Renormalization-group study of Anderson and Kondo impurities in gapless Fermi systems
Analysis of Genetic Diversity and Population Structure

Agricultural Sciences in China2010, 9(9): 1251-1262September 2010Received 30 October, 2009 Accepted 16 April, 2010Analysis of Genetic Diversity and Population Structure of Maize Landraces from the South Maize Region of ChinaLIU Zhi-zhai 1, 2, GUO Rong-hua 2, 3, ZHAO Jiu-ran 4, CAI Yi-lin 1, W ANG Feng-ge 4, CAO Mo-ju 3, W ANG Rong-huan 2, 4, SHI Yun-su 2, SONG Yan-chun 2, WANG Tian-yu 2 and LI Y u 21Maize Research Institute, Southwest University, Chongqing 400716, P.R.China2Institue of Crop Sciences/National Key Facility for Gene Resources and Genetic Improvement, Chinese Academy of Agricultural Sciences,Beijing 100081, P.R.China3Maize Research Institute, Sichuan Agricultural University, Ya’an 625014, P.R.China4Maize Research Center, Beijing Academy of Agricultural and Forestry Sciences, Beijing 100089, P.R.ChinaAbstractUnderstanding genetic diversity and population structure of landraces is important in utilization of these germplasm in breeding programs. In the present study, a total of 143 core maize landraces from the South Maize Region (SR) of China,which can represent the general profile of the genetic diversity in the landraces germplasm of SR, were genotyped by 54DNA microsatellite markers. Totally, 517 alleles (ranging from 4 to 22) were detected among these landraces, with an average of 9.57 alleles per locus. The total gene diversity of these core landraces was 0.61, suggesting a rather higher level of genetic diversity. Analysis of population structure based on Bayesian method obtained the samilar result as the phylogeny neighbor-joining (NJ) method. The results indicated that the whole set of 143 core landraces could be clustered into two distinct groups. All landraces from Guangdong, Hainan, and 15 landraces from Jiangxi were clustered into group 1, while those from the other regions of SR formed the group 2. The results from the analysis of genetic diversity showed that both of groups possessed a similar gene diversity, but group 1 possessed relatively lower mean alleles per locus (6.63) and distinct alleles (91) than group 2 (7.94 and 110, respectively). The relatively high richness of total alleles and distinct alleles preserved in the core landraces from SR suggested that all these germplasm could be useful resources in germplasm enhancement and maize breeding in China.Key words :maize, core landraces, genetic diversity, population structureINTRODUCTIONMaize has been grown in China for nearly 500 years since its first introduction into this second biggest pro-duction country in the world. Currently, there are six different maize growing regions throughout the coun-try according to the ecological conditions and farming systems, including three major production regions,i.e., the North Spring Maize Region, the Huang-Huai-Hai Summer Maize Region, and the Southwest MaizeRegion, and three minor regions, i.e., the South Maize Region, the Northwest Maize Region, and the Qingzang Plateau Maize Region. The South Maize Region (SR)is specific because of its importance in origin of Chi-nese maize. It is hypothesized that Chinese maize is introduced mainly from two routes. One is called the land way in which maize was first brought to Tibet from India, then to Sichuan Province in southwestern China. The other way is that maize dispersed via the oceans, first shipped to the coastal areas of southeast China by boats, and then spread all round the country1252LIU Zhi-zhai et al.(Xu 2001; Zhou 2000). SR contains all of the coastal provinces and regions lie in southeastern China.In the long-term cultivation history of maize in south-ern China, numerous landraces have been formed, in which a great amount of genetic variation was observed (Li 1998). Similar to the hybrid swapping in Europe (Reif et al. 2005a), the maize landraces have been al-most replaced by hybrids since the 1950s in China (Li 1998). However, some landraces with good adapta-tions and yield performances are still grown in a few mountainous areas of this region (Liu et al.1999). Through a great effort of collection since the 1950s, 13521 accessions of maize landraces have been cur-rently preserved in China National Genebank (CNG), and a core collection of these landraces was established (Li et al. 2004). In this core collection, a total of 143 maize landrace accessions were collected from the South Maize Region (SR) (Table 1).Since simple sequence repeat ( SSR ) markers were firstly used in human genetics (Litt and Luty 1989), it now has become one of the most widely used markers in the related researches in crops (Melchinger et al. 1998; Enoki et al. 2005), especially in the molecular characterization of genetic resources, e.g., soybean [Glycine max (L.) Merr] (Xie et al. 2005), rice (Orya sativa L.) (Garris et al. 2005), and wheat (Triticum aestivum) (Chao et al. 2007). In maize (Zea mays L.), numerous studies focusing on the genetic diversity and population structure of landraces and inbred lines in many countries and regions worldwide have been pub-lished (Liu et al. 2003; Vegouroux et al. 2005; Reif et al. 2006; Wang et al. 2008). These activities of documenting genetic diversity and population structure of maize genetic resources have facilitated the under-standing of genetic bases of maize landraces, the utili-zation of these resources, and the mining of favorable alleles from landraces. Although some studies on ge-netic diversity of Chinese maize inbred lines were con-ducted (Yu et al. 2007; Wang et al. 2008), the general profile of genetic diversity in Chinese maize landraces is scarce. Especially, there are not any reports on ge-netic diversity of the maize landraces collected from SR, a possibly earliest maize growing area in China. In this paper, a total of 143 landraces from SR listed in the core collection of CNG were genotyped by using SSR markers, with the aim of revealing genetic diver-sity of the landraces from SR (Table 2) of China and examining genetic relationships and population struc-ture of these landraces.MATERIALS AND METHODSPlant materials and DNA extractionTotally, 143 landraces from SR which are listed in the core collection of CNG established by sequential strati-fication method (Liu et al. 2004) were used in the present study. Detailed information of all these landrace accessions is listed in Table 1. For each landrace, DNA sample was extracted by a CTAB method (Saghi-Maroof et al. 1984) from a bulk pool constructed by an equal-amount of leaves materials sampled from 15 random-chosen plants of each landrace according to the proce-dure of Reif et al. (2005b).SSR genotypingA total of 54 simple sequence repeat (SSR) markers covering the entire maize genome were screened to fin-gerprint all of the 143 core landrace accessions (Table 3). 5´ end of the left primer of each locus was tailed by an M13 sequence of 5´-CACGACGTTGTAAAACGAC-3´. PCR amplification was performed in a 15 L reac-tion containing 80 ng of template DNA, 7.5 mmol L-1 of each of the four dNTPs, 1×Taq polymerase buffer, 1.5 mmol L-1 MgCl2, 1 U Taq polymerase (Tiangen Biotech Co. Ltd., Beijing, China), 1.2 mol L-1 of forward primer and universal fluorescent labeled M13 primer, and 0.3 mol L-1 of M13 sequence tailed reverse primer (Schuelke 2000). The amplification was carried out in a 96-well DNA thermal cycler (GeneAmp PCR System 9700, Applied Biosystem, USA). PCR products were size-separated on an ABI Prism 3730XL DNA sequencer (HitachiHigh-Technologies Corporation, Tokyo, Japan) via the software packages of GENEMAPPER and GeneMarker ver. 6 (SoftGenetics, USA).Data analysesAverage number of alleles per locus and average num-ber of group-specific alleles per locus were identifiedAnalysis of Genetic Diversity and Population Structure of Maize Landraces from the South Maize Region of China 1253Table 1 The detailed information about the landraces used in the present studyPGS revealed by Structure1) NJ dendragram revealed Group 1 Group 2 by phylogenetic analysis140-150tian 00120005AnH-06Jingde Anhui 0.0060.994Group 2170tian00120006AnH-07Jingde Anhui 0.0050.995Group 2Zixihuangyumi00120007AnH-08Zixi Anhui 0.0020.998Group 2Zixibaihuangzayumi 00120008AnH-09Zixi Anhui 0.0030.997Group 2Baiyulu 00120020AnH-10Yuexi Anhui 0.0060.994Group 2Wuhuazi 00120021AnH-11Yuexi Anhui 0.0030.997Group 2Tongbai 00120035AnH-12Tongling Anhui 0.0060.994Group 2Yangyulu 00120036AnH-13Yuexi Anhui 0.0040.996Group 2Huangli 00120037AnH-14Tunxi Anhui 0.0410.959Group 2Baiyumi 00120038AnH-15Tunxi Anhui 0.0030.997Group 2Dapigu00120039AnH-16Tunxi Anhui 0.0350.965Group 2150tianbaiyumi 00120040AnH-17Xiuning Anhui 0.0020.998Group 2Xiuning60tian 00120042AnH-18Xiuning Anhui 0.0040.996Group 2Wubaogu 00120044AnH-19ShitaiAnhui 0.0020.998Group 2Kuyumi00130001FuJ-01Shanghang Fujian 0.0050.995Group 2Zhongdouyumi 00130003FuJ-02Shanghang Fujian 0.0380.962Group 2Baixinyumi 00130004FuJ-03Liancheng Fujian 0.0040.996Group 2Hongxinyumi 00130005FuJ-04Liancheng Fujian 0.0340.966Group 2Baibaogu 00130008FuJ-05Changding Fujian 0.0030.997Group 2Huangyumi 00130011FuJ-06Jiangyang Fujian 0.0020.998Group 2Huabaomi 00130013FuJ-07Shaowu Fujian 0.0020.998Group 2Huangbaomi 00130014FuJ-08Songxi Fujian 0.0020.998Group 2Huangyumi 00130016FuJ-09Wuyishan Fujian 0.0460.954Group 2Huabaogu 00130019FuJ-10Jian’ou Fujian 0.0060.994Group 2Huangyumi 00130024FuJ-11Guangze Fujian 0.0010.999Group 2Huayumi 00130025FuJ-12Nanping Fujian 0.0040.996Group 2Huangyumi 00130026FuJ-13Nanping Fujian 0.0110.989Group 2Hongbaosu 00130027FuJ-14Longyan Fujian 0.0160.984Group 2Huangfansu 00130029FuJ-15Loangyan Fujian 0.0020.998Group 2Huangbaosu 00130031FuJ-16Zhangping Fujian 0.0060.994Group 2Huangfansu 00130033FuJ-17Zhangping Fujian0.0040.996Group 2Baolieyumi 00190001GuangD-01Guangzhou Guangdong 0.9890.011Group 1Nuomibao (I)00190005GuangD-02Shixing Guangdong 0.9740.026Group 1Nuomibao (II)00190006GuangD-03Shixing Guangdong 0.9790.021Group 1Zasehuabao 00190010GuangD-04Lechang Guangdong 0.9970.003Group 1Zihongmi 00190013GuangD-05Lechang Guangdong 0.9880.012Group 1Jiufengyumi 00190015GuangD-06Lechang Guangdong 0.9950.005Group 1Huangbaosu 00190029GuangD-07MeiGuangdong 0.9970.003Group 1Bailibao 00190032GuangD-08Xingning Guangdong 0.9980.002Group 1Nuobao00190038GuangD-09Xingning Guangdong 0.9980.002Group 1Jinlanghuang 00190048GuangD-10Jiangcheng Guangdong 0.9960.004Group 1Baimizhenzhusu 00190050GuangD-11Yangdong Guangdong 0.9940.006Group 1Huangmizhenzhusu 00190052GuangD-12Yangdong Guangdong 0.9930.007Group 1Baizhenzhu 00190061GuangD-13Yangdong Guangdong 0.9970.003Group 1Baiyumi 00190066GuangD-14Wuchuan Guangdong 0.9880.012Group 1Bendibai 00190067GuangD-15Suixi Guangdong 0.9980.002Group 1Shigubaisu 00190068GuangD-16Gaozhou Guangdong 0.9960.004Group 1Zhenzhusu 00190069GuangD-17Xinyi Guangdong 0.9960.004Group 1Nianyaxixinbai 00190070GuangD-18Huazhou Guangdong 0.9960.004Group 1Huangbaosu 00190074GuangD-19Xinxing Guangdong 0.9950.005Group 1Huangmisu 00190076GuangD-20Luoding Guangdong 0.940.060Group 1Huangmi’ai 00190078GuangD-21Luoding Guangdong 0.9980.002Group 1Bayuemai 00190084GuangD-22Liannan Guangdong 0.9910.009Group 1Baiyumi 00300001HaiN-01Haikou Hainan 0.9960.004Group 1Baiyumi 00300003HaiN-02Sanya Hainan 0.9970.003Group 1Hongyumi 00300004HaiN-03Sanya Hainan 0.9980.002Group 1Baiyumi00300011HaiN-04Tongshi Hainan 0.9990.001Group 1Zhenzhuyumi 00300013HaiN-05Tongshi Hainan 0.9980.002Group 1Zhenzhuyumi 00300015HaiN-06Qiongshan Hainan 0.9960.004Group 1Aiyumi 00300016HaiN-07Qiongshan Hainan 0.9960.004Group 1Huangyumi 00300021HaiN-08Qionghai Hainan 0.9970.003Group 1Y umi 00300025HaiN-09Qionghai Hainan 0.9870.013Group 1Accession name Entry code Analyzing code Origin (county/city)Province/Region1254LIU Zhi-zhai et al .Baiyumi00300032HaiN-10Tunchang