快速增长。十多年后,由于西方国家市场接近饱和,OCT眼科市场增速放缓。 但是,医疗保健和生命科学领域的OCT市场有望从2013年的5亿欧元增长至2019年的10亿欧元。新的生物医学应用的强劲需求、持续的技术创新,以及发展中国家的庞大需求,都将驱动未来OCT市场的增长。 本报告提供2014-2019年OCT医疗应用的市场预测。 2013-2019年全球OCT系统市场 OCT系统进入新的生物医学应用 除了眼科,OCT系统进入一些新的生物医学应用领域,如心血管疾病、皮肤病、胃肠病、小动物影像技术等。事实上,作为无标记、无创、高分辨率的技术代表,在一些公共健康问题方面,如与年龄相关的黄斑病、皮肤癌、心脑血管疾病、乳腺癌等,OCT系统是非常有效的诊断和监测工具。 现在的问题是:哪个应用会给OCT市场带来新的生机? 本报告提供OCT在眼科、其它医疗保健和生命科学领域的技术趋势和市场数据,全面介绍最有希望的OCT新应用:心脏病和皮肤病,也提供2014-2019年每个应用市场的预测。 OCT在医疗保健和生命科学领域中的应用 新技术提高OCT性能 随着OCT新组件和新系统的出现,新的应用出现转机。 为了让OCT在新的生物医学领域中获得更广泛地接受,研发人员努力改善OCT性能、组件和子系统的紧凑性。随着技术的发展,如芯片光谱仪,OCT正朝着小型化的方向发展。 此外,功能性OCT系统的发展也朝着诊断更精确的方向前进,未来将提供生物过程或化学成分的定量信息。本报告详细介绍了当前和未来OCT组件和系统的发展趋势。 不同成像技术的分辨率和穿透深度 报告目录 Executive summary • Introduction Context of the study Study goals and objectives Information sources and methodology Glossary Definitions List of companies • OCT History, market analysis and forecast History of OCT General presentation of OCT OCT market segmentation, forecast and analysis OCT players Research in OCT • OCT for ophthalmology Presentation Competing technologies Healthcare issues Drivers of growth • New applications of OCT Cardiology - Presentation - Competing technologies - Healthcare issues Dermatology - Presentation - Competing technologies - Healthcare issues Other applications Technical trends • OCT components and systems trends and challenges General information – Evolution of key parameters Systems - Typology of today’s systems - Incoming OCT techniques - Other incoming techniques Components and Sub-Systems - Presentation / Critical components and subsystems - State of the art - Currently emerging components and subsystems - Manufacturers • Regulation aspects European regulations Regulations in the USA • Conclusion • Appendices Methodology Presentation of TEMATYS 若需要《医疗保健和生命科学领域的光学相干断层成像技术》样刊,请发E-mail:wuyue@memsconsulting.com
为您呈现 计算机科学与信息系统学 领域内 2013 年中国作者优秀论文精选 On the evolution of Linux kernels: a complex network perspective Lei Wang 、 Pengzhi Yu 、 Zheng Wang 、 Chen Yang 和 Qiang Ye Journal of Software: Evolution and Process 影响因子: 1.32 Topical community detection from mining user tagging behavior and interest Xiaoling Sun 和 Hongfei Lin Journal of the Association for Information Science and Technology 影响因子: 2.23 Consolidation of Low-quality Point Clouds from Outdoor Scenes Jun Wang 、 Kai Xu 、 Ligang Liu 、 Junjie Cao 、 Shengjun Liu 、 Zeyun Yu 和 Xianfeng David Gu International Journal of Intelligent Systems 影响因子: 1.595 A survey of fuzzy web mining Chun-Wei Lin 和 Tzung-Pei Hong Wiley Interdisciplinary Reviews: Data Mining and Knowledge Discovery 影响因子: 1.358 Determination of the Attitudinal Character by Self-Evaluation for the Maximum Entropy OWA Approach Feng-Mei Ma 和 Ya-Jun Guo International Journal of Intelligent Systems 影响因子: 1.411 Acculock: accurate and efficient detection of data races Xinwei Xie 、 Jingling Xue 和 Jie Zhang Software: Practice and Experience 影响因子: 1.148 Content-Based Colour Transfer Fuzhang Wu1 、 Weiming Dong 、 Yan Kong 、 Xing Mei 、 Jean-Claude Paul 和 Xiaopeng Zhang Computer Graphics Forum 影响因子: 1.595 A TWO-STAGE WIN–WIN MULTIATTRIBUTE NEGOTIATION MODEL: OPTIMIZATION AND THEN CONCESSION Li Pan 、 Xudong Luo 、 Xiangxu Meng 、 Chunyan Miao 、 Minghua He 和 Xingchen Guo Computational Intelligence 影响因子: 0.87 An adaptive service selection method for cross-cloud service composition Jun Yang 、 Wenmin Lin 和 Wanchun Dou Concurrency and Computation: Practice and Experience 影响因子: 0.784 Simulating realistic crowd based on agent trajectories Libo Sun 、 Xiaona Li 和 Wenhu Qin Computer Animation and Virtual Worlds 影响因子: 0.422 注:以上文章是由中国作者发表的,2014年 在 Wiley Online Library上高访问或高下载的文章。
CRISPR 先驱者荣获 2015 生命科学突破奖 诸平 据《 科学家 》( The Scientist )网站 2014 年 11 月 18 日 报道, 2015 生命科学突破奖 ,被 CRISPR 的先驱者荣获。下面的3人照片从左到右依次是 艾曼纽·卡彭特( Emmanuelle Charpentier )、詹妮弗·杜德纳( Jennifer Doudna )以及 维克托·安布罗斯( Victor Ambros )。 Alim-Louis Benabid en 2013 Gary Ruvkun 2015 年生命科学突破奖确认了六位科学家,艾曼纽·卡彭特( Emmanuelle Charpentier )、詹妮弗·杜德纳( Jennifer Doudna )、 维克托·安布罗斯( Victor Ambros ) 、阿里姆·路易斯·本纳比德( Alim Louis Benabid )、加里·鲁夫昆( Gary Ruvkun )以及 C. 戴维·阿里斯( C. David Allis ),其成就在于基因编辑、基因调控和帕金森氏症治疗方面的突出贡献。 300 万美元的奖项是由一群包括俄罗斯企业家尤里·米尔纳( Yuri Milner )及其夫人茱莉雅·米尔纳( Julia Milner )、脸书( Facebook )的创办人马克 • 扎克伯格 ( Mark Zuckerberg ) 及其夫人普莉希拉·陈( Priscilla Chan )、 谷歌公司的创始人谢尔盖 • 布林 ( Sergey Brin ) 和安妮 · 沃西基( Anne Wojcicki ) , 马云夫妇( Jack Ma and Cathy Zhang )等科技亿万富翁提供的。该奖项于 2014 年 11 月 9 日 在美国加利福尼亚的山景城举行了电视授奖仪式。由亿万富翁企业家共同设立的“科学突破奖”旨在奖励在生命科学等领域取得重要成就的科学家,给他们提供更自由和更多的机会,帮助他们取得更大的成就。每年的获得者将加入评选委员会,参与下一届获奖者的评选。 自 2013 年这一奖项首次颁发以来,已有多位科学家荣获了巨额奖金,最新的突破奖在物理学和生命科学外还增加了数学奖项,尤里·米尔纳本人表示我们的世界总是围绕体育和娱乐名人转。但科学名人可能进入不了前 200 或 300 名,这种排名结果与其贡献相比,极不对称。 本次生命科学突破奖获得者,德国亥姆霍兹感染研究中心( HelmholtzCenter for Infection Research in Germany )和瑞典于默奥大学( Umeå University in Sweden )的艾曼纽·卡彭特( Emmanuelle Charpentier )及美国加州大学伯克利分校( University of California, Berkeley )詹妮弗·杜德纳( Jennifer Doudna ),因为他们发现了 CRISPR 的细节而获奖 , CRISPR 是一种被广泛应用于基因工程的细菌抗病毒系统。另外还有法国约瑟夫·傅里叶大学( Joseph Fourier University in France )的神经外科医生阿里姆·路易斯·本纳比德,是因为将 深层脑部刺激术( deep-brain stimulation ) 作为帕金森症一种治疗方法而获奖;而美国麻省大学医学院( University of Massachusetts Medical School )的维克托·安布罗斯( VictorAmbros )和美国哈佛医学院( Harvard Medical School )的加里·鲁夫昆( Gary Ruvkun )是因为他们对 miRNAs ( microRNAs )调控基因研究的突出贡献而获奖。美国洛克菲勒大学( Rockefeller University )的 C. 戴维·阿里斯( C. David Allis )获奖原因,是因为特别在表观遗传学( epigenetics )、组蛋白( histone proteins )的共价修饰蛋白对基因调控和疾病有广泛影响方面的研究。 詹妮弗·杜德纳告诉《卫报》 ( The Guardian )说, 她得到获奖的信息,使她 “ 激动和震惊 , 同时也非常兴奋。我们的研究成果是在 2012 年发表了的,但是谁也没有预料到,它竟然会有如此的变革力。” CRISPR-Cas9 系统已经被证明是一种强大的研究工具 , 并显示有望作为一种基因治疗的方法, 治疗囊肿性纤维化( cystic fibrosis )和血液疾病( blood disorders )。 洛克菲勒大学的 C. 戴维·阿里斯( C. David Allis )告诉《卫报》说: “ 当你决定追求生命科学领域一个非常基本的问题如基因调控时 , 对于得到一个引人注目的突破奖从来就不抱任何希望。它显示了将科学研究作为一种事业是多么美妙绝伦。 ” 这种精神境界是何等的高尚和值得可敬,与那些魂牵梦绕,无时无刻不再想如何快步直奔领奖台的唯利是图者相比较,可以说有天壤之别!科学研究的真谛是探索未知,而不是获得何种奖项。更多阿里斯的信息请浏览 ( NASprofile.pdf )。 CRISPR 基因组编程技术是近两年兴起的一种新技术, 2013 年,两篇 Science 新闻开创了 CRISPR 基因组编辑技术的新时代,随后生命科学界刮起了 CRISPR 风暴,迄今为止 CRISPR 方法已迅速席卷了整个动物王国,成为 DNA 突变和编辑的一种重要技术。 CRISPR 全称为 clustered regularly interspersed short palindromic repeats ,是源于细菌及古细菌中的一种后天免疫系统,它可利用靶位点特异性的 RNA 指导 Cas 蛋白对靶位点序列进行修饰。直到今年,科学家们才开始利用这一系统在活体动物基因组中生成靶向突变,删除原有的基因或插入新基因。对于这一技术詹妮弗·杜德纳表示,“修改生物体基因特定部分的能力,对于增加我们对生物体的认知是必不可少的。这是该领域的一种巨大跨越,因为它意味着基本上任何人都能够使用这种基因编辑或者重新编写的技术带给哺乳动物基因变化。” 与过去数十年里进行基因工程的其它任何方法相比, CRISPR 技术的优点就在于它使用的是单一的酶。这种酶不需要改变你设定目标的每一个点,你只需要使用一个不同的 RNA 副本对它进行重新编辑,这很容易设计和实现。生命科学突破奖获得者中有几位科学家则分别是在遗传学, RNAi 等领域的突出贡献而获奖,如哈佛医学院遗传学教授加里·鲁夫昆 就是一位微小 RNA(miRNA) 研究领域的著名科学家,他曾发现了首例微小 RNA : lin-4 通过与目标信使 RNA 不完全碱基配对,来调控这些目标的翻译的机制,并发现了第二个微小 RNA —— let-7 ,以及它在动物(包括人类)系统发育中如何保护的。 2008 年获 拉斯克基础医学奖 ( Albert Lasker Basic Medical Research Award )。 miRNA 是一类非编码小 RNA ,其长度为 19 到 25 个核苷酸,在真核生物的多种发育和生理过程中发挥着重要的调节作用。加里·鲁夫昆等人就曾通过分析比较了 86 个不同真核基因组序列,分析了小 RNA 辅助因子的系统发生谱,并指出,在 RNA 剪接和小 RNA 介导的基因沉默之间存在密切关联。 The 2015 Breakthrough Prizes in Life Sciences The Breakthrough Prize in Life Sciences honors transformative advances toward understanding living systems and extending human life, with one prize dedicated to work that contributes to the understanding of Parkinson’s disease. Alim Louis Benabid , Joseph Fourier University, for the discovery and pioneering work on the development of high-frequency deep brain stimulation (DBS), which has revolutionized the treatment of Parkinson’s disease. C. David Allis , The Rockefeller University, for the discovery of covalent modifications of histone proteins and their critical roles in the regulation of gene expression and chromatin organization, advancing the understanding of diseases ranging from birth defects to cancer. Victor Ambros , University of Massachusetts Medical School, and Gary Ruvkun , Massachusetts General Hospital and Harvard Medical School, for the discovery of a new world of genetic regulation by microRNAs, a class of tiny RNA molecules that inhibit translation or destabilize complementary mRNA targets. Each received a $3 million award. Jennifer Doudna , University of California, Berkeley, Howard Hughes Medical Institute and Lawrence Berkeley National Laboratory, and Emmanuelle Charpentier , Helmholtz Center for Infection Research and Umeå University, for harnessing an ancient mechanism of bacterial immunity into a powerful and general technology for editing genomes, with wide-ranging implications across biology and medicine. Each received a $3 million award. 更多信息请浏览: https://breakthroughprize.org/?controller=Pageaction=newsnews_id=21
为您呈现 生命科学 领域内 2013 年中国作者优秀论文精选(第一期) Reliable, verifiable and efficient monitoring of biodiversity via metabarcoding Yinqiu Ji 、 Louise Ashton 、 Scott M. Pedley 、 David P. Edwards 、 Yong Tang 、 Akihiro Nakamura 、 Roger Kitching 、 Paul M. Dolman 、 Paul Woodcock 、 Felicity A. Edwards 等 Ecology Letters 影响因子: 17.949 Antimicrobial strategies centered around reactive oxygen species – bactericidal antibiotics, photodynamic therapy, and beyond Fatma Vatansever 、 Wanessa C.M.A. de Melo 、 Pinar Avci 、 Daniela Vecchio 、 Magesh Sadasivam 、 Asheesh Gupta 、 Rakkiyappan Chandran 、 Mahdi Karimi 、 Nivaldo A. Parizotto 、 Rui Yin 、 George P. Tegos 和 Michael R. Hamblin FEMS Microbiology Reviews 影响因子: 13.231 BOLDMirror: a global mirror system of DNA barcode data D. Liu 、 L. Liu 、 G. Guo 、 W. Wang 、 Q. Sun1, M. Parani 和 J. Ma Molecular Ecology Resources 影响因子: 7.432 Predicting invasion in grassland ecosystems: is exotic dominance the real embarrassment of richness? Eric W. Seabloom 、 Elizabeth T. Borer 、 Yvonne Buckley 、 Elsa E. Cleland 、 Kendi Davies 、 Jennifer Firn 、 W. Stanley Harpole 、 Yann Hautier 、 Eric Lind 、 Andrew MacDougall 、 John L. Orrock 、 Suzanne M. Prober 、 Peter Adler 、 Juan Alberti 、 T. Michael Anderson 、 Jonathan D. Bakker 、 Lori A. Biederman 、 Dana Blumenthal 、 Cynthia S. Brown 、 Lars A. Brudvig 、 Maria Caldeira 、 Chengjin Chu 等 Global Change Biology 影响因子: 6.91 Distinct laterality alterations distinguish mild cognitive impairment and Alzheimer's disease from healthy aging: Statistical parametric mapping with high resolution MRI Xiaojing Long 、 Lijuan Zhang 、 Weiqi Liao 、 Chunxiang Jiang 、 Bensheng Qiu 和 the Alzheimer's Disease Neuroimaging Initiative Human Brain Mapping 影响因子: 6.878 Inhibition of cadmium ion uptake in rice (Oryza sativa) cells by a wall-bound form of silicon Jian Liu 、 Jie Ma 、 Congwu He 、 Xiuli Li 、 Wenjun Zhang 、 Fangsen Xu 、 Yongjun Lin 和 Lijun Wang New Phytologist 影响因子: 6.736 A dominant repressor version of the tomato Sl-ERF.B3 gene confers ethylene hypersensitivity via feedback regulation of ethylene signaling and response components Mingchun Liu 、 Julien Pirrello 、 Ravi Kesari 、 Isabelle Mila 、 Jean-Paul Roustan 、 Zhengguo Li 、 Alain Latché 、 Jean-Claude Pech 、 Mondher Bouzayen 和 Farid Regad The Plant Journal 影响因子: 6.582 Novel bioresources for studies of Brassica oleracea: identification of a kale MYB transcription factor responsible for glucosinolate production Ryoichi Araki 、 Akiko Hasumi 、 Osamu Ishizaki Nishizawa 、 Katsunori Sasaki 、 Ayuko Kuwahara 、 Yuji Sawada 、 Yasushi Totoki 、 Atsushi Toyoda 、 Yoshiyuki Sakaki 、 Yimeng Li 等 Plant Biotechnology Journal 影响因子: 6.279 Pliocene intraspecific divergence and Plio-Pleistocene range expansions within Picea likiangensis (Lijiang spruce), a dominant forest tree of the Qinghai-Tibet Plateau Long Li 、 Richard J. Abbott 、 Bingbing Liu 、 Yongshuai Sun 、 Lili Li 、 Jiabin Zou 、 Xi Wang 、 Georg Miehe 和 Jianquan Liu Molecular Ecology 影响因子: 6.275 Regional homogeneity changes in heavy male smokers: a resting-state functional magnetic resonance imaging study Rongjun Yu 、 Liyan Zhao 、 Jie Tian 、 Wei Qin 、 Wei Wang 、 Kai Yuan 、 Qiang Li 和 Lin Lu Addiction Biology 影响因子: 5.914
正在UCLA的数学研究中心参加从癌症数据分析和数学模型到临床应用的会议。 http://www.ipam.ucla.edu/programs/cdm2014/ 很有意思的是,不少与会者都是从物理研究,尤其是理论物理研究转行进入生命研究领域的。鸿飞在最近的博文中调侃说,生物领域是物理学家退休以后的理想职业。到底 物理学家为什么会转行呢?物理学家进入癌症领域能做什么呢?关于为什么癌症研究需要物理学家, 我有博文如下: 为什么癌症研究需要物理学家? 与会者中有前辈读了Sui的文章,感触良多,细细讲述了 为什么 物理学家会转行 进入生命研究领域 : I have had now the chance to read your article on the role of theoretical physics (and physicists) in cancer research. Congratulations – it is very eloquent and inspiring. I was particularly touché by the last paragraph, which describes my own attitude quite accurately and in highly non-complimentary manner. I have been assimilated completely. Let me try to explain the reason for this. As you see things, physicists worry about the big picture and seek the fundamental universal laws. In a sense this is correct and in some sense it is not. 95% of the theoretical physicists spend more than 95% of their time calculating something. This something may be the approximate solution of some model or some equations. In some sense you may be able to connect this activity to the quest for deep principles, but in the vast majority of cases the connection is very tenuous. My own background was in Statistical Physics, phase transition, critical phenomena. The renormalization group, introduced by Wilson, provided a very deep philosophical and technical tool to understand and unify many phenomena and systems. Many of us rushed in the early seventies to the field, calculated everything calculable and in the process testing the theory to its limits. After 10 years we took off to other fields – there were no deep problems to worry about (which had some hope of being solved). At the same time another thing happened –physics ran out of phenomena. To see something interesting you have to dig a 27 km long tunnel 100 m under the earth and run a super-sophisticated apparatus for 10 years with 5000 people involved. Or – send very expensive equipment to outer space to collect data. There are some exceptions but they are very few. Most theory became some form of mathematics. To me biology was a total surprise in terms of the accessibility and immediacy of phenomena, and I was captivated by the ease with which simple analysis and modeling can throw light on something that can be easily observed, is absolutely fascinating and – not well understood (even on what you call the mechanistic level). At the same time I was annoyed and turned off by several physicist-turned biologist colleagues who did good biology and modeling but shrouded everything in sentences like design principles – I felt that it was using high language to describe rather straightforward mechanistic studies. I think that trying to understand isolated interesting phenomena is a challenge and if one succeeds – it is good science. Also, my very few attempts at formulating some basic principle (I can give you one example, if you ask for it) – were totally ignored by the community of biologists, whereas some more technical (albeit – theoretical) studies were embraced and cited. This in itself is not a reason to abandon deep thinking – but combined with the other things I mentioned – perhaps it is. I have no idea why I threw all this at you – perhaps felt uneasy about the implications of the last paragraph of what you wrote.
