揣少坤博士，毕业于南开大学生物化学系，后于美国德州农机大学取得统计与应用数学硕士学位，于宾夕法尼亚大学取得生物统计博士学位。曾供职于美国纽约斯隆癌症研究中心，负责该中心早期临床试验的设计与数据分析工作。后供职于宾夕法尼亚大学医学院，负责医学院分子遗传学与生物信息学方面研究课题的基金申请、方案撰写、及数据分析工作。

2009年 进入诺华新泽西园区，任靶向药物RAD001(Everolimus)两项大型三期临床试验的首席统计分析师。

2010年 海归诺华中国（上海）研发中心，负责靶向药物早期研发的生物信息学平台以及转化医学平台。

2014年 共同创立燃石医学。揣少坤博士拥有生物信息学与转化医学领域13年的资历，掌握国际领先的技术，积累了涵盖二代测序数据分析、分子诊断、临床试验设计、生物标志物开发等与癌症个体化诊疗密切相关的多方面研发经验。

Shannon Chuai received her Bachelor's degree in Biochemistry from NanKai University, her Master's degree in Statistics from Texas A&M University, and her Ph.D in Biostatistics from University of Pennsylvania. She co-founded Burning Rock Biotech in 2014. Before that, she worked in Novartis Institute for Biomedical Research in Shanghai on Oncology drug discovery and translational research for five years. She also served as lead statistician on two Phase III trials of RAD001 (Everolimus) before she relocated back to Shanghai. Before Novartis, Dr. Chuai worked in the Biostatistics Analysis Center at University of Pennsylvania School of Medicine. She was in charge of protocol development and data analysis of a number of clinicians iniated NIH trials and biomarker studies while she pursued her Ph.D in PENN. Before PENN, She served as Research Statistican in Memorial Sloan-Kettering Cancer Center from 2002 to 2005 and participated in numerous microarray and GWAS studies in cancer. She has accumulated rich experience in next-generation sequencing, high-dimensional modeling, clinical trial design, and biomarker development in cancer.

[工作经历]

一、 2014/5至今：广州燃石医学检验所有限公司-首席技术官

（1）作为研发团队领头人带领产品研发团队成功开发基于二代测序的分子诊断产品 ；

（2）已开发跨越8种实体瘤的21个个体化诊断panel，以及泛癌种遗传易感基因panel。经过约2000例临床组织样本验证，与传统分子病理方法（PCR/IHC/FISH）对比，吻合度超过99%，且对于低频突变拥有比传统方法更高的灵敏度；

（3）燃石针对ctDNA的产品经过～500例临床液体活检样本验证，对主要基因突变（EGFR/ALK/ROS1/KRAS等）在IIIB-IV期肺癌患者中敏感性达到93%，特异性接近100%；

（4）燃石的技术平台可以在DNA水平同时检测突变、融合重排、扩增、缺失等多种变异类型。无需提取RNA；

（5）燃石在过去的一年已完结及进行中的临床科研合作项目共27个，已合作发表1篇JCO，1篇JTO，1篇Scientific Reports，1篇BMC Cancer，投稿1篇OncoTarget，另有10余篇文章在撰写中；