Hainan 0.9960.004Group 1Huangyumi 00300051HaiN-11Baisha Hainan 0.9980.002Group 1Baihuangyumi 00300055HaiN-12BaishaHainan 0.9970.003Group 1Machihuangyumi 00300069HaiN-13Changjiang Hainan 0.9900.010Group 1Hongyumi00300073HaiN-14Dongfang Hainan 0.9980.002Group 1Xiaohonghuayumi 00300087HaiN-15Lingshui Hainan 0.9980.002Group 1Baiyumi00300095HaiN-16Qiongzhong Hainan 0.9950.005Group 1Y umi (Baimai)00300101HaiN-17Qiongzhong Hainan 0.9980.002Group 1Y umi (Xuemai)00300103HaiN-18Qiongzhong Hainan 0.9990.001Group 1Huangmaya 00100008JiangS-10Rugao Jiangsu 0.0040.996Group 2Bainian00100012JiangS-11Rugao Jiangsu 0.0080.992Group 2Bayebaiyumi 00100016JiangS-12Rudong Jiangsu 0.0040.996Group 2Chengtuohuang 00100021JiangS-13Qidong Jiangsu 0.0050.995Group 2Xuehuanuo 00100024JiangS-14Qidong Jiangsu 0.0020.998Group 2Laobaiyumi 00100032JiangS-15Qidong Jiangsu 0.0050.995Group 2Laobaiyumi 00100033JiangS-16Qidong Jiangsu 0.0010.999Group 2Huangwuye’er 00100035JiangS-17Hai’an Jiangsu 0.0030.997Group 2Xiangchuanhuang 00100047JiangS-18Nantong Jiangsu 0.0060.994Group 2Huangyingzi 00100094JiangS-19Xinghua Jiangsu 0.0040.996Group 2Xiaojinhuang 00100096JiangS-20Yangzhou Jiangsu 0.0010.999Group 2Liushizi00100106JiangS-21Dongtai Jiangsu 0.0030.997Group 2Kangnandabaizi 00100108JiangS-22Dongtai Jiangsu 0.0020.998Group 2Shanyumi 00140020JiangX-01Dexing Jiangxi 0.9970.003Group 1Y umi00140024JiangX-02Dexing Jiangxi 0.9970.003Group 1Tianhongyumi 00140027JiangX-03Yushan Jiangxi 0.9910.009Group 1Hongganshanyumi 00140028JiangX-04Yushan Jiangxi 0.9980.002Group 1Zaoshuyumi 00140032JiangX-05Qianshan Jiangxi 0.9970.003Group 1Y umi 00140034JiangX-06Wannian Jiangxi 0.9970.003Group 1Y umi 00140038JiangX-07De’an Jiangxi 0.9940.006Group 1Y umi00140045JiangX-08Wuning Jiangxi 0.9740.026Group 1Chihongyumi 00140049JiangX-09Wanzai Jiangxi 0.9920.008Group 1Y umi 00140052JiangX-10Wanzai Jiangxi 0.9930.007Group 1Huayumi 00140060JiangX-11Jing’an Jiangxi 0.9970.003Group 1Baiyumi 00140065JiangX-12Pingxiang Jiangxi 0.9940.006Group 1Huangyumi00140066JiangX-13Pingxiang Jiangxi 0.9680.032Group 1Nuobaosuhuang 00140068JiangX-14Ruijin Jiangxi 0.9950.005Group 1Huangyumi 00140072JiangX-15Xinfeng Jiangxi 0.9960.004Group 1Wuningyumi 00140002JiangX-16Jiujiang Jiangxi 0.0590.941Group 2Tianyumi 00140005JiangX-17Shangrao Jiangxi 0.0020.998Group 2Y umi 00140006JiangX-18Shangrao Jiangxi 0.0310.969Group 2Baiyiumi 00140012JiangX-19Maoyuan Jiangxi 0.0060.994Group 260riyumi 00140016JiangX-20Maoyuan Jiangxi 0.0020.998Group 2Shanyumi 00140019JiangX-21Dexing Jiangxi 0.0050.995Group 2Laorenya 00090002ShangH-01Chongming Shanghai 0.0050.995Group 2Jinmeihuang 00090004ShangH-02Chongming Shanghai 0.0020.998Group 2Zaobaiyumi 00090006ShangH-03Chongming Shanghai 0.0020.998Group 2Chengtuohuang 00090007ShangH-04Chongming Shanghai 0.0780.922Group 2Benyumi (Huang)00090008ShangH-05Shangshi Shanghai 0.0020.998Group 2Bendiyumi 00090010ShangH-06Shangshi Shanghai 0.0040.996Group 2Baigengyumi 00090011ShangH-07Jiading Shanghai 0.0020.998Group 2Huangnuoyumi 00090012ShangH-08Jiading Shanghai 0.0040.996Group 2Huangdubaiyumi 00090013ShangH-09Jiading Shanghai 0.0440.956Group 2Bainuoyumi 00090014ShangH-10Chuansha Shanghai 0.0010.999Group 2Laorenya 00090015ShangH-11Shangshi Shanghai 0.0100.990Group 2Xiaojinhuang 00090016ShangH-12Shangshi Shanghai 0.0050.995Group 2Gengbaidayumi 00090017ShangH-13Shangshi Shanghai 0.0020.998Group 2Nongmeiyihao 00090018ShangH-14Shangshi Shanghai 0.0540.946Group 2Chuanshazinuo 00090020ShangH-15Chuansha Shanghai 0.0550.945Group 2Baoanshanyumi 00110004ZheJ-01Jiangshan Zhejiang 0.0130.987Group 2Changtaixizi 00110005ZheJ-02Jiangshan Zhejiang 0.0020.998Group 2Shanyumibaizi 00110007ZheJ-03Jiangshan Zhejiang 0.0020.998Group 2Kaihuajinyinbao 00110017ZheJ-04Kaihua Zhejiang 0.0100.990Group 2Table 1 (Continued from the preceding page)PGS revealed by Structure 1) NJ dendragram revealed Group1 Group2 by phylogenetic analysisAccession name Entry code Analyzing code Origin (county/city)Province/RegoinAnalysis of Genetic Diversity and Population Structure of Maize Landraces from the South Maize Region of China 1255Liputianzi00110038ZheJ-05Jinhua Zhejiang 0.0020.998Group 2Jinhuaqiuyumi 00110040ZheJ-06Jinhua Zhejiang 0.0050.995Group 2Pujiang80ri 00110069ZheJ-07Pujiang Zhejiang 0.0210.979Group 2Dalihuang 00110076ZheJ-08Yongkang Zhejiang 0.0140.986Group 2Ziyumi00110077ZheJ-09Yongkang Zhejiang 0.0020.998Group 2Baiyanhandipinzhong 00110078ZheJ-10Yongkang Zhejiang 0.0030.997Group 2Duosuiyumi00110081ZheJ-11Wuyi Zhejiang 0.0020.998Group 2Chun’an80huang 00110084ZheJ-12Chun’an Zhejiang 0.0020.998Group 2120ribaiyumi 00110090ZheJ-13Chun’an Zhejiang 0.0020.998Group 2Lin’anliugu 00110111ZheJ-14Lin’an Zhejiang 0.0030.997Group 2Qianhuangyumi00110114ZheJ-15Lin’an Zhejiang 0.0030.997Group 2Fenshuishuitianyumi 00110118ZheJ-16Tonglu Zhejiang 0.0410.959Group 2Kuihualiugu 00110119ZheJ-17Tonglu Zhejiang 0.0030.997Group 2Danbaihuang 00110122ZheJ-18Tonglu Zhejiang 0.0020.998Group 2Hongxinma 00110124ZheJ-19Jiande Zhejiang 0.0030.997Group 2Shanyumi 00110136ZheJ-20Suichang Zhejiang 0.0030.997Group 2Bai60ri 00110143ZheJ-21Lishui Zhejiang 0.0050.995Group 2Zeibutou 00110195ZheJ-22Xianju Zhejiang 0.0020.998Group 2Kelilao00110197ZheJ-23Pan’an Zhejiang 0.0600.940Group 21)The figures refered to the proportion of membership that each landrace possessed.Table 1 (Continued from the preceding page)PGS revealed by Structure 1) NJ dendragram revealed Group 1 Group 2 by phylogenetic analysisAccession name Entry code Analyzing code Origin (county/city)Province/Regoin Table 2 Construction of two phylogenetic groups (SSR-clustered groups) and their correlation with geographical locationsGeographical location SSR-clustered groupChi-square testGroup 1Group 2Total Guangdong 2222 χ2 = 124.89Hainan 1818P < 0.0001Jiangxi 15621Anhui 1414Fujian 1717Jiangsu 1313Shanghai 1515Zhejiang 2323Total5588143by the software of Excel MicroSatellite toolkit (Park 2001). Average number of alleles per locus was calcu-lated by the formula rAA rj j¦1, with the standarddeviation of1)()(12¦ r A AA rj jV , where A j was thenumber of distinct alleles at locus j , and r was the num-ber of loci (Park 2001).Unbiased gene diversity also known as expected heterozygosity, observed heterozygosity for each lo-cus and average gene diversity across the 54 SSR loci,as well as model-based groupings inferred by Struc-ture ver. 2.2, were calculated by the softwarePowerMarker ver.3.25 (Liu et al . 2005). Unbiased gene diversity for each locus was calculated by˅˄¦ 2ˆ1122ˆi x n n h , where 2ˆˆ2ˆ2¦¦z ji ijij i X X x ,and ij X ˆwas the frequency of genotype A i A jin the sample, and n was the number of individuals sampled.The average gene diversity across 54 loci was cal-culated as described by Nei (1987) as follows:rh H rj j ¦1ˆ, with the variance ,whereThe average observed heterozygosity across the en-tire loci was calculated as described by (Hedrick 1983)as follows: r jrj obsobs n h h ¦1, with the standard deviationrn h obs obsobs 1V1256LIU Zhi-zhai et al.Phylogenetic analysis and population genetic structureRelationships among all of the 143 accessions collected from SR were evaluated by using the unweighted pair group method with neighbor-joining (NJ) based on the log transformation of the proportion of shared alleles distance (InSPAD) via PowerMarker ver. 3.25 (FukunagaTable 3 The PIC of each locus and the number of alleles detected by 54 SSRsLocus Bin Repeat motif PIC No. of alleles Description 2)bnlg1007y51) 1.02AG0.7815Probe siteumc1122 1.06GGT0.639Probe siteumc1147y41) 1.07CA0.2615Probe sitephi961001) 2.00ACCT0.298Probe siteumc1185 2.03GC0.7215ole1 (oleosin 1)phi127 2.08AGAC0.577Probe siteumc1736y21) 2.09GCA T0.677Probe sitephi453121 3.01ACC0.7111Probe sitephi374118 3.03ACC0.477Probe sitephi053k21) 3.05A TAC0.7910Probe sitenc004 4.03AG0.4812adh2 (alcohol dehydrogenase 2)bnlg490y41) 4.04T A0.5217Probe sitephi079 4.05AGATG0.495gpc1(glyceraldehyde-3-phosphate dehydrogenase 1) bnlg1784 4.07AG0.6210Probe siteumc1574 4.09GCC0.719sbp2 (SBP-domain protein 2)umc1940y51) 4.09GCA0.4713Probe siteumc1050 4.11AA T0.7810cat3 (catalase 3)nc130 5.00AGC0.5610Probe siteumc2112y31) 5.02GA0.7014Probe sitephi109188 5.03AAAG0.719Probe siteumc1860 5.04A T0.325Probe sitephi085 5.07AACGC0.537gln4 (glutamine synthetase 4)phi331888 5.07AAG0.5811Probe siteumc1153 5.09TCA0.7310Probe sitephi075 6.00CT0.758fdx1 (ferredoxin 1)bnlg249k21) 6.01AG0.7314Probe sitephi389203 6.03AGC0.416Probe sitephi299852y21) 6.07AGC0.7112Probe siteumc1545y21)7.00AAGA0.7610hsp3(heat shock protein 3)phi1127.01AG0.5310o2 (opaque endosperm 2)phi4207018.00CCG0.469Probe siteumc13598.00TC0.7814Probe siteumc11398.01GAC0.479Probe siteumc13048.02TCGA0.335Probe sitephi1158.03A TAC0.465act1(actin1)umc22128.05ACG0.455Probe siteumc11218.05AGAT0.484Probe sitephi0808.08AGGAG0.646gst1 (glutathione-S-transferase 1)phi233376y11)8.09CCG0.598Probe sitebnlg12729.00AG0.8922Probe siteumc20849.01CTAG0.498Probe sitebnlg1520k11)9.01AG0.5913Probe sitephi0659.03CACCT0.519pep1(phosphoenolpyruvate carboxylase 1)umc1492y131)9.04GCT0.2514Probe siteumc1231k41)9.05GA0.2210Probe sitephi1084119.06AGCT0.495Probe sitephi4488809.06AAG0.7610Probe siteumc16759.07CGCC0.677Probe sitephi041y61)10.00AGCC0.417Probe siteumc1432y61)10.02AG0.7512Probe siteumc136710.03CGA0.6410Probe siteumc201610.03ACAT0.517pao1 (polyamine oxidase 1)phi06210.04ACG0.337mgs1 (male-gametophyte specific 1)phi07110.04GGA0.515hsp90 (heat shock protein, 90 kDa)1) These primers were provided by Beijing Academy of Agricultural and Forestry Sciences (Beijing, China).2) Searched from Analysis of Genetic Diversity and Population Structure of Maize Landraces from the South Maize Region of China1257et al. 2005). The unrooted phylogenetic tree was finally schematized with the software MEGA (molecular evolu-tionary genetics analysis) ver. 3.1 (Kumar et al. 2004). Additionally, a chi-square test was used to reveal the correlation between the geographical origins and SSR-clustered groups through FREQ procedure implemented in SAS ver. 9.0 (2002, SAS Institute, Inc.).In order to reveal the population genetic structure (PGS) of 143 landrace accessions, a Bayesian approach was firstly applied to determine the number of groups (K) that these materials should be assigned by the soft-ware BAPS (Bayesian Analysis of Population Structure) ver.5.1. By using BAPS, a fixed-K clustering proce-dure was applied, and with each separate K, the num-ber of runs was set to 100, and the value of log (mL) was averaged to determine the appropriate K value (Corander et al. 2003; Corander and Tang 2007). Since the number of groups were determined, a model-based clustering analysis was used to assign all of the acces-sions into the corresponding groups by an admixture model and a correlated allele frequency via software Structure ver.2.2 (Pritchard et al. 2000; Falush et al. 2007), and for the given K value determined by BAPS, three independent runs were carried out by setting both the burn-in period and replication number 100000. The threshold probability assigned individuals into groupswas set by 0.8 (Liu et al. 2003). The PGS result carried out by Structure was visualized via Distruct program ver. 1.1 (Rosenberg 2004).RESULTSGenetic diversityA total of 517 alleles were detected by the whole set of54 SSRs covering the entire maize genome through all of the 143 maize landraces, with an average of 9.57 alleles per locus and ranged from 4 (umc1121) to 22 (bnlg1272) (Table 3). Among all the alleles detected, the number of distinct alleles accounted for 132 (25.53%), with an av-erage of 2.44 alleles per locus. The distinct alleles dif-fered significantly among the landraces from different provinces/regions, and the landraces from Guangdong, Fujian, Zhejiang, and Shanghai possessed more distinct alleles than those from the other