最新上线的 SCIENCE CHINA Life Sciences 2014年第1期出版了清华大学专刊,包括16篇研究论文,集中介绍了清华大学生命科学领域最新的一些原创性研究成果,施一公院士为该专辑撰写了编者按: “ A glimpse of life science research at Tsinghua ” 专辑网址: http://life.scichina.com:8082/sciCe/EN/volumn/current.shtml http://link.springer.com/journal/11427/57/1/page/1 敬请关注~
《科学家》( The Scientist )杂志网站 2013年12月24日 报道了2013年生命科学领域的大进展,摘引如下,供大家参考。 2013’s Big Advances in Science A roundup of the stunning progress made in the life sciences this year By Kerry Grens | December 24, 2013 Most spectacularly evident in 2013 was how easily new techniques caught fire and spread to labs around the globe. Even researchers who don’t specialize in methods development are able to rapidly adopt—and improve upon—new approaches to answering their questions, and the result is an acceleration of progress and a cross pollination of disciplines. Here are some of the most exciting advances in the life sciences from 2013. JINSONG LI What can’ t CRISPR do? Clustered regularly interspaced short palindromic repeats, or CRISPR, is a tool used for genome editing. In tandem with an enzyme called Cas9, the CRISPR approach allows scientists to write the genetic code any which way they want. A few years ago, CRISPR was known only for its role in immunity in bacteria and archaea. Now, labs around the globe are wrapping their arms around the technique for myriad purposes. “This new method is a game changer,” Rudolf Jaenisch, a founding member of the Whitehead Institute in Cambridge, Massachusetts, told The Scientist back in May. He and his colleagues generated a genetically modified mice with five mutations in less than a month, “whereas the conventional way would take three to four years.” In 2013, advances in CRISPR applications decorated the pages of high profile journals with head-spinning frequency. In December alone, scientists demonstrated that CRISPR/Cas9 can correct disease causing genetic defects in mammals and human stem cells. And two papers in Science just last week laid out ways to use CRISPR in genomic screens. MADELINE A. LANCASTER Organoids galore New types of lab-grown organ buds, also called organoids, popped up in 2013. In August, scientists raised small, three-dimensional models of embryonic human brains that could form some of the complex structures of the organ. “This demonstrates the enormous self-organizing power of human cells,” Jürgen Knoblich from the Institute of Molecular Biotechnology of the Austrian Academy of Science told The Scientist when his results were published. In November, American and Spanish researchers published their data on functional, renal progenitor-like cells developed from human stem cells. A few months earlier, scientists reprogrammed human induced pluripotent stem cells (iPSCs) into liver buds that also took on three dimensions. The liver buds had seemingly normal metabolism and even hooked up to the host’s circulatory system when implanted in a mouse. Grow-your-own organs may not be so far off. “If you could use iPSCs to generate a truly functioning organ, then you would have this unlimited suitcase of spare parts that would be genetically matched to individuals,” Stephen Duncan, the director of the Regenerative Medicine Center at the Medical College of Wisconsin, told The Scientist in July. COURTESY RICARDO ROSSELLO Potent stem cells The ability to reprogram skin cells to pluripotent stem cells by a simple gene-expression formula opened up a world of new experiments. This year, researchers continued to push ahead with better and faster methods to reinvent the identity of cells. Several months ago, scientists in Israel found a way to overcome one of the biggest limitations of inducing stem cells—the technique’s inefficiency. Typically, just about one out of every 10 cells prodded toward pluripotency actually do what researchers want it to, but Jacob Hanna from Israel’s Weizmann Institute of Science and his colleagues disabled a gene that represses pluripotency and voilà : near-perfect efficiency. “I never believed we’d get to 100 percent,” Hanna told The Scientist in September. “This shows that the process of reprogramming need not be random and inefficient.” The induction of pluripotent stem cells reached new lows, as it were, in 2013. Researchers were able to generate in vivo more primitive forms of stem cells that had been accomplished before. Another group reprogrammed cells from animals lower on the tree of life than mammals, including birds, fish, and insects. And yet another team skirted the usual step of inserting genes into cells and instead used small molecules to coax cells into a pluripotent state. J. CONNELL ET AL., UNIVERSITY OF TEXAS AT AUSTIN Expanded uses for 3-D printing 3-D printers can make everything from test tube racks to centrifuges to tonight’s dinner. So why not print out your own custom mini microbial universe? Researchers have developed a gelatin mold that can house bacteria in separate compartments. “It’s basically Jell-O with things suspended in it,” chemist and bioengineer Jason Shear from the University of Texas at Austin told The Scientist in October. The laser from a 3-D printer then builds a little entrapment around the bacteria. Although the bacteria are held in place, signals from the cells can move through the gel. Aleksandr Ovsianikov of the Vienna University of Technology in Austria, who was not involved in the project, pointed out that the technique allows researchers to build the mold any way they want. “This is a tool which potentially allows you to cross-link your gel, dress up your gel with biomolecules, or create channels in the same way,” said Ovsianikov. “This is a tool which is much more than 3-D printing.” M. CHOI Hydrogel implants In another brilliant example of manipulating scaffolded cells, researchers developed a hydrogel implant embedded with a fiber optic cable that can direct the activity of cells with light. In this case, the light stimulated cells in the hydrogel to suppress high blood sugar levels in diabetic mice. The hydrogel not only delivers light, it can detect it as well when the cells express fluorescent proteins. Seok Hyun Yun at Harvard University explained in October that his group didn’t actually invent anything new. “We put together somewhat disconnected, beautiful technologies to make work in a single system . . . and then found a way to make it all work inside the body,” he told The Scientist . The approach could give a new angle for developing cell-based therapies. The technique certainly needs some tweaking. HeLa cells are potentially tumorigenic and it’s not clear how the hydrogel would perform in different settings. WIKIMEDIA, METOC MacGuyver-style microfabrication Not all in scientific progress must involve fancier methods to solving problems. In fact, a little ingenuity and some Scotch tape goes a long way , according to Raquel Perez-Castillejos, a biomedical engineer at the New Jersey Institute of Technology in Newark. Scientists can use photolithographic technology to build little wells for culturing cells, but Perez-Castillejos and her colleagues found that cutting shapes into Scotch tape stuck to a glass slide works just fine. The team cut small rectangles and other shapes into the tape. They then peeled away the tape, leaving the shapes of tape on the glass and made a cast of the slide with a silicon-based polymer. Once the casts were hard, they could be taken off the slide, turned upside down and plated with cells for microfluidics experiments. “Sometimes we are trying to provide very high precision to problems that don’t require it, and we make it complicated for no reason,” Perez-Castillejos said in the March issue of The Scientist . WIKIMEDIA, INFERIS The next generation Up-and-coming in vitro fertilization techniques gave parents in Philadelphia their next generation, a baby boy born in May. Researchers at the University of Oxford used next-generation sequencing to create a method to check embryos for chromosomal abnormalities, gene mutations, and mitochondrial genome mutations. “Next-generation sequencing improves our ability to detect these abnormalities and helps us identify the embryos with the best chances of producing a viable pregnancy,” said Dagan Wells, a molecular geneticist at the NIHR Biomedical Research Centre at the University of Oxford, in a statement . “Potentially, this should lead to improved IVF success rates and a lower risk of miscarriage.” The fertility doctor in Pennsylvania who used the technique to screen little Connor Levy when he was still a ball of cells said he expects the test to take off. Thumbnail image credit: Wikimedia, National Institute of Health . techniques , stem cells , roundup , end of year and crispr
生命科学就只有发论文吗?( 130902 ) 闵应骅 生命科学如今很火。生物信息学用信息科学技术研究基因序列。反过来,生命科学能不能帮助解决信息科学中的问题呢?本文用信息存储的革命为例,企图来说明这一点,未知可否?欢迎批评 . 以我这个外行看来, 1990 年开始的人类基因组计划,就像美国发动的一场运动,各大国都参与,中国也承担了 1% 的任务。大批雄壮的科研队伍开进来,搞信息科学的人也加入来帮忙解读这本天书。大量生命科学的文章, NSC 的文章,影响因子达到几十。这些文章我们外行看不懂,但这些研究很热门,引用次数就多。信息科学方面文章的影响因子真是望尘莫及。外行人看到,现在可以做亲子鉴定,可以有转基因食品,但离医治癌症还不知道差多远。更多的是 paper ,那么,这方面的创新研究难道只能停留在纸面上吗? 最近, CACM 发表一篇新闻“信息存储新途径”,引用了今年一月《自然》杂志上的两篇文章,介绍欧洲生物信息学研究所集中搞 DNA 存储,而 MIT 搞分子存储。 存储技术是信息技术的关键。几十年来,磁存储和固态存储一直是当前信息存储的基础。其性能包括存储量、存储密度、存储速度、存储寿命、读写可靠性等。而现在的个人存储设备已经接近其物理极限,改进余地已经没有多少油水了。正需要革命性的创新。人们注意到: DNA 存储信息已有 35 亿年。 DNA 表示为四种成分的序列: A , G , C , T ,可以翻译成二进制。非生命的 DNA 包含 54898 个数据块,每一个存储在单个的蛋白丝上。用 3D 打印机把该序列打印到 DNA 丝上,从而建造了一个实在的存储装置。用一本书做试验,编码这本书,写进去,读出来。该书的 10 亿个复印件就嵌入到了玻璃杯或小真空管的底部。 DNA 能够存大量数据,但 DNA 的制造过程比较慢,而且昂贵,也许光写入更现实一些。摩尔定律每年只改进 1.5 倍,而 DNA 测序技术现在每年增长 10 倍。所以,有人预计, 5 年以内此项技术即可商业化。这些写入和读出系统可以像计算机的 USB 接口一样,借助于计算机。但这种存储技术,目前来看,作为日常使用尚不适宜,而对于长期保存却非常有意义。这种数据在没有电的情况下可以存储 50 万年。而且取消膨大的存储网络,有利环保。现在的存储媒体,譬如 CD , DVD 等等都有格式的变化问题和相容性的问题,千年以后,即使数据还存在,但是人们已经没有读出的工具了。英国欧洲生物信息学院的科学家们编码 DNA ,写入马丁 . 路德 . 金的 26 秒讲演,一个照片,一篇学术文章和 154 首莎士比亚的十四行诗。该 DNA 干燥在一块玻璃板上。研究人员可以 99.99% 的精确度读到这些数据。改正一个小故障以后,他们可以得到 100% 。不但要能读写,而且要建立适当的元数据和索引系统。不但能存千年,而且能被正确地指向相应的文件、装置或系统。斯坦福大学的科学家在研究用大肠杆菌中的活性 DNA 存储数字编码。这将有助于研究癌症、老化和有机体发育。 另一个方向是分子数据存储。 MIT 一个研究组研究分子存储。他们发现一种方法用分子组装成超分子,这种组装已经由加尔各答的印度科学教育和研究所组装成功。这种超分子捆绑着两类不同的原子:石墨烯片,包括碳原子和锌原子的薄片。当这些原子放置在磁性表面上时,磁化的超分子约 1 纳米大小,其存储密度达到每平方英寸 1000 兆兆字节(目前的硬盘小于每平方英寸 1 兆兆字节)。研究人员把一个分子材料薄膜放在 铁磁体电极 上,再在上面加第二个铁磁体电极。当一个电极的磁取向改变时,系统的电导性将有急剧的增加或减少。这两个状态就表示二进制码的 0 和 1 。 MIT 的研究人员发现,电导性的这两种跳跃,即使铁磁体电极只有一个,而不是一对,也会令人惊奇地出现。只有一个铁磁体电极的分子电导性的改变就可以极大地简化分子存储器的制造。存储密度 1000 倍的增加将改变从数据中心到个人计算机的所有装置。 iPhone 里同样大小的存储器,其容量不知道要大多少倍。当然还有大量工作要做。譬如科学家希望分子有两个稳定且非易失性的状态。现在是在 -9 华氏度,即约 -27.8 摄氏温度下工作的。要能在室内外普通温度下工作才能商业化。而且,这电导性的变化至少要从现在的 20% 提高到 50% 才行。也许需要 10 年,以及材料发明和制造技术的进步。 我不知道我们国内在这方面的研究是否有安排。我们高谈大数据,却只谈软件,基础设施建设,不谈下一代的存储设备,眼光就不够远大。我们往往是国外提出一个方向就跟进,较少有真正创新的方向。如果国外仅仅是一个 idea ,与我们处在同一个起跑线上,我们原创的东西就会多。当然,有我们自己全新的 idea 更好。这样的立项才真需要有眼光的评审。不要老盯着“我那份申请书怎么没通过呀?”。
本文精选了 3 月份中国作者发表在 Wiley 优秀生命科学期刊上的 23 篇文章,其中 Stem Cells 1 篇、 Ecology Letters 1 篇、 Global Change Biology 5 篇、 Journal of Pineal Research 2 篇、 Molecular Ecology 2 篇、 New Phytologist 4 篇、 Pigment Cell Melanoma Research 1 篇、 Plant Cell and Environment 3 篇、 Plant Journal 4 篇。 -------------------------------------------------------------------------------------------- 其他学科: Wiley化学材料学优秀期刊(A) Wiley化学材料学优秀期刊(B) Wiley医学类优秀期刊 -------------------------------------------------------------------------------------------- 一、 Stem Cells Transforming Growth Factor β1 Signal is Crucial for Dedifferentiation of Cancer Cells to Cancer Stem Cells in Osteosarcoma 作者: Haixia Zhang( 中山大学 ), Haotong Wu( 中山大学 ), Junheng Zheng( 中山大学 ), Pei Yu( 中山大学 ), Lixiao Xu( 中山大学 ), Pan Jiang( 中山大学 ), Jin Gao(James Cook University), Hua Wang( 中山大学 ), Yan Zhang( 中山大学 ) -------------------------------------------------------------------------------------------- 二、 Ecology Letters Suppression of terpenoid synthesis in plants by a virus promotes its mutualism with vectors 作者: Jun-Bo Luan ( 浙江大学 ), Dan-Mei Yao( 浙江大学 ), Tong Zhang( 浙江大学 ), Linda L. Walling(University of California, Riverside), Mei Yang( 浙江大学 ), Yu-Jun Wang( 浙江大学 ), Shu-Sheng Liu( 浙江大学 ) -------------------------------------------------------------------------------------------- 三、 Global Change Biology Environmental changes impacting Echinococcus transmission: research to support predictive surveillance and control 作者: Jo-An M. Atkinson(University of Queensland), Darren J. Gray(University of Queensland), Archie C.A. Clements(University of Queensland), Tamsin S. Barnes(University of Queensland), Donald P. McManus(Queensland Institute of Medical Research), Yu R. Yang( 宁夏医科大学 ) -------------------------------------------------------------------------------------------- Modern maize hybrids in Northeast China exhibit increased yield potential and resource use efficiency despite adverse climate change 作者: Xiaochao Chen( 中国农业大学 ), Fanjun Chen( 中国农业大学 ), Yanling Chen( 中国农业大学 ), Qiang Gao( 吉林农业大学 ), Xiaoli Yang( 中国农业大学 ), Lixing Yuan( 中国农业大学 ), Fusuo Zhang( 中国农业大学 ), Guohua Mi( 中国农业大学 ) -------------------------------------------------------------------------------------------- Changes in satellite-derived spring vegetation green-up date and its linkage to climate in China from 1982 to 2010: a multimethod analysis 作者: Nan Cong( 北京大学 ), Tao Wang(CEA CNRS UVSQ), Huijuan Nan( 北京大学 ), Yuecun Ma( 北京大学 ), Xuhui Wang( 北京大学 ), Ranga B. Myneni(Boston University), Shilong Piao( 北京大学 ) -------------------------------------------------------------------------------------------- Consistent shifts in spring vegetation green-up date across temperate biomes in China, 1982–2006 作者: Xiuchen Wu, Hongyan Liu( 北京大学 ) -------------------------------------------------------------------------------------------- Spatial patterns and climate drivers of carbon fluxes in terrestrial ecosystems of China 作者: Gui-Rui Yu( 中国科学院地理科学与资源研究所 ), Xian-Jin Zhu( 中国科学院地理科学与资源研究所 ), Yu-Ling Fu( 中国科学院地理科学与资源研究所 ), Hong-Lin He( 中国科学院地理科学与资源研究所 ), Qiu-Feng Wang( 中国科学院地理科学与资源研究所 ), Xue-Fa Wen( 中国科学院地理科学与资源研究所 ), Xuan-Ran Li( 中国科学院地理科学与资源研究所 ), Lei-Ming Zhang( 中国科学院地理科学与资源研究所 ), Li Zhang( 中国科学院地理科学与资源研究所 ), Wen Su( 中国科学院地理科学与资源研究所 ), Sheng-Gong Li( 中国科学院地理科学与资源研究所 ), Xiao-Min Sun( 中国科学院地理科学与资源研究所 ), Yi-Ping Zhang( 中国科学院西双版纳热带植物园 ), Jun-Hui Zhang( 中科院沈阳应用生态研究所 ), Jun-Hua Yan( 中国科学院华南植物园 ), Hui-Min Wang( 中国科学院地理科学与资源研究所 ), Guang-Sheng Zhou( 中国科学院植物所 ), Bing-Rui Jia( 中国科学院植物所 ), Wen-Hua Xiang( 中南林业科技大学 ), Ying-Nian Li( 中国科学院西北高原生物研究所 ), Liang Zhao( 中国科学院西北高原生物研究所 ), Yan-Fen Wang( 中国科学院大学 ), Pei-Li Shi( 中国科学院地理科学与资源研究所 ), Shi-Ping Chen( 中国科学院植物所 ), Xiao-Ping Xin( 中国农业科学院 ), Feng-Hua Zhao( 中国科学院地理科学与资源研究所 ), Yu-Ying Wang( 中国科学院遗传与发育生物学研究所 ), Cheng-Li Tong( 中国科学院亚热带农业生态研究所 ) -------------------------------------------------------------------------------------------- 四、 Journal of Pineal Research Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia–reperfusion injury 作者: Hon-Kan Yip(Chang Gung University), Yi-Chih Chang( 厦门长庚纪念医院 ), Christopher Glenn Wallace(University Hospital of South Manchester), Li-Teh Chang(Meiho University), Tzu-Hsien Tsai(Chang Gung University), Yung-Lung Chen(Chang Gung University), Hsueh-Wen Chang(National Sun Yat-Sen University), Steve Leu(Chang Gung University), Yen-Yi Zhen(Chang Gung University), Ching-Yen Tsai(Academia Sinica), Kuo-Ho Yeh(Chang Gung University), Cheuk-Kwan Sun(Academia Sinica), Chia-Hung Yen(National Pingtung University of Science and Technology) -------------------------------------------------------------------------------------------- Melatonin influences proliferation and differentiation of rat dental papilla cells in vitro and dentine formation in vivo by altering mitochondrial activity 作者: Jie Liu, Hongyu Zhou, Wenguo Fan, Weiguo Dong, Shenli Fu, Hongwen He, Fang Huang( 中山大学 ) -------------------------------------------------------------------------------------------- 五、 Molecular Ecology High diversity and widespread occurrence of mitotic spore mats in ectomycorrhizal Pezizales 作者: R. A. Healy(University of Minnesota), M. E. Smith(University of Florida), G. M. Bonito(Duke University), D. H. Pfister(Harvard University), Z. -W. Ge( 中国科学院昆明植物研究所 ), G. G. Guevara(Instituto Tecnológico de Cd. Victoria), G. Williams(Duke University), K. Stafford(Duke University), L. Kumar(University of Minnesota), T. Lee(University of Minnesota), C. Hobart(University of Sheffield), J. Trappe(Oregon State University), R. Vilgalys(Duke University), D. J. McLaughlin(University of Minnesota) -------------------------------------------------------------------------------------------- Impact of climate changes from Middle Miocene onwards on evolutionary diversification in Eurasia: Insights from the mesobuthid scorpions 作者: Cheng-Min Shi, Ya-Jie Ji, Lin Liu, Lei Wang, De-Xing Zhang ( 中科院动物所 ) -------------------------------------------------------------------------------------------- 六、 New Phytologist Epigenetic modification contributes to the expression divergence of three TaEXPA1 homoeologs in hexaploid wheat (Triticum aestivum) 作者: Zhaorong Hu, Zongfu Han, Na Song, Lingling Chai, Yingyin Yao, Huiru Peng, Zhongfu Ni, Qixin Sun( 中国农业大学 ) -------------------------------------------------------------------------------------------- SlNAC1, a stress-related transcription factor, is fine-tuned on both the transcriptional and the post-translational level 作者: Weizao Huang( 四川省农业科学院 ), Min Miao( 四川大学 ), Joanna Kud(University of Idaho), Xiangli Niu( 合肥工业大学 ), Bo Ouyang( 杭州农业大学 ), Junhong Zhang( 杭州农业大学 ), Zhibiao Ye( 杭州农业大学 ), Joseph C. Kuhl(University of Idaho), Yongsheng Liu( 四川省农业科学院 ), Fangming Xiao(University of Idaho) -------------------------------------------------------------------------------------------- Molecular evolution and expression divergence of the Populus polygalacturonase supergene family shed light on the evolution of increasingly complex organs in plants 作者: Zhi-Ling Yang( 中科院植物所 ), Hai-Jing Liu( 中科院植物所 ), Xiao-Ru Wang(Ume University), Qing-Yin Zeng( 中科院植物所 ) -------------------------------------------------------------------------------------------- Jasmonate and ethylene signaling mediate whitefly-induced interference with indirect plant defense in Arabidopsis thaliana 作者: Peng-Jun Zhang( 浙江省农业科学院 ), Colette Broekgaarden(Wageningen University and Research Centre), Si-Jun Zheng(Wageningen University), Tjeerd A. L. Snoeren(Wageningen University), Joop J. A. van Loon(Wageningen University), Rieta Gols(Wageningen University), Marcel Dicke(Wageningen University) -------------------------------------------------------------------------------------------- 七、 Pigment Cell Melanoma Research Hermansky–Pudlak syndrome: pigmentary and non-pigmentary defects and their pathogenesis 作者: Ai-Hua Wei( 首都医科大学附属北京同仁医院 ), Wei Li( 中国科学院遗传与发育生物学研究所 ) -------------------------------------------------------------------------------------------- 八、 Plant, Cell Environment Chloroplast ultrastructure regeneration with protection of photosystem II is responsible for the functional ‘stay-green’ trait in wheat 作者: P. G. LUO( 四川农业大学 ), K. J. DENG( 电子科技大学 ), X. Y. HU( 四川农业大学 ), L. Q. LI( 四川农业大学 ), X. LI( 四川农业大学 ), J. B. CHEN( 四川农业大学 ), H. Y. ZHANG( 四川农业大学 ), Z. X. TANG( 四川农业大学 ), Y. ZHANG( 电子科技大学 ), Q. X. SUN( 中国农业大学 ), F. Q. TAN( 四川农业大学 ), Z. L. REN( 四川农业大学 ) -------------------------------------------------------------------------------------------- A novel protein kinase involved in Na+ exclusion revealed from positional cloning 作者: S. J. ROY(Australian Centre for Plant Functional Genomics and the University of Adelaide), W. HUANG(Australian Centre for Plant Functional Genomics and the University of Adelaide), X. J. WANG( 兰州大学 ), A. EVRARD(Australian Centre for Plant Functional Genomics and the University of Adelaide), S. M. SCHMCKEL(Australian Centre for Plant Functional Genomics and the University of Adelaide), Z. U. ZAFAR(Australian Centre for Plant Functional Genomics and the University of Adelaide), M. TESTER(Australian Centre for Plant Functional Genomics and the University of Adelaide) -------------------------------------------------------------------------------------------- OsARF16, a transcription factor, is required for auxin and phosphate starvation response in rice (Oryza sativa L.) 作者: CHENJIA SHEN( 浙江大学 ), SUIKANG WANG( 浙江大学 ), SAINA ZHANG( 浙江大学 ), YANXIA XU( 浙江大学 ), QIAN QIAN( 中国农业科学院 ), YANHUA QI( 浙江大学 ), DE AN JIANG( 浙江大学 ) -------------------------------------------------------------------------------------------- 九、 The Plant Journal Gene family evolution in green plants with emphasis on the origination and evolution of Arabidopsis thaliana genes 作者: Ya-Long Guo( 中科院植物所 ) -------------------------------------------------------------------------------------------- Wheat centromeric retrotransposons: the new ones take a major role in centromeric structure 作者: Baochun Li( 中国农业科学院 ), Frédéric Choulet(Genetic Diversity and Ecophysiology of Cereals), Yanfang Heng( 中国农业科学院 ), Weiwei Hao( 中国农业科学院 ), Etienne Paux(Genetic Diversity and Ecophysiology of Cereals), Zhao Liu( 中国农业科学院 ), Wei Yue( 中国农业科学院 ), Weiwei Jin( 中国农业大学 ), Catherine Feuillet(Genetic Diversity and Ecophysiology of Cereals), Xueyong Zhang( 中国农业科学院 ) -------------------------------------------------------------------------------------------- Oryza sativa actin-interacting protein 1 is required for rice growth by promoting actin turnover 作者: Meng Shi( 中科院植物所 ), Yurong Xie( 中科院植物所 ), Yiyan Zheng( 中科院植物所 ), Junmin Wang( 浙江省农业科学院 ), Yi Su( 湖南农业大学 ), Qiuying Yang( 中科院植物所 ), Shanjin Huang( 中科院植物所 ) -------------------------------------------------------------------------------------------- C2-mediated decrease in DNA methylation, accumulation of siRNAs, and increase in expression for genes involved in defense pathways in plants infected with beet severe curly top virus 作者: Li-Ping Yang1, Yuan-Yuan Fang( 中科院微生物研究所 ), Chun-Peng An( 中科院微生物研究所 ), Li Dong( 中科院微生物研究所 ), Zhong-Hui Zhang( 中国科学院遗传与发育生物学研究所 ), Hao Chen( 中国科学院遗传与发育生物学研究所 ), Qi Xie( 中国科学院遗传与发育生物学研究所 ), Hui-Shan Guo( 中科院微生物研究所 ) --------------------------------------------------------------------------------------------
欧洲显微学会(EMS)最近公布了2012年EMS优秀论文奖获奖名单,一共有28篇优秀论文获奖。其中的这28篇论文的研究领域分别是“仪器和技术发展”,”材料科学“,”生命科学“三大领域。 得奖名单是: 1。仪器和技术发展:宇宙大爆炸“断层摄影术作为一种新的路由原子分辨率电子断层扫描。作者:Dirk Van Dyck, Joerg R Jinschek Fu-Rong Chen; Nature 486, 243-246 (2012) 2。材料科学:环形电浆的本征模的在低聚物Nanocavities为可见,作者:Burcu Ögüt, Nahid Talebi, Ralf Vogelgesang, Wilfried Sigle, and Peter A van Aken; Nano Letters 12, 5239-5244 (2012) 3。生命科学:虚拟纳米显微产生的超大规模的高分辨率电子显微镜图,作者:Frank GA Faas, M Cristina Avramut, Bernard M van den Berg, A. Mieke Mommaas, Abraham J Koster, and Raimond BG Ravelli; Cell Biology 198, 457-469 (2012)
随着中国近些年在航天器、载人飞船、深空探索等领域的快速进步,成为仅次于美国与俄罗斯的第三个独立把航天员送入太空的国家,德国以及欧空局跟都表示要进一步加强双边未来在太空领域的广泛合作。 尤其是在微重力生命科学领域,在2011年11月1日发射的神舟8号无人飞船上,搭载了由德国人设计制造的SIMBOX实验装置,共完成中方、德方以及中德双边合作项目十六七项。 本人于本月初访问德宇航DLR,跟DLR负责太空环境科研管理的Ruyter教授、Preu博士有所交流,另外也与DLR的国际事务部主任Weissenberg博士,以及包括专利以及技术转让在内的一些部分人进行了沟通交流。 下面附件是Preu博士提供的两份报告材料:德国在太空环境下的科学实验探索,第五届中德微重力与生命科学研讨会。据悉,双边科研人员以及项目管理层都在关注和研究下一步的新的合作计划与方案。 一些网页链接与相关消息: Frame Agreement DLR-CMSEO 16.12.2008 http://www.dlr.de/rd/desktopdefault.aspx/tabid-4809/7974_read-14864/ SIMBOX auf Shenzhou-8: · Startklar 28.10.11: http://www.dlr.de/dlr/desktopdefault.aspx/tabid-10081/151_read-1791/year-2011/151_page-2/ · Start 01.11.2011: http://www.dlr.de/dlr/desktopdefault.aspx/tabid-10081/151_read-1805/year-2011/151_page-2/ Landung 17.11.2011 http://www.dlr.de/rd/desktopdefault.aspx/tabid-7224/12028_read-32829/ Deutsch-Chinesischer Workshop 10.-14. Sept. 2012: · http://www.dlr.de/rd/desktopdefault.aspx/tabid-7864/13381_read-35308/ · Gruppenphoto Proceedings (Programme, Abstracts, Participants) ACC-Besuch bei DLR Bonn 16.03.2012: Gruppenphoto The German Program “Research under Space Conditions“ The cooperation between China and Germany has a long-standing and successful tradition which reaches back to the late eighties. Areas of cooperation: Scientific cooperation between scientists of both countries Joint workshops and symposia Joint projects and missions Some examples: German protein crystallization facility COSIMA on Chinese Reentry Satellite FSW-1 (1988) (launched from Jiuquan launching site) MIKROBA - balloon borne drop capsule (1998, Zhengding Airport) 10 Humboldt-Research Scholarships and joint Research Projects at DLR Institutes DLR-China Workshops, Symposia Scientific China-Germany Workshops Microgravity and Space Life Sciences (CAS/CNSA and DLR) : -1995: Xi’an, China -2002: Dunhuang, China -2006: Berlin, Germany (about 90 participants) -2009: Shanghai, China (about 120 participants) -2012: Rottach-Egern, Germany (September,10-14) Sino-German Symposium on Space Life Sciences funded by the Sino-German Center for Research Promotion (NFSC and DFG) -2006: Xi’an, China -2008: Beijing, China, 第五届中德微重力与生命科学研讨会.pdf 5th China – Germany Workshop on Microgravity and Space Life Sciences Weissach/Rottach-Egern, Germany September 10 to 14, 2012 2012年3月16日:中国航天员中心陈所长等一行访问DLR 2012年9月10-14日,中德微重力与生命科学研讨会集体照片
The Scientist 杂志社举办的年度生命科学领域内最具影响力的创新比赛结果12月初已经揭晓,现摘录如下,供大家参考。 Top 10 Innovations 2012 The Scientist ’s 5th installment of its annual competition attracted submissions from across the life science spectrum. Here are the best and brightest products of the year. By The Scientist Staff | December 1, 2012 1)BioFab( GEN9) 2)Ion Proton System( Life Technologies) 3)MyCell Services( Cellular Dynamics International) 4)Labguru( BioData) 5)MiSeq( Illumina) 6)ONIX Microfluidic Platform( CellASIC) 7)NanoLuc Luciferase Technology( Promega) 8)xSCELL Digital Scientific Camera( Photonis) 9)Photo-Morpholinos( Gene Tools) 10)HubioGEM + the Wiggler( Vivo Biosciences + Global Cell Solutions) more information: http://www.the-scientist.com/?articles.view/articleNo/33341/title/Top-10-Innovations-2012/
Table S2. Investigators with Ten or More Retracted Articles* Author No. of Retractions Reason for Retraction Boldt, J 80 fraud Mori, N 36 fraud Herrmann, F 21 fraud Reuben, SS 18 fraud Slutsky, RA 18 fraud Matsuyama, W 17 fraud Schn, JH 17 fraud Darsee, JR 14 fraud Goldstein, G 14 error Pease, LR 14 fraud Bulfone-Paus, S 13 fraud Wang, Z 12 fraud Soman, VR 11 fraud Chiranjeevi, P 10 fraud Potti, A 10 fraud Sudb, J 10 fraud Thomas, JM 10 fraud *when multiple individuals from a single research group have been authors on retracted articles, the individual from the group on the greatest number of articles is listed .