（6）燃石已成功申报13个二代测序技术及生物信息学专利。并开发出二代测序临床一键式报告分析软件与样本全自动管理系统。（基于Illumina平台）。

二、 2009/12至2014/5：诺华生物医学研究有限公司（中国上海）-正研究员（生物信息学）

（1）建立基于中国癌症患者的遗传学与表观遗传学全基因组数据库；

（2）利用高通量数据挖掘及高维建模的手段寻找针对肝癌胃癌等中国地区多发疾病的创新性靶点 ；

（3）深入研究中国癌症病人的分子分型，并基于此与转化医学部密切合作，将公司内部2，3期临床药物引进与相关靶点匹配的中国患者人群；

（4）为针对中国病人群体设计的临床试验和概念验证试验（POC ）寻找预测治疗有效性的生物靶标 ；

（5）带领生物信息团队全方位支持生物部门的实验设计及数据分析需求。

三、2009/6至2009/12：诺华制药（美国新泽西）-高级生物统计师

（1）服务于临床试验统计分析部门；

（2）主管两个诺华明星产品（RAD001）三期临床试验的实验设计，分析计划，以及数据分析工作。

四、2005/5至2009/5：宾西法尼亚大学生物统计咨询部（美国费城）-统计遗传学部门经理

带领一个六名统计师与程序员组成的团队，与宾夕法尼亚大学医学院的临床医生和教授合作，负责临床试验以及统计遗传学方面的所有项目。

五、2003/6至2005/6 ：斯隆癌症研究中心（美国纽约）-统计师

运用统计学计算方法进行基因芯片以及SNP方面的数据分析，以帮助医生研究癌症机制，对癌症进行基于遗传学，而非病理学的分子分型。

六、2002/5至2003/5：ONDEO Nalco 能源有限公司（美国德克萨斯州）-统计咨询师

建立石油添加物的数据库，进行高通量数据分析和挖掘，以预测石油添加物的油水分离效果。

[教育背景]

一、博士，生物统计学，美国宾西法尼亚大学（常青藤之一）医学院，2009年 ：

 GPA 3.9/4.0

 论文: “Statistical methods for analysis of structured genomic data”

二、硕士，统计学，美国德克萨斯农机大学，2002年：

 GPA 4.0/4.0

 论文: "Two-stage two-dimensional design for clinical trials controlling for efficacy and safety"

三、本科，生物化学，中国南开大学，1997年：

 GPA 3.6/4.0

[发表研究论文]

1、Liang W, He Q, Chen Y, Chuai S, Yin W, Wang W, Peng G, Zhou C, He J. “Metastatic EML4-ALK fusion detected by circulating DNA genotyping in an EGFR-mutated NSCLC patient and successful management by adding ALK inhibitors: a case report.” BMC Cancer. 2016 Feb 5;16(1):62.

2、Cai W, Lin D, Wu C, Li X, Zhao C, Zheng L, Chuai S, Fei K, Zhou C, Hirsch FR “Intratumoral Heterogeneity of ALK-Rearranged and ALK/EGFR Coaltered Lung Adenocarcinoma.” J Clin Oncol. 2015 Nov 10;33(32):3701-9. Epub 2015 Sep 28.

3、Fei Q, Shang K, Zhang J, Chuai S, Kong D, Zhou T, Fu S, Liang Y, Li C, Chen Z, Zhao Y, Yu Z, Huang Z, Hu M, Ying H, Chen Z, Zhang Y, Xing F, Zhu J, Xu H, Zhao K, Lu C, Atadja P, Xiao ZX, Li E, Shou J. “Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53.” Nat Commun. 2015 Oct 16;6:8651.

4、Gao H, Korn JM, Ferretti S, Monahan JE, Wang Y, Singh M, Zhang C, Schnell C, Yang G, Zhang Y, Balbin OA, Barbe S, Cai H, Casey F, Chatterjee S, Chiang DY, Chuai S, Cogan SM, Collins SD, Dammassa E, Ebel N2, Embry M, Green J, Kauffmann A, Kowal C, Leary RJ, Lehar J, Liang Y, Loo A, Lorenzana E, Robert McDonald E 3rd, McLaughlin ME, Merkin J, Meyer R, Naylor TL, Patawaran M, Reddy A, Röelli C, Ruddy DA, Salangsang  F, Santacroce F, Singh AP, Tang Y, Tinetto W, Tobler S, Velazquez R, Venkatesan K, Von Arx F, Wang HQ, Wang Z, Wiesmann M, Wyss D, Xu F, Bitter H, Atadja P, Lees E, Hofmann F, Li E, Keen N, Cozens R, Jensen MR, Pryer NK, Williams JA, Sellers WR “High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response.” Nat Med. 2015 Nov;21(11):1318-25. Epub 2015 Oct 19.

5、Yu Y, Dong L, Li D, Chuai S, Wu Z, Zheng X, Cheng Y, Han L, Yu J, Gao M “Targeted DNA Sequencing Detects Mutations Related to Susceptibility among Familial Non-medullary Thyroid Cancer.” Sci Rep. 2015 Nov 4;5:16129.