provinces/regions, while those from southern Anhui possessed the lowest distinct alleles, only counting for 3.28% of the total (Table 4).Table 4 The genetic diversity within eight provinces/regions and groups revealed by 54 SSRsProvince/Region Sample size Allele no.1)Distinct allele no.Gene diversity (expected heterozygosity)Observed heterozygosity Anhui14 4.28 (4.19) 69 (72.4)0.51 (0.54)0.58 (0.58)Fujian17 4.93 (4.58 80 (79.3)0.56 (0.60)0.63 (0.62)Guangdong22 5.48 (4.67) 88 (80.4)0.57 (0.59)0.59 (0.58)Hainan18 4.65 (4.26) 79 (75.9)0.53 (0.57)0.55 (0.59)Jiangsu13 4.24 700.500.55Jiangxi21 4.96 (4.35) 72 (68.7)0.56 (0.60)0.68 (0.68)Shanghai15 5.07 (4.89) 90 (91.4)0.55 (0.60)0.55 (0.55)Zhejiang23 5.04 (4.24) 85 (74)0.53 (0.550.60 (0.61)Total/average1439.571320.610.60GroupGroup 155 6.63 (6.40) 91 (89.5)0.57 (0.58)0.62 (0.62)Group 2887.94 (6.72)110 (104.3)0.57 (0.57)0.59 (0.58)Total/Average1439.571320.610.60Provinces/Regions within a groupGroup 1Total55 6.69 (6.40) 910.57 (0.58)0.62 (0.62)Guangdong22 5.48 (4.99) 86 (90.1)0.57 (0.60)0.59 (0.58)Hainan18 4.65 (4.38) 79 (73.9)0.53 (0.56)0.55 (0.59)Jiangxi15 4.30 680.540.69Group 2Total887.97 (6.72)110 (104.3)0.57 (0.57)0.59 (0.58)Anhui14 4.28 (3.22) 69 (63.2)0.51 (0.54)0.58 (0.57)Fujian17 4.93 (3.58) 78 (76.6)0.56 (0.60)0.63 (0.61)Jiangsu13 4.24 (3.22) 71 (64.3)0.50 (0.54)0.55 (0.54)Jiangxi6 3.07 520.460.65Shanghai15 5.07 (3.20) 91 (84.1)0.55 (0.60)0.55 (0.54)Zhejiang23 5.04 (3.20) 83 (61.7)0.53 (0.54)0.60 (0.58)1258LIU Zhi-zhai et al.Among the 54 loci used in the study, 16 (or 29.63%) were dinucleotide repeat SSRs, which were defined as type class I-I, the other 38 loci were SSRs with a longer repeat motifs, and two with unknown repeat motifs, all these 38 loci were defined as the class of I-II. In addition, 15 were located within certain functional genes (defined as class II-I) and the rest were defined as class II-II. The results of comparison indicated that the av-erage number of alleles per locus captured by class I-I and II-II were 12.88 and 10.05, respectively, which were significantly higher than that by type I-II and II-I (8.18 and 8.38, respectively). The gene diversity re-vealed by class I-I (0.63) and II-I (0.63) were some-what higher than by class I-II (0.60) and II-II (0.60) (Table 5).Genetic relationships of the core landraces Overall, 143 landraces were clustered into two groups by using neighbor-joining (NJ) method based on InSPAD. All the landraces from provinces of Guangdong and Hainan and 15 of 21 from Jiangxi were clustered together to form group 1, and the other 88 landraces from the other provinces/regions formed group 2 (Fig.-B). The geographical origins of all these 143 landraces with the clustering results were schematized in Fig.-D. Revealed by the chi-square test, the phylogenetic results (SSR-clustered groups) of all the 143 landraces from provinces/regions showed a significant correlation with their geographical origin (χ2=124.89, P<0.0001, Table 2).Revealed by the phylogenetic analysis based on the InSPAD, the minimum distance was observed as 0.1671 between two landraces, i.e., Tianhongyumi (JiangX-03) and Hongganshanyumi (JiangX-04) collected from Jiangxi Province, and the maximum was between two landraces of Huangbaosu (FuJ-16) and Hongyumi (HaiN-14) collected from provinces of Fujian and Hainan, respectively, with the distance of 1.3863 (data not shown). Two landraces (JiangX-01 and JiangX-21) collected from the same location of Dexing County (Table 1) possessing the same names as Shanyumi were separated to different groups, i.e., JiangX-01 to group1, while JiangX-21 to group 2 (Table 1). Besides, JiangX-01 and JiangX-21 showed a rather distant distance of 0.9808 (data not shown). These results indicated that JiangX-01 and JiangX-21 possibly had different ances-tral origins.Population structureA Bayesian method was used to detect the number of groups (K value) of the whole set of landraces from SR with a fixed-K clustering procedure implemented in BAPS software ver. 5.1. The result showed that all of the 143 landraces could also be assigned into two groups (Fig.-A). Then, a model-based clustering method was applied to carry out the PGS of all the landraces via Structure ver. 2.2 by setting K=2. This method as-signed individuals to groups based on the membership probability, thus the threshold probability 0.80 was set for the individuals’ assignment (Liu et al. 2003). Accordingly, all of the 143 landraces were divided into two distinct model-based groups (Fig.-C). The landraces from Guangdong, Hainan, and 15 landraces from Jiangxi formed one group, while the rest 6 landraces from the marginal countries of northern Jiangxi and those from the other provinces formed an-other group (Table 1, Fig.-D). The PGS revealed by the model-based approach via Structure was perfectly consistent with the relationships resulted from the phy-logenetic analysis via PowerMarker (Table 1).DISCUSSIONThe SR includes eight provinces, i.e., southern Jiangsu and Anhui, Shanghai, Zhejiang, Fujian, Jiangxi, Guangdong, and Hainan (Fig.-C), with the annual maize growing area of about 1 million ha (less than 5% of theTable 5 The genetic diversity detected with different types of SSR markersType of locus No. of alleles Gene diversity Expected heterozygosity PIC Class I-I12.880.630.650.60 Class I-II8.180.600.580.55 Class II-I8.330.630.630.58。
药品研究中心

药品研究中心佚名【期刊名称】《世界建筑导报》【年(卷),期】2015(000)004【总页数】4页(P82-85)【正文语种】中文地点:荷兰莱顿市业主:莱顿药品研究中心面积:6 961平方米办公室和实验室完工:2013年摄影:Jannes LindersAddress: Zernikedreef 8, Leiden, the NetherlandsClient: Centre for Human Drug Research, Leiden, the NetherlandsGfa: 6 961 m2offices and labsRealization: 2013Photography: Jannes Linders上世纪九十年代中期,cepezed为药品研究中心(CHDR)设计了一座引人注目的企业大楼。
CHDR主要从事药品功效及其副作用测试。
虽然该公司之前已进行了扩建,但仍然拥挤不堪。
如今,在莱顿市生物科学园内,一座新大楼在旧楼旁拔地而起,为此,cepezed实现了为其他制药公司共用大楼的设计方案。
这座新楼占地面积22.5×34米,地上八层,地下一层为停车场。
此外,大楼四周和首层也设有部分停车区域。
该大楼从前到后分成三个不相同的条形区域。
Zernikedreef的最前方区域内,首层设有入口、前台,以及一个中等规模的礼堂。
其上方为会议室和办公室,以及试验区和一个带花园的屋顶平台。
中央区域为便利设施区,设有卫生间、两部观光电梯,以及两个相连的、可用作疏散通道的层叠式楼梯。
如遇火灾,楼梯将会被自动落下的防火帘隔开。
后方区域设有开放且空间宽敞的公司餐厅、深度护理区、与药房相连的研究实验室、暗室及各种储存和冷冻设施。
顶层设有供长期留守人员使用的卧室,以及与屋顶花园邻接的客厅。
该建筑的承重结构包含一个细长的钢骨架,以及镂空楼板。
各立面完全齐平;北立面完全由玻璃制成,其他立面由交错的条窗水平衔接,窗上装有可打开的小窗户以及带白色釉面玻璃外板的夹板。
诺如病毒研究进展及一起邮轮诺如病毒感染疫情的实验室检测课件.ppt

克样病毒抗体总检出率为88.8%以上。太原市总检出率在
78.6%以上。
1998-2002在福州地区用RT-PCR方法对288份腹泻患者粪
便标本诺瓦克样病毒病原检测显示,诺瓦克样病毒基因组I
的阳性率为11.1%,主要是7岁以上儿童及成人;诺瓦克样
病毒基因组Ⅱ的阳性率为 28.8%,主要是6月龄至3岁婴幼
elementary school in Norwalk OH: 50% of students and teachers
developed gastroenteritis
➢ Kaplan used immune electronmicroscopy to identify viral particles
in the stools of volunteers infected with the “Norwalk” strain
➢ Virus initially classified as small round viruses, later reclassified as
caliciviruses when genome cloned
的阳性率只有20%左右。固相免疫电镜的方法是将特异性抗体直接包被载网,同时加入蛋
白A增加抗体与标本中抗原结合的机会,从而提高检测的灵敏度。上述三种方法都要求观察
者具有丰富的经验,同时,精密的检测仪器、较大的劳动强度,都制约了该方法在NVs检测
中的应用。
免疫学检测(EIA)主要通过检测标本中的抗原来确认诺如病毒。该方法操作
•
•
•
•
Dr. Albert Kapikian
1972, electron microscopy
健康心理学外文文献翻译

Collaborative Relationships: School Counselors andNon-School Mental Health Professionals WorkingTogether to Improve the Mental Health Needs ofStudents浅议基于合作关系的学校辅导员和非学校的心理健康专家对学生心理健康需要的改善作用Chris Brown, Ph.D.David T. DahlbeckLynette Sparkman Barnes摘要:本研究调查了53名受聘于各初中、高中的辅导员和管理员关于他们对校内与校外心理健康专家协同工作来回应学生的心理健康需求的看法。
除此之外,本研究还试图了解学校辅导员和学校校长或副校长是如何看待学校辅导员的角色、职责以及对学校辅导员培训的范围。
正文:为了努力提供一系列广泛的服务来帮助学生处理他们带进课堂的社交及情绪问题,学校和社会心理健康机构已经开始实施合作伙伴关系(Walsh & Galassi, 2002)。
沃尔什和加拉西断言,如果我们想要成功的使结构复杂的校内和校外儿童生活产生交叉,我们就必须以整个儿童的发展为重点。
这样做将需要“跨越专业和机构界限的合作”。
体现着学校与社区心理健康机构建立伙伴关系的扩展的学校心理健康计划在美国有不断发展的倾向。
在这些计划中,学校聘请的心理健康专业人员在强调有效地预防、评估和干预方面提供了无数的服务(Weist, Lowie, Flaherty, & Pruitt, 2001)。
这项合作活动是为了减轻教育系统的负担和责任,同时提高了服务的零散和不完整传递给适龄儿童和青年。
研究表明,在申请心理健康服务的年轻人中只有不到三分之一的人得到了他们所需要的关心(美国卫生与人类服务部,1999)。
考虑到提高儿童与青少年心理健康的多系统协作的重要性和认可度,这些合作伙伴关系的知觉功效就是这项调查议程的驱动力。
2023日本循环学会等8个学术组织指南:重点更新冠脉痉挛性心绞痛和冠脉微血管功能障碍完整版

2023日本循环学会等8个学术组织指南:重点更新冠脉痉挛性心绞痛和冠脉微血管功能障碍(完整版)缩写:ACE血管紧张素转换的ACh乙酰胆碱ACS急性冠脉综合征AF心房领幼A1DH2乙解脱氢的2MI急性心肌梗塞ARB血管紧张素受体阻翻ASCD复苏的心原性猝死ATP三磷酸眼甘BMS裸金属支架CAD冠心病CAG冠脉造影CAS冠脉血管循检查CCB钙通道阻滞剂CCS慢性冠脉综合征CCTA冠脉CTACFR冠脉血流储骨CK肌酸激酶CMD冠脉微血管功能障碍CMR心血管磁共振COR推荐类别C OVADIS冠脉血管舒缩障碍国际研究CSA冠脉痉挛性心绞痛CTP CT灌注DES药物洗脱支架EES依维莫司洗脱支架eNOS内皮一氧化氮合酶1GE后期乱强化EPS电生理学研究1OE证据水平ER早期复极MACE主要心脏不良事件ET-I内皮素1MBF心肌血流里FCA侵入性功能性CAG MFR心肌血流储管FFR血流储蓊分数MI-CAD冠心病所致心肌梗死FFRCT CT扫描的血流储备分数MINOCA冠豚非阻塞性心肌梗死FDM血流介导的内反依莓性血管野光M1C肌球蛋白轻糙HF心脏衰竭M1CK肌球蛋白轻梃激酶HFpEF射血分数保留的HF+ M1CPh肌球蛋白轻链磷酸酶HMR充血性微血管阻力MPRI心肌灌注储爸指数HR危险几率MRI磁共振成像ICD植入式心脏复律除颤器MVA微血管性心绞痛IDP介入诊断程序MVS微血管痉挛IHD缺血性心脏病NO一氧化氮IMR微循环阻力指数OCT光学相干断层扫描INOCA冠状动脉非阻塞性心肌缺血OR优势比IVUS血管内超声PCI经皮冠脉介入治疗KD川峭病PET正电子发射断层扫描PVAT 血管周围脂肪组织QO1生活质里RH-PAT反应性充血外周动脉光力测定ROS 活性氧SCAD自发性冠脉夹层SCD 心源性猝死SPECT 单光子发射计算机断层扫描TIMI 心肌梗死的溶栓治疗TP-NOCA肌钙蛋白阳性的非恒塞性CADTWA T波交替VF 心室颤动VSA 血管痉掌性心绞痛VSMC 血管平清肌细胞VT 室性心动过速W 血管滋养管■■■刖百2008年,日本循环学会制定了血管痉挛性心绞痛(冠脉痉挛性心绞痛)患者的诊断和治疗指南1,并于2013年发布了修订版2。
Becoming a Scientist The Role of Undergraduate Research in Students ’ Cognitive, Personal,

Becoming a Scientist:The Roleof Undergraduate Research in Students’Cognitive,Personal, and Professional DevelopmentANNE-BARRIE HUNTER,SANDRA URSEN,ELAINE SEYMOUR Ethnography&Evaluation Research,Center to Advance Research and Teaching in the Social Sciences,University of Colorado,Campus Box580,Boulder,CO80309,USAReceived9November2005;revised2May2006;accepted2June2006DOI10.1002/sce.20173Published online12October2006in Wiley InterScience().ABSTRACT:In this ethnographic study of summer undergraduate research(UR)expe-riences at four liberal arts colleges,where faculty and students work collaboratively on aproject of mutual interest in an apprenticeship of authentic science research work,analysisof the accounts of faculty and student participants yields comparative insights into thestructural elements of this form of UR program and its benefits for parison ofthe perspectives of faculty and their students revealed considerable agreement on the nature,range,and extent of students’UR gains.Specific student gains relating to the process of “becoming a scientist”were described and illustrated by both groups.Faculty framed these gains as part of professional socialization into the sciences.In contrast,students emphasizedtheir personal and intellectual development,with little awareness of their socialization intoprofessional practice.Viewing studyfindings through the lens of social constructivist learn-ing theories demonstrates that the characteristics of these UR programs,how faculty practiceUR in these colleges,and students’outcomes—including cognitive and personal growth and the development of a professional identity—strongly exemplify many facets of these theo-ries,particularly,student-centered and situated learning as part of cognitive apprenticeshipin a community of practice.C 2006Wiley Periodicals,Inc.Sci Ed91:36–74,2007Correspondence to:Anne-Barrie Hunter;e-mail:abhunter@Contract grant sponsor:NSF-ROLE grant(#NSF PR REC-0087611):“Pilot Study to Establish the Nature and Impact of Effective Undergraduate Research Experiences on Learning,Attitudes and Career Choice.”Contract grant sponsor:Howard Hughes Medical Institute special projects grant,“Establishing the Processes and Mediating Factors that Contribute to Significant Outcomes in Undergraduate Research Experiences for both Students and Faculty:A Second Stage Study.”This paper was edited by former Editor Nancy W.Brickhouse.C 2006Wiley Periodicals,Inc.BECOMING A SCIENTIST37INTRODUCTIONIn1998,the Boyer Commission Report challenged United States’research universities to make research-based learning the standard of students’college education.Funding agencies and organizations promoting college science education have also strongly recommended that institutions of higher education provide greater opportunities for authentic,interdis-ciplinary,and student-centered learning(National Research Council,1999,2000,2003a, 2003b;National Science Foundation[NSF],2000,2003a).In