First Author Journal Year Published PMID (PubMed identifer) Original Reason for Retraction Final Reason for Retraction Retraction Announcement Secondary Source Abdelkefi Blood 2008 19520824 unknown fraud "data. . . were inappropriately collected" Retraction Watch (Marcus): "inconsistencies and inaccuracies that cast doubt on the integrity of the study and resulted in retraction" Ahluwalia J Neurochem 2003 12558978 error possible fraud "concentration. . . is inaccurate" Retraction Watch (Oransky): findings could not be replicated, first author "found guilty of faking data" Ahluwalia Nature 2004 14985765 unknown fraud no reason provided Retraction Watch (Oransky): institutional report concluded that first author "falsified and misrepresented the results of experiments" Alsabti Jpn J Med Sci Biol 1979 396398 unknown plagiarism retraction announcement not included in e-journal British Medical Journal: first author "published 13 scientific articles, but at least 5 of these were plagiarised" Aoki J Biol Chem 1996 8910608 unknown fraud no reason provided Retraction Watch (Oransky): "lead author manipulated figures" Aoki J Biol Chem 2000 10993888 unknown fraud no reason provided Retraction Watch (Oransky): "lead author manipulated figures" Aoki J Biol Chem 2004 14679216 unknown fraud no reason provided Retraction Watch (Oransky): "lead author manipulated figures" Asiedu J Immunol 2005 16339543 error fraud "a recently uncovered error compromises some of the data" Office of Research Integrity: "respondent engaged in scientific misconduct by falsifying. . . reports of research results" Bois J Cell Biol 2005 16157701 error fraud "follow-up experiments. . . have shown that. . . Figure 1 is not correct" Office of Research Integrity: first author "knowingly and intentionally falsified data" Bonnefoi Lancet Oncol 2007 18024211 error fraud "Re-examination of the validation datasets. . . has uncovered errors in the labeling of the clinical response" 60 Minutes (Pelley): co-author states it is "abundantly clear" that the data were fabricated Brodie J Leukoc Biol 2000 10985251 possible fraud fraud "figures are not authentic" Office of Research Integrity: first author "intentionally fabricated and falsified data" Chandok Cell 2003 12757708 error possible fraud "difficulties in reproducing the data" Science (Travis): principal investigator "suspicious that misconduct was involved;" first author declined to sign retraction and unsuccessfully sued principal investigator for defamation Chandok Proc Natl Acad Sci U S A 2004 15146069 error possible fraud "unable to repeat the results" Science (Travis): principal investigator "suspicious that misconduct was involved;" first author declined to sign retraction and unsuccessfully sued principal investigator for defamation Chen J Immunol 1998 9780201 error fraud "errors in the presentation of data" Office of Research Integrity: senior author "engaged in scientific misconduct by falsifying and fabricating data" Constantoulakis Science 1993 7680491 error fraud "some experiments have not been reproducible" Office of Research Integrity: first author "committed scientific misconduct by falsifying and fabricating data" Contreras Transplantation 1998 9603161 error fraud "we discovered that some of our published studies. . . included animals that had not undergone bilateral nephrectomies" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying in seven publications reports of research results" Contreras Transplantation 1999 10440390 possible fraud fraud "these articles contain inaccurate data. . . Dr. Thomas has resigned from the university" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying in seven publications reports of research results" Cressman Mol Cell Biol 1999 10490643 unknown fraud "data reported in these panels cannot be relied upon" Office of Research Integrity: co-author "engaged in scientific misconduct by falsifying DNA samples and constructing falsified figures" Davidson Circ Res 1981 6257420 error fraud "unable to reproduce similar experiments" New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" Davidson J Clin Invest 1984 6365971 unknown fraud no reason provided New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" DeFronzo J Clin Invest 1978 350903 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" DeFronzo J Clin Invest 1979 376552 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Degenhardt J Mol Biol 2009 19289130 error fraud "incorrect data handling for the ChIP analysis" Retraction Watch (Marcus): graduate student found to have falsified data Doree J Bacteriol 2001 11222596 error unknown "questions concerning the validity of the data in this paper have arisen" Associated Press: first author sentenced to 10 months in prison for data fabrication Duan Proc Natl Acad Sci U S A 1994 8197188 error possible fraud "sequence of the heavy chain. . . has been reanalyzed and found to be not what was reported" Office of Research Integrity: first author "engaged in scientific misconduct by reporting research that was inconsistent with original data or could not be supported because original data were not retained" Elsheikh Blood 2005 15985545 unknown fraud "results published cannot be considered reliable" Retraction Watch (Marcus): data fabrication "convincingly shown" Erin Am J Respir Crit Care Med 2006 16850747 unknown fraud "concerns regarding the veracity of the data and the validity of the conclusions" Retraction Watch (Marcus): first author responsible for "serious data anomalies" in which he "manipulated the data. . . to give a more favourable outcome" Erin Am J Respir Crit Care Med 2008 17962642 unknown fraud "concerns regarding the veracity of the data and the validity of the conclusions" Retraction Watch (Marcus): first author responsible for "serious data anomalies" in which he "manipulated the data. . . to give a more favourable outcome" Friedman Fertil Steril 1993 8339817 unknown fraud "invalid data" Office of Research Integrity: first author "committed scientific misconduct by falsifying and fabricating data" Friedman Obstet Gynecol 1995 7898846 unknown fraud "invalid data" Office of Research Integrity: first author "committed scientific misconduct by falsifying and fabricating data" Fukuda J Biol Chem 2009 19047050 unknown fraud no reason provided Retraction Watch (Oransky): authors "used the same (Western blot) data in several figures" Fukuhara Science 2005 15604363 unknown error an institutional council "recommended that we retract the entire paper" The Scientist (Scheff): errors undermined certain conclusions of the article Garey Nat Genet 1994 7914452 unknown fraud "serious inconsistences under investigation" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying research" Gelband Hypertension 2000 10642299 unknown fraud no reason provided Office of Research Integrity: first author "falsified data" Gold Clin Immunol Immunopathol 1994 7911078 unknown fraud "based on inaccurate data" New York State Board for Professional Medical Conduct: first author "inappropriately listed himself as holding a Ph.D. . . (and) fabricated animal research studies." Gold Clin Immunol Immunopathol 1994 7923908 unknown fraud "based on inaccurate data" New York State Board for Professional Medical Conduct: first author "inappropriately listed himself as holding a Ph.D. . . (and) fabricated animal research studies." Gold Eur J Cancer 1994 7880620 unknown fraud no reason provided New York State Board for Professional Medical Conduct: first author "inappropriately listed himself as holding a Ph.D. . . (and) fabricated animal research studies." Gold J Surg Res 1995 7543632 unknown fraud "based on inaccurate data" New York State Board for Professional Medical Conduct: first author "inappropriately listed himself as holding a Ph.D. . . (and) fabricated animal research studies." Goodwill J Neuroimmunol 2007 17229471 error fraud "analysis. . . (is) not accurate" Office of Research Integrity: first author "engaged in research misconduct by the fabrication of data" Greger Mol Cell Biol 2007 17194752 unknown fraud "data. . . are unreliable" Office of Research Integrity: senior author "engaged in misconduct. . . by intentionally falsifying figures" Hajra Genomics 1995 7607682 unknown fraud "new information which casts significant doubt on the correctness of the experimental conclusions" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying and fabricating research data" Hajra Mol Cell Biol 1995 7651416 unknown fraud "new information which casts significant doubt on the correctness of the experimental conclusions" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying and fabricating research data" Hajra Proc Natl Acad Sci U S A 1995 7892201 unknown fraud "information not reliable" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying and fabricating research data" Han J Biol Chem 2005 16061473 unknown fraud no reason provided Retraction Watch (Oransky): first author committed "data manipulation" Han J Biol Chem 2006 16882662 unknown fraud no reason provided Retraction Watch (Oransky): first author committed "data manipulation" Han J Biol Chem 2007 17237224 unknown fraud no reason provided Retraction Watch (Oransky): first author committed "data manipulation" Herman Int J Radiat Oncol Biol Phys 1989 2689396 error fraud "not all tumor measurements were made weekly as reported. . . main finding of this paper remains" Office of Research Integrity: first author "committed scientific misconduct by falsely reporting. . . that research had been conducted according to a stated protocol, when, in fact, (he) knew at the time that the protocol. . . had not been carried out exactly as described." Hoffmann J Biol Chem 2001 11509576 unknown fraud "some of the data are not reproducible" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying and fabricating research data" Hutchings Immunol Res 2002 12403353 error fraud "our published studies. . . included some animals that had not undergone bilateral nephrectomies" Office of Research Integrity: senior author "engaged in scientific misconduct by falsifying reports" Hutchings Transpl Immunol 2003 12967786 error fraud "recipients. . . later proved to have retained an intrinsic kidney" Office of Research Integrity: senior author "engaged in scientific misconduct by falsifying reports" Jiang J Biol Chem 2010 20826813 unknown duplicate publication no reason provided Blood (2011 retraction notice): "contains multiple instances of duplicate (redundant) publication of data, text and images" Kawabata Intern Med 2004 15575251 error fraud "inclusion of incorrect experimental data" Journal of Immunology (2008 retraction notice): co-author found to have committed "scientific misconduct that resulted in falsified or fabricated data." Khansari Eur J Immunol 1983 6363100 error possible fraud "contains unsubstantiated data or incorrect methodology or procedural information" State of New York Department of Health: senior author later found "guilty of dishonorable, unethical or unprofessional conduct" Kindzelskii J Immunol 2003 12496384 unknown possible fraud "findings reported have not been reproduced in subsequent experiments" Cell Calcium (Hallett): "fantastic and spurious;" senior author "told the audience. . . an enquiry into the affair at his home institution was underway" Kobayashi Haematologica 2008 18508798 unknown error "study had not been approved by the IRB" Science (Normile): author "may have believed that approval of another aspect of his research covered this study as well" Komazawa Nat Med 2004 15489860 error fraud some of the primary data were erroneously or artificially presented" Cambridge Quarterly of Healthcare Ethics (Slingsby): "data fabricated by a medical student" Krishna Murthy Acta Crystallogr D Biol Crystallogr 1999 10393310 unknown fraud no reason provided Nature (Borrell): first author "acted alone in fabricating and falsifying results" Kugler Nat Med 2000 10700237 error fraud "incorrect statements and erroneous presentation of primary data, results and conclusions" The Scientist (Zwirner): "data manipulation and illegal treatment" Kumar J Exp Med 1989 2555431 error fraud "Southern blots. . . were mislabeled. . . We have attempted to reproduce the deletion experiments. . . and have been unsuccessful" Office of Research Integrity: first author "committed scientific misconduct by falsfying and/or fabricating figures" Kumar Proc Natl Acad Sci U S A 1990 1689484 unknown fraud "much of the data are no longer available" Office of Research Integrity: first author "committed scientific misconduct by falsfying and/or fabricating figures Lambert J Lab Clin Med 1984 6270222 unknown fraud "records available for review failed to support adequately the results and conclusions" The Scientist (Hollis): post-doctoral fellow "turned in" mentor for questionable publications Leadon Mutat Res 1995 7491120 error fraud "data cannot be relied upon" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying DNA samples and constructing falsified figures" Leadon Cancer Res 1997 9288788 error fraud "methodologic errors" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying DNA samples and constructing falsified figures" Leadon Mutat Res 1998 9637246 unknown fraud "errors" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying DNA samples and constructing falsified figures" Lee Biochem Biophys Res Commun 1989 2665742 error fraud "flaws in methodological execution and data analysis" Office of Research Integrity: first author "fabricated and falsified research" Lee Diabetes 1989 2555243 unknown fraud no reason provided Office of Research Integrity: first author "fabricated and falsified research" Lee J Clin Invest 1989 2536048 error fraud "flaws in methodology, execution and data analysis" Office of Research Integrity: first author "fabricated and falsified research" Lipsky J Biol Chem 2008 18458091 unknown fraud no reason provided Retraction Watch (Oransky): "An internal Mt. SInai investigation found that (principal investigator) committed research misconduct" Liu J Mol Cell Cardiol 2001 11708844 unknown fraud no reason provided Office of Research Integrity: senior author "engaged in scientific misconduct" (falsified data) Lobashevsky Hum Immunol 2002 11821158 error fraud "methodology stated that the animals had undergone bilateral nephrectomy, but years later, it was discovered that some animals. . . had retained a native kidney" Office of Research Integrity: senior author "engaged in scientific misconduct by falsifying reports" Luo J Biol Chem 2008 18458081 unknown fraud no reason provided Retraction Watch (Oransky): "an investigation had found evidence of misconduct" Ma J Biol Chem 2007 17347151 unknown fraud no reason provided Retraction Watch (Oransky): "image manipulation" Ma J Biol Chem 2009 19019824 unknown fraud no reason provided Retraction Watch (Oransky): "image manipulation" Mi Nat Med 2006 16732280 error fraud "contains several errors" Office of Research Integrity: co-author "engaged in scientific/research misconduct by falsifying research results" Milanese J Immunol 1985 3160783 unknown fraud "certain data are unreliable" Science News (Greenberg): first author admitted data tempering Milanese J Exp Med 1986 3519831 unknown fraud "unable to reproduce results" Science News (Greenberg): first author admitted data tempering Milanese Science 1986 2935936 unknown fraud "unable to reproduce results" Science News (Greenberg): first author admitted data tempering Mishra J Biol Chem 2005 16154993 unknown fraud no reason provided Retraction Watch (Oransky): "image manipulation" Mishra J Biol Chem 2007 17158886 unknown fraud no reason provided Retraction Watch (Oransky): "image manipulation" Murthy J Biol Chem 1999 10026173 unknown fraud no reason provided Nature (Borrell): first author "acted alone in fabricating and falsifying results" Nakao Am J Nephrol 2004 15528874 unknown fraud "apprehension about the data" CardioBrief (Husten): an institutional committee found that "proper consent had not been obtained" and "the trial was not a double-blind study" Ninnemann J Immunol 1978 307018 unknown fraud "data are flawed" Office of Research Integrity: first author agreed to retract article to settle ORI allegations that he "falsified and misrepresented scientific experiments;" author maintained his innocence but acknowledged that the reported results were highly improbable or impossible. NY Times: author's institutions agreed to pay U.S. government $1.6M to settle charges that they helped to cover up researcher's misconduct. Ninnemann J Trauma 1980 6444674 unknown fraud "the data are flawed. . . data relating to this figure are not available" Office of Research Integrity: first author agreed to retract article to settle ORI alleagations that he "falsified and misrepresented scientific experiments;" author maintained his innocence but acknowledged that the reported results were highly improbable or impossible. NY Times: author's institutions agreed to pay U.S. government $1.6M to settle charges that they helped to cover up researcher's misconduct. Ninnemann J Trauma 1982 6182304 unknown fraud "the data are flawed. . . primary data do not exist for the figures" Office of Research Integrity: first author agreed to retract article to settle ORI allegations that he "falsified and misrepresented scientific experiments;" author maintained his innocence but acknowledged that the reported results were highly improbable or impossible. NY Times: author's institutions agreed to pay U.S. government $1.6M to settle charges that they helped to cover up researcher's misconduct. Ninnemann J Trauma 1984 6231383 unknown fraud "result is improbable. . . I do not have the primary data" Office of Research Integrity: first author agreed to retract article to settle ORI allegations that he "falsified and misrepresented scientific experiments;" author maintained his innocence but acknowledged that the reported results were highly improbable or impossible. NY Times: author's institutions agreed to pay U.S. government $1.6M to settle charges that they helped to cover up researcher's misconduct. O'Brodovich J Clin Invest 1981 7007439 unknown fraud no reason provided New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" Orme Infect Immun 1993 8418058 error fraud "mitogenic contaminant" Office of Research Integrity: senior author "committed scientific misconduct by falsifying data" Pang J Appl Physiol 1982 7037714 unknown fraud "unable to confirm the results" New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" Paul Biochemistry 1996 8885844 unknown fraud retraction notice not found Office of Research Integrity: first author "falsified an experiment" Paul Biochemistry 1996 8909298 unknown fraud "Uncertain validity of the data and the failure to reproduce some of the results" Office of Research Integrity: first author "falsified an experiment" Paul Proc Natl Acad Sci U S A 1996 8692921 unknown fraud "Uncertain validity of the data and the irreproducibility of some of the results" Office of Research Integrity: first author "falsified an experiment" Puckerin J Biol Chem 2006 16912040 unknown fraud no reason provided Retraction Watch (Oransky): "An internal Mt. SInai investigation found that (principal investigator) committed research misconduct" Qian J Med Chem 2009 19271734 unknown fraud "violation of the ACS ethical guidelines" Retraction Watch (Oransky): "data duplication" Qiuping Oncogene 2005 15580304 unknown possible fraud no reason provided Retraction Watch (Marcus): other articles by this group retracted due to "image manipulation" Racker Science 1981 6264596 unknown fraud "discrepancy. . . cast doubt on some of the published and unpublished claims we made" Nature (Racker): a detailed discussion of fraud by Racker's graduate student Mark Spector Rakoff-Nahoum J Immunol 2001 11490022 error fraud "an error in the presentation of data" Office of Research Integrity: senior author "engaged in scientific misconduct by falsifying and fabricating data" Ramalingam Nat Cell Biol 2000 11146662 error fraud "images. . . were inappropriately processed" Office of Research Integrity: first author "plagiarized" and "falsified figures" Ramalingam EMBO J 2002 11847107 unknown fraud and plagiarism "result cannot be replicated" Office of Research Integrity: first author "plagiarized" and "falsified figures" Rangaswami J Biol Chem 2005 15757900 unknown fraud no reason provided The Telegraph (Jayan): the Indian Academy of Sciences sanctioned the senior author for "reusing images" Razem J Biol Chem 2004 14699092 unknown fraud "data. . . are not reproducible" Retraction Watch (Oransky): first author's "results were fabricated" Razem Nature 2006 16421562 error fraud "errors in the calculations" Retraction Watch (Oransky): first author's "results were fabricated" Razem Biochem Cell Biol 2007 17901904 unknown fraud "previous work has been found to be not reproducible" Retraction Watch (Oransky): first author's "results were fabricated" Richman J Biol Chem 2004 15047708 unknown fraud no reason provided Retraction Watch (Oransky): "An internal Mt. SInai investigation found that (principal investigator) committed research misconduct" Rooney Genes Dev 2001 11711437 unknown fraud "experiments. . . could not be reproduced" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying" figures Roy J Biol Chem 1995 7559549 unknown fraud "unable to reproduce the results" Office of Research Integrity: first author "intentionally falsified the data" Ruggiero J Pers Soc Psychol 1999 10531671 unknown fraud "data reported in this article are invalid" Office of Research Integrity: first author "engaged in scientific misconduct by fabricating data" Ruggiero Psychol Sci 2000 11202499 error fraud "improper exclusion of some participants" Office of Research Integrity: first author "engaged in scientific misconduct by fabricating data" Salter PLoS One 2008 18382581 error possible fraud "presence of errors in the labeling of clinical response" 60 Minutes (Pelley): co-author states it is "abundantly clear" that the data were fabricated Seki J Biol Chem 2006 16714283 unknown fraud no reason provided Nature (Abbott et al.): senior author "fabricated data" Shao Clin Cancer Res 2001 11489795 unknown fraud "after reviewing the sources for some of the data. . . we have concluded that the article