6、Yang LL, Zhang XC, Chuai SK, Chen ZH, Xie Z, Guo WB, Chen SL, Lei YY, Guo LH, Gou L, Sun HW, Zhang Q, Yang JJ, Tu HY, Su J, Wu YL “Integrative Analyses of Lung Squamous Cell Carcinoma in Ten Chinese Patients with Transcriptome Sequencing” J Genet Genomics. 2015 Oct 20;42(10):579-87. Epub 2015 Sep 30.

7、Huang Z, Wu H, Chuai S, Xu F, Yan F, Englund N, Wang Z, Zhang H, Fang M, Wang Y, Gu J, Zhang M, Yang T, Zhao K, Yu Y, Dai J, Yi W, Zhou S, Li Q, Wu J, Liu J, Wu X, Chan H, Lu C, Atadja P, Li E, Wang Y, Hu M “NSD2 Is Recruited through Its PHD Domain to Oncogenic Gene Loci to Drive Multiple Myeloma” Cancer Res. 2013 Oct 15; 73(20):6277-88.

8、Fitzgerald MP, Anderson RU, Potts J, Payne CK, Peters KM, Clemens JQ, Kotarinos R, Fraser L, Cosby A, Fortman C, Neville C, Badillo S, Odabachian L, Sanfield A, O'Dougherty B, Halle-Podell R, Cen L, Chuai S, Landis JR, Mickelberg K, Barrell T, Kusek JW, Nyberg LM; Urological Pelvic Pain Collaborative Research Network “Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes” J Urol. 2013 Jan;189(1 Suppl):S75-85.

9、Qi W, Chan H, Teng L, Li L, Chuai S, Zhang R, Zeng J, Li M, Fan H, Lin Y, Gu J, Ardayfio O, Zhang JH, Yan X, Fang J, Mi Y, Zhang M, Zhou T, Feng G, Chen Z, Li G, Yang T, Zhao K, Liu X, Yu Z, Lu CX, Atadja P, Li E “Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation” Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21360-5.

10、Jiang J, Zhang Y, Chuai S, Wang Z, Zheng D, Xu F, Zhang Y, Li C, Liang Y, Chen Z “Trastuzumab (herceptin) targets gastric cancer stem cells characterized by CD90 Phenotype” Oncogene. 2012 Feb 9;31(6):671-82.

11、Shijun Fu, Qi Fei, Hua Jiang, Shannon Chuai, Song Shi, Wen Xiong, Lei Jiang, Chris Lu, Peter Atadja, En Li, Jianyong Shou “Involvement of histon acetylation of Sox17 and Foxa2 promoters during mouse definitive endoderm differentiation revealed by microRNA profiling” PLoS ONE 6(11): e27965. doi: 10.1371.

12、Michel A Pontari, John N Krieger, Mark S Litwin, Paige C White, Rodney U Anderson, Mary McNaughton-Collins, J Curtis Nickel, Daniel A Shoskes, Richard B Alexander, Michael O’Leary, Scott Zeitlin, Shannon Chuai, J. Richard Landis, Liyi Cen, Kathleen J. Propert, John W Kusek, Leroy M Nyberg, Anthony J Schaeffer, and The Chronic Prostatitis Collaborative Research Network−2 (CPCRN−2) “Pregabalin for the Treatment of Men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized Controlled Trial” Arch Intern Med. 2010;170(17):1586-1593.

13、Rebbeck TR, Mitra N, Domchek SM, Wan F, Chuai S, Friebel TM, Panossian S, Spurdle A, Chenevix-Trench G; kConFab, Singer CF, Pfeiler G, Neuhausen SL, Lynch HT, Garber JE, Weitzel JN, Isaacs C, Couch F, Narod SA, Rubinstein WS, Tomlinson GE, Ganz PA, Olopade OI, Tung N, Blum JL, Greenberg R, Nathanson KL, Daly MB. “Modification of ovarian cancer risk by BRCA1/2-interacting genes in a multicenter cohort of BRCA1/2 mutation carriers” Cancer Res. 2009 Jul 15;69(14):5801-10. Epub 2009 Jul 7.