line with these recommen-dations,tremendous resources are expended to provide undergraduates with opportunities to participate in faculty-mentored,hands-on research(e.g.,the NSF-sponsored Research Experience for Undergraduates[REU]program,Howard Hughes Medical Institute Science Education Initiatives).Notwithstanding widespread belief in the value of undergraduate research(UR)for stu-dents’education and career development,it is only recently that research and evaluation studies have produced results that begin to throw light on the benefits to students,faculty,or institutions that are generated by UR opportunities(Bauer&Bennett,2003;Lopatto,2004a; Russell,2005;Seymour,Hunter,Laursen,&DeAntoni,2004;Ward,Bennett,&Bauer, 2002;Zydney,Bennett,Shahid,&Bauer,2002a,2002b).Other reports focus on the effects of UR experiences on retention,persistence,and promotion of science career pathways for underrepresented groups(Adhikari&Nolan,2002;Barlow&Villarejo,2004;Hathaway, Nagda,&Gregerman,2002;Nagda et al.,1998).It is encouraging tofind strong convergence as to the types of gains reported by these studies(Hunter,Laursen,&Seymour,2006).How-ever,we note limited or no discussion of some of the stronger gains that we document,such as students’personal and professional growth(Hunter et al.,2006;Seymour et al.,2004) and significant variation in how particular gains(especially intellectual gains)are defined. Ongoing and current debates in the academic literature concerning how learning occurs, how students develop intellectually and personally during their college years,and how communities of practice encourage these types of growth posit effective practices and the processes of students’cognitive,epistemological,and interpersonal and intrapersonal de-velopment.Although a variety of theoretical papers and research studies exploring these topics are widely published,with the exception of a short article for Project Kaleidoscope (Lopatto,2004b),none has yet focused on intensive,summer apprentice-style UR experi-ences as a model to investigate the validity of these debates.1Findings from this research study to establish the nature and range of benefits from UR experiences in the sciences,and in particular,results from a comparative analysis of faculty and students’perceptions of gains from UR experiences,inform these theoretical discussions and bolsterfindings from empirical studies in different but related areas(i.e.,careers research,workplace learning, graduate training)on student learning,cognitive and personal growth,the development of professional identity,and how communities of practice contribute to these processes. This article will presentfindings from our faculty andfirst-round student data sets that manifest the concepts and theories underpinning constructivist learning,development of professional identity,and how apprentice-style UR experience operates as an effective community of practice.As these bodies of theory are central tenets of current science education reform efforts,empirical evidence that provides clearer understanding of the actual practices and outcomes of these approaches inform national science education pol-icy concerns for institutions of higher learning to increase diversity in science,numbers of students majoring in science,technology,engineering,or mathematics(STEM)disci-plines,student retention in undergraduate and graduate STEM programs and their entry 1David Lopatto was co-P.I.on this study and conducted quantitative survey research on the basis of our qualitativefindings at the same four liberal arts colleges.Science Education DOI10.1002/sce38HUNTER ET AL.into science careers,and,ultimately,the production of greater numbers of professional scientists.To frame discussion offindings from this research,we present a brief review of theory on student learning,communities of practice,and the development of personal and professional identity germane to our data.CONSTRUCTIVIST LEARNING,COMMUNITIES OF PRACTICE,AND IDENTITY DEVELOPMENTApprentice-style URfits a theoretical model of learning advanced by constructivism, in which learning is a process of integrating new knowledge with prior knowledge such that knowledge is continually constructed and reconstructed by the individual.Vygotsky’s social constructivist approach presented the notion of“the zone of proximal development,”referencing the potential of students’ability to learn and problem solve beyond their current knowledge level through careful guidance from and collaboration with an adult or group of more able peers(Vygotsky,1978).According to Green(2005),Vygotsky’s learning model moved beyond theories of“staged development”(i.e.,Piaget)and“led the way for educators to consider ways of working with others beyond the traditional didactic model”(p.294).In social constructivism,learning is student centered and“situated.”Situated learning,the hallmark of cultural and critical studies education theorists(Freire,1990; Giroux,1988;Shor,1987),takes into account students’own ways of making meaning and frames meaning-making as a negotiated,social,and contextual process.Crucial to student-centered learning is the role of educator as a“facilitator”of learning.In constructivist pedagogy,the teacher is engaged with the student in a two-way,dialog-ical sharing of meaning construction based upon an activity of mutual ve and Wenger(1991)and Wenger(1998)extended tenets of social constructivism into a model of learning built upon“communities of practice.”In a community of practice“newcomers”are socialized into the practice of the community(in this case,science research)through mutual engagement with,and direction and support from an“old-timer.”Lave and Wenger’s development of the concept and practice of this model centers on students’“legitimate pe-ripheral participation.”This construct describes the process whereby a novice is slowly,but increasingly,inducted into the knowledge and skills(both overt and tacit)of a particular practice under the guidance and expertise of the master.Legitimate peripheral participation requires that students actively participate in the authentic practice of the community,as this is the process by which the novice moves from the periphery toward full membership in the community(Lave&Wenger,1991).Similar to Lave and Wenger’s communities of practice, Brown,Collins,and Duguid(1989)and Farmer,Buckmaster,and LeGrand(1992)describe “cognitive apprenticeships.”A cognitive apprenticeship“starts with deliberate instruction by someone who acts as a model;it then proceeds to model-guided trials by practition-ers who progressively assume more responsibility for their learning”(Farmer et al.,1992, p.42).However,these latter authors especially emphasize the importance of students’ongoing opportunities for self-expression and reflective thinking facilitated by an“expert other”as necessary to effective legitimate peripheral participation.Beyond gains in understanding and exercising the practical and cultural knowledge of a community of practice,Brown et al.(1989)discuss the benefits of cognitive ap-prenticeship in helping learners to deal capably with ambiguity and uncertainty—a trait particularly relevant to conducting science research.In their view,cognitive apprenticeship “teaches individuals how to think and act satisfactorily in practice.It transmits useful, reliable knowledge based on the consensual agreement of the practitioners,about how to deal with situations,particularly those that are ill-defined,complex and risky.It teachesScience Education DOI10.1002/sceBECOMING A SCIENTIST39‘knowledge-in-action’that is‘situated”’(quoted in Farmer et al.,1992,p.42).Green(2005) points out that Bowden and Marton(1998,2004)also characterize effective communities of practice as teaching skills that prepare apprentices to negotiate undefined“spaces of learning”:“the‘expert other’...does not necessarily‘know’the answers in a traditional sense,but rather is willing to support collaborative learning focused on the‘unknown fu-ture.’In other words,the‘influential other’takes learning...to spaces where the journey itself is unknown to everyone”(p.295).Such conceptions of communities of practice are strikingly apposite to the processes of learning and growth that we have found among UR students,particularly in their understanding of the nature of scientific knowledge and in their capacity to confront the inherent difficulties of science research.These same issues are central to Baxter Magolda’s research on young adult development. The“epistemological reflection”(ER)model developed from her research posits four categories of intellectual development from simplistic to complex thinking:from“absolute knowing”(where students understand knowledge to be certain and view it as residing in an outside authority)to“transitional knowing”(where students believe that some knowledge is less than absolute and focus onfinding ways to search for truth),then to“independent knowing”(where students believe that most knowledge is less than absolute and individuals can think for themselves),and lastly to“contextual knowing”(where knowledge is shaped by the context in which it is situated and its veracity is debated according to its context) (Baxter Magolda,2004).In this model,epistemological development is closely tied to development of identity. The ER model of“ways of knowing”gradually shifts from an externally directed view of knowing to one that is internally directed.It is this epistemological shift that frames a student’s cognitive and personal development—where knowing and sense of self shift from external sources to reliance upon one’s own internal assessment of knowing and identity. This process of identity development is referred to as“self-authorship”and is supported by a constructivist-developmental pedagogy based on“validating students as knowers, situating learning in students’experience,and defining learning as mutually constructed meaning”(Baxter Magolda,1999,p.26).Baxter Magolda’s research provides examples of pedagogical practice that support the development of self-authorship,including learning through scientific inquiry.As in other social constructivist learning models,the teacher as facilitator is crucial to students’cognitive and personal development:Helping students make personal sense of the construction of knowledge claims and engagingstudents in knowledge construction from their own perspectives involves validating thestudents as knowers and situating learning in the students’own perspectives.Becoming socialized into the ways of knowing of the scientific community and participating in thediscipline’s collective knowledge creation effort involves mutually constructing meaning.