should be retracted" Office of Research Integrity: senior author "falsified and fabricated the results" Shin Infect Immun 2004 15039353 unknown fraud "results presented. . . cannot be verified in the data record" Office of Research Integrity: first author "engaged in research misconduct by falsifying data" Simmons Immunogenetics 1993 8344721 unknown fraud "reason to doubt the validity of the data" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying research" Simmons J Immunol 1996 8568273 unknown fraud "results. . . cannot be confirmed and are not valid" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying research" Simmons Immunity 1997 9390688 unknown fraud "critical data can't be reproduced" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying research" Simmons J Immunol 1997 9300696 unknown fraud "results. . . cannot be confirmed and are not valid" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying research" Slutsky Am Heart J 1983 6401372 unknown fraud "certain information has recently come to the attention of (first author) which has convinced him that the results. . . are subject to serious question" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Invest Radiol 1983 6345451 unknown fraud "certain information has recently come to the attention of (first author) which has convinced him that the results. . . are subject to serious question" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Am Heart J 1984 6380255 unknown fraud "certain information has recently come to the attention of (first author) which has convinced him that the results. . . are subject to serious question" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Am Heart J 1984 6382990 unknown fraud "certain information has recently come to the attention of (first author) which has convinced him that the results. . . are subject to serious question" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Invest Radiol 1984 6392156 unknown fraud "certain information has recently come to the attention of (first author) which has convinced him that the results. . . are subject to serious question" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Radiology 1984 6385104 unknown fraud "subject to serious question. . . conclusions set forth therein cannot be relied upon" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Radiology 1984 6379743 unknown fraud "subject to serious question. . . conclusions set forth therein cannot be relied upon" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky Radiology 1985 3881789 unknown fraud "subject to serious question. . . conclusions set forth therein cannot be relied upon" JAMA (Friedman): first author repeatedly engaged in "research fraud" Slutsky RA Radiology 1984 1985 3883412 unknown fraud "subject to serious question. . . conclusions set forth therein cannot be relied upon" JAMA (Friedman): first author repeatedly engaged in "research fraud" Smith Ann NY Acad Sci 2002 12446313 unknown duplicate publication no reason provided Nature (Reich): "material copied without acknowledgment from previous publications" Smith Ann NY Acad Sci 2002 12446324 unknown duplicate publication no reason provided Nature (Reich): "material copied without acknowledgment from previous publications" Smith Ann NY Acad Sci 2004 15644350 unknown duplicate publication no reason provided Nature (Reich): "material copied without acknowledgment from previous publications" Soman J Clin Invest 1977 326810 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman J Clin Invest 1978 205552 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman N Engl J Med 1978 460062 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman Nature 1978 205799 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman J Clin Endocrinol Metab 1978 400712 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman Am J Med 1980 6985768 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman Diabetes 1980 6986303 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Soman J Clin Endocrinol Metab 1980 6243667 unknown fraud "review of the raw data has revealed some discrepancies" New York Times (Hunt): co-author "falsified data" Sotolongo J Urol 1990 2329615 unknown fraud no reason provided Office of Research Integrity: first author "commited scientific misconduct by falsifying research" Sperber J Immunol 2003 12538722 error fraud "despite these errors, the message of the manuscript remains unchanged" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying and fabricating data" Stalcup Circ Res 1978 213200 unknown fraud "unable to reproduce certain experiments" New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" Stalcup J Appl Phys 1979 217854 unknown fraud "unable to confirm the results" New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" Stalcup J Clin Invest 1979 221532 unknown fraud no reason provided New York Times (Wilford): technician admitted taking actions resulting "in the biasing of experimental data" Tanaka Mol Cell Biol 2000 16782903 unknown fraud "questions have arisen concerning the validity of. . . figures" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying data" Tanaka Mol Cell Biol 2002 12024037 unknown fraud "questions have arisen concerning the validity of. . . figures" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying data" Tewari Lancet 1990 2684782 error fraud "arithmetical errors made in summarising the data" Office of Research Integrity: first author "committed scientific misconduct. . . falsified and fabricated data" Thomas Transplantation 1999 10609942 error fraud "contain inaccurate data" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying reports" Thomas Transplantation 2000 10920269 error fraud "contain inaccurate data" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying reports" Thomas Immunol Rev 2001 11782260 error fraud "recipients did not undergo intrinsic bilateral nephrectomies as specified" Office of Research Integrity: first author "engaged in scientific misconduct by falsifying reports" Tombler J Biol Chem 2006 16293615 unknown fraud no reason provided Retraction Watch (Oransky): "An internal Mt. SInai investigation found that (principal investigator) committed research misconduct" Urban Cell 1989 2478292 unknown fraud "certain of the original data. . . are unavailable" Office of Research Integrity: first author "engaged in scientific misconduct. . . fabricating certain research data" Van Parijs J Exp Med 1997 9314560 error fraud "figure. . . is erroneous" Office of Research Integrity: first author "engaged in scientific misconduct. . . by including false data" Wang Hypertension 2000 10642298 unknown fraud no reason provided Office of Research Integrity: co-author "engaged in scientific misconduct. . . falsified data" Weiser Proc Natl Acad Sci U S A 1992 1518830 unknown fraud no reason provided Office of Research Integrity: first author "committed scientific misconduct by falsifying data" Weiss J Urol 1990 1977932 unknown fraud no reason provided Office of Research Integrity: first author "committed scientific misconduct by falsifying research" Wong Proc Natl Acad Sci U S A 2002 12415108 unknown fraud "it is our view that the cell-based data. . . are unreliable" Office of Research Integrity: senior author "engaged in misconduct in science. . . by intentionally falsifying figures" Xiao J Biol Chem 2007 17344217 unknown fraud no reason provided Retraction Watch (Oransky): "image manipulation" by senior author Xu J Biol Chem 2000 10849424 unknown fraud no reason provided Office of Research Integrity: first author "engaged in scientific misconduct. . . falsified data" Yun J Biol Chem 2003 12968031 unknown possible fraud "failed to confirm the conclusion" Biochemistry (Walsh, 2007): provides a detailed account of inability to replicate results and possible misconduct by a co-author Zhi J Cell Physiol 2006 16575915 unknown possible fraud "concern regarding duplication of figure 2" Retraction Watch (Oransky): investigation of "possible fraud" in progress Zhu J Biol Chem 2001 11535583 unknown fraud no reason provided Office of Research Integrity: first author "engaged in misconduct in science by intentionally and knowingly fabricating and falsifying data" 如果浏览困难,请下载附件。 1977-2012部分生物医学-生命科学撤稿.pdf
1. Stanford University 2. Harvard University 2. Massachusetts Institute of Technology 2. University of California-Berkeley 5. California Institute of Technology 5. Johns Hopkins University 7. Princeton University 7. Scripps Research Institute 7. University of California-San Francisco 7. Yale University 11. Cornell University 11. Washington University in St. Louis 13. Duke University 13. University of Chicago 15. Columbia University 15. Rockefeller University 15. University of California-San Diego 15. University of Washington 15. University of Wisconsin-Madison 20. University of Michigan-Ann Arbor 20. University of Pennsylvania 20. University of Texas Southern Medical Center-Dallas 24. University of California-Los Angeles 24. University of North Carolina-Chapel Hill 26. Baylor College of Medicine 26. Cornell University (Weill) 26. Northwestern University 26. University of Texas-Austin 30. University of Colorado-Boulder 30. University of Illinois-Urbana-Champaign 32. University of Minnesota-Twin Cities 32. Vanderbilt University 34. Brown University 34. Case Western Reserve University 34. Dartmouth College 34. Emory University 34. Indiana University-Bloomington 34. University of Alabama-Birmingham 34. University of Arizona 34. University of California-Irvine 42. Mayo Medical School 42. Mount Sinai School of Medicine 42. Pennsylvania State University-University Park 42. Rice University 46. Carnegie Mellon University 46. Michigan State University 46. Ohio State University 46. University of California-Santa Barbara 46. University of Florida 46. University of Georgia 46. University of Massachusetts Medical Center-Worcester 46. University of Pittsburgh 46. University of Southern California 46. University of Virginia 56. Arizona State University 56. Brandeis University 56. Georgia Institute of Technology 56. New York University 56. Purdue University-West Lafayette 56. Tufts University 56. University of California-Riverside 56. University of California-Santa Cruz 56. University of Iowa 56. University of Maryland-College Park 56. University of Oregon 56. University of Utah 68. Stony Brook University-SUNY 68. University of Colorado-Denver 68. Yeshiva University (Einstein) 71. Oregon Health and Science University 71. Oregon State University 71. Rutgers, the State University of New Jersey-New Brunswick 71. Texas AM University-College Station 71. University of Connecticut 71. University of Illinois-Chicago 71. University of Kansas 71. University of Massachusetts-Amherst 71. University of Notre Dame 71. University of Rochester 71. University of Texas Health Science Center-Houston 82. Baylor University 82. Boston University 82. Colorado State University 82. Iowa State University 82. North Carolina State University 82. University of Medicine and Dentistry of New Jersey-Newark 82. University of Miami 82. University of Missouri 82. University of Nebraska-Lincoln 82. University of Texas Health Science Center-San Antonio 92. Florida State University 92. George Washington University 92. Georgetown University 92. Montana State University 92. San Diego State University 92. University of Cincinnati 92. University of Montana 92. Virginia Tech 100. Auburn University 100. Boston College 100. Claremont Graduate University 100. Kansas State University 100. Rensselaer Polytechnic Institute 100. Thomas Jefferson University 100. Tulane University 100. University of Maryland-Baltimore 100. University of Nebraska Medical Center 100. University of New Mexico 100. University of Oklahoma 100. University of Tennessee Health Science Center 100. University of Texas Medical Branch-Galveston 100. Wake Forest University 115. Washington State University 115. Medical College of Wisconsin 115. Northeastern University 115. St. Louis University 115. Syracuse University 115. Temple University 115. Texas AM Health Science Center-Baylor College of Dentistry 115. University at Buffalo SUNY 115. University of Alabama 115. University of Arkansas for Medical Sciences 115. University of Hawaii-Manoa 115. University of Kentucky 115. University of Tennessee-Knoxville 115. University of Texas-San Antonio 115. University of Vermont 115. Wesleyan University 130. College of William and Mary 130. CUNY Graduate School and University Center 130. Louisiana State University School of Medicine-New Orleans 130. Loyola University Chicago 130. Medical University of South Carolina 130. Miami University 130. Rutgers, the State University of New Jersey-Newark 130. Uniformed Services University of the Health Sciences 130. University of Alaska-Fairbanks 130. University of Arkansas-Fayetteville 130. University of Delaware 130. University of Rhode Island 130. University of Texas-Dallas 130. Wayne State University 144. Brigham Young University 144. Bryn Mawr College 144. Creighton University 144. Drexel University 144. Louisiana State University-Baton Rouge 144. New York Medical College 144. Rosalind Franklin University of Medicine and Science 144. University of Idaho 144. University of Louisville 144. University of Maryland-Baltimore County 144. University of Missouri-St. Louis 144. University of South Florida 144. University of Wisconsin-Milwaukee 144. University of Wyoming 144. Virginia Commonwealth University 160. Albany Medical College 160. Drexel University (College of Medicine) 160. Florida Institute of Technology 160. Florida International University 160. Georgia State University 160. Loma Linda University 160. Louisiana State University School of Medicine-shreveport 160. Northern Arizona University 160. Ohio University 160. Oklahoma State University 160. Southern Methodist University 160. SUNY College of Environmental Science and Forestry 160. SUNY Upstate Medical Center 160. University at Albany-SUNY 160. University of Houston 160. University of Massachusetts-Boston 160. University of Mississippi Medical Center 160. University of New Hampshire 160. University of South Carolina 160. Worcester Polytechnic Institute 160. Wright State University 181. Binghamton University-SUNY 181. Clemson University 181. Illinois Institute of Technology 181. Marquette University 181. Old Dominion University 181. Southern Illinois University-Carbondale 181. University of Maine 181. University of Mississippi 181. University of Missouri-Kansas City 181. University of South Dakota 181. University of Toledo. 181. West Virginia University 195. Clark University 195. East Carolina University 195. Idaho State University 195. Indiana State University 195. Lehigh University 195. Rush University 195. South Dakota State University 195. Teachers College, Columbia University 195. Texas Tech University 195. University of Nevada-Las Vegas 195. University of North Carolina-Charlotte 195. Utah State University 207. Fordham University 207. George Mason University 207. Howard University 207. Illinois State University 207. Michigan Technological University 207. New Mexico State University 207. SUNY Downstate Medical Center 207. University of Central Florida 207. University of Dayton 207. University of North Carolina-Greesboro 207. University of North Dakota 207. University of Southern Mississippi 207. University of Texas-Arlington 220. Bowling Green State University 220. Duquesne University 220. Kent State University 220. Marshall University 220. Mississippi State University 220. Morehouse College of Medicine 220. Northern Illinois University 220. Oakland University 220. Portland State University 220. St. John's University 220. University of Alabama-Huntsville 220. University of Denver 220. University of Memphis 220. University of Puerto Rico-Rio Piedras 220后没有具体排名。
近来仍有不少喜欢琢磨衰老之谜的“独立思考者”在俺的博客以及邮箱里就衰老机理与我“过不去”。在耐心解释之际,觉得仍有进一步科普的必要。以下附上两篇衰老研究大师 Holliday 近来的文章,供大家一阅并一悦 ……. Aging and the decline in health.pdf Longivity mutants do not establish any 'new science' of ageing.pdf
根据QS World University Rankings 2010 - Life Sciences Medicine公布的排名结果,我国北京大学排名位于生命科学与医学类第21名,居于中国高校医学与生命科学排行榜之首,其次是香港大学,排名37,台湾大学排名43, 北京的清华大学位于第55名,香港科技大学则位于第63名。我国位于世界排行榜前百名的高校还有,香港中文大学(67),复旦大学(69)。101-150名的我国高校有中国科技大学(102)、浙江大学(120)、南京大学(123)以及上海交通大学(141)。下表仅仅列出一部分(250名之前的大学),详细排名结果请浏览相关网站: http://www.topuniversities.com/ ,我们期待2011年的新结果。 QS World University Rankings 2010 - Life Sciences Medicine Rank School Name Country/Region Size Research Focus Score 1 Harvard University United States L VH FC 100.00 2 University of Cambridge United Kingdom L VH FC 92.00 3 University of Oxford United Kingdom L VH FC 82.00 4 Stanford University United States L VH FC 75.00 5 University of California, Berkeley (UCB) United States XL VH FC 70.00 6 The University of Tokyo Japan L VH FC 66.00 7 Johns Hopkins University United States L VH FC 66.00 8 Massachusetts Institute of Technology (MIT) United States M VH CO 64.00 9 Yale University United States M VH FC 63.00 10 University of California, Los Angeles (UCLA) United States XL VH FC 60.00 11 Imperial College London United Kingdom L VH FC 58.00 12 University of California, San Diego (UCSD) United States L VH FC 57.00 13 National University of Singapore (NUS) Singapore XL VH FC 54.00 14 The University of Melbourne Australia XL VH FC 53.00 15 UCL (University College London) United Kingdom L VH FC 53.00 16 University of Toronto Canada XL VH FC 52.00 17 University of Edinburgh United Kingdom L VH FC 50.00 18 Kyoto University Japan L VH FC 50.00 19 The University of Sydney Australia XL VH FC 49.00 20 University of British Columbia Canada XL VH FC 49.00 21 Peking University China L VH FC 48.00 22 McGill University Canada L VH FC 46.00 23 Karolinska Institute Sweden S VH SP 46.00 24 Columbia University United States L VH FC 45.00 25 Cornell University United States L VH FC 45.00 26 University of California, San Francisco United States S CO 45.00 27 Duke University United States L VH FC 44.00 28 California Institute of Technology (Caltech) United States S VH CO 43.00 29 University of Washington United States XL VH FC 43.00 30 King’s College London (University of London) United Kingdom L VH FC 43.00 31 University of Chicago United States M VH FC 42.00 32 ETH Zurich (Swiss Federal Institute of Technology) Switzerland L VH FO 41.00 33= University of Michigan United States XL VH FC 41.00 33= University of Pennsylvania United States L VH FC 41.00 35 Princeton University United States M VH CO 40.00 36 Australian National University Australia M VH CO 40.00 37 University of Hong Kong Hong Kong L VH FC 39.00 38 Seoul National University Korea, South L VH FC 38.00 39 The University of Manchester United Kingdom XL VH FC 37.00 40 The University of Queensland Australia XL VH FC 36.00 41 The University of Auckland New Zealand L VH FC 36.00 42 Washington University in St. Louis United States L VH FC 36.00 43 National Taiwan University (NTU) Taiwan, China XL VH FC 35.00 44 University of California, Davis United States L VH FC 35.00 45 Ruprecht-Karls-Universitt Heidelberg Germany L VH FC 34.00 46 The University of New South Wales Australia XL VH FC 34.00 47= University of Wisconsin-Madison United States XL VH FC 33.00 47= Rockefeller University United States S CO 33.00 49 Monash University Australia XL VH FC 33.00 50= Ludwig-Maximilians-Universitt München Germany XL VH FC 32.00 55 Tsinghua University China L VH FC 31.00 62= The Hong Kong University of Science and Technology Hong Kong M VH CO 27.00 67 The Chinese University of Hong Kong Hong Kong L VH FC 27.00 69 Fudan University China L VH FC 27.00 102 University of Science and Technology of China China L VH CO 22.00 120 Zhejiang University China XL VH FC 21.00 123= Nanjing University China L VH FC 20.00 141= Shanghai Jiao Tong University China L VH FC 18.00 184 National Yang Ming University Taiwan,China S VH FC 16.00 197= National Tsing Hua University Taiwan,China M VH CO 15.00 209= National Central University Taiwan M VH CO 15.00 209= National Taiwan University of Science And Technology (formerly National Taiwan Institute of Technology) Taiwan M VH FO 15.00 214= The Hong Kong Polytechnic University Hong Kong L VH CO 15.00 228 Wuhan University China XL VH FC 14.00 242= Xiamen University China XL HI FC 13.00 247= Taipei Medical University Taiwan M VH SP 13.00
尝试新的介绍方法,以主题分类,每次介绍几本书。 Delusions of Gender: The Real Science Behind Sex Differences 作者 Cordelia Fine 出版社 Icon Books (平装本2011年2月3日出版) ISBN 978-1848312203 这本书的书名《性别的误识》,全书就是为了反驳大众文化中对于性别的误识,特别针对是目前流行的“男女有别是由大脑结构与发育决定”这一观点。作者重点攻 击的是两种论点:其一是男女在数理分析和善解人意上天然有别,其二是这种差别是在胚胎期形成,与性别荷尔蒙有关,可以用“大脑扫描”证明。她分析了大量大 众读物以及原始研究,指出许多流行观点并无科研证据,而有些科研成果由于设计缺陷或数据不足,仍有争议,却常被拿来作为“科学依据”。她批评的作者之一就 是 Simon Baron-Cohen,指出他的一个著名的“男婴爱看手机、女婴爱看人脸”的实验存在重大设计缺陷。 Zero Degrees of Empathy: A New Theory of Human Cruelty 作者 Simon Baron-Cohen 出版社 Allen Lane (精装本2011年4月7日出版) ISBN 978-0713997910 作者是剑桥大学教授、自闭症研究专家。这本题为《设身处地能力为零》的书中,他以“设身处地”度(empathy)作为中心,试图以此解释为什么人类可以 对他人施暴,他指出其中的关键不是有些人“邪恶”,而且他们缺少“设身处地”的能力。这种“设身处地”的能力,并不仅仅是后天学会的,是在大脑中已有构 建,并且还能找到相关基因。当然缺少“设身处地”的能力,并不等于“邪恶”,比如自闭症就是一种表象,缺少这一能力也不是永远只会产生负面影响。 Mathematics of Life: Unlocking the Secrets of Existence 作者 Ian Stewart 出版社 Profile (精装本2011年4月7日出版) ISBN 978-1846681981 上面两本书都涉及到了心理学和生物学的交叉,另一本新书《生命之数学》谈的是数学和生物学的交叉。本来这是两个反差较大的学科,数学重抽象概括,生物学重 具体描述,连从事这两门学科研究的似乎都是两种不同的人。不过近年以来这两门学科开始大规模的合作,生命科学研究中产生的大量数据需要数学模型,数学理论 也可以应用到某些生命科学研究,比如神经科学中去。这本书既是对历史回顾,也是对未来的展望。
为什么世界各地的生物医学科学家们都如此钟爱她?想必也是有她的道理,这里只是一部分答案。 “阴阳是一个正在全世界风靡的中国概念。” 引自 Cook S . Coronary artery disease, nitric oxide and oxidative stress: the "Yin-Yang" effect--a Chinese concept for a worldwide pandemic . Swiss Med Wkly. 2006, 18, 136(7-8):103-13. “ 古代的哲学家们早已知道了健康的本质就是平衡,但其所代表的机理是复杂的,以至数千来,我们还一直在试图回答着同样的问题。” 引自 Aikawa M . The balance of power: the law of Yin and Yang in smooth muscle cell fate. Is YY1 a vascular protector? . Circ Res. 2007, 20, 101(2):111-3. “令人惊奇的是,这种古代的中医阴阳学说在探讨疾病是如何发生的,却现在被证实在分子水平上” 引自 Dai MS , Jin Y , Gallegos JR , et al. Balance of Yin and Yang: ubiquitylation- mediated regulation of p53 and c-Myc . Neoplasia. 2006,8(8):630-44. “阴阳概念提供了一个智慧的架构,它充分体现了中国人的科学思维,特别是在生物学和医学领域 。” 引自 Dutt T , Toh CH . The Yin-Yang of thrombin and activated protein C . Br J Haematol. 2008, 140(5):505-15. “届时我们将在细胞生物学的基础之上完全揭开动态阴阳的奥秘 。” 引自 Zhu X . Seeing the yin and yang in cell biology . Mol Biol Cell. 2010, 21(22): 3827-8.