14、Beth D. Kaufman MD, Shannon Chuai MS, Fabienne Dobbels PhD and Robert E. Shaddy MD. “Wasting or Obesity at Time of Transplant Does Not Predict Pediatric Heart Transplant Outcomes: Analysis of ISHLT Pediatric Heart Transplant Registry” The Journal of Heart and Lung Transplantation Volume 28, Issue 12, December 2009, Pages 1273-1278.

15、J. Curtis Nickel, John Krieger, Paige C White, Mary McNaughton-Collins, Michael O’Leary, Rodney U Anderson, Robert Nadler, Michel Pontari, Daniel A. Shoskes, Mark S Litwin, Scott Zeitlin, Richard B Alexander, Richard Berger; Liong Men Long, Shannon Chuai, J. Richard Landis, John W Kusek, Leroy M Nyberg, Anthony J Schaeffer, and The Chronic Prostatitis Collaborative Research Network “Alfuzosin and Symptoms of Chronic Prostatitis–Chronic Pelvic Pain Syndrome” N Engl J Med 2008; 359:2663-2673.

16、James D. Lewis, Shaokun Chuai, Lisa Nessel, Gary R. Lichtenstein, Faten N. Aberra, Jonas H. Ellenberg "Use of the Non-invasive Components of the Mayo Score to Assess Clinical Response in Ulcerative Colitis" Inflamm Bowel Dis. 2008 Jul 11.

17、Curtis Nickel, Dean A. Tripp, Shannon Chuai, MarkS. Litwin, Mary McNaughton-Collins, J. Richard Landis, Richard B. Alexander,Anthony J. Schaeffer, Michael P. O’Leary, Michel A. Pontari, Paige White,Christopher Mullins, Leroy Nyberg, John Kusek, the NIH-CPCRN Study Group (2008) “Psychosocial variables affect the quality of life of men diagnosed with chronic prostatitis/chronic pelvic pain syndrome” BJU International 101 (1), 59–64.

18、Esther E. Vorovich, Shaokun Chuai, Mingyao Li, Justin Averna, Victor Marwin, David Wolfe, Muredach P. Reilly, Thomas P. Cappola “Comparison of matrix metalloproteinase 9 and brain natriuretic peptide as clinical biomarkers in chronic heart failure” American Heart JournalIn Press, Corrected Proof, , Available online 21 February 2008.

19、Desireddi NV, Campbell PL, Stern JA, Sobkoviak R, Chuai S, Shahrara S, Thumbikat P, Pope RM, Landis JR, Koch AE, Schaeffer AJ “Monocyte chemoattractant protein-1 and macrophage inflammatory protein-1alpha as possible biomarkers for the chronic pelvic pain syndrome.” J Urol. 2008 May;179(5):1857-61.

20、Inderpal S. Sarkaria, Maureen F. Zakowski, Duykhanh Pham, Michael Hezel, Michael I. Ebright, Shaokun Chuai, Ennapadam S. Venkatraman, Mark G. Kris, Valerie W. Rusch, Bhuvanesh Singh “Epidermal Growth Factor Receptor Signaling in Adenocarcinomas With Bronchioloalveolar Components” The Annals of Thoracic SurgeryVolume 85, Issue 1, , January 2008, Pages 216-223.

21、J. Lewis, G. Lichtenstein, J. Deren, S. Chuai, J. Ellenberg, L. Nessel, G. Wu, B. Sands, S. Hanauer, J. Katz “Rosiglitazone for Active Ulcerative Colitis: A Randomized Placebo-Controlled Trial.” Gastroenterology. 2008 Mar ;134 (3):688-695.

22、Ian Ganly, Simon Talbot, Diane Carlson, Agnes Viale, Ellie Maghami, Iman Osman, Eric Sherman, David Pfister, Shaokun Chuai, Ashok R. Shaha, Dennis Kraus, Jatin P. Shah, Nicholas D. Socci, Bhuvanesh Singh “Identification of Angiogenesis/Metastases Genes Predicting Chemoradiotherapy Response in Patients With Laryngopharyngeal Carcinoma” Journal of Clinical Oncology, Vol 25, No 11 (April 10), 2007: pp. 1369-1376.