(Baxter Magolda,1999,p.105)Here Baxter Magolda’s constructivist-developmental pedagogy converges with Lave and Wenger’s communities of practice,but more clearly emphasizes students’development of identity as part of the professional socialization process.Use of constructivist learning theory and pedagogies,including communities of practice, are plainly evident in the UR model as it is structured and practiced at the four institutions participating in this study,as we describe next.As such,the gains identified by student and faculty research advisors actively engaged in apprentice-style learning and teaching provide a means to test these theories and models and offer the opportunity to examine the processes,whereby these benefits are generated,including students’development of a professional identity.Science Education DOI10.1002/sce40HUNTER ET AL.THE APPRENTICESHIP MODEL FOR UNDERGRADUATE RESEARCH Effective UR is defined as,“an inquiry or investigation conducted by an undergraduate that makes an original intellectual or creative contribution to the discipline”(NSF,2003b, p.9).In the“best practice”of UR,the student draws on the“mentor’s expertise and resources...and the student is encouraged to take primary responsibility for the project and to provide substantial input into its direction”(American Chemical Society’s Committee on Professional Training,quoted in Wenzel,2003,p.1).Undergraduate research,as practiced in the four liberal arts colleges in this study,is based upon this apprenticeship model of learning:student researchers work collaboratively with faculty in conducting authentic, original research.In these colleges,students typically underwent a competitive application process(even when a faculty member directly invited a student to participate).After sorting applications, and ranking students’research preferences,faculty interviewed students to assure a good match between the student’s interests and the faculty member’s research and also between the faculty member and the student.Generally,once all application materials were reviewed (i.e.,students’statements of interest,course transcripts,grade point averages[GPA]), faculty negotiated as a group to distribute successful applicants among the available summer research advisors.Students were paid a stipend for their full-time work with faculty for 10weeks over summer.Depending on the amount of funding available and individual research needs,faculty research advisors supervised one or more students.Typically,a faculty research advisor worked with two students for the summer,but many worked with three or four,or even larger groups.In most cases,student researchers were assigned to work on predetermined facets of faculty research projects:each student project was open ended,but defined,so that a student had a reasonable chance of completing it in the short time frame and of producing useful results.Faculty research advisors described the importance of choosing a project appropriate to the student’s“level,”taking into account their students’interests,knowledge, and abilities and aiming to stretch their capacities,but not beyond students’reach.Research advisors were often willing to integrate students’specific interests into the design of their research projects.Faculty research advisors described the intensive nature of getting their student re-searchers“up and running”in the beginning weeks of the program.Orienting students to the laboratory and to the project,providing students with relevant background information and literature,and teaching them the various skills and instrumentation necessary to work effectively required adaptability to meet students at an array of preparation levels,advance planning,and a good deal of their time.Faculty engaged in directing UR discussed their role as facilitators of students’learning.In the beginning weeks of the project,faculty advisors often worked one-on-one with their students.They provided instruction,gave “mini-lectures,”explained step by step why and how processes were done in particular ways—all the time modeling how science research is done.When necessary,they closely guided students,but wherever possible,provided latitude for and encouraged students’own initiative and experimentation.As the summer progressed,faculty noted that,based on growing hands-on experience,students gained confidence(to a greater or lesser degree)in their abilities,and gradually and increasingly became self-directed and able,or even eager, to work independently.Although most faculty research advisors described regular contact with their student researchers,most did not work side by side with their students everyday.Many research advisors held a weekly meeting to review progress,discuss problems,and make sure students(and the projects)were on the right track.At points in the research work,facultyScience Education DOI10.1002/sceBECOMING A SCIENTIST41 could focus on other tasks while students worked more independently,and the former were available as necessary.When students encountered problems with the research,faculty would serve as a sounding board while students described their efforts to resolve difficulties. Faculty gave suggestions for methods that students could try themselves,and when problems seemed insurmountable to students,faculty would troubleshoot with them tofind a way to move the project forward.Faculty research advisors working with two or more student researchers often used the research peer group to further their students’development.Some faculty relied on more-senior student researchers to help guide new ones.Having multiple students working in the laboratory(whether or not on the same project)also gave student researchers an extra resource to draw upon when questions arose or they needed help.In some cases,several faculty members(from the same or different departments)scheduled weekly meetings for group discussion of their research monly,faculty assigned articles for students to summarize and present to the rest of the group.Toward the end of summer, weekly meetings were often devoted to students’practice of their presentations so that the research advisor and other students could provide constructive criticism.At the end of summer,with few exceptions,student researchers attended a campus-wide UR conference, where they presented posters and shared their research with peers,faculty,and institution administrators.Undergraduate research programs in these liberal arts colleges also offered a series of seminars andfield trips that explored various science careers,discussed the process of choosing and applying to graduate schools,and other topics that focused on students’professional development.We thus found that,at these four liberal arts colleges,the practice of UR embodies the principles of the apprenticeship model of learning where students engage in active,hands-on experience of doing science research in collaboration with and under the auspices of a faculty research advisor.RESEARCH DESIGNThis qualitative study was designed to address fundamental questions about the benefits (and costs)of undergraduate engagement in faculty-mentored,authentic research under-taken outside of class work,about which the existing literature offers fewfindings and many untested hypotheses.2Longitudinal and comparative,this study explores:•what students identify as the benefits of UR—both following the experience,and inthe longer term(particularly career outcomes);•what gains faculty advisors observe in their student researchers and how their view of gains converges with or diverges from those of their students;•the benefits and costs to faculty of their engagement in UR;•what,if anything,is lost by students who do not participate in UR;and•the processes by which gains to students are generated.This study was undertaken at four liberal arts colleges with a strong history of UR.All four offer UR in three core sciences—physics,chemistry,and biology—with additional programs in other STEMfields,including(at different campuses)computer science,engi-neering,biochemistry,mathematics,and psychology.In the apprenticeship model of UR practiced at these colleges,faculty alone directed students in research;however,in the few2An extensive review and discussion of the literature on UR is presented in Seymour et al.(2004). Science Education DOI10.1002/sce42HUNTER ET AL.instances where faculty conducted research at a nearby institution,some students did have contact with post docs,graduate students,or senior laboratory technicians who assisted in the research as well.We interviewed a cohort of(largely)“rising seniors”who were engaged in UR in summer2000on the four campuses(N=76).They were interviewed for a second time shortly before their graduation in spring2001(N=69),and a third time as graduates in 2003–2004(N=55).The faculty advisors(N=55)working with this cohort of students were also interviewed in summer2000,as were nine administrators with long experience of UR programs at their schools.We also interviewed a comparison group of students(N=62)who had not done UR. They were interviewed as graduating seniors in spring2001,and again as graduates in 2003–2004(N=25).A comparison group(N=16)of faculty who did not conduct UR in summer2000was also interviewed.Interview protocols focused upon the nature,value,and career consequences of UR experiences,and the methods by which these were achieved.3After classifying the range of benefits claimed in the literature,we constructed a“gains”checklist to discuss with all participants“what faculty think students may gain from undergraduate research.”Dur-ing the interview,UR students were asked to describe the gains from their research experience(or by other means).If,toward the end of the interview,a student had not mentioned a gain identified on our“checklist,”the student was queried as to whether he or she could claim to have gained the benefit and was invited to add further com-ment.Students also mentioned gains they had made that were not included in the list. With slight alterations in the protocol,we invited comments on the same list of possi-ble gains from students who had not experienced UR,and solicited information about gains from other types of experience.All students were asked to expand on their an-swers,to highlight gains most significant to them,and to describe the sources of any benefits.In the second set of interviews,the same students(nearing graduation)were asked to reflect back on their research experiences as undergraduates,and to comment on the rel-ative importance of their research-derived gains,both for the careers they planned and for other aspects of their lives.In thefinal set of interviews,they were asked to of-fer a retrospective summary of the origins of their career plans and the role that UR and other factors had played in them,and to comment on the longer term effects of their UR experiences—especially the consequences for their career choices and progress, including their current educational or professional engagement.Again,the sources of gains cited were explored;especially gains that were identified by some students as arising from UR experiences but may also arise from other aspects of their college education.The total of367interviews represents more than13,000pages of text data.We are currently analyzing other aspects of the data and will reportfindings on additional topics, including the benefits and costs to faculty of their participation in UR and longitudinal and comparative outcomes of students’career choices.This article discussesfindings from a comparative analysis of all faculty and administrator interviews(N=80),withfindings from thefirst-round UR student interviews(N=76),and provides empirical evidence of the role of UR experiences in encouraging the intellectual,personal,and professional development of student researchers,and how the apprenticeship modelfits theoretical discussions on these topics.3The protocol is available by request to the authors via abhunter@.Science Education DOI10.1002/sceBECOMING A SCIENTIST43METHODS OF DATA TRANSCRIPTION,CODING,AND ANAL YSISOur methods of data collection and analysis are ethnographic,rooted in theoretical work and methodological traditions from sociology,anthropology,and social psychol-ogy(Berger&Luckman,1967;Blumer,1969;Garfinkel,1967;Mead,1934;Schutz& Luckman,1974).Classically,qualitative studies such as ethnographies precede survey or experimental work,particularly where existing knowledge is limited,because these meth-ods of research can uncover and explore issues that shape informants’thinking and actions. Good qualitative software computer programs are now available that allow for the multiple, overlapping,and nested coding of a large volume of text data to a high degree of complexity, thus enabling ethnographers to disentangle patterns in large data sets and to reportfindings using descriptive