学习计算机理论,却读到一些关于生物进化和意识这两大“随机过程”的一些文字,觉得生命真是伟大,真是奇妙。 如果你有幸进入大学的专业就是生命科学相关的,更是幸福了。呵呵。。 来自:Swarm Intelligence: Doug Hosknis (1995) has shown how the simplest behaviors of the simplest organisms in the animal kingdom can be shown to function as an optimization algorithm... Eshel Ben-Jacobs...argues that colonies of bacteria are able to communicate and even alter their genetic makeup in response to environmental challenges.... bacteria are able to organize into what is essentially a single, multicellular superorganism...(这还很值得进一步研究呢) It is surprsing to think that single-celled microbes might posses sophisticated intelligence-maybe it is just because they are so small, so removed from our perceptions... Perhaps the most extreme example of the intimate relation between the individual and the social group is found in the life of the lowly slime mold... 。。。 另:计算机算法,很多出于生物现象的启发。与其说是我们受启发而发明了一些新的算法,不如说我们的新智能是更为复杂更为高级智能的一个简单抄袭版本。 humble.... http://www.cyberlifespace.org/index.php?p=14a=viewr=88
2010年度生命科学十大论文撤销事件盘点 撤销给作者的研究造成打击,有的甚至给整个学术界带来极坏影响 近期刊登在《医学伦理学期刊》上的一项研究显示,在过去的十年中,至少有788篇学术文章遭遇撤销。撤销的原因有很多,有的文章是因为作者的学术不端行为而被撤,有的只是因为数据分析过于草率而被撤。不论如何,论文撤销给文章作者的研究造成打击,有的甚至给整个学术界都带来极坏的影响。 鉴于此,《科学家》网站于近日公布2010年十大论文撤销事件名单,该名单分别按照被撤销文章的引用率和被撤文章作者的知名度进行排名。 按文章引用率排名: 第五名:惠氏制药前雇员雌激素信号转导机制研究文章(引用次数(累计,下同):232次) 惠氏制药公司曾经的研究人员Boris Cheskis撰写的有关激素信号转导机制的两篇文章被认为数据不可靠而先后被撤。 科学网相关报道: 两篇高被引论文因数据不可靠遭撤回 第四名:美国梅奥医学中心发表的文章(引用次数:268次) 梅奥医学中心(Mayo Clinic)免疫学实验室的一名高级研究人员Suresh Radhakrishnan被发现数据造假而导致至少10篇论文遭到撤销。 科学网相关报道: 美国梅奥医学中心撤回十篇学术论文 第三名:美国杜克大学肿瘤学家有关乳腺癌的文章(引用次数:约300次) 杜克大学肿瘤学家Anil Potti发明的肿瘤分析方法被同行质疑而接受调查,最终被认定论文造假而被校方辞退。此外,该名科学家还被指控曾伪造简历。 科学网相关报道: 美国杜克大学一肿瘤学家因造假而引咎辞职 第二名:干细胞自发转变成癌细胞的文章(引用次数:317次) 发表在2005年《癌症研究》(Cancer Research)期刊上的一篇文章认为成体干细胞能自发转变为癌细胞,并暗示成体干细胞研究存在风险。该文章于今年8月被撤销。值得一提的是,据媒体报道,其他研究也得出了与该论文类似的结论,因而该论文结论被认为可能依然有效。 相关论文: Spontaneous Human Adult Stem Cell Transformation 第一名:《柳叶刀》有关麻风腮疫苗的文章(引用次数:640) 今年2月,《柳叶刀》正式撤销了一篇发表于1998年的研究论文,这篇论文的主要作者Andrew Wakefield指出,疫苗接种可能会导致孤独症。 科学网相关报道: 《柳叶刀》撤销麻风腮疫苗致不良反应论文 按文章作者知名度排名: 第五名:获得诺奖得主支持的反应组芯片文章 这篇发表在《科学》上的涉及反应组芯片的文章被指缺乏合适的实验对照而引发争议。文章作者所在单位为西班牙国家研究委员会(CSIC),包括诺奖得主理查德罗伯茨(Richard Roberts)在内的科学家表示支持该文章。《科学》杂志主编Bruce Alberts也为此发表了主编关注。 科学网相关报道: 《科学》要求作者撤销反应组芯片文章 第四名:知名基因治疗学家撤销文章 因数据存在错误且图表存在复制,美国西奈山医学院基因与细胞医学系创始人、主任胡流清(Savio Woo)撤销了6篇论文。 科学网相关报道: 国际著名基因治疗学家宣布收回四篇论文 美知名基因治疗学家胡流清再次撤回两篇论文 第三名:哈佛大学心理学家的文章 哈佛大学认定该校心理学教授、知名心理学家Marc Hauser存在学术不端行为,要求其离职一年,同时,其发表在《认知》(Cognition)期刊上的文章也被撤销。 科学网相关报道: 哈佛大学调查认定一教授存在学术不端行为 哈佛知名教授学术不端事件调查进展缓慢 第二名:哈佛医学院干细胞生物学家的文章 这篇今年发表在《自然》上的文章被发现数据和图片存在问题而遭撤销,文章作者之一Amy Wagers也在美国霍华德休斯医学研究院担任研究组组长。 科学网相关报道: 《自然》撤销一篇血液干细胞文章 第一名:诺奖得主琳达巴克的文章 诺贝尔奖获得者琳达巴克(Linda Buck)再次撤销了两篇文章,因为关键结论无法重现。 科学网相关报道: 诺贝尔奖得主再次撤销两篇论文 更多阅读 《科学家》网站相关报道(英文) http://news.sciencenet.cn/htmlnews/2010/12/241683.shtm http://www.the-scientist.com/news/display/57864/ Top retractions of 2010 A list of the biggest papers -- and scientists -- involved in retractions in the last year Retractions are a scientist's worst nightmare. In the last 10 years, at least 788 scientific papers have been pulled from the literature, according to a study published this year in the Journal of Medical Ethics . Whether it is a result of research misconduct, duplicate publication, or simply sloppy data analysis, a retracted paper can devastate a scientist's research, or even impact a whole scientific field. Here are 10 of the biggest retraction stories of the last year. Highly cited retractions Two papers on the mechanism of estrogen signaling were retracted after a former Wyeth employee, Boris Cheskis, was found to have unreliable data. The papers, published in PNAS and one in Molecular and Cellular Biology , were together cited 232 times. 4. 10+ retractions from one Mayo lab (268 citations) A senior research associate in an immunology lab at the Mayo Clinic in Rochester, Minnesota, was found guilty of falsifying nearly a decade's worth of data, resulting in at least 10 retractions and the cancellation of a clinical trial. The researcher, Suresh Radhakrishnan, did not admit to the misconduct, and subsequently authored an opinion article for The Scientist arguing that he, and others in his position, should not be blacklisted from science. The retracted publications accrued at least 268 citations. 3. I am a Rhodes Scholar...or not (perhaps up to 300 citations) Duke researcher Anil Potti posed as a Rhodes Scholar and apparently invented the statistical analyses used in his research on how breast cancer responds to chemotherapy. Last month, the Journal of Clinical Oncology pulled his 2007 paper, cited 50 times, and one of Potti's collaborators has requested the retraction of a 2006 Nature Medicine paper. The paper, cited 253 times, has already been the subject of two corrections, according to Retraction Watch . Potti has since stepped down from his position at Duke's Institute for Genome Sciences and Policy. 2. Stem cells turn cancerous? (317 citations) A 2005 Cancer Research paper, which suggested that adult stem cells can spontaneously turn into cancerous cells and held safety implications for the use of such cells in research, was retracted in August. The actual finding may still be valid, however, as several other studies have found similar results, according to Retraction Watch . The paper was cited 317 times. 1. There is no autism-vaccine link. We repeat, there is no autism-vaccine link (640 citations) In February, The Lancet pulled a controversial study published in 1998 by Andrew Wakefield and colleagues. Based on a sample of 12 children, the authors claimed to have found a link between autism and the widely used MMR (measles, mumps, and rubella) vaccination. Ten of the paper's 13 authors had already acknowledged some of the problems with the paper, publishing a retraction of an interpretation in 2004. The paper was cited 640 times. Most notable retractors A powerful new tool known as the reactome, developed by Manuel Ferrer of the CSIC Institute of Catalysis in Madrid and Peter Golyshin of Bangor University in the UK and collaborators, claimed to assess the functionality of hundreds of active proteins simultaneously, and stirred much excitement among the scientific community. But not long after its publication last October in Science , its validity was called into question. Though it has many supporters, including Nobel Laureate Richard Roberts of New England Biolabs, Science published an 'Editorial Expression of Concern in January of this year, and finally retracted the paper in November, after an investigating committee convened by CSIC found that it did not provide sufficient evidence for its conclusions. It was cited 18 times in its short tenure in the literature. 4. A whoops from gene therapy expert As a result of data irregularities and duplicated figures, six papers by notable gene therapy researcher Savio Woo of The Mount Sinai Medical Center were retracted this year, including two that claimed to have found potential breakthroughs -- even a possible cure -- for high-mortality diseases such as pancreatic cancer, according to Retraction Watch . The papers, published in Molecular , Therapy PNAS , the Journal of the National Cancer Institute and Human Gene Therapy , were cited a total of 60 times. 3. Cognition expert takes hard look at his data Well-known psychologist and author of the book Moral Minds Marc Hauser is taking a year of leave from his position at Harvard University after an internal investigation found evidence of scientific misconduct. The questionable data also led to the retraction of a 2002 Cognition paper, cited 38 times, which demonstrated that, like human infants, cotton-top tamarins have the capacity to generalize patterns. 2. Rising stem cell star stumbles Amy Wagers, a stem cell biologist at the Joslin Diabetes Center and assistant professor at Harvard Medical School, retracted a 2010 Nature paper, cited 13 times, that found factors in the blood of young mice could rejuvenate blood stem cells in older mice after discovering issues with the data, including a duplicated figure. A second paper, published in Blood and cited 28 times, is under review. Wagers, a Howard Hughes Medical Investigator, was dubbed a Scientist to Watch by The Scientist in 2008. While a postdoc in Irving Weissman's lab, she earned a reputation for putting other people's findings to the test. She is the author of a series of highly cited papers in the stem cell field, including a 2002 Science paper cited 828 times, a 2004 Nature paper cited 727 times, and a 2004 Cell paper cited 412 times. 1. More retractions from Nobelist Nobel Laureate Linda Buck retracted two papers from prominent journals because she was unable to reproduce key findings of experiments done by a former postdoc, according to a statement made by the Fred Hutchinson Cancer Research Center (FHCRC), where Buck worked at the time of the publications. The retractions, a 2006 Science paper and a 2005 PNAS paper, are tied to yet another Buck retraction -- a 2001 Nature paper that she pulled in 2008 for similar reasons. The three retracted papers have been cited 291 times. Related stories: High-profile paper retracted More retractions from Nobelist 10 retractions and counting 5. Researchers retract reactome Image: Wikimedia commons, Tttrung 5. The mechanism of estrogen signaling -- that wasn't (232 citations) Read more: Top retractions of 2010 - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/news/display/57864/#ixzz18QIZBNpc
由清华大学生命科学院院长 施一公 教授为通讯作者的论文 Structure and mechanism of the S component of a bacterial ECF transporter 在自然上发表。科学网以 研究发现能量耦合因子转运蛋白 为题作了报道。清华大学生科院、医学院、普林斯顿大学Lewis Thomas实验室等单位的研究人员报道了这种重要的能量耦合转运因子的蛋白结构。 使我特别感兴趣的是涉及能量耦合,而这一点恰恰就是我研究现代热力学的核心内容。相信这方面的问题是很多领域的一个发展方向。
Best Places to Work 2010: Academia - Top 15 US Academic Institutions Click here for a printable version (PDF) Rank Company Name No. Full-Time Life Science Researchers Federal Funding (in millions USD) Papers Published in the Life Sciences Citations per Paper*,** 10 Institute for Systems Biology 192 192 27.0 $27.0 612 612 76 76 1 Princeton University, Princeton 225 225*** 42.7 $42.7 3323 3,323 33.35 33.35 6 Trudeau Institute 39 39 10.0 $10.0 251 251 32 32 3 Van Andel Research Institute, Grand Rapids 127 127 5.9 $5.9 173 173 31.16 31.16 13 Stanford University, Stanford 826 826 338.7 $338.7**** 24571 24,571 30.69 30.6 2 St. Judes Children's Hospital, Memphis 837 837 66.5 $66.5 4493 4,493 26.98 26.98 12 Vanderbilt University, Nashville 645 645 370.0 $370.0 14335 14,335 24.64 24.64 5 The Samuel Roberts Noble Foundation, Ardmore 172 172 1.3 $1.3 297 297 24.6 24.6 15 University of Rochester, Rochester 1352 1,352 194.6 $194.6 10371 10,371 21.66 21.66 11 Georgia Institute of Technology 350 350 32.6 $32.6 1856 1,856 15.52 15.52 14 Michigan State University, East Lansing 950 950 240.0 $240.0 10869 10,869 14.83 14.83 7 Children's Hospital Boston, Boston 1191 1,191 119.1 $119.1 378 378 11.25 11.25 4 J. David Gladstone Institutes, San Francisco 330 330 34.0 $34.0 0 NA 0 NA 8 Calvin College 12 12 2.0 $2.0 0 NA 0 NA 9 University of Oklahoma Health Sciences Center, Oklahoma City 304 304 80.2 $80.2 0 NA 0 NA * From ISI Web of Knowledge Essential Science Indicators, which covers the period Jan 1,2000 to February 28,2010. ** Includes papers in Agricultural Sciences, Biology/Biochemistry, Clinical Medicine, Environment/Ecology, Immunology, Microbiology, Molecular Biology/Genetics, Neuroscience/Behavior, Pharmacology/Toxicology, and Plant Animal Science. *** Only researchers who received federal funding for life science research were counted. **** Figures are for the medical school only. Best Places to Work 2010: Academia - Top 10 International Academic Institutions Rank Company Name No. Full-Time Life Science Researchers Federal Funding (in millions USD) Papers Published in the Life Sciences Citations per Paper*,** 4 John Innes Centre, Norwich, United Kingdom 209 209 5 $33.8 1999 1,999 32.9 32.9 3 University of Dundee, Dundee, United Kingdom 650 650 2 $11.7 5994 5,994 24.65 24.65 5 Hebrew University of Jerusalem, Israel 346 346 6 $70.5 9914 9,914 16.34 16.34 8 University of Nottingham, United Kingdom 883 883 3 $30.9 8146 8,146 16.09 16.09 9 University of Copenhagen, Copenhagen, Denmark 388 388 0 *** 16515 16,515 15.65 15.65 10 Dalhousie University, Halifax, Canada 220 220 4 $31.3 5964 5,964 15.4 15.4 6 University of Alberta, Edmonton, Canada 910 910 9 $210.0 14917 14,917 15.32 15.32 2 Weizmann Institute of Science, Rehovot, Israel 100 100 1 $4.0 11873 11,873 15.29 15.29 1 The University of Queensland, Brisbane, Australia 1303 1,303 8 $106.0 14595 14,595 14.34 14.34 7 INRA, Versilles, France 610 610 7 $82.9 0 NA 0 NA * From ISI Web of Knowledge Essential Science Indicators, which covers the period Jan 1,2000 to February 28,2010. ** Includes papers in Agricultural Sciences, Biology/Biochemistry, Clinical Medicine, Environment/Ecology, Immunology, Microbiology, Molecular Biology/Genetics, Neuroscience/Behavior, Pharmacology/Toxicology, and Plant Animal Science. *** declined to report information. Read more: Best Places to Work 2010: Academia - Top Institutions http://www.the-scientist.com/fragments/bptw/2010/academia/bptw-academia-top.jsp#small#ixzz0sIacf8nt
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前面博文所述广义衰老学说是怎么炼成 之( 3 )夺命审稿经过生死抗争,终于过关斩将,凤凰涅槃,被美国《实验老年学》杂志作为标新立异之作刊登在 2005 年第六期的首页( Exp. Gerontol. 2005, 40(6); 455-465 . )。于是就有了后来笔者在衰老,千古之谜的终结文章里叙述的世界衰老研究领域的突然认知大转变。至此,衰老不再是生物学的不解之谜 在笔者的科学生涯中,曾喜欢把一句话经常放在嘴边:这一辈子争取为科学做成一件事 前面的半件 解读为什么衰老 。现在这前半件事既然玩成得差不多了,那么后面半件事如何抗衰老也许可以拿出来弄弄玩玩了。于是就有了与剑桥大学 千岁教授 Aubrey de Grey 之间的太极推手 笔者与 Aubrey 之间的交往应该是始于世纪之交的一个偶然机遇(准确年代最好得问 Aubrey )。因有事回瑞典林雪平大学医学院去找曾把我引入科学世界的博士导师 Ulf Brunk ,在走廊上遇到了一个大胡子,就是 Aubrey 。闲聊中知道他是来探讨衰老机理和体内随增龄蓄积的生物垃圾(老年色素形成)等问题(这个问题后来成为他抗衰老 7 大战役中 2 个大战役的内容)。因为笔者的导师 Brunk 教授是老年色素研究的欧洲大牌,所以他特地前来咨询。谈笑中他终于知道, Brunk 教授实验室真正在玩老年色素形成机制的化学白痴却是来自东土大唐的取经人 Great China ,大中 是耶。 1995 年那篇 Yin 与 Brunk 一道署名的羰基毒化衰老学说以及老年色素生化形成机理等综述其实是中国创造,只是 Made in Sweden 。(又:自从 Great China 回东土大唐当特聘教授以后, Brunk 实验室的哪些玩不转化学的师弟们只能膜拜顶礼所谓的垃圾堆积衰老学说了,参见后面的对话 de Grey )。 然而,令人哭笑不得的是当 Great China 回到东土大唐后因为大唐的评价标准等等原因,又只好试图请西洋菩萨保佑,共同发表衰老和抗衰老的 SCN 文章,于是有了下面的与千岁教授之间关于衰老和抗衰老的风云对话 将抗衰老工程策略介绍来中国 印大中给千岁教授奥布里 德格雷的信: 星期五 2006 年 8 月 4 日 亲爱的奥布里,感谢您授权让我们将你的抗衰老工程策略( SENS )介绍来中国。然而为了能真正成功地做 SENS ,我们首先需要对于衰老机理的正确地理解和解释。我个人认为,衰老过程的生物化学本质已经在我 ( 我们 ) 早期的文章里得到了深刻地阐述。随函附上我的一篇对衰老过程的生化本质的文章,请查阅。 希望能听到你的专家意见和评论。 如果你在阅读之后觉得有共识,我将乐意邀请你一同写文章向《自然》或者《科学》杂志投稿,标题可为 衰老,千古之谜的终结 。 问好! 大中 Aubrey 的答复:将抗衰老工程策略介绍来中国 星期六 2006 年 8 月 5 日 你好,大中,非常感谢发来的文章,昨晚读过。总的说来,我同意你的很多观点。的确, Brunk 教授及他的思想在我早期认识衰老机制的过程里起了非常重要的作用。通过与他交谈 ( 以及过后与亚历克斯 特曼的交谈 ) ,我开始构想抗衰老蓝图,尽管并非完全集中在对付线粒体的衰老改变。 我认为你我之间在衰老问题上的主要差别是,我认为尚无足够的证据表明突变在衰老过程中没有很大关系,因此我以为我们应该既防止基因突变又阻止蛋白质聚集和交联的增加。另外,我们也不能忘记细胞数目的增龄性变化 有些细胞逐渐走向死亡而不被替换, 例如在心脏或者黑质体中;有些细胞累积,例如不活泼免疫细胞等,尽管他们死去最好。 这些事件可能在衰老过程中也很重要 或许不象大多数组织中的蛋白质聚集物和交联结构那样 但是即使一两个身体组织中有那些成分,仍然将坏得足以杀死我们,因此我们不可忽视他们。 你我的之间的一个相对较次要的认识差别是,我认为区分衰老和疾病是一个孬想法。我喜欢认为老年退行性疾病是衰老过程中的一个晚期阶段。这意思也就是说,如果我们推迟身体各个组织的衰老也将推迟老年性疾病的发生,这也就是说衰老性疾病告诉了我们衰老包括了哪些方面的内涵。例如,如果我们说癌症是一种衰老相关的疾病而并非衰老的一部分,并因此决定我们能忽视在衰老过程中的染色体突变 但是那将是一个错误 ,因为我们若忽视了染色体的突变,我们将不能推迟癌症的发生,进而我们将全部死于癌症,那将很不令人满意! 请读我的一些概述文章并且告诉我你的想法。 http://www.sens.org/manu12.pdf http://www.sens.org/manu16.pdf http://www.sens.org/FHT-PP.pdf 祝祺! 奥布里 印大中给奥布里 德格雷的信 : 抗衰老与理解衰老本质 星期四, 2006 年 8 月 10 日 亲爱的奥布里, 感谢你的评论意见和坦率的讨论。我高兴地感到这是真正科学家之间的难得的高水平讨论。我从你的文章受益良多,并非常欣赏你在抗衰老研究领域极为宽广的知识面和睿智的抗衰老策略。 有关我曾经工作学习过的瑞典 Linkoping 大学,你可能已经注意到,虽然我出自(博士毕业于) Brunk 教授的研究室,我的观点与乌尔夫 布伦克和(师弟)亚历克斯 特曼的观点颇为不同。乌尔夫在亚细胞水平,以线粒体溶酶体为轴心研究衰老现象。亚历克斯则在近年提出了一个生物垃圾积累衰老理论,这甚至可以是一个 500 年前就被人推出的衰老学说 ( 开个玩笑 ) 。 我的衰老学术 语言 主要是化学语言,聚焦于生物化学的分子功能团的作用这个层面。这不是象基因组学和蛋白质组学这些当前时髦的概念,相反 在亚分子水平看衰老机制 。从这个角度看错综复杂的衰老过程,衰老的本质则变得显而易见,一目了然。 我很理解你我在衰老相关问题上的认知差别,这些差别合情合理,因为你的主攻目标是做 SENS (抗衰老),而我的首要目标是诠释衰老的真正机制,我称之为衰老过程的生理生化本质。毫无疑义,很多疾病与衰老相关,疾病 ( 象炎症和糖尿病等等 ) 可能加速人体衰老,反过来衰老也可能潜移默化导致疾病 ( 尤其是老年退行性疾病 ) 的产生。在我看来,在一个人能活到他的最大的寿命之前,全部衰老相关的疾病应该首当其冲地被有效地治疗。 ( 这可能使治疗癌症在你主题中变得极为重要,然而(癌变)在我的研究主题内只是诸多损伤的后果之一 ) 。 癌症是与衰老相关的最危险的疾病之一;不过,衰老过程中的其它老年退行性疾病,象动脉粥样硬化,老年痴呆症,糖尿病等与癌症一样有害。即使现代医学能够成功地限制癌症的发生,我们身体仍将面对与增龄相伴而来,并且无所不在的器官纤维化和蛋白质交联聚集 ( 例如皮肤,肺脏,血管,肝脏,肾脏,膀胱等器官和细胞的弹性纤维组织的硬化改变 ) 。 这就是我乐意称之为 真正衰老 或 生理性衰老 的身体变化。 我当然同意细胞数目随龄减少可能是寿命长短的一个制约因子。然而我的主要兴趣在细胞 为什么死 和 什么 使它们死。通过研究大量的生化副反应,我认识到我们已经查明了导致生物体损伤的主要上游起因,包括第一原因,第二原因等。第一伤害原因主要是外因 ( 像氧自由基 ) 这类伤害一般为可修理性伤害 ( 或疾病性伤害,身体组织往往无法忍受这类伤害 ) ;第二伤害原因,正如我 10 年以前便已明确提出的,主要指羰基应激类交联性损伤积累,而今已经被认识到是最关键的衰老性生化大分子改变 ,因为这是一大类不能被修复的永久性熵增改变。 回到抗衰老( SENS ),我相信当我们真正认清衰老过程的本质之日,便是能制定正确的抗衰老策略之时。如果你认为我们的讨论确有意思,我将期望人类的抗衰老实践会更有些意思了。 致最好的问候! 大中 TJ Lyons, Glycation, Carbonyl Stress, EAGLEs, and the Vascular Complications of Diabetes. Seminals in Vascular Medicine Vol 2 (2). 2002, 175-189. The glycation hypothesis has developed over the past 30 years, evolving gradually into a carbonyl stress hypothesis ( 经过 30 年的发展,非酶糖基化假说逐渐衍进为羰基应激假说 ) 奥布里 德格雷的回信:抗衰老与理解衰老本质 星期四, 2006 , 8 月 10 日 你好,大中, 感谢你精致的解答。