23、Laé M, Ahn EH, Mercado GE, Chuai S, Edgar M, Pawel BR, Olshen A, Barr FG, Ladanyi M “Global Gene Expression Profiling of PAX-FKHR fusion-positive alveolar and PAX-FKHR fusion-negative embryonal rhabdomyosarcomas” Journal of Pathology 2007 Jun; 212(2): 143-151.

24、O'Reardon JP, Cristancho P, Pilania P, Bapatla KB, Chuai S, Peshek AD “Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion.” Depress Anxiety. 2007;24(8):537-44.

25、Javier Cotignola, Boris Reva, Nandita Mitra, Nicole Ishill, Shaokun Chuai, Ami Patel, Shivang Shah, Gretchen Vanderbeek, Daniel Coit, Klaus Busam, Allan Halpern, Alan Houghton, Chris Sander, Marianne Berwick and Irene Orlow “Matrix Metalloproteinase-9 (MMP-9) polymorphisms in patients with cutaneous malignant melanoma” BMC Medical Genetics 2007, 8:10.

26、DuyKhanh Pham, Mark G. Kris, Gregory J. Riely, Inderpal S. Sarkaria, Tiffani McDonough, Shaokun Chuai, Ennapadam S. Venkatraman, Vincent A. Miller, Marc Ladanyi, William Pao, Richard K. Wilson, Bhuvanesh Singh, Valerie W. Rusch. “Use of Cigarette-Smoking History to Estimate the Likelihood of Mutations in Epidermal Growth Factor Receptor Gene Exons 19 and 21 in Lung Adenocarcinomas” Journal of Clinical Oncology, Vol 24, No 11 (April 10), 2006: pp. 1700-1704.

27、Fernando López-Ríos, Shannon Chuai, Raja Flores, Shigeki Shimizu, Takatoshi Ohno, Kazuhiko Wakahara, Peter B. Illei, Sanaa Hussain, Lee Krug, Maureen F. Zakowski, Valerie Rusch, Adam B. Olshen and Marc Ladanyi. “Global Gene Expression Profiling of Pleural Mesotheliomas: Overexpression of Aurora Kinases and P16/CDKN2A Deletion as Prognostic Factors and Critical Evaluation of Microarray-Based Prognostic Prediction” Cancer Research 66, 2970-2979, March 15, 2006.

28、Hiltzik D, Carlson DL, Tuttle RM, Chuai S, Ishill N, Shaha A, Shah JP, Singh B, Ghossein RA. “Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis: a clinicopathologic study of 58 patients” Cancer. 2006 Mar 15;10 (6):1286-95.

29、Ellis NA, Kirchhoff T, Mitra N, Ye TZ, Chuai S, Huang H, Nafa K, Norton L, Neuhausen S, Gordon D, Struewing JP, Narod S, Offit K. “Localization of breast cancer susceptibility loci by genome-wide SNP linkage disequilibrium mapping” Genet Epidemiol. 2006 Jan;30(1):48-61.

30、Deborah Goldfrank , Shannon Chuai, Jonine L Bernstein , Teresa Ramon Y Cajal , Johanna B Lee , M Carmen Alonso , Orland Diez , Monserrat Baiget , Noah D Kauff , Kenneth Offit , Mark Robson. “Effect of Mammography on Breast Cancer Risk in Women with Mutations in BRCA1 or BRCA2” Cancer Epidemiol Biomarkers Prev. 2006 Nov ;15 (11):2311-2313.

31、Leiser AL, Anderson SE, Nonaka D, Chuai S,Olshen AB, Chi DS, Soslow RA. “Apoptotic and cell cycle regulatory markers in uterine leiomyosarcoma” Gynecol Oncol. 2006 Apr;101(1):86-91.

32、S.E. Anderson, D. Nonaka, S. Chuai, A.B. Olshen, D. Chi, P. Sabbatini & R.A. Soslow. “p53, epidermal growth factor, and platelet-derived growth factor in uterine leiomyosarcoma and leiomyomas” International Journal of Gynecological Cancer, 2006, Volume 16: 849.

33、J. Dupont, C. Aghajanian, G. Andrea, M. Lovegren, S. Chuai, E. Venkatraman, M. Hensley, S. Anderson, D. Spriggs & P. Sabbatini. “Topotecan and liposomal doxorubicin in recurrent ovarian cancer: is sequence important?” International Journal of Gynecological Cancer, 2006,Volume 16: 68.