statistics.Although conditions for statistical significance are rarely met, the results from analysis of text data gathered by careful sampling and consistency in data coding can be very powerful.Interviews took between60and90minutes.Taped interviews and focus groups were transcribed verbatim into a word-processing program and submitted to“The Ethnograph,”a qualitative computer software program(Seidel,1998).Each transcript was searched for information bearing upon the research questions.In this type of analysis,text segments referencing issues of different type are tagged by code names.Codes are not preconceived,but empirical:each new code references a discrete idea not previously raised.Interviewees also offer information in spontaneous narratives and examples,and may make several points in the same passage,each of which is separately coded.As transcripts are coded,both the codes and their associated passages are entered into“The Ethnograph,”creating a data set for each interview group(eight,in this study). Code words and their definitions are concurrently collected in a codebook.Groups of codes that cluster around particular themes are assigned and grouped by“parent”codes.Because an idea that is encapsulated by a code may relate to more than one theme,code words are often assigned multiple parent codes.Thus,a branching and interconnected structure of codes and parents emerges from the text data,which,at any point in time,represents the state of the analysis.As information is commonly embedded in speakers’accounts of their experience rather than offered in abstract statements,transcripts can be checked for internal consistency;that is,between the opinions or explanations offered by informants,their descriptions of events, and the reflections and feelings these evoke.Ongoing discussions between members of our research group continually reviewed the types of observations arising from the data sets to assess and refine category definitions and assure content validity.The clustered codes and parents and their relationships define themes of the qualita-tive analysis.In addition,frequency of use can be counted for codes across a data set, and for important subsets(e.g.,gender),using conservative counting conventions that are designed to avoid overestimation of the weight of particular opinions.Together,these frequencies describe the relative weighting of issues in participants’collective report. As they are drawn from targeted,intentional samples,rather than from random samples, these frequencies are not subjected to tests for statistical significance.They hypothesize the strength of particular variables and their relationships that may later be tested by random sample surveys or by other means.However,thefindings in this study are un-usually strong because of near-complete participation by members of each group under study.Before presentingfindings from this study,we provide an overview of the results of our comparative analysis and describe the evolution of our analysis of the student interview data as a result of emergentfindings from analysis of the faculty interview data.Science Education DOI10.1002/sce。
美国国立卫生研究院国家促进转化科学发展中心最新临床和转化科学基金项目

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研究联合体(Agreenium)合作奖学金介绍

国家留学基金管理委员会与法国农业、食品、动物健康与环境研究联合体(Agreenium)合作奖学金介绍一、简介法国农业、食品、动物健康与环境研究联合体(Agreenium)是一所公立科研合作机构。
由法国农业、食品和林业部、法国高等教育与科研部、法国外交和欧洲事务部联合于2009年5月批准成立,旨在加强法国农业和兽医科研及高等教育,并推向国际化水准。
主要成员包括:法国农业科学研究院(INRA),法国农业国际合作研究发展中心(Cirad),法国西部农学院(Agrocampus Ouest),巴黎高科农学院(AgroParisTech),图卢兹国立理工学院(INPT),蒙彼利埃高等农学院(Montpellier SupAgro),第戎高等农学院(AgroSup Dijon),波尔多农学院(Bordeaux Sciences Agro)。
根据国家留学基金管理委员会(以下简称国家留学基金委)与Agreenium签署的合作备忘录,双方每年将联合资助优秀学生赴该联合体下属高校或科研机构进行博士生联合培养或攻读博士学位。
二、协议内容1. 协议名额15人/年2. 选派类别及留学期限联合培养博士生: 6-24个月赴国外攻读博士学位研究生:不超过48个月3. 重点资助学科、专业领域:优先支持与农业相关专业领域,如:生产系统的适应和可持续性;生物生长环境及多样性的保护和改善;土地使用和所有;自然资源管理(水、空气、土壤、生物等);食品工程与质量;人体营养和健康;知识建模及表达; 公共政策和农业发展; 食品健康安全;农业食品和生物工业领域的创新和实现;环境与健康风险管理的评估和预防;农业生态学;全球变化;景观管理;植物健康与治疗;热带农业学;动物健康和安全等。
4. 资助内容Agreenium将提供注册费以外的学费和科研经费,并免费提供法语培训课程,优先为被录取人员提供住宿、银行开户和办理居留手续的协助;国家留学基金提供一次往返国际旅费和资助期限内的奖学金。
法玛西亚-普强

第二组:
罗根生发药!! 哈哈。。
目录
公司简介 行业及市场分析 SWOT分析 财务分析
解决方案及营销方案
公司简介
• 1995年,瑞典的法玛西亚和美国的普强药厂合并 为法玛西亚普强(Pharmacia&Upjohn)公司;2000 年4月3日,法玛西亚普强(Pharmacia&Upjohn)公 司再同孟山都(Monsanto)公司合并,形成世界最 大的医药公司之一的法玛西亚公司。公司的总部 位于美国新泽西,其药物化学业务的范围,除处 方药剂外,还包括消费者保健品,动物健康产品 (包括针对动物的药品及食品),血浆制品以及大 规模的药品销售 。
估计罗根非处方的销售额和销售量销售额为184亿美元销售量为6922万瓶对于罗根来说预测其变为非处方药之后的第一年的销售额为184亿美元销售量为6922万瓶由于生发药市场已接近成熟假设1996年到2000年的销售额每年按1的增长率增长可得到五年的预测销售额如下
法玛西亚-普强公司: 罗根生发药
主讲人:***
行业及市场分析
• 据统计,美国有4000万男性谢顶和2000万 名女性头发稀疏,他们每年在寻求不同的 治疗方式。
38.6%的 女性有治 疗意愿 约772万人 30.4%的 男性有治 疗意愿 约1216 万人 13.3%的 女性真正 寻求治疗 约266万人 9.9%的 男性真 正寻求 治疗 约396万 人
解决方案
定位: 低价,高品质的生发品牌产品
1
2
分销渠道 原营销计划不变,利用网络扩大分销量
知名度
将罗根和普罗根整合为一个品牌名称体系
3
营销建议
• 注重广告宣传,除了电视广告以外可以拓宽广告 宣传渠道,但是要以电视广告为中心。 • 在原定渠道的基础上尝试增加网络营销渠道,在 不同的营销渠道上用不同的促销手段吸引消费者。 • 定期进行促销活动,注重价格奖励措施,吸引新 的顾客并保持原有顾客。 • 努力提升普罗根的知名度,将罗根和普罗根整合 为一个品牌名称体系。 • 加快开发新产品。改进药物方面的效益和开发更 有效的新产品是保证罗根在竞争激烈的市场上立 于不败之地的重要举措。
德谷门冬双胰岛素与门冬胰岛素30对糖尿病患者治疗效果的差异分析

DOI:10.16658/ki.1672-4062.2023.14.023德谷门冬双胰岛素与门冬胰岛素30对糖尿病患者治疗效果的差异分析贺颖吉林医药学院附属医院内分泌科,吉林吉林132013[摘要]目的比较和分析德谷门冬双胰岛素与门冬胰岛素30对糖尿病患者治疗效果。
方法选择2021年1月—2022年12月在吉林医药学院附属医院治疗的糖尿病患者60例为研究对象。
采取随机数表法将其分为对照组和研究组,每组30例。
对照组皮下注射门冬胰岛素30进行治疗。
研究组皮下注射德谷门冬双胰岛素进行治疗。
治疗后,从患者的空腹血糖和餐后2 h血糖检测结果、血糖波动情况、低血糖发生率等方面,比较治疗效果。
结果治疗后对照组空腹血糖和餐后2 h血糖指标为(6.48±0.71)mmol/L和(9.38±1.36)mmol/L,研究组空腹血糖和餐后2 h血糖指标为(6.42±0.82)mmol/L和(9.08±1.19)mmol/L,两者比较差异无统计学意义(P>0.05)。
研究组日间血糖平均绝对值、日内平均血糖波动幅度为(1.94±0.32)mmol/L和(2.81±0.43)mmol/L,均小于对照组的(2.33±0.46)mmol/L和(3.21±0.63)mmol/L,差异有统计学意义(P<0.05)。
研究组低血糖总发生率为10.00%,低于对照组的33.33%,差异有统计学意义(P<0.05)。
结论德谷门冬双胰岛素能够进一步控制和改善患者的血糖波动情况,低血糖的发生率也相对较低。
[关键词] 德谷门冬双胰岛素;门冬胰岛素30;血糖;血糖波动;低血糖[中图分类号] R587.1 [文献标识码] A [文章编号] 1672-4062(2023)07(b)-0023-04Difference Analysis of Therapeutic Effect of Degludec Aspart Double Insu⁃lin and Insulin Aspart 30 on Diabetic PatientsHE YingDepartment of Endocrinology, Affiliated Hospital of Jilin University of Medicine, Jilin, Jilin Province, 132013 China [Abstract] Objective To compare and analyze the therapeutic effects of insulin degludec aspart and insulin aspart 30 on diabetic patients. Methods A total of 60 patients with diabetes who were treated in the Affiliated Hospital of Jilin University of Medicine from January 2021 to December 2022 were selected as research objects. Random number table method was used to divide them into control group and study group, with 30 patients in each group. The control group received subcutaneous injection of insulin aspart 30 for treatment. The study group received subcutaneous injection of insulin degludec aspart for treatment. After treatment, from the patient's fasting blood glucose and 2h postprandial blood glucose test results, blood glucose fluctuations, incidence of hypoglycemia, etc. Compare treatments. Results Af‐ter treatment, the fasting plasma glucose and 2-hour postprandial blood glucose indexes in the control group were (6.48±0.71) mmol/L and (9.38±1.36) mmol/L, while the fasting plasma glucose and 2-hour postprandial blood glucose indexes in the study group were (6.42±0.82) mmol/L and (9.08±1.19) mmol/L, there was no statistically significant dif‐ference between the two groups (P>0.05). The average absolute value of daytime blood glucose and the average daily blood glucose fluctuation range of the study group were (1.94±0.32) mmol/L and (2.81±0.43) mmol/L, which were lower than those of the control group (2.33±0.46) mmol/L and (3.21±0.63) mmol/L, and the difference was statistically significant (P<0.05). The total incidence of hypoglycemia in the study group was 10.00%, which was lower than that in the control group (33.33%), and the difference was statistically significant (P<0.05). Conclusion Insulin degludec can [基金项目]吉林市医疗卫生指导性计划项目(20210409021)。
新型抗心绞痛药物雷诺嗪的研究进展

Zhao G 等人实验发现雷诺嗪既 不会影响心率,也不调节血液动力状 态或增加冠状动脉血流量。 Antzelevitch C 等人发现,雷诺嗪是
18 中国处方药 2007.10 No.67
新药指南
晚钠离子的选择性抑制剂。在离体的 心肌细胞中,晚钠离子病理性增加, 雷诺嗪可以防止或逆转其导致的机 能失常,改善心室复极化的异常情 况。Gralinski MR 通过研究发现,雷 诺嗪能防止肌原纤维结构紊乱和 Z 带的模糊,并能减轻线粒体嵴及膜损 伤。Zacharowski K 等研究发现雷诺 嗪能显著降低心肌梗死面积和肌钙 蛋白 T 的释放。
目前雷诺嗪的具体作用机制仍 不清楚。起初,人们认为它主要是通 过抑制脂肪酸 β- 氧化,增加丙酮酸 脱 氢 酶 (PDH) 活 性 ,从 而 使 另 一 能 量 来源— ——葡萄糖氧化增加。由于每摩 尔氧耗葡萄糖产生的三磷酸腺苷 (ATP)摩尔数比脂肪酸高 12%,因而 提高了心肌在缺血缺氧时氧的利用 率。然而,在临床试验中发现,只有当 Байду номын сангаас 药 浓 度 超 过 治 疗 浓 度 (>10 μmol/L)才会显示出这种药理作用。 所以以前假设的作用机制似乎不能
临床应用及不良反应
Ranexa(商品名)为薄膜包衣长 方形的缓释片,有两种规格,含雷诺 嗪 500 mg 的 鲜 橙 色 片 及 含 雷 诺 嗪 1000 mg 的淡黄色片。开始应该服用 500 mg/ 次,日两次,再根据临床症状 提高到 1000 mg/ 次。使用雷诺嗪时, 如果同时服用系 HMG 辅酶 A 还原酶
新型抗心绞痛药物雷诺嗪的研究进展
□ 广东药学院药科学院 张 浩 梁 可 曹 蕾 朱尔佳 谭载友 *
心绞痛是冠心病中较为常见的 类型。在我国,随着生活方式的改变 以及生活节奏的加快,心绞痛的发病 率逐年增高。目前仍呈上升趋势,已 接近欧美国家水平。目前广泛应用于 缺血性心脏病的药物包括硝酸酯类、 肾上腺素能受体阻滞剂、钙通道拮抗 剂等,这些药物都是通过减慢心率、 降低血压或削弱心脏泵血功能,从而 使心脏做功减少以缓解心绞痛症状。 然而,这些药物会对已经衰弱的心脏 功能产生进一步损害。因此,研究人 员一直致力于寻找其他更有效而副 作用少的途径来改善心肌缺血。
叶黄素与玉米黄质的HPLC分析文献

Nutritional Manipulation of Primate Retinas,III:Effects of Lutein or Zeaxanthin Supplementation on Adipose Tissue and Retina of Xanthophyll-Free MonkeysElizabeth J.Johnson,1Martha Neuringer,2,3,4Robert M.Russell,1Wolfgang Schalch,5and D.Max Snodderly6,7,8P URPOSE.Macular pigment(MP)is composed of the xantho-phylls lutein(L)and zeaxanthin(Z)and may help to prevent age-related macular degeneration or retard its progression.In this study the effects of L or Z supplementation on carotenoid levels was examined in serum,adipose tissue,and retina in rhesus monkeys with no previous intake of xanthophylls.M ETHODS.From birth to7to16years of age,18rhesus mon-keys were fed semipurified diets containing all essential nutri-ents but no xanthophylls.Six were supplemented with pure L and6with pure Z at3.9mol/kg per day for24to101weeks. At baseline and at4-to12-week intervals,carotenoids in adi-pose tissue were measured by HPLC.At study completion, carotenoids in serum and retina(central4mm,8-mm annulus, and the periphery)were determined.Results were compared with data from control monkeys fed a standard laboratory diet. R ESULTS.Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues.After L or Z supplementation,serum and adipose tissue concentrations significantly increased in the supplemented groups.Both L and3R,3ЈS-Z(RSZ or meso-Z,not present in the diet)were incorporated into retinas of monkeys supplemented with L,with RSZ present only in the macula (central4mm).All-trans Z,but no RSZ,accumulated in retinas of monkeys supplemented with Z.C ONCLUSIONS.L is the precursor of RSZ,a major component of macular pigment.Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examin-ing their uptake and conversion.