是的,你说的很对,细胞走向死亡,一定是有某些因素使它们发生了病变,而当他们本该死亡又奋力抵抗也一定是有某些因子使然。 因此,如果我们真的能如你所说在亚分子水平处理细胞内部的种种麻烦,我们将能 ( 虽然间接地,但是有效地! ) 应对细胞死亡和细胞拒绝死亡的诸多问题。或许全面思考这些问题的最科学理性的策略是时时注意,让细胞生存或死亡均与抗衰老息息相关,只是有时这一个策略简便易行,有时却是另一个。 祝祺! 奥布里 (信件英文原文) To make SENS in China Friday, August 4, 2006 8:33PM Dear Aubrey, Thanks for your courtesy to let us introduce your SENS to China. To go straight forward to make SENS, we need to have a right explanation on the aging mechanisms. Personally, I believe the biochemical process (essence) of aging has been already highlighted in my (our) early works. Attached please find one of my recent papers relevant to the key biochemistry of aging. Your expertise and comments are greatly appreciated. If you have a common sense after your reading, Id like to invite you to together write a paper with a title such as Aging, time to draw resolution to the journal like Nature or Science. Regards! Dazhong Re: To make SENS in China Saturday,August5,20063:52PM Hi Dazhong, Many thanks for sending this paper. I read it last night. In general I agree very much with what you say. Indeed, Ulf played a very important part in my early thinking about aging: it was through talking to him (and later to Alex Terman) that I began to formulate a model of how to address aging that did not centre wholly on mitochondrial mutations. I think the main difference between your position and mine is that I think there is still not enough evidence to be sure that mutations don't matter much in aging, so I think we should attack those as well as attacking the buildup of aggregates and crosslinks. We must also not forget that there are changes in cell number cells dying and not being replaced, such as in the heart or the substantia nigra, and cells accumulating when it would be better if they died, such as inactive immune cells. These things may also matter in aging maybe not so much as aggregates and crosslinks in most tissues, but even if there are only one or two tissues where these things matter more than aggregates or crosslinks, that would still be bad enough to kill us, so we must not ignore them. A more minor difference between your position and mine is that I think it is a bad idea to distinguish aging from disease. I prefer to think of age-related diseases as some of the later stages of aging. That means, if we postpone all aspects of aging we will also postpone the diseases of aging, but it also means that the diseases of aging can tell us what aspects of aging we should include. For example, if we say that cancer is an age-related disease and not part of aging, we may decide that we can ignore chromosomal mutations in aging but that would be wrong, because if we ignore those mutations we will not delay cancer and we'll all die of cancer, which would be ... unsatisfactory! Please read some of my overview papers and tell me what you think. http://www.sens.org/manu12.pdf http://www.sens.org/manu16.pdf http://www.sens.org/FHT-PP.pdf Cheers, Aubrey To make SENS vs to understand essence Thursday,August10,20069:35AM Dear Aubrey , Thanks for your comments and frank discussion. I feel this is a rear communication between real scientists and I enjoy the high level of discussion. I learned a lot from your papers and admire very much your broad scientific knowledge and intelligent strategies towards anti-aging. Referring to Linkoping you may already notice, although I come from Ulfs lab, my perspective is quite different from those of Ulf Brunk and Alex Terman. Ulf is looking the aging problem at the sub-cellular lever, the mitochondria-lysosome axis. Alex is talking an aging theory of biological garbage accumulation which could be a theory of 500 years ago (a joke). My language is mostly chemical language, focusing on functional groups of biochemical molecules. This is not the currently popular concept, like genomics or proteomics instead its looking at the aging mechanisms at a sub-molecular level . From this angle the complicated aging process then becomes simplified and obvious (transparent). I understand very well the differences between yours and mine and it is very reasonable. Because your intension is to make SENS, whereas mine is to explain the real aging, the physiological aging process, which I call the ESSENCE of aging. It is true that many diseases are aging dependent, namely diseases can accelerate aging process (like inflammation, diabetes etc), aging may in turn underlie diseases (particularly chronic diseases). In my opinion, all aging-related diseases should be effectively treated, for the first hand, before a person can live to his Maximum Life-span. (This may make treating cancer become so important in your subject, although its only one of the damage-related consequences in my subject). Cancer is one of the most dangerous aging-related diseases however, its just as harmful as atherosclerosis, Alzheimer disease, diabetes mellitus and other chronic diseases during aging. Even modern medicine can successfully restrict cancer our body may still face overwhelming fibrosis and/or protein aggregation developing in almost every organ (e.g. skin, lung, blood vessel, liver, kidney, bladder) in our body. This is what Id like to call the real aging, the physiological aging. I certainly agree that cell number is decline during aging which could be the limit of a life. But my interest is mainly on Why the cells die and What make them die. Through studying biochemical side-reactions, I understood we have already found out the main causes, the primary and the secondary upstream causes. The primary causes or damages are basically extrinsic (like free radicals) and mainly repairable (intolerable) the secondary, the carbonyl stress, as I pinpointed ten years ago, has become the most critical today mainly because it is irreparable. Come back to SENS, I believe we can make right strategies when we understand the ESSENCE. If you think my discussion do make sense to you, Id expect that human beings may make better SENS in the future. Best Regards! Dazhong TJ Lyons, Glycation, Carbonyl Stress, EAGLEs, and the Vascular Complications of Diabetes. Seminals in Vascular Medicine Vol 2 (2). 2002, 175-189. Re: To make SENS vs to understand essence Thursday,August10,20067:35PM Hi Dazhong, Thanks for this elaboration. Yes, you are right that when cells die there must be something that makes them sick, and conversely when cell refuse to die when they should there must also be something that makes them do that. Therefore, if we can really address internal cellular problems, which are mostly sub-molecular as you say, we can (indirectly, but effectively!) fix the cell death and cell death-resistance problems. Maybe the best way to look at the overall problem is to keep in mind always that both of these approaches can work, and sometimes one will be easier, sometimes the other. Cheers, Aubrey
现代生物科学关于老年色素研究的第一本国际权威著作由美籍印度学者主编,该学者从此在该领域,声名鹊起,独霸一方。关于老年色素研究的系列国际会议连续开了六届。作为该领域另一位 权威 教授,瑞典国家医学会副主席乌尔夫-波龙克的学生,有幸出席了最后几届该系列会议,踏及世界诸国,交会各路豪杰,将老年色素的生化形成机理写成了我的博士论文,也写成了一些集大成综述(综述发表后该系列国际会议从此没有再开)。我们的工作为老年色素研究竖立了一个近乎结论的里程碑,然而也无意中夺取了别人头顶耀眼的光环。从此在该领域,中国人不再无足轻重,中国人成为竞争对手,中国崛起与中国威胁论一起被提上了议事日程。在当年集大成综述被审稿的过程中,我隐约感到了科学竞争的残酷,一句该领域的常识用语老年色素是生物体衰老的重要指标被指责为盗用了 xxx 的原创思想 十多年后,当我们的广义衰老学说又落在了 xxx 国际权威学术大师的手中,其命运可想而之。 如果说审稿大师超一流的夺命否定并没有直截了当的刀起头落,然而在故意歪解和近乎无赖(也许是无知)的审稿评论的字里行间随处都可以感觉到 泰山压顶式的刀光剑影。 无奈,只有一件事可做据理力争! 或者在烈火中凤凰涅槃,或者在烈火中化为灰烬 (先给英文原文 , 中文译文在后) 《 Experimental Gerontology 》杂志编辑部来信: Dear Dr. Yin, We have now received the comments to your article mentioned above from the referees. Could you please comment on them and let us have your reply as soon as possible? Reviewer 1: The review authored by Dazhong Yin and Keji Chen entitled The Essential Mechanisms of Aging: Irreparable Damage Accumulation of Biochemical Side-Reactions argues for a mechanism of aging. As stated by the authors: In summary, direct DNA damage and mutation in comparison with protein impairments are either less important or disease-related, which may not be the crucial issue of physiological aging of higher animals. Whereas biological systems of anti-stresses, protein turnover, metabolisms and homeostasis regulated by genetic network are the key elements of aging mechanisms, various irreparable accumulations of protein alterations induced by spontaneous biological side-reactions turn out to be the center of aging biochemistry. The authors state that there are numerous hypotheses of aging. They conclude that protein cross-linking brought about by free radical derived mechanisms is the most important determinant of normal aging. Unfortunately, this conclusion is neither novel nor is it supported by literature precedence. While cross-linked forms of protein do appear to accumulate during aging the functional consequence of this accumulation is largely unknown. The authors simply assume that this in turn results in deranged function. In addition, the authors do not make a convincing argument for why other theories can be excluded other than referencing these claims with articles that do not support their contention. In short, this review does little more than repackage a hypothesis that has been stated before and does little to convince the reader of its validity. Reviewer 2: This is a clearly written review of the many factors that are associated with the aging process and merits publication. The only issue that might give a wrong impression is the statement (top 3 lines on page 11) that protein degradation is a result rather than a cause of aging. It is well established that oxidation of proteins renders them susceptible to proteolytic degradation. Accordingly, a decline with age in the levels of proteases that degrade oxidized proteins may lead to the accumulation of oxidatively modified proteins, which the author points out is an important function in aging. An error on page 23, line 9: A basic notion... not An basic notion.... 我们给编辑部的回复: Dear Dr. Beatrix, Thank you very much for facilitating the publication of our review paper The essential mechanisms of aging: irreparable damage accumulation of biochemical side-reactions ( Ms.#7078) and sending us the reviewers comments on March 22, 2005. We are delighted to read that the reviewers have confirmed positively our scientific and literature descriptions on current status of aging studies (as this topic covered an enormous huge realm, its very hard to command all relevant fields) just as the 1 st Reviewer concluded in his comments this review does little more than repackage a hypothesis that has been stated before . Referring to reviewers comments we wish to present our discussions as follows: 1) The reviewer 1 stated: They conclude that protein cross-linking brought about by free radical derived mechanisms is the most important determinant of normal aging. We regret to say this is a misunderstanding of our proposed theory. The free radical mechanisms, in our opinion, is narrow-minded (as we have already clarified in our Ms.) in explaining aging mechanisms. Our key issue about the causes of aging (not yet the aging mechanisms) are biological side-reactions, particularly those side-reactions related to biological energy metabolisms. For instance, the diabetes accelerated glycation and related carbonyl stress may also be very critical for physiological aging alterations. 2) The reviewer 1 continued: Unfortunately, this conclusion is neither novel nor is it supported by literature precedence. The free radical mechanisms of aging is surely not novel (and even is scientifically problematic), but the biological side-reactions, the entropy biochemistry of aging, the focusing on process beyond causes, the direct DNA damages and mutations are mainly disease-related , and the carbonyl stress may be one of the most crucial culprits of aging are all our original contributions in the review as well as in the scientific field related. 3) The reviewer 1 also stated: While cross-linked forms of protein do appear to accumulate during aging the functional consequence of this accumulation is largely unknown. It is true that the functional consequence of intra-cellular accumulates, such as lipofuscin, is largely unknown. However, a variety of other crosslinkage-related functional retardations are well studied and some examples are listed below: a) opacity of lens and further cataract formation due to cross-linked crystallins b) crosslinkage of elastic tissues (e.g. collagen in blood vessels) during aging c) increase of AGEs (GOLD, MOLD, CML, pentosidine et al.) and ALEs d) cellular membrane and cytoskeleton rigidity and in-solubility e) increased thickness of glomerular basement membrane f) multiple fibrosis during aging (speeded by inflammation) g) stiffening of joints, decline of lung elasticity, et al. h) and probably atherosclerosis and amyloid formation due to deficient clearance Moreover, organ-specific and disease-accelerated protein alterations may largely be viewed as speeded aging-related changes (when repairing is disturbed or inhibited). The author would also refer to a recent review by Grune and Davies (2004) IJBCB, 36: 2519-2530 for obtaining more information about protein aggregation during aging. 4) Finally, the reviewer 1 wrote: In addition, the authors do not make a convincing argument for why other theories can be excluded. this review does little more than repackage a hypothesis that has been stated before and does little to convince the reader of its validity. We wonder why reviewer 1 suggested us to exclude the other theories and tended to overlook the validity of our hypothesis as well. Our theory has evolved from those principal aging hypotheses and many of them are our solid foundation. We are standing on a stage supported by numerous scientific achievements in the related fields, so they are not going to be excluded arbitrary rather being interpreted properly. A specific progress we made is that we went down to a sub-molecular level and extracted the essential (general) biochemistry behind the aging process. This is obviously much more than a simple repackage (also see point 2), rather approaching (or revealing?) a resolution of the ever confusing mechanism of aging. 5) The reviewer 2 thinks that might give a wrong impression is the statement that protein degradation is a result rather than a cause of aging. It is well established that oxidation of proteins renders them susceptible to proteolytic degradation. We believe that protein degradation is neither a result nor a cause of aging. Protein degradation (for an adult), in our opinion, is mainly for routing restorative turnover or repairing of damages due to biological side-reactions. We fully agree with further statement by reviewer 2: A decline with age in the levels of proteases that degrade oxidized proteins may lead to the accumulation of oxidatively modified proteins . We wish to acknowledge our sincere thanks for his kind suggestion on an error correction on page 23. We hope these discussion answered the reviewers questions clearly and correctly. Best Regards ! Dazhong Yin Professor, Chairman of the Aging Biochem Lab Hunan Normal University 实验老年学杂志编辑部来信(译文) : 亲爱的 印 博士, 我们现在已经得到了审稿人对你们的综述文章的意见。 请对他们的意见作出评论,并且尽快给我们回复。 审稿专家 1 : 印大中和陈可冀的综述 衰老机制本质:生物化学副反应损伤的失修性累积 提出了一个衰老机制。 如作者所说总之,尽管直接的 DNA 损伤和突变与种种老年性疾病息息相关,但与衰老过程中生理性的无所不在的蛋白质损变的积累相比, DNA 损伤的影响则为次重要或主要呈现病理特征。尽管由遗传所调控的抗应激、蛋白质更新、新陈代谢和机体稳态等基因网络系统扮演着高等动物衰老的先天性制约因子的角色,而自发进行的生化副反应导致的机体失修性改变则为环境相关因素导致衰老的主要表现形式。 作者罗列了众多衰老假说。 他们认为自由基导致的蛋白质交联是正常老化最重要的决定因素。 令人遗憾,这个结论既不新鲜也没有文献的支持。蛋白质的交联确实似乎在衰老过程中积累,但这个积累的后果基本上未知。作者仅仅是假设该积累造成了机体功能的紊乱。另外,作者没有提出可信的论点来说明为什么其他衰老理论可以被排除。简而言之,这篇综述仅仅是在简单重新包装以前已经被阐明的诸多衰老假说,很难能使读者信服它的价值。 审稿专家 2 : 该综述写作清楚,给出了与衰老过程相关的诸多因素,值得发表。唯一可能产生错误印象的地方是说蛋白质降解是衰老的一个结果而不是衰老的起因 ( 在第 11 页上的前 3 条线 ) 。 然而确定的事实是蛋白质的氧化使得它们更易受到降解。因此,蛋白酶水平增龄性下降可能导致蛋白质的氧化性损伤累积,正如作者指出那是衰老的一个重要的表 象。 另外,在第 23 页第 9 行: A basic notion... 不是 An basic notion... . 我们的回复(译文) : 非常感谢协助我们的综述文章衰老机制本质:生物化学副反应损伤的失修性累积 (#7078) 的发表进程和寄给我们审稿专家( 2005 年 3 月 22 日 )的意见。我们很高兴注意到审稿专家对我们关于衰老研究的科学描述和文献知识的认可 ( 衰老问题涉及到非常巨大的研究领域,贯通掌握相关的学科领域本身就已非常难能可贵 ) 。正象第 1 审稿专家在他的意见里断定: 这篇综述将过往的种种理论重新装配成了一个新假说 . 参照审稿专家的意见,我们提出讨论如下: 1) 审稿专家 1 说: 作者断定自由基伤害造成的蛋白质交联是最重要的正常衰老的决定因素 。我们遗憾地说这是对我们提出的衰老理论的一个误读。我们认为,以自由基损伤解释衰老机制是狭隘的 ( 我们已经在综述里阐明 ) 。我们关于衰老起因 ( 且不谈衰老的机制 ) 的关键词是 生化副反应 ,特别是那些与生物能量代谢有关的生化副反应。例如,糖尿病加速的非酶糖基化过程以及与之相关的羰基应激,也可以是生理性衰老改变的重要原因。 2) 审稿专家 1 继续说道: 令人遗憾,这个结论(自由基损伤蛋白质造成交联衰老)既不新鲜也没有文献的支持 。我们同意:衰老的自由基机制肯定不是新理念 ( 并且在科学上很成问题 ) 。 不过 生化副反应 , 衰老的熵增生物化学 , 在衰老原因之外关注衰老过程 , 直接的 DNA 损害和突变主要与老年病有关 , 以及羰基应激可能是生物体老化最主要的罪犯 等理念都是我们在本文中的原创,同样也是对于相关科学领域的原创性贡献。 3) 审稿专家 1 又说: 蛋白质的交联确实似乎在衰老过程中积累,但这个积累的后果基本上未知 。可以认为这些交联蓄积的后果在细胞内部还基本不明,例如脂褐素对细胞功能的影响基本未知。然而,大量其它与蛋白质交联相关的机体功能退变已被研究得非常深入,现举例如下: a) 由于眼球晶体蛋白交联造成的眼球晶体混浊和白内障的形成 b) 伴随衰老出现的弹性蛋白及组织的交联硬化 ( 例如在血管里的胶原 ) c) 与龄俱增的 AGEs (GOLD, MOLD, CML, pentosidine) and ALEs 等 d) 随增龄而出现的细胞膜和细胞骨架的刚性增加和溶解度下降 e) 伴随衰老进程出现的肾小球基底膜增厚 f) 在老化期间越来越普遍的器官纤维化 ( 被炎症加速 ) g) 伴随衰老出现的关节变硬和肺组织的弹性下降等等 h) 以及也许由于代谢产物清理缺陷而形成的动脉粥样硬化和淀粉样蛋白形成 另外,有器官特异性的和被疾病加速的蛋白质结构改变也基本上可被认为是被加速了的衰老表象 ( 一旦机体的修复机能被扰乱或者被抑制 ) 。 在此,作者也提请大家注意参考 Grune 和 Davies 最新发表的综述 (2004) IJBCB , 36 ; 2519-2530 以获得更多的关于衰老过程中蛋白质聚集变性的资料。 4) 最后,审稿专家 1 写到: 另外,作者没有提出可信的论点来说明为什么其他衰老理论可以被排除。简而言之,这篇综述仅仅是在简单重新包装以前已经被阐明的诸多衰老假说,很难能使读者信服它的价值 。我们觉得奇怪为什么审稿专家 1 建议我们否定其它衰老理论的价值并且倾向于也忽略我们的学说的价值。我们的理论从那些当今最主要的衰老学说中逐步衍生发展而成,它们中的许多理论是我们衰老学说的坚实基础。我们站在一个有着很多科学成就支持的平台上,因此那些学说不会被粗暴地排除而只会被正确地解读。我们的衰老学说取得的独特的进步是我们走入了一个新水平亚分子水平,并且抽象出了潜藏在衰老过程背后的基本的 ( 广义的 ) 生物化学本质。这远远超过 ( 也可参见本回答中的第 2 点 ) 审稿专家 1 所说的简单重新包装;相反,接近 ( 或揭示 ) 了一个至今仍无比混乱的衰老机制的极佳答案。 5) 审稿专家 2 说:该文 唯一可能产生错误印象的地方是说蛋白质降解是衰老的一个结果而不是衰老的起因,然而确定的事实是蛋白质的氧化使得它们更易受到降解。 我们认为,蛋白质被降解既不是衰老的结果也不是衰老的原因。在我们看来,蛋白质降解 ( 对于成年人来说 ) 主要是机体对于日常生化副反应损害的修复和更新。我们完全赞成审稿专家 2 的观点: 蛋白酶水平增龄性下降可能导致蛋白质的氧化性损伤累积。 ,我们诚挚感谢审稿专家 2 关于改正在第 23 页上的一项错误的友好建议。 我们希望这些讨论清楚而正确回答了审稿专家的问题。 最好的祝福! 印大中 湖南师范大学 教授, 衰老生化研究室 主任