34、John P O'reardon , Pilar Cristancho , Pramod Pilania , Kiran B Bapatla , Shaokun Chuai , Andrew D Peshek. “Patients with a major depressive episode responding to treatment with repetitive transcranial magnetic stimulation (rTMS) are resistant to the effects of rapid tryptophan depletion” Depress Anxiety. 2006 Nov.

35、Paolo Peterlongo, Nandita Mitra, Shaokun Chuai, Tomas Kirchhoff, Crystal Palmer, Helen Huang, Khedoudja Nafa, Kenneth Offit, Nathan A. Ellis. “Colorectal cancer risk in individuals with biallelic or monoallelic mutations of MYH” Int J Cancer. 2005 Apr 10;114(3):505-7.

36、Noah D. Kauff, Nandita Mitra, Mark E. Robson, Karen E. Hurley, Shaokun Chuai, Deborah Goldfrank, Eve Wadsworth, Johanna Lee, Tessa Cigler, Patrick I. Borgen, Larry Norton, Richard R. Barakat, Kenneth Offit. “Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Negative Hereditary Breast Cancer Families” J Natl Cancer Inst. 2005; 97: 1382-1384.

37、M. A. Sovak, S. Chuai, S. Anderson, R. Barakat, J. Dupont, M. L. Hensley, P. Sabbatini, D. R. Spriggs and C. Aghajanian . “Paclitaxel and carboplatin (TP) for treatment of advanced or recurrent endometrial cancer: A retrospective study” American Society of Clinical Oncology, Vol 23, No 16S (June 1 Supplement), 2005: 5020.

38、Michael K. Poindexter, Shaokun Chuai, Robert A. Marble, and Samuel C. Marsh “Solid Content Dominates Emulsion Stability Predictions” Energy Fuels 2005, 19 (4), 1346-1352.

39、Adam Olshen, Shaokun Chuai, William Gerald. “Validating Microarray Results across Institutions or over Time” The Joint Statistical Meeting, Minneapolis, MN, USA, 7-11 August 2005. (Presentation)

40、Nandita Mitra, Tian-Zhang Ye, Alex Smith, Shaokun Chuai, Tomas Kirchhoff, Paolo Peterlongo, Khedoudja Nafa, Michael S. Phillips, Kenneth Offit and Nathan A. Ellis. “Localization of Cancer Susceptibility Genes by Genome-wide Single-Nucleotide Polymorphism Linkage-Disequilibrium Mapping” Cancer Res. 2004 Nov 1;64(21):8116-25.

41、Inderpal S. Sarkaria, DuyKhanh Pham, Ronald A. Ghossein, Simon G. Talbot, Michael Hezel, Maria E. Dudas, Michael I. Ebright, Shaokun Chuai, Natalie Memoli, Ennapadam S. Venkatraman, Vincent A. Miller, Mark G. Kris, Maureen F. Zakowski, Valerie W. Rusch, Bhuvanesh Singh “SCCRO Expression Correlates With Invasive Progression in Bronchioloalveolar

Carcinoma” Ann Thorac Surg 2004; 78: 1734-1741.

42、C. D. Murphy, A. B. Olshen, S. Chuai, A. Viale, S.-W. Kim, P. I. Borgen, C. Hudis and J. Boyd “Gene Expression Profiling of BRCA1-mutant Human Breast Cancer Cells after Exposure to Tamoxifen Plus Estrogen” Journal of Clinical Oncology 2004, Vol 22, No 14S: 9620.

43、Jiang Liu, Zhaoxia Liu, Shaokun Chuai and Xun Shen “Phospholipase C and Phosphatidylinositol 3-Kinase Signaling are Involved in the Exogenous Arachidonic Acid-stimulated Respiratory Burst in Human Neutrophils” Journal of Leukocyte Biology 2003; 74: 428-437.

44、Shaokun Chuai, Tianhui Hu, and Xun Shen “Regulation of the Arachidonic Acid-stimulated Respiratory Burst in Neutrophils by Intra-cellular and Extra-cellular Calcium” Chinese Science Bulletin 2000, Vol.46 (4), 314-317.