(Invest Ophthalmol Vis Sci. 2005;46:692–702)DOI:10.1167/iovs.02-1192L utein(L)and zeaxanthin(Z)are xanthophylls(carotenoids that contain one or more polar functional groups)that selectively accumulate in the retina and are particularly dense in the foveal region,or macula,where they are the main components of the macular pigment.1L and Z are known to function as antioxidants2,3and blue-lightfilters and thereby may protect the macular retina and retinal pigment epithelium from light-initiated oxidative damage.4Recent studies in quail exposed to bright light provide evidence that long-term zeax-anthin supplementation leads to increased retinal zeaxanthin and reduced photoreceptor death.5,6Bone et al.7have studied the retinal distribution of L and Z in human retina.The L-to-Z ratio increased from an average of ϳ1:2.4in the central macula(0–0.25mm eccentricity)toϾ2:1 in the periphery(8.7–12.2mm eccentricity).7,8These investi-gators have shown the components of human macular pigment to be L[(3R,3ЈR,6ЈR)-,⑀-carotene-3,3Јdiol];Z[3R,3ЈR)-,car-otene-3,3Јdiol or RRZ];and RSZ or meso-Z,3R,3ЈS-Z[(3R,3ЈS)-♦-carotene-3,3Јdiol].9RSZ is primarily located in the center of the macula,where it is found to be in an approximate ratio of 1:1with RRZ.RSZ is not generally present in the diet,but probably results from chemical processes occurring within the eye.9,10Some investigators have speculated that the origin of RSZ is dietary L.9,10However,until now,proving this sugges-tion was difficult,given the lack of both an appropriate animal model(i.e.,primates with no macular pigment)and sufficient quantities of pure L and Z for controlled feeding studies.There is epidemiologic evidence that intake of foods high in L and/or Z,as well as high serum levels of LϩZ,are related to reduced risk of advanced age-related macular degeneration (AMD)(SanGiovanni JP,et al.IOVS2004;45:ARVO E-abstract 2242).11,12Thisfinding has raised the question of whether supplemental intake of L and Z may be effective in reducing the risk for AMD or slowing its progression.12–14However, there are many gaps in the knowledge about the uptake and metabolism of dietary L and Z and their effectiveness in raising macular pigment levels.The present study was made possible by the existence of a group of xanthophyll-free adult rhesus monkeys.These animals were fed semipurified xanthophyll-free diets from birth and therefore had no detectable xanthophylls in serum and little or no macular pigment,as measured with an in vivo photographic method.15Thus,the effect of dietary supplementation with individual pure carotenoids could readily be followed.We examined the effects of dietary supplementation of these xan-thophyll-free animals with pure L or pure Z.Pure sources of these two carotenoids were made available to us by DSM Nutritional Products,Ltd.(formerly Roche Vitamins,Ltd., Basel,Switzerland)to allow comparisons between the retinalFrom the1Jean Mayer USDA Human Nutrition Research Center onAging at Tufts University,Boston,Massachusetts;the2Division ofNeuroscience,Oregon National Primate Research Center and Depart-ments of3Medicine and4Ophthalmology,Oregon Health and ScienceUniversity,Portland,Oregon;5DSM Nutrition Ltd.(formerly RocheVitamins Ltd.),Basel,Switzerland;and6Schepens Eye Research Insti-tute,Department of Ophthalmology and7Program in Neuroscience,Harvard Medical School,Boston,Massachusetts.8Present affiliation:Department of Ophthalmology,Medical Col-lege of Georgia,Augusta,Georgia.Any opinion,findings,conclusions,or recommendations ex-pressed in this publication are those of the authors and do not neces-sarily reflect the view of the U.S.Department of Agriculture.Supported by DSM Nutritional Products,Ltd.(formerly RocheVitamins Ltd.,Basel,Switzerland);Grant581950-9-001from the U.S.Department of Agriculture;Grant DK-29930from the Institute ofDiabetes and Digestive and Kidney Diseases(MN);Grant RR-00163from the Division of Research Resources,National Institutes of Health;and a grant from The Foundation Fighting Blindness(MN).Submitted for publication November21,2002;revised July1,2003and January26and October6,2004;accepted October18,2004.Disclosure:E.J.Johnson,DSM Nutritional Products,Ltd.(F);M.Neuringer,DSM Nutritional Products,Ltd.(F);R.M.Russell,DSMNutritional Products,Ltd.(F);W.Schalch,DSM Nutritional Products,Ltd.(E,F);D.M.Snodderly,DSM Nutritional Products,Ltd.(F)The publication costs of this article were defrayed in part by pagecharge payment.This article must therefore be marked“advertise-ment”in accordance with18U.S.C.§1734solely to indicate this fact.Corresponding author:Elizabeth J.Johnson,Jean Mayer USDAHuman Nutrition Research Center on Aging at Tufts University,711Washington Street,Boston,MA02111;elizabeth.johnson@.Investigative Ophthalmology&Visual Science,February2005,Vol.46,No.2 692Copyright©Association for Research in Vision and Ophthalmologyresponse to L and to Z.Two prior papers in this series describe the time course of increases in serum xanthophylls and macu-lar pigment optical density in vivo,15morphologic changes in the retinal pigment epithelium,16and the effects of acute blue-light exposure.In the present paper,we report longitu-dinal measures of adipose tissue xanthophylls and the analysis of serum and retinal carotenoids at the end of supplementa-tion,including the levels of L and Z and their metabolites in the macula and periphery.This study provided a unique opportu-nity to determine the effectiveness of pure L and Z in increas-ing macular pigment and to identify the dietary origin of RSZ. M ETHODSAnimals and DietsAll procedures were approved by the Institutional Animal Care and Use Committee of the Oregon National Primate Research Center and con-formed to NIH guidelines and the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.Eighteen rhesus monkeys (Macaca mulatta)were reared on one of two semipurified diets,both of which contained adequate levels of all known nutrients,including vitamin A(as vitamin A acetate)and␣-tocopherol,but no detectable xanthophylls,as analyzed by our laboratory.As described in more detail in Neuringer et al.,15the two diets differed only in their fat sources and therefore in fatty acid composition,with one containing low levels and one adequate levels of n-3fatty acids in the form of ␣-linolenic acid.Because no differences related to fatty acid status were found in any of the analyses reported herein,the data for these two diet groups were in this article.The animals also received limited amounts of very low xanthophyll foods such as wheat or rice cereals,white rice, sweetened drinks,gelatin,pineapple,and banana.Beginning at7to16years of age,the diets of six of these monkeys were supplemented with pure L and six with pure Z,at3.9mol/kg per day(2.2mg/kg per day).This dose represented7.7times the average daily xanthophyll intake from the standard laboratory diet (described later).The L and Z supplements were purified or synthe-sized by DSM Nutritional Products,Ltd.(formerly Roche Vitamins Ltd., Basel,Switzerland)and formulated into gelatin beadlets.Doses of beadlets were determined for each animal based on our analysis of xanthophyll content and current body weight.The supplements were inserted into marshmallows,sweetened gelatin,or small pieces of fruit. Beadlets and individual supplement doses were stored at4°C in the dark.Supplements were provided daily for4to12months and,due to limited supply of the pure xanthophylls,four times per week thereafter until the conclusion of the study.The duration of daily supplementa-tion varied within each group but was matched between the two groups.However,because L had to be specially purified,its supply was more limited,resulting in a shorter duration of supplementation at four times per week for the L-fed group(3Ϯ1month compared to7Ϯ2 months for the Z-fed group).The L-and Z-fed groups were balanced to the extent possible based on sex,n-3diet group,and body weight.The remaining six animals continued on their semipurified diets but re-ceived no xanthophyll supplements(xanthophyll-free).Two L-fed and two Z-fed animals were killed after6to8months of supplementation, two from each group at13to14months and two from each group each at15to24months(see Table1for details).Data from the L-and Z-fed monkeys were compared with data from normal control monkeys fed a standard stock diet(Purina5047Mon-key Chow;Ralston Purina,Richmond,IN)providing a daily carotenoid intake of0.26mol/kg per day L,0.24mol/kg per day Z,and0.035mol/kg per day-carotene(means of four analyses).These animals also received supplemental fruits and vegetables(typically,one fourth to one half an apple,or one half a carrot approximately three times per week),which contributed an estimated maximum additional daily average ofϳ3nmol/kg of L plus Z orϽ1%of the intake from the stock diet.17They were housed under the same conditions as the experi-mental diet groups.Tissues analyzed from control monkeys included 17serum samples and10adipose tissue samples.Retinal tissue was analyzed from14control monkeys(2male,12female)including7for 4-mm macular samples,11for8-mm annular samples,and8for pe-ripheral samples(see description of retinal tissue dissection in the next section).T ABLE1.Characteristics of MonkeysGroup,Animal ID Sex Age(y)Body wt(kg)*Supplement†n-3Fatty AcidStatusXanthophyll-freeMean2M,4F13.77.504,lowSEM 1.60.602,adequateZeaxanthin-fed642F9.07.114(12,2)Low567F10.97.914(12,2)Low224F18.37.624(10,14)Low217F18.4 6.924(10,14)Adequate586M11.612.78(4,4)Low398M15.411.18(4,4)AdequateMean13.98.911(9,3)SEM 1.6 1.02(2,1)Lutein-fed602F10.0 6.713(12,1)Low585F10.5 5.313(12,1)Low362F15.0 6.815(10,5)Low397F14.68.615(10,5)Adequate636M10.211.56(4,2)Low463M13.812.06(4,2)AdequateMean12.48.515(9,7)SEM 1.0 1.13(2,2)Control2M,12FMean13.87.00AdequateSEM 1.60.70*Body weight at study’s end.†Numbers in parentheses indicate duration of supplementation(in months)at7days/wk and4days/wk,respectively.IOVS,February2005,Vol.46,No.2Xanthophyll Accumulation and Transformation in Monkeys693Serum and Tissue CollectionSamples of subcutaneous adipose tissue(ϳ40mg)were taken from the subscapular region of the back under ketamine sedation(10mg/kg)at 2,4,8,12,16,20,24,36,and48weeks of supplementation.At the time of death,fasting blood samples(15mL)were drawn from the saphenous or femoral vein into foil-wrapped tubes under dim light and centrifuged at800g for15minutes to obtain serum.Animals were perfused with4%paraformaldehyde plus0.5%glu-taraldehyde for morphologic studies.16Previous studies18have shown that thefixatives have no effect on measurement of carotenoids. However,fixation prevents the reliable separation of neural retina from the retinal pigment epithelium(RPE),so the two tissues were kept attached and analyzed together.Analyses of a separate set of individual fresh neural retinas and RPE from normal stock diet-fed rhesus monkeys showed that carotenoids in the small mass of RPE cells of our single samples were below the detection limit and were there-fore negligible compared with the carotenoids in the much larger tissue mass of the retina.After hemisection of the globe,samples of three retinal areas were taken.Biopsy punches were used to dissect the central retina into a4-mm diameter circle centered on the fovea and a concentric annulus of8mm outside diameter(referred to here as the8-mm samples).Four-millimeter and8-mm retinal tissue sample weights are given in Table2.There were no significant differences in sample weight among the groups.A portion of the remaining periph-eral retina that varied in area from one animal to another also was collected for xanthophyll analysis.For comparing data across samples, values are referenced to the sample weights.All serum and tissue samples were protected from light and were stored atϪ70°C until analysis for carotenoids.Chemicals for Carotenoid AssaysHPLC grade methanol,water,hexane,and2-propanol were purchased from J.T.Baker Chemical Co.(Phillipsburg,NJ).Methyl-tert-butyl ether and ammonium acetate were purchased from Sigma-Aldrich(St.Louis, MO).Solvents were passed through a0.45-m membranefilter and degassed before use.Echinenone,used as an internal standard,was from Hoffmann-La Roche,Inc.