美国衰老研究在世界上既引领时代潮流,又宏大包罗万象。当今世界,没有哪个国家的衰老研究处于如此高、大、全的状态,其它英语母语国家均因国力人力不足,只能有所为而有所不为。美国老年学会是世界老年学界的大哥大,美国老年学会主席亦足以堪称老年学界的美军司令,或者称其为学术界的武林大师或一流高手应该不算夸大。美国老年学会主 席 Yu 教授 1992 年(在我点破羰氨交联共性数月之后)提出合并自由基氧化和非酶糖基化衰老学说,然而此后两个衰老学说一直貌合神离。想当年我前往该实验室探个究竟,主 席 先生正在接电话,顺便在电话里把我一顿藐视:正在作一个无意义的接见。于是心中暗暗立志:一定要争一口气,改变这次接见的意义! 十多年之后,当我写成广义衰老学说,又征求当年的主 席 先生(此时已成为学术好友)的意见时,这位武林一流高手再也没有轻蔑其词,而是大袖一挥抽出科学宝剑 下面请看广义衰老学说是怎么炼成的 之2华山论剑(英文原文附后): 美国老年学会主席 Yu 教授的信 : 我为这个迟到的答复道歉。 我一直在为我怎样能帮助你写这篇文章深思。我很欣赏你对发表一篇将对老年学专家和衰老研究产生重大影响的文章所作的努力。我对此不仅毫无疑义,实际上非常支持。如你来信的开头所述,你希望在《自然》或者《科学》那样的杂志发表它。坦白地说,我不能确信,因为那两本杂志对于一篇没有发现新的衰老基因或者一组延长寿命的基因的衰老机制的文章,甚至将没有兴趣进行审稿,因为我们知道,这些杂志的政策是向文章的时髦度倾斜,而不是向硬科学。为了如你所说对衰老的机理提出结论性的解释,你必须有一个统一的机制解释包括大部分 ( 如果不是全部 ) 关于衰老的现有的理论和假说。我的问题进而便是羰基应激衰老学说能否胜任如此重任?或者它仅仅是另一假说?我以为在其他人眼中,该学说并不比其他基于损害的衰老理论有何不同,为此已有太多有关衰老的文献和理论。因此,在开始撰写之前,我们必须达到一个共识, 那就是你的学说将为何并且如何统一我们今天知道的全部衰老机制 。我想,如果你能让我信服,然后我将相信这是一篇值得写的文章。 印 博士,请别误会,我所作的一切,旨在试图助你一臂之力! 保持联系! Byung Pal Yu 2483 Via Del Aguacate Fallbrook, CA 92028 给 Yu 教授的回信 : 亲爱的 Yu 教授,我为迟到和实际上较有难度的回信抱歉。我反复阅读了您的非常诚恳的来信,并且深深地被您的直言不讳而感动。关于衰老研究领域当今的困惑和混乱,的确如您所述。这样的混乱的形势可能主要是因为衰老的问题博大精深和包罗万象进而需要哲学地综合地深思熟虑。眼下,我也许不能一下子就用我的衰老理论说服您,不过,我可以告诉您,我怎样说服了我自己而使我的思维到达了今天的状态。 由于我的受教育经历,我有幸提出了衰老的羰基毒化假说并且坚持至今。我的大学本科是在几乎纯(理科的)化学学科方面主修了 5 年,然后致力于食品的加工储藏(类似食品老化)的有关工作,进而在我的博士学习期间研究和揭示了老年色素形成的生物化学机制。这样知识背景,让我的思维产生了一个学术优势,即种种生物学现象在我的眼中很容易被显示成为了化学分子键和功能团(电子相互作用)的生动的图像过程。当我看见自由基生物化学反应和非酶糖基化生物化学反应时,我立即从化学键及功能团反应的角度看出了它们的异同。我在 1992 年的一篇文章里一针见血地指出了它们在自由基氧化和非酶糖基化衰老过程中的共性特征,就在同年,您和 Kristal 提出了合并这两个衰老学说。在分子水平,这两个衰老理论是与能量代谢相关的生化过程的最重要的衰老的理论。根据我的食品科学知识,我深知这两个过程也是食品老化的最关键的生物化学起因,因为在食品贮存期间,尽管微生物作用和酶催化也是食物败坏变质的重要因素,但它们(后两者)不是自发产生的生物化学反应过程。 自由基氧化和非酶糖基化衰老过程是至今我们发现的两个,并且是最关键的两个,能够自发进行的毒性(分子水平的)衰老生化过程。这个过程其实隐含于 ( 大多数衰老理论植根其中的 ) 各个生物学水平,包括细胞水平,器官 / 系统水平和整体动物水平。有趣的是,我偶然意识到这两个衰老的理论有一个共同的毒化过程,即羰基毒化过程!这个过程现在一般被公认为二级衰老起因。 在开始时,我没敢说羰基毒化是衰老的机制的关键,因为在过去二十年期间,分子遗传学专家不断地报告发现衰老相关基因。我需要首先理解他们所报道的衰老基因的精确含意。当越来越多的这种基因在低等动物体内发现后,我们清楚地知道了它们在生命过程的病理和生理状态中的功能。例如 sir2 , SIRT1 ,就是与能量代谢相关的基因,这样的基因和基因群对动物体机能的调控实际上影响了能量代谢或其它诸多系统,象应激保护系统,修理恢复系统和自动平衡系统等等。因此我们现在可以十分自信地说,动物体内的数以万计的遗传因子是以一种合作的方式通过基因组成的网系统调节着各种动物的寿命。 基于上述讨论,环境伤害对先天遗传形成的机体地挑战则无疑成为导致衰老的关键的因素。至此,我仍不敢断言羰基毒化是衰老过程的核心,因为氧自由基对机体的损伤如此强大,并且无所不在,几乎与绝大多数疾病密切相关。其实我们都明白疾病加速衰老这个道理。这就是为什么我在最近的一篇文章中指出生化副反应是广义的衰老起因。但是我们现在面临的一个难题是如何关联生化副反应损伤与衰老的速率,或最大寿命 (MLS) ,我们从未找到它们之间正相关的有力证据。我们含糊地知道环境伤害和衰老变化(或 MLS )之间隔了一堵高墙,一堵机体赖以生存的具有防护维修功能的万里长城。绝大多数衰老 / 抗衰老的研究只在墙的一边瞎扑腾,却期望找出墙的另一边发生的真正衰老过程! 损伤 修复(之墙) = 衰老 (译者根据以前的文章通讯补充) 到底墙的另一边发生了什么? 所谓真正衰老过程?衰老相关的改变到底主要有哪些? 实际上,我们早已不是这个领域的外行,我们已经拥有了大量的资料和信息。我们已经从老年退行性疾病和在尸体解剖研究中获得了许多知识,无论在器官水平还是在细胞水平,特别是在分子水平的衰老研究中,例如皮肤起皱,血管硬化,老年斑形成,种种病理生理相关的器官纤维化,以及我所熟悉的白内障和脂褐素的增龄性累积等等。这里,就在这里,我们看见了所谓真正衰老,诸多衰老相关的蛋白质的改变 ( 令人吃惊,与基因很少有关 ) ,竟然,不饱和羰基化合物造成的交联在其间起着关键的作用,并且恰到好处地给熵增衰老理论提供了具体的生化诠释。 由于许多衰老起因(如氧化应激,虽然作为衰老性改变的间接因子,或为外因)在加速衰老(生物体本身的分子改变)的过程中均扮演了很重要的角色,我原本并没打算以羰基毒化理论的优点批判 ( 或者取代 ) 其他重要的理论,直到最近我才被迫思考这件事。现在我愿更清楚地说明, 羰基毒化衰老理论的最大突破旨在从亚分子水平观察和思考衰老过程的变化。 换句话说, 从分子功能团的视角思考和诠释衰老之谜 !在具代表性的主要几类生物大分子结构中,例如脂类,碳水化合物,蛋白质和核酸,仅存在有限的几种亚分子功能基团(例如 -COH , -CHO , -COOH , -NH , -SH ,等等),它们的生物化学反应特性均在现代科学的理解和掌握之中。从亚分子水平思考衰老原理,似可认为是羰基毒化理论给我们彰显的一个崭新地思维方式。我相信从这观察视角 / 水平, 我们能够最终统一绝大部分 ( 如果不是全部的 ) 现有的衰老的理论 。 最后,考虑到限制饮食延寿(或者肥胖短寿)的机理,一个简单的解释可能就是由于对我们的消化系统的解毒能力有限(能力饱和)。我们的消化体系对食品中的羰基化合物的解毒至关重要,例如仅谷胱甘肽转移酶( GSHT ,且不说 P-450 的解毒功效)已经占了肝脏可溶性蛋白质总量的 3-5% ( Yu 教授为国际限食抗衰老研究的 权威 教授,译者注)。 我希望上述关于羰基毒化衰老机理的思维发展过程,可以帮助您理解我的手稿之外的一些情况。 我希望这些信息可能有用,并且没有浪费您宝贵的时间,顺致圣诞和新年的最好祝愿! 大中 ( 英文原文 ) Dear Dr. Yin: I apologize for this belated reply. I have been thinking hard for how I couldhelp you out with MS writing. I appreciate that you are eager to publish a paper that will have a great impact on the minds of gerontologists and the aging literature. And I have no problem with the intent, and in fact Id support the idea. As you stated at the beginning, you like to have it published in something like the Nature or Science. Frankly, I am not sure that short of discovery of aging mechanism, or a aging gene or a group of genes that are involved in life extension, those two journals would not be interested in even reviewing the type of the MS you are writing because as we know their policy is slanted toward to popularism among the reader rather than hard science. In order to create a impact on the aging literature and/or draw a resolution as you said, you have to have a unified mechanism that encompasses most, if not all, existing hypotheses and theories of aging. So my question is then that can the carbonyl toxification of aging be capable of doing that, or is it just another hypothesis? I am afraid that to others eyes, it is no different than other damage-based hypotheses, for which too many are already in the aging literature. So, before starting to writing, we have to come to some resolution and understanding on the fundamentals of your proposal as to why and how it can unifying all aging mechanisms as we know today . I think that If you could convenience me, then I believe such a paper worth writing. Dr. Yin, please dont misunderstand me, I am just trying to help you more objectively. Keep in touch. Byung Pal Yu Dear Professor Yu, I am sorry for the slow and actually quite difficult correspondence. I read over your very honest letter again and deeply moved by your sincerity. Your descriptions about the current confusions of aging are true in scientific society in the field. Such chaotic situation may be mainly because of that the aging problem is too extensive and comprehensive and need collective philosophical pondering. At this time I may not be able to convince you with my aging hypothesis, however, Id like to tell you how I convinced myself and reached current state. I happened to propose and stick to the carbonyl stress hypothesis of aging partly due to my educational background. I was majored almost in the subject of pure (theoretical) chemistry for 5 years, and then worked through food reservation (a sort of food aging), and came up with the study of biochemical mechanisms of age pigment formation (during my Ph.D. study). Such education built an advantage that what so ever biological phenomena appear to me may easily turn to be pictures of chemical (molecular) bonding process. When I see free radical biochemistry and glycation biochemistry I see immediately their similarities and differences as I pinpointed in a paper in 1992, the same year you and Kristal combined the two aging theories. At the molecular level these two aging theories are the most important aging theories relating with the energy consumption process. With my food reservation knowledge, I understood that these two processes are also the most critical biochemistry of food aging, besides microbial and enzymatic deteriorations during food storage, which (the latter two) are not spontaneous chemical processes. The oxidative and glycative stresses are two, and the only two, crucial spontaneous deleterious biochemical aging causes (at molecular level ) that we can find up to date, and they are implied at all the other biological levels, including cellular level , organ/system level and the whole animal level (in which most other aging theories rooting out). Interestingly, I realized by chance that these two aging theories have a common toxification process, namely, the carbonyl stress process! These process is now generally agreed as a secondary aging cause. At beginning, I did not dare to say the carbonyl stress is the very key of aging mechanisms because genetic scientists keep on reporting aging-associated genes during the past two decades. I need to understand what they are talking about and the exact meaning behind their findings. When more and more such kind of genes have been discovered in lower animals, we see clear their functions which are scattered in different physiological and pathological systems, such as sir2, SIRT1, which are energy metabolism related. Manipulation of such genes are actually playing with energy metabolism, and/or similarly the other systems, like stress defending system, repairing system and homeostasis etc. Thus we are quite confident to say, genetic system regulates life-span by a net system of genes in a co-operative pattern to settle a relatively species-specific longevity. When environmental challenges turn out to be the critical factors of aging following above discussion, I did not dare to conclude that carbonyl stress is the center of the story because free radical damages are so overwhelmingly related with most diseases, and we all understand diseases accelerate aging. That is why I stated biochemical side-reactions for a broad definition of aging causes in a recent paper. But now the most difficult problem we are facing is when trying to correlate damages with aging speed or the maximum life span (MLS), we never make the end meet. We vaguely know that the damages and MLS are separated by a wall, the Great Wall of our repairing system. Most aging studies are kicking at one side of the wall and expected to draw the pictures of aging process which is progressing at the other side! What is happening at the other side of the wall, the real aging process? The aging related alterations?! Actually, we are not laymen in this field, we do have a plenty of information. We have collected a large body of knowledge from chronic diseases and autopsies at organ level, cellular levels etc. particularly at the molecular level, as wrinkled skin, stiffened blood vessels, the senile plaques, versatile disease-related fibrosis, the cataract and lipofuscin that I am familiar with. Here, it is here, we see the aging, the aging-related alterations (surprisingly, have very little to do with genes), where unsaturated carbonyl-related crosslinkings play a crucial role as even to give explanation to the entropy theory of aging. Since many aging causes (like oxidative stress) are important (although in an indirect manner and as an external factor ) to underlie aging alterations (which are internal molecular alterations), I have not intended to specify the unique significance of the carbonyl stress theory to criticize (or replace) other great theories, until I was pushed to do something like that recently. Now Id indicate more clearly that the carbonyl stress aging is tackling the aging alterations (process) at a sub-molecular level . In other words, at the level of the molecular functional groups ! In typical bio-macromolecules, such as lipids, carbohydrates, proteins and nuclear acids, there are only a few functional groups (e.g. -COH, -CHO, COOH, -NH, -SH, etc.) all with clearly understood biochemical reactivity. The concern at sub-molecular level may, therefore, be the key progress that the carbonyl stress theory has highlighted/developed in aging study, and I believe we can, from this base/level, unify most (if not all) existing aging theories. Finally, referring to the advantages of dietary restriction (or the disadvantage of over-diet), an simple explanation may be due to the limitation (saturation) of the detoxification capability of our digestion system. Since the detoxification of food is so important that even the decarbonylation enzyme GSHT (need not to mention P-450) already consists of 3-5% of the total soluble proteins in liver. I hope the story of my thinking may help you understand more the development of my ideas in addition to the descriptions written in my manuscript. I hope these information may be useful and bring a nice time to you, together with my best wishes for the Merry Christmas and the New Year season. Yours, Dazhong
今天是第10个 “ 世界睡眠日 ” 。 睡眠是人体的一种主动过程,可以恢复精神和解除疲劳。当年在农村插队常说“没钱打肉吃,睡觉养精神”。现在改职业,研究生命科学了,睡眠机理也成了经常思考的问题之一。 睡眠不足可导致人体机能发生紊乱。科学家们研究发现,健康人能忍受饥饿长达3个星期之久,但只要缺觉3昼夜,人就会变得坐立不安、情绪波动、记忆力减退、判断力下降,甚至出现错觉和幻觉,以致难以坚持日常生活中的活动。医学研究表明,偶尔失眠会造成第二天疲倦和动作不协调,长期失眠则会带来注意力不能集中、记忆出现障碍和工作力不从心等后果。 记得十年前把衰老和睡眠生化作了一个大胆的链接,在大化学家鲍林创办主编的《 Medical Hypothesis 》发表了一篇‘天方夜谭’文章 : “去羰基应激是否就是睡眠过程重要的抗衰老生化 ? ( Is carbonyl detoxification an important anti-aging process during sleep?(原文附在本文末尾) )”。一晃十年过去了,衰老之谜已成过去,睡眠之谜应该走上前台。 下面先附上一篇相关的论文,供科学家伙(陈安专利词汇)们一起来烤烤火,做做白日梦如何? 睡眠生化机制初探 何志恒,印大中 (湖南师范大学生命科学学院衰老生化实验室, 中国湖南长沙 410081 ) 摘要: 关于睡眠机制的研究是一门历史悠久的学科。在过去的几十年中,运用细胞电生理学来研究睡眠取得了可喜的成果。由于种种技术上的困难,近年来该领域的研究多集中于临床和医学范围,例如嗜睡症、抑郁症等。虽说睡眠的节律性较易理解,但作为其本质——睡眠的基因和分子水平的自动平衡调节仍是一个迷。细胞因子( IL - 1 和 TNF α )对睡眠的诱导作用已显示从分子水平上了解睡眠的可能性。到目前为止,关于睡眠的功能已有不少理论和假说,但人类对睡眠的生化机制的认识尚处于起步阶段。 关键词: 觉醒;快波睡眠;睡眠机制;慢波睡眠 The Elementary Studies of Biochemical Mechanisms of Sleep HE Zhi-Heng, YIN Da-Zhong ( Laboratory of Aging Biochemistry , College of Life Sciences , Hunan Normal University , Changsha 410081 , Hunan , China ) Abstract: Sleep research is an old discipline. Over the past century, much progress in the field has been achieved, e.g., through the cellular electro - physiology. Due to some unsolvable technical difficulties, sleep researchers are more focused on clinical aspects of sleep problems, such as narcolepsy, depression and so on. Although the circadian component of sleeping comparatively has been well understood, the homeostatic component - the true essence of sleep - remains a mystery. The induction of cell factors ( IL - 1 and TNF α ) to sleep has shown the possibility to understand sleep in molecular level. So far, there have been a number of theories and hypotheses, but humans ’ knowledge about the molecular mechanism of sleep are still in the primary stage. Key words : awakening; rapid eye-movement sleep (REM); sleep mechanisms; slow wave sleep (SWS) 自古以来,睡眠占据了生活在地球上的人类生命 1/3 左右的时间,是生命过程的一大奥秘。由于睡眠研究涉及面宽,难度大,诸多领域的科学家都在不断进行探索。 1949 年Moruzzi和Magoun揭示了觉醒状态的维持与脑干网状结构上行激动系统作用有关,该发现标志着关于睡眠的神经科学研究的兴起 。随着 1953 年电生理研究对快动眼睡眠( REM )的发现,睡眠神经科学研究进入了一个崭新的时期 。 1 细胞电生理学研究与快波及慢波睡眠 电生理学从细胞水平上把睡眠和觉醒成功地联系在了一起。在过去的几十年中,运用离子通道和基电流( elementary currents )假说成功解释了睡眠脑电图( EEG )的形成机制。加拿大学者 Steriade 的研究表明:小于 1Hz 的低频振动协调着各种睡眠节率,如:慢波( 1-4Hz )、纺锤波( 8-13Hz ),和高频波( 40Hz ) 。 REM 是由Jouvet 40 年前发现的 ,它由脑干中心引发,并与边缘区域(如:杏仁核,扣带回前部)的显著激活作用有关。Maquet 提供的一组数据显示,处于工作状态下活跃的大脑区域在 REM 状态下又被激活。该结果与Wilson和McNaughton 对大鼠的 SWS 研究结果有类似之处。然而睡眠过程中再激活的特征有待进一步解释,因为被训练过的大鼠在觉醒的安静状态下也能出现再激活现象 。关于代表深睡状态的慢波睡眠和睡眠中的异相期和梦境等已有许多专门论述,由于篇幅所限,本文不作赘叙。 美国学者McCormick 详细研究了在以上振动频率下的离子电导率和它们受上行网状激动系统的调节情况。通过研究去甲肾上腺素、乙酰胆碱、组胺和谷氨酸代谢亲和受体( metabotropic glutamate receptors )的作用,尤其是 1,4,5- 三磷酸肌醇的生成而实现了睡眠的细胞电生理研究。很可能谷氨酸代谢受体也具有激活管理大脑皮层Ⅳ的肾皮质神经元的功能,这样就构成了“下行激动系统” 。 对于产生 REM 的脑干神经中枢群的研究也很成功。该研究还在下丘脑和前脑基底部进行了成功的重复,该区域是控制和协调慢波睡眠( SWS )和 REM 的神经元集中部位。美国学者McCarley提供了令人信服的证据证明在长期的觉醒状态下,腺苷在前脑基底部积累,并通过其受体将腺苷定位于神经元中 。日本的Osamu Hayaishi 的研究同样指出腺苷在调节睡眠和觉醒中起关键作用,虽说该作用对于前列腺 D2 来说是下游的。但必须指出还有许多矛盾的地方,希望能从所涉及的各类细胞来解释,包括它们的(神经)输入与输出以及调节其活动的化学物质。 本人利用 KT88 - AV2000 数字视频脑电地形图监测了人在正常状态下由觉醒致深度睡眠的不同阶段,枕部的 EEG 呈现特征性改变。随着睡眠的加深, EEG 表现为频率逐渐变慢、振幅加大, δ波所在比例逐渐增多。( Figure1 - 5. ) 2 睡眠的昼夜节律和自动平衡 在不同的研究水平,对于区分组成睡眠的两个基本要素:平衡和节律的理论和实验是认识睡眠要素的重要进步 。睡醒平衡,或称之为睡醒稳态,是指处于觉醒的时间越长,所需睡眠的时间就越长;节律则与每日睡眠的习惯性时间的改变有关。这两个要素在人类身上可运用强加的去同步化实验来分离。 睡眠的节律性要素较易理解,其功能就是根据日夜交替来调整人体处于一系列的行为状态中,其作用机制最终将通过基因和分子水平的研究了解清楚。例如:运用双光子显微技术,美国的Gillette 研究表明谷氨酸和乙酰胆碱通过作用于细胞的 Ca2+ 库,引起 Ca2+ 在时间和空间上的释放而引起明显的上交叉核节律钟( suprachiasmatic nucleus circadian clock )的变化。 作为睡眠的自动平衡调节至今仍然是一个迷。许多研究表明该要素可从 EEG 的慢波睡眠的时间长短和总量上得以表现(Borbély )。例如:慢波睡眠在睡眠剥夺之后的增加。在处于冬眠,甚至是一般麻痹状态下也可出现 SWS 增强的现象,这非常有趣并且暗示睡眠能进行活跃的身体修复过程,而此过程在低温代谢状态下是不能进行的。然而,由于对影响睡眠的局部调节因素──生长因子、细胞素和其它分子正在研究之中,所以该修复过程的本质还不清楚 。尽管如此,可自动平衡这个因素似乎是一个相当普遍的现象,它存在于被研究过的所有哺乳类和鸟类中。有证据表明果蝇也同样具有类似的睡眠状态,在长期的睡眠中其感知阈增大;若被剥夺睡眠达 12h 之久,则显示出睡眠反弹,即受试对象长期被剥夺 REM 的情况下,一旦得以宁静地睡眠,就使 REM 增加而得到补偿。现在对大鼠和果蝇在睡眠周期中基因表达的变化的分析正在一步步揭示与行为状态有关的许多体内分子的作用。 3 睡眠和细胞因子 已报道的睡眠因子包括单胺类和多肽类因子等。细胞因子诱导睡眠的研究目前主要在生化和神经元水平上进行。例如白细胞介素( IL )、干扰素( IFN )、集落刺激因子( CSF )、肿瘤坏死因子 (TNF) 、转化生长因子( TGF -β)、羰基毒素等,他们在免疫系统中起着非常重要的调控作用。同时,也发现细胞因子与睡眠之间有着十分密切的联系。 在动物实验中, IL - 1 注射后数分钟,即可引起 SWS 的增加; IL - 1 β无论是直接注射到脑还是静脉注射,均可引起 SWS 持续时间和幅度的增加。有研究发现 IL - 1 的效应依赖于其运用的剂量和时间的长短,小剂量 IL - 1 β促进 SWS ,而大剂量 IL - 1 β则抑制 SWS 。 同样发现 TNF α无论是脑室注射还是静脉注射,均使 SWS 增加;因此, TNF α对睡眠也有一定的调节作用。 大多数实验均证实:睡眠剥夺后,其血浆 IL - 1 和 TNF α样物质升高,从而促进睡眠,达到维持机体平衡的目的;如表达量过高或持续时间过长,则会损伤机体免疫功能。 