(Nutley,NJ),and all-trans lutein,RRZ, and RSZ standards were a gift from DSM Nutritional Products(Roche Vitamins,Ltd.,at the time of the gift).All carotenoid standards were stored atϪ70°C.The cis isomers of xanthophylls were made by adding 2to3drops of iodine in hexane solution(5mg/100mL)to a hexane solution of xanthophylls.This was then placed under an infrared heat lamp for2hours.The solution was dried under nitrogen gas and redissolved in ethanol.The resultant solution contained cis and trans isomers of xanthophylls,as identified by absorption spectra and mass spectrometry.Analysis of Diet and Lutein andZeaxanthin SupplementsThe carotenoid concentrations of the stock diet were determined by the official method of analysis of the Association of Official Analytical Chemists19and analyzed with the same reversed-phase HPLC system used for serum and tissue analysis.15For analysis of L and Z supple-mentation,an exact amount of the supplement beadlets(ϳ0.5mg)was dissolved in1.0mL of distilled water.This solution was extracted with 2mL of chloroform-methanol(2:1)three times.The chloroform ex-tract was evaporated to dryness under nitrogen.The residue wasredissolved in1mL of ethanol,vortexed,and sonicated for30seconds and then taken up to100mL of ethanol.A50-L aliquot was used for HPLC analysis.For each batch of xanthophylls the analysis was per-formed in triplicate and completed before the beadlets were fed.From batch to batch,the xanthophyll beadlets were found to contain4%to 9%of the purified carotenoid,with the content in the Z beadlets being consistently higher.The L beadlets were found to contain only all-trans L and no Z.In the Z beadlets,approximately90%was in the all-trans form,and10%was present as a cis isomer of Z;no L was detectable. The cis isomer was tentatively identified as13-cis Z based on compar-ison of absorption spectra and HPLC retention time with a known standard.The presence of cis isomer in only the Z beadlets may be explained by the different formulation processes.The L beadlets con-tained L that was specially purified in a noncommercial process that did not induce isomerization,whereas the Z beadlets were from a commercially synthesized product(DSM Nutritional Products Ltd.). The noncarotenoid portion of the beadlets was identical for the L and Z supplements.Serum and Adipose Tissue Extractionfor CarotenoidsSerum carotenoids were measured as described previously.15Adipose tissue samples(38Ϯ2mg wet weight)were lyophilized(20hours at Ϫ20°C,Ͻ100psi,29Ϯ2mg dry weight).To the sample was added 100L12%pyrogallol in ethanol,200L30%KOH,and1mL ethanol. The mixture was vortexed and incubated at37°C for2hours.After incubation,the sample was cooled to room temperature,1mL H2O was added,and the mixture was vortexed.Echinenone in ethanol(100L)was added as an internal standard.The mixture was extracted by using3mL ether-hexane(2:1,vol/vol).The mixture was vortexed and then centrifuged at800g at4°C for5minutes.The upper layer was removed.The extraction with ether-hexane was repeated and theupper layers combined.To the extract was added1mL H2O.The mixture was vortexed,1mL ethanol was added to make the solutionclear,and the mixture was centrifuged at800g for5minutes.The H2Olayer(lower layer)was removed and discarded.Another1mL H2O was added and removed as just described.The extract was evaporated to dryness under nitrogen.The residue from adipose tissue was redis-solved in100L of ethanol,vortexed,and sonicated for30seconds.A 50-L aliquot was used for HPLC analysis.Adipose tissue concentra-tions of carotenoids are expressed as picomoles per milligram dry weight.Retinal Extraction and General Procedurefor Determination of Lutein andZeaxanthin StereoisomersThe retinal samples(4-mm central punch,8-mm annulus,and the periphery)were weighed and ground with a glass rod while on ice.To the sample was added3mL chloroform-methanol(2:1),1mL0.85% saline and150L echinenone in ethanol(as the internal standard).The mixture was vortexed for30seconds and centrifuged at800g for15 minutes at4°C.The chloroform layer was removed and evaporated to dryness under nitrogen.A second extraction was performed on the mixture by using3mL hexane,and the mixture was vortexed and centrifuged as described earlier.The hexane layer was combined with thefirst extraction and evaporated to dryness under nitrogen.The residue from retina samples was redissolved in75L of ethanol, vortexed,and sonicated for30seconds.A60-L aliquot was used for HPLC analysis.The extracted samples were analyzed for carotenoids with a re-versed-phase,gradient HPLC system and method of separating L and Z that has been described.20In the reversed-phase HPLC system,RRZ and RSZ eluted in one peak.The L and Z peak samples(retention times, 7to10minutes)of each retinal sample were collected from thereversed-phase HPLC system and dried under N2and the residue redissolved in75L hexane.A60-L aliquot was injected into aT ABLE2.Retinal Sample Wet Weights4mm8mmXanthophyll-free 6.2Ϯ0.113.1Ϯ2.5Zeaxanthin-fed 5.8Ϯ0.314.7Ϯ0.6Lutein-fed 5.9Ϯ0.113.3Ϯ0.6Control 4.7Ϯ0.611.8Ϯ0.9Data are expressed as mean milligramsϮSE.694Johnson et al.IOVS,February2005,Vol.46,No.2normal-phase HPLC system to separate the Z stereoisomers(RRZ,RSZ) and L.The L and Z content of the4-mm macula,8-mm annulus,and peripheral samples were expressed as picomoles per milligram wet weight for easy comparison of the retinal regions.Reversed-Phase HPLC AnalysisThe reversed-phase,gradient HPLC system consisted of a pump(616 LC;Waters Corp.,Milford,MA),an autosampler(model717plus; Waters Corp.),a C-30column(carotenoids S-3,4.6ϫ150mm;YMC, Kyoto,Japan)and a detector(model490E;Waters Corp.).This gradi-ent method allows adequate separation of L,the cis isomer of Z, all-trans Z(RRZϩRSZ),cryptoxanthin,␣-carotene,13-cis-carotene, all-trans-carotene,and9-cis-carotene,as well as four geometrical isomers of lycopene(15-cis,13-cis,9-cis,and all-trans lycopene).20 Carotenoids were quantified at455nm by determining peak areas in the HPLC chromatograms calibrated against known amounts of stan-dards.Concentrations were corrected for extraction and handling losses by monitoring the recovery of the internal standards.The lower limit of detection was0.2pmol for carotenoids.A reversed-phase HPLC chromatogram of standards of L,Z,and RSZ(meso-Z)is shown in Figure1A.Normal-Phase HPLC SystemThe normal-phase HPLC system consisted of a pump and autosampler from the reversed-phase system(Waters Corp.),a column(amilose derivative coated on silica-gel,Chiralpak AD;Daicel Chemical Indus-tries,Ltd.,Tokyo,Japan)and a programmable photodiode array detec-tor(model994;Waters).The HPLC mobile phase was hexane(solvent A)and hexane-isopropanol(1:1,solvent B).The procedure began at 90%solvent A and10%solvent B at0.8mL/min for55minutes.This was followed by a1-minute gradient to100%solvent A at1.5mL/min. The system was held at100%solvent A for10minutes,followed by a 4-minute gradient to90%solvent A and10%solvent B at1.5mL/min. The system was held at this condition for15minutes followed by a 1-minute gradient to0.8mL/min.The system was held at90%solvent A and10%solvent B at0.8mL/min for10minutes for equilibration back to initial conditions.This method separated RSZ,RRZ,and L.The lower limit of detection was0.2pmol for each xanthophyll.A normal-phase HPLC chromatogram of standards for L,RRZ,and RSZ is shown in Figure1B.For retinal samples,the identifications of RRZ,RSZ,and L were confirmed by comparing absorption spectra of samples with those of known standards.Further confirmation was obtained by coelution of sample peaks from extracts of two samples from each xanthophyll-supplemented group with known standards of RRZ,RSZ,or L.In our quantitation of the retinal xanthophylls,we followed the same ratio-nale as Bone et al.21That is,no internal standard was necessary for the normal-phase system because the total quantity of Z stereoisomers was obtainable from the reversed-phase chromatography,and the normal-phase separation permitted measurement of their relative proportions. This procedure was carefully worked out using tissue from control monkeys.StatisticsAll data are presented as the meanϮSEM.The significance of differ-ences in serum,adipose tissue,and retinal xanthophyll levels among groups(L-fed,Z-fed,and stock-diet controls)were tested with one-way ANOVAs(␣level PϽ0.05)followed when appropriate by post hoc pair-wise Bonferroni-Dunn tests(␣level PՅ0.05for comparisons between two groups,orՅ0.017for pair-wise comparisons among three groups).Significant differences in xanthophyll concentration in serum and adipose tissue at the end of the seven-times-per week (7ϫ/wk)supplementation schedule and at the time of death were evaluated using two-way repeated-measures ANOVA followed,when appropriate,by post hoc comparisons for effect of time in each group and effect of diet at each time point.Significant differences from baseline xanthophyll concentrations in adipose tissue were evaluated with a repeated-measures ANOVA.Although the L-and Z-fed groups were balanced with respect to sex and fatty acid status,two-way ANOVAs were used to test for effects of these variables or interactions with supplement type.Linear regression was used to explore whether tissue xanthophyll concentrations were related to age,body weight(at the beginning or end of the study),or the duration of supplementation (total duration or the duration of7ϫ/wk four-times-per week[4ϫ/wk] supplementation).In addition,analyses of covariance(ANCOVAs) were used to test the effects of L versus Z supplementation after adjusting for these factors.R ESULTSSerum CarotenoidsThe serum concentrations of xanthophylls at the end of the 7ϫ/wk supplementation schedule and at the time of death are presented for comparison,with postmortem tissue concentra-tions shown in Table3.Longitudinal measures of serum xan-thophylls in these monkeys over the course of L and Z supple-mentation have been reported.15The unsupplemented xanthophyll-free monkeys had no detectable xanthophylls in serum and are not included in the table.There was a trend toward higher total xanthophyll concentrations in the L-fed group(Pϭ0.052)at the end of the7ϫ/wk supplementation period but no difference at study’s end(Pϭ0.2).In the L-fed monkeys,serum concentrations of L were significantly lower at the study’s end than at the end of the7ϫ/wk supplementation period(PϽ0.015),but in the Z-fed group there was no difference between the two time points.Serum xanthophyll concentrations at the end of the study were significantly higher in both the L-and Z-fed groups than in the stock-diet control group(PϽ0.014and PϽ0.0001,respectively).Serum L in the L-fed monkeys was entirely in the trans form.Serum Z in the Z-fed monkeys was in both the trans(72%)and cis(27%) forms.There was also a small amount of3Јdehydrolutein(1%) present in the serum of these animals.The identification of this metabolite as3Јdehydrolutein was suggested by coelution with a known standard,absorption spectra comparison with a known standard,and LC/MS(data not shown).Final serum xanthophyll concentration was not significantly related to sex or n-3fatty acid status(by two-way ANOVA)or to body weight or the duration of supplementation(by linear regression),and the difference between the Z-and L-fed groups remained non-significant when adjusted for these factors by ANCOVA.Al-though serum xanthophyll concentrations initially decreased after the reduction in the frequency of supplementation,15the duration of4ϫ/wk supplementation was not related tofinal serum xanthophyll levels(Pϭ0.366,overall;Pϭ0.857for the L-fed group and0.790for the Z-fed group).Adipose Tissue CarotenoidsThe adipose tissue concentrations of individual and total xan-thophylls at the end of the7ϫ/wk supplementation schedule and at study end are presented in Table3.Before supplemen-tation,monkeys fed the xanthophyll-free semipurified diets had no measurable L or Z in the adipose tissue.Adipose tissue carotenoid concentrations increased by2weeks of supplemen-tation but were highly variable thereafter in both groups. Therefore,there were no significant differences between the two supplement groups at any time point.However,adipose tissue concentrations of total xanthophyll were significantly greater at the end of the study than at the end of the7ϫ/wk supplementation period(Pϭ0.017overall;Pϭ0.087in the L-fed group alone,Pϭ0.038in the Z-fed group alone).By the end of the study,adipose total xanthophyll concentrations in both supplement groups had risen to the level found in normal control monkeys.Adipose total xanthophyll concentrations atIOVS,February2005,Vol.46,No.2Xanthophyll Accumulation and Transformation in