人体的睡眠研究表明,剥夺睡眠后尿液中氧化和糖基化代谢产物会大幅度增高,说明缺少睡眠造成的生物垃圾产物的蓄集和生理平衡的打破。关于这方面的研究目前正在兴起。 4 临床研究 由于多种原因,目前大量的工作集中在对于睡眠的临床研究。在对狗进行了长期地研究后,美国科学家 Mignot 正在进行与嗜睡症有关基因的筛选。该症状的特点是患者在觉醒状态下突然进入 REM 。法国巴黎的Adrien 和美国的 Gillin 报道了睡眠和抑郁症之间的有趣联系 。这是一个复杂的研究,似乎完全的睡眠或选择性的 REM 剥夺可减轻抑郁症,若患者再一次睡眠,则又可出现抑郁症。但相反的是,一些抗抑郁剂,特别是单胺氧化酶抑制剂,可消除 REM 达几个月,并且没有出现明显的不良后果。 我国临床部分的研究偏重失眠和睡眠呼吸障碍的诊治两方面。前者包括各种中西药物,推拿,按摩,针灸和生物反馈等 ,后者着重睡眠呼吸暂停综合症( sleep apnea syndrome , SAS )的诊断和治疗 。 5 睡眠的意义 为什么睡眠对人类如此重要?现代科学一般认为,在睡眠过程中,大脑和神经系统得到了修复整理,营养补充,能量储存。因此有人用三个“ R ”( Repairing, Restoration, Regeneration )来描述这个过程。 19 世纪 20 年代的后半期曾有人进行过人的断眠实验,有三个青年人坚持断眠了 90 个小时,结果虽然他们的感觉、反应的敏捷度、运动速度、记忆力,以及计算能力都变得迟钝。其中一个人,在断睡第二个晚上出现了幻视,体温下降等异常状况。还有些科学家发现与发育密切相关的“生长激素”在夜间比白天分泌得多(哈达等, 1966 年)。最近又进一步确认了生长激素分泌旺盛的时期是在 SWS 阶段(高桥等, 1968 年) 。然而,睡眠过程到底如何驱除疲劳,恢复脑力和体力,从细胞水平和分子水平上,现代科学对于神经和大脑的睡眠生化过程了解得还很肤浅。 在诸多假说中,一些假说认为睡眠在某种程度上与学习和记忆有关。在睡眠的纺锤波和慢波阶段,伴随着突发性放电,该现象虽到目前为止还未得到直接证明,但由于大量 Ca2+ 流入神经元而造成电生理改变的可能性是有的。英国的Berridge 提出了他个人的观点,认为内质网是神经元内的神经元。内质网是一个延伸到细胞各个角落(包括神经元的树突和棘突)的连续的网状结构。该结构既可通过其上的电压和受体门控通道,使 Ca2+ 进入其中,成为 Ca2+ 库;又可作为瞬间 Ca2+ 流的源泉导致反馈现象,包括 Ca2+ 波。这种 Ca2+ 的释放是一种信号机制,能有效的调节神经的兴奋性和基因表达对环境的可塑性、适应性。因此,很容易想到在 SWS 期间, Ca2+ 流入能诱导基因表达,从而产生长期的适应性变化。 然而,虽然在睡眠中可能存在其他调控机制以保持体内平衡。但有证据表明,正常的与睡醒平衡(睡醒可塑性)有关的基因表达是在觉醒期间被诱导的,并非睡眠期间。例如:在觉醒期间, CREB 的磷酸化,以及其它转录因子和一些早期表达基因的水平都很高,而睡眠期间则很低。近年来,一种早期表达基因, Arc ( activity-regulated cytoskeletal ),得到了广泛的关注,因为 Arc 选择性的出现于被激活的突触中,而且这种现象仅出现在觉醒期间而非睡眠期间(Tononi)。事实上,不论睡眠是否对于可塑性重要,但运用觉醒和睡眠之间的比较可了解可塑性变化与细胞和分子水平上的调控相关。对于在睡眠期间各种与可塑性标示物水平低的原因目前认为是在睡眠期间特定的神经调节系统处于休止状态,如:去甲肾上腺素系统(而不是血清素激活系统) 。目前一些实验室(Borbély,Krueger,Tononi )正在进行相关地研究 。最近Siegel 用一种原始的单孔类动物 ── 针鼹所作实验的结果还显示了一种复合的睡眠前兆现象 。 刘同想等人的研究表明 :长期睡眠较差的老年人老年环、老年斑、脱牙数得分、冠心病、高血压病、脑血管病、慢性胃炎、糖尿病患病率及血清过氧化脂质( LPO )明显偏高,红细胞超氧化物歧化酶( SOD )活性明显偏底,提示睡眠质量差对老人健康有害,并可加速衰老。最近美国芝家哥大学的研究人员在他们的研究中发现,人如果一段时间睡眠不足,身体会出现衰老症状,严重者会患上心脏病、糖尿病等疾病,提示衰老过程与睡眠有密切的相关性。 印大中 教授最近( 2000 年) 根据衰老生化的最新研究成果提出睡眠过程的神经元膜的去毒化假说,认为觉醒过程中种种生化副反应(如氧化和糖基化)造成的垃圾堆积造成了神经系统的“疲劳”。指出睡眠过程的单胺复原(去羰基毒化)可能是重要的睡眠生化机理或者就是日复一日的“返老还童”过程。 睡眠到底是生物体的局部现象还是总体的现象?单个神经元能睡眠吗?神经元会感到累吗?其原因是什么?睡眠到底能提供什么益处,致使大脑如此地依赖于睡眠?睡眠能否促进突触生长或重塑? 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略论中医药抗病毒的科学性 “ 中医治本 ” 为本博客 “3+X 理论 ” 的第一论,可认为是中医补充(拯救)西医露的 “ 第一手 ” 。 这样本文“论中医药抗病毒的科学性”应该算作‘第二论’。这一论猛一看似乎不那么惊心动魄,细思量其实价值连城!轻松一论能顶亿万科研基金,能救千万人性命 ! 其实无论 SARS , 艾滋 , 禽流感还是今年出现的‘猪流感’都属于这‘第二论’问津的范畴。因为艾滋病毒、 SARS 病毒、以至多种流感病毒均属于 RNA 病毒。而 RNA 病毒善变,所以临床上很难对付。西医研发疫苗永远是跟踪追击,劳民伤财,总是处于被动挨打的局面。这是西医永远的痛,也是现代生物医学顾头不顾腚的无奈之处——又一处‘软肋’! 然而今年应对猪流感中国有关部门表面上如临大敌,实际上从容不迫。中国‘外紧内松’,而美国则相反‘内紧外松’,深怕给金融危机雪上加霜,造成巨大动乱。为何如此 ? 中医抗病毒的科学道理已在两年前一举突破,正式文章在‘猪流感’发作之前已及时的问世。下面请看本博客的中医理论 ‘第二论’:“从模糊数学看中医药抗病毒的科学性”。文章 发表在《医学与哲学》 2009 年 2 月,第 30 卷第 2 期, 78-79. 因为本博客的第一论给中医治本的千年难题作了科学解读,在发表第二论时,本博客已被广东省中医药科学院(广东省中医院治未病中心)特邀为客座特聘教授,因此署名有了双重身份。(合作作者卢传坚为广东省中医院副院长) 下面请欣赏: 从模糊数学看中医药抗病毒的科学性_.pdf 从模糊数学看中医药抗病毒的科学性 ——中医药理论研究及发展的新视野 印大中 1,2 卢传坚 2 1. 湖南师范大学生命科学学院 , 长沙 410081, 中国 湖南 2. 广东省中医院,广州 510120, 中国广东 摘要: 由于病毒身体较小,且在不停地变异,有点类似物理学微观世界中电子的“测不准”状态,西医应用疫苗抗击病毒的战役往往被动艰辛,防不胜防。应用模糊数学的理论和概念,本文提出,中医药物中所含的成百上千种“不确定” 、 “干扰态”生物成分正是其拮抗善变病毒的优势所在,所谓以干扰态打破常态,以模糊应对变异,以“不测准”对付“测不准”。此类中医实践以系统生物学思维见长,既“扶正”又“驱邪”,尤以广谱“驱邪”为特色。该理念亦为“鸡尾酒疗艾滋”战略的延伸,只要调控适当,便可显现出中医药治疗病毒性疾病的特殊功效及其科学价值。总之,模糊医学有望成为中 - 西医学理念衔接的“立交桥”。 关键词 病毒,变异,测不准,中医 Scientific Explanation on Anti-virus Potential of Traditional Chinese Medicine Based on Uncertainty Theory YIN Dazhong 1 , LU Chuanjian 2 1. College of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China 2. Guangdong Provincial Hospital of TCM, Guangzhou 510120, Guangdong, China Abstract : Due to their mutability and variability, infective viruses existed and developed in a manner of uncertainty, which is analogous to the uncertainty of electrons in physics. Human’s battle against viruses is therefore very difficult. With the concept of uncertainty mathematics, this paper suggested for the first time that thousands of unknown chemical components of the traditional Chinese medicine (TCM) may play an inhibitive and disruptive role in conquering viruses. Such using uncertainty of chemicals to direct disturbances against non-predictive mutation of viruses may act as an advanced cocktail treatment on viruses. A rational manipulation of such uncertainty strategy with the advantages of systems biology may prove to be efficient as well as scientific to prohibit virus-based diseases and establish a theoretical bridge connecting the TCM with modern medicine. ____________________________________ 基金项目 : 科技部十一五科技支撑计划项目:亚健康状态中医辨识研究 ( 2006BAI13B02 ) 和国家高技术研究发展 (863) 计划 : 针对亚健康的药物分子设计 (2008AA02Z411) Key words : Virus, Mutation, Uncertainty, Traditional Chinese Medicine 至细则迷,多变则惑,以细微精确见长的现代生物医学在千变万化的生命体活动营造的迷惑中徘徊挣扎。本文提出模糊哲学指导下的中西医学理念大结合,愿能为“后现代生物医学”回归宏观,处变不乱提供有价值的战略思路。 从模糊数学说起 在过去相当长的时间里,精确数学在描述自然界多种事物的运动规律中,获得了显著效果。但是,在客观世界中还普遍存在着大量的模糊现象。随着现代科技所面对的系统日益复杂,模糊性终于伴随着复杂性频频出现在科学家的面前。许多复杂系统,如航天系统、尤其是人文社会、生物医学及其它 “ 软科学 ” 的数学化、定量化趋向不断地把数据处理的模糊性问题推向前台 。 1986 年,司岩在《大科学的模糊观念》一文中讲叙了一个耐人寻味的故事:将以计算机控制的摄像机把某人的生物学参数摄取,并储入信息库中,当需对此人实施辨认时,则按程序进行信息核对,参数对了便显示 “ 是 ” 的报告。然而第二天电子计算机系统却否认了受试人的合法身份,原因是因为一夜间受试者脸部长出了一粒粉刺。试想,即便是一个婴儿,也不会因妈妈脸上长了一颗粉刺而失认。过份地追求精确反而失去了真实!现实世界其实有成千上万这样的事例。 作为一门新兴学科,模糊数学已被初步应用于模糊识别、模糊评判、模糊控制、模糊决策、系统理论、信息检索等诸多领域。在气象、生物、心理等许多方面获得了丰硕的研究成果。 生物的可变性 上文所述的“脸上长了一颗粉刺”是生物体的宏观变化,实际上生物体时时刻刻都在整体,器官,细胞和分子水平发生着改变。 生物细胞中的遗传物质在复制时也很容易出错,也就是会发生变异。高等生物有一套检查修补机制,可以把出错的概率降低,然而诸多 RNA 病毒仅为单链的 RNA 结构,没有像双链 DNA 那样拥有另一条可以用来校对检修的复制版本。艾滋病毒、肝炎病毒、 SARS 病毒、以至多种流感病毒均属于 RNA 病毒。因为它们的善变,所以临床上很难对付 。 流感病毒基因每隔几年便可能会发生一些个碱基位点的突变 。例如近五年来,科学工作者已经研究鉴定出了十多种基因型的 H5N1 禽流感病毒,主要包括 H5N1 的 A , B , C , D , E , G , V , W , X , Y , Z 和 Z+ 基因型等。面对如此状况,人们每年都该重打一次新的疫苗,以防御流感病毒可能的入侵。 近百年来,现代医学对抗微生物的战役尽管历经艰辛,却也频频告捷,急性传染病对人类造成的死亡威胁已大大降低。然而大自然中的微生物群体从来就不甘束手被擒,它们不断地改变身体“形状”,躲避人类的反击。细菌的变异令人类使用抗生素的功效每况愈下;病毒的快速变异更是让现代医学的免疫研究被动应对,捉襟见肘 。 例如,因为艾滋病毒通过反转录酶等(图 1 )将其 RNA 转录成 DNA 而整合入宿主细胞。现代医学针对艾滋病毒的药物则有:反转录酶抑制剂、蛋白酶抑制剂、 HIV 整合酶和 Tat 酶抑制剂,以及针对核衣壳蛋白的锌指结构和糖蛋白 gp120 的药物等。这些药物在应用初期往往有显效,但 HIV 很快便表现出抗药性,就是由于病毒相应基因发生了突变,使得种种针对性单一的药物效果越来越差。何大一教授开拓设计的“三合一”制剂以采用针对多靶点的同时干预疗法,所谓 “鸡尾酒疗法”而著称,显示出了中西医学理念结合的潜力与优势,但 HIV 病毒还是发生了新的变异,又逐渐重新逍遥法外。 图 1. 艾滋病毒(人类免疫缺陷病毒, HIV )及其内部结构 上述情形在现代医学拮抗那些身体结构与 HIV 类似的感冒病毒和 SARS 病毒时也大同小异。令人啼笑皆非的是,现代主流医学在小小的病毒性感冒面前居然无所作为,让大家“一周以后自愈”……。因为现代医学一般认为:病毒性感冒“治与不治一个样”,治也几乎白费力气!据有关资料统计,目前已知的人类感冒病毒已多达百种,相关的免疫抗战似乎永远只能是被动挨打之后的“跟踪追击”。 值得注意的是,中医药在防治流感,战胜 SARS ,医治艾滋等病毒性疾病时,有些时候却似乎能“草草”了事,化险为夷 。但对于解释为什么“一把小草”就能出现广谱的疗效还缺少站在哲学高度的医学理论的指导。 中医药“模糊疗法”的科学性 现在我们应用模糊数学的理论和相关概念,来看看中医药在某些状况下是如何通过不那么精确的方法来实现科学治病的目的的。 中医药物不说复方,就是单味药也含成百上千种“不确定”的,并且可能在炮制过程中不断变化着的生物成分。所谓良药苦口,从这些苦得让人打颤的药液,我们可以自然而然地想象,病毒在我们体内也同样会遭遇“四面楚歌”,“险象环生”的“药难”。 事实上,与正常人体内的“血液营养”相比,这些稀奇古怪的药物成分堪称病毒生长繁殖的“复合干扰素”,或可比作“喷砂枪弹药流”。所谓以变制变,以乱治变。病毒纵然千变万化,仍是生物大分子,仍服从生化反应的诸多必然规律。千奇百怪的 中医药成分对 DNA 、 RNA 在复制衍生过程中的转录翻译 、 表达代谢和生化平衡,尤其是对其体内各种生物酶类的“工作环境”,造成了极大地干扰。这些突如其来的生理生化状态改变,对于整个人体也许只是一时的“添乱之变”,但对于偶而外来的,或者那些乘虚发作的捣乱分子,应该是灭顶之灾(这些微生物本来就属寄人篱下,在苟且偷生)。此时此刻“倒霉(酶)的病毒”即使不能全军覆没,也差不多十去八九,成不了什么气候了(一如人体的正常状态,病毒无能力攻入人体的细胞组织)。如此“药难”,越早越有成效,越怪越出精彩。因此有些及时应用了中成药的病毒性感冒往往只有两三天的病程,便迅速得以康复 。 上述以模糊应对变异,以干扰态打破常态,以“不测准”反制“测不准”,似喷砂枪打苍蝇,电网拍掳飞蚊,只要辨证施治,对药物调整合理,便可显现出中医药治疗病毒性疾病的奇效 。病毒再变也翻不出中医药有针对性的模糊疗法的“如来手心”。事实上,人体本身的免疫体系在抵抗疾病过程中分泌的细胞因子也往往应用了同样的干扰战术——表达分泌多种干扰素,以扰乱病毒增殖的途径和过程,问题只是人体表达干扰素的反馈过程需要时间,因此不如人工用药迅即。 如此针对病毒的“测不准变异”的模糊疗法的有效性及科学性决非空穴来风。有关实验室已经做了大量地研究,发现在细胞培养体系加入的种种病毒以至病菌可被多种中草药或中成药混合成分高效杀死 。这早已不是什么难题或新闻,例如目前获得公认的具有广谱杀菌抑毒作用的中成药有:大蒜、柴胡、鱼腥草、双黄连、清开灵等等。 许多生活经验告诉我们,其实要 抑制千变万化的感冒病毒的生长往往并 不一定需要去寻什么“灵丹妙药”,调控环境的 酸碱度(如,醋疗法)、调控身体的温度(如,热水浴疗法)、合理补充抗氧化物质的“阴阳”平衡疗法等就是一些切实有效的措施。当然大量中成药中富含的多糖、黄酮和皂苷类的药物还能够从“扶正”的角度提高机体的免疫力,进而从“治本”的层次改善我们身体的抗病能力。 如果说“科学主义”的僵化思维只习惯于承认“可道之道”,如今对“中医药治病毒有特效”的哲学解释无疑将有助于把中医药从“非常道”中解放出来,这里有模糊数学的功劳,也有“易学”思想的 精髓,“易”者“变”也!生命万物时时在变,科学岂能一成不变?病毒在变,西医药跟在后面追之不及,中医药却早已在前面设好了天罗地网,只是我们缺少火眼金睛! 如果说《 相对论》让我们意会出了“时空之变”;《大陆漂移说》令我们感悟到了“大地之变”;《模糊医学》则提醒了我们应该如何应对“生物之变”。关注模糊医学将为人类成功地应对充满变数的生物世界提供科学思维的睿智,本文提出的“不测准”理论或将建立起一个整合还原论和系统论的医学大框架 ,在拮抗微生物的医学领域建立起一座衔接中西医学理论的“立交桥”。 参考文献 1. 陈可冀,主编.中国传统医学发展的理性思考 . 北京:人民卫生出版社,1997:16-21. 2. 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衰老,千古之谜告破! 日前(20090705-0709)第19届世界老年学和老年医学大会在巴黎胜利落下了纬幕。大会规模宏伟空前,收到600多个专题,4000多场学术报告申请。其中最引人注目的是美国著名衰老研究科学家 Hayflick 教授主持的专题衰老不再是生物学的不解之谜, AGEING IS NO LONGER AN UNSOLVED BIOLOGICAL PROBLEM!专题在报告栏中的编号为: SA6044 。 现将其中的四篇文摘原文给出,向有关专家和同仁传个快讯! SA6 044 AGEING IS NO LONGER AN UNSOLVED BIOLOGICAL PROBLEM (SUPPORTED BY THE ELLISON MEDICAL FOUNDATION AND CO-SPONSORED BY THE GERONTOLOGICAL SOCIETY OF AMERICA) SA6 044-1 THE CAUSES OF BIOLOGICAL AGEING ARE KNOWN L. HAYFLICK - University of California, San Francisco (The Sea Ranch, CA, United States of America) The finitude of life is divided into aging, longevity determination, age associated diseases and death. The efficacy of repair and turnover systems is favored over molecular dysfunction until reproductive maturation when the balance slowly shifts in favor of accumulating dysfunctional molecules caused by increasing entropy (dispersal of energy) and resulting in the aging phenotype. The molecules that compose repair and turnover systems also suffer the same fate as do their substrate molecules. It is these maintenance systems that are the determinants of longevity. The genome indirectly governs the anabolic determinants of longevity. This is fundamentally different from the stochastic, catabolic processes of aging. Age changes simply increase vulnerability to age-associated diseases. SA6 044-2 UNDERSTANDING THE BIOLOGICAL REASONS FOR AGEING R. HOLLIDAY - The Australian Academy of Science (Canberra, Australia) A broad biological approach makes it possible to understand why ageing exists and also why different mammalian species have very different maximum lifespans. It has become apparent that the best strategy for animals survival is to develop to an adult and reproduce, but not to invest resources in maintaining the soma indefinitely. There is a trade-off between the investment of resources in reproduction, and the survival time of the soma. At a stroke, this solves the problem of different rates of ageing in different species, because those that develop and reproduce fast have short lifepans, and those that develop and reproduce slowly have long lifespans. This difference is due to the resources invested in the maintenance of the adult soma. There is much evidence that the efficiency of maintenance correlates with maximum longevity. Thus, ageing can be defined as the eventual failure of maintenance. It has also become evident that there are many maintenance mechanisms, and these depend on very many genes, and the investment of considerable metabolic resources. A broad interpretation of the different degenerative changes during ageing should be adopted, with the general conclusion that ageing is multi-causal. SA6 044-3 AGEING IS SOLVED BUT ITS SOLUTION ALSO HIGHLIGHTS ITS COMPLEXITY - GEARING UP FOR THE CHALLENGES AHEAD T. KIRKWOOD - Institute for Ageing and Health, Campus for Ageing and Vitality, University of Newcastle (Newcastle upon Tyne, United Kingdom) After a long period when ageing was dismissed as just too complicated for serious scientific study, we now have a very good idea about the underlying reasons for why ageing occurs and how it is caused. Ageing occurs through the gradual, lifelong accumulation of damage that results from the limited capacity for maintenance and repair, which in turn has been strongly shaped through natural selection (the disposable soma). Nevertheless, the fact that the enigma of ageing is now solved does not mean that the detailed understanding that will be needed to make practical use of its solution is near at hand. The intrinsic complexity of the mechanisms indicated by the solution requires the adoption of systems-biology approaches to the analysis of: (i) how the networks of cellular maintenance are vulnerable to damage, (ii) how these networks are regulated, (iii) how damage plays into the pathogenesis of degenerative diseases, and (iv) where interventions might most successfully be targeted. These challenges will require radical changes in the ways that ageing has been investigated to date. Reference: Kirkwood TBL. A systematic look at an old problem. Nature 2008; 45:644-647. SA6 044-4 MAKING SENSE (AND MAKING USE) OF PATTERNS OF MAMMALIAN LONGEVITY S. AUSTAD - University of Texas, Health Science Center (San Antonio, United States of America) The new understanding of aging that emerged near the end of the 20th century, combined with advances in understanding evolutionary relationships among species, offers an explanatory framework for certain patterns of aging and longevity among mammals. For instance, large species typically live longer and decay more slowly than small species, although there are numerous exceptions to this pattern. If one corrects for body size and focuses on evolutionary history of mammals, it can be seen that exceptionally slow aging and long healthspan has evolved many times. This repeated evolution of slow aging, such as seen in bats, marsupials, and multiple times in rodents allows us to ask new questions about the evolution of long life, such as whether there are many, few, or even one mechanism by which aging processes can be combated. Focused investigation of the molecular processes embodied by multiple species that have achieved exceptionally long life will yield insight into processes relevant to retarding aging in all species. This talk will discuss several candidate processes that have emerged from initial comparative studies.
欧洲生命科学合作组织( ELSO )的重头戏是一年一度的欧洲生命科学 年度 会议,是欧洲分子生物学、细胞生物学科研前沿的展示与交流。其会议组织与规模都与美国细胞生物学学会( American Society for Cell Biology )的 年 会相似,试图为欧洲分子生物学、细胞生物学的研究者提供一个交流平台。今年的会议在 地中海沿岸的海滨城市尼斯 (Nice) 举行,从飞机上望下去,阳光下的地中海一片湛蓝,朵朵白帆点缀其间。海岸则是山峦起伏,色彩鲜艳的小屋在茂盛的热带植物中时隐时现,海鸥起处,浪花点点。 一些精彩的讲座 整个 会议共有近两百场讲座,一个下午同时有七个平行会议。 Science, Nature 和 Cell 是这场会议的赞助商,都在发送纪念品或积极地吸纳新的会员,努力在新一代的作者群中建立自己的声望。会议的重头戏是大约 400 个 poster ,平均一天有近 150 个 poster 。在熙熙攘攘的大厅里穿行,人头攒动,讨论声声,真有科研赶集的味道。但这也是会议当中最有可能取得收获的时机,碰到自己感兴趣的问题,可以和本人面对面的交流与讨论,真正让人受益匪浅。这次会议 的官方网站( http://www.elso.org )对整个会议的内容有一个介绍,我在这里谈谈影响深刻的讲座。 系统生物学已经无可辩驳的影响到了整个生命科学的发展,会议的第一场特邀报告就是由哈佛大学的 Pamela Silver 做的 Design Biological system ,主要介绍了哈佛大学新近成立的 Institute for Biologically Inspired Engineering ( http://hibie.harvard.edu/ )的科研方向。随着近五十年细胞生物学与分子生物学的飞速发展,人类已经就基因与遗传、细胞的结构与各种生理机制,发现了大量的事实。正如十八世纪天文学大量观测数据的积累导致了物理学的大发展一样,目前生物学的大量事实与观测数据的积累,也必然促进系统生物学的发展,即通过建立系统模型来推动对生命现象的深刻认识,揭示生命功能的构成规则。通过生物学与物理学、微观工程技术和计算模型相接合,创造出新的材料、微型生物机器和揭示出新的控制理论。 系统生物学的发展直接改变了人们对疾病的认识。细胞生物学与分子生物学的研究成果不再束之高阁,分子生物学家需要和临床医生交流,以基因、细胞生化机制为基础,以系统生物学为方法,对疾病建立分子和细胞生物学的系统模型,为疾病的诊断和治疗提供新的思路。基于分子生物学的 Disease Models Mechanisms ,正在成为一个热门话题。 当人们研究的对象不再是单一的生化路径,而是一个综合系统时,很自然的,生命科学的另一个发展方向是对同一生命现象的多领域综合研究。比如今年赢得 Louis-Jeantet 年度大奖的法国巴斯德研究所的 Pascale Cossart 研究感染性细菌进入人体细胞的生化过程,其结合了 biochemisty, cell biology, molecular biology, gene analysis and Immunology 等各领域,其研究的细致与全面,令人赞叹。最近读到有文章感叹,国际知名的《细胞》杂志上,中国 1981 - 2004 年空白,近年仍不到 1% 。听了 Pascale Cossart 的研究,不仅对其中原因有所感悟:她坦诚相告,就这一项研究,她已经作了近二十年。 第二天剑桥的 Magdalena Zernicka-Goetz 关于多细胞发育的实验也非常精彩。通常的认识以为受精卵细胞的极性( Polarity )就决定了将来细胞分裂的位置,然后其位置决定了其基因表达模式 (gene expression pattern) ,人的四肢五官也就逐渐发育成型。她精心设计的实验表明,细胞分裂的方向也会决定细胞的命运,并且令人吃惊的发现是,不但是细胞的位置决定其基因表达模式,反过来改变基因表达模式也会改变细胞的位置。通常是出于外围纵向分裂的干细胞,通过改变某种基因蛋白的浓度,会被挤入内部变为横向分裂。 Magdalena 讲得很生动,可能是兴高采烈之时有些用力过猛,她的苹果电脑从一米多高的讲台上摔下来,居然安然无恙。(真应该把这段录像拍下来,应该是绝佳的苹果电脑的广告)。 她 关于干细胞与胚胎发育的图片做得非常漂亮. Fig. 1 3D reconstruction of the mouse blasotcyst showing how the first set of pluripotent cells that will give rise to the future body (yellow) is cradled by the outside cells of the embryo (blue). (Image from Emlyn Parfitt and Magdalena Zernicka-Goetz). Fig. 2 Over-expression of Carm1 in a single 2-cell stage blastomere directs cells to the pluripotency at the blastocyst stage. Daughters of cells in which Carm1 was overexpressed are in red. (Image from Maria-Elena Torres-Padilla and Emlyn Parfitt). 第三天哈佛大学的 Donald Ingber 关于细胞的力学结构模型和基因控制的动力系统模型也很精彩。他的发现改变了人们对细胞的认识:通常人们认为细胞只不过是装满水的气球而已,但是由于细胞骨架 cytoskeleton 的存在,细胞更像由若干绷紧绳索拉起来的 帐篷。通过改变细胞环境的压强,我们可以人为的使细胞进入分裂、生长和自我调亡。 Donald Ingber 也是 Institute for Biologically Inspired Engineering 的一员。 Fig. 3 细胞更像由若干绷紧绳索拉起来的 帐篷 这场会议的内容很多,目前正在消化与整理,以后会就有特色的内容写一些专题。 关于 鼓励青年研究者 没想到在这样一场高水平的国际会议当中,会对青年研究者给于如此高度的关注。除了学术交流之外,会议专门有 session 来指导青年研究者如何选择职业道路,如何申请泛欧洲科研基金、如何建立和管理自己的实验室,如何与公共媒体打交道等。 Cell 杂志的前任执行主编,还以自己的现身经历来如何说明选择最适合自己的职业道路。并且由欧洲科研基金( ERC )负责人、西班牙国家癌症研究中心所长等政策制定者们,与刚出道的博士生、博士后进行对话 (Open floor debate) ,就青年研究者遇到的问题进行讨论。为什么青年研究者成长得快?其后面确实有很多政策支持,比如: 欧洲科研基金由专门的 Junior Research fellowship , 每年 10-40 万欧元,支持 3-5 年,这笔钱给人而不是给所在的机构。青年研究者可以自由选择科研机构,独立的建立自己的实验室和购买设备,人走到哪里,基金就跟到哪里。 鼓励青年研究者流动。在英国作了 4 年博士后,在德国拿到位置,可以将实验设备无偿带走。彼此承认相互的学术职称。 对新成立实验室的 PI, 不要求写详细的 Plan of Budget 。因为对新成立实验室的 PI ,还不太可能有太详细的科研方向,需要摸索和尝试,基金部门对他们有特殊的政策照顾。 这些政策的背后,也正是因为欧洲的青年研究者成长起来有诸多的困难。一般在欧洲大约 10 个博士毕业生中,只有大约 3 个人能拿到终身的职位。在长幼分明的学术机构中,很困难能独立的得到资助和建立自己的实验室。而且欧盟国家学术机构林林总总,各不相同,比如英国的 Lecturer 很难流动到法国作 Group Leader 。欧陆的大学教职都是政府公务员,对新人做独立科研和得到稳定职位并不热心,所以去年成立的欧洲科研基金( ERC )正尝试在改变这些不利于青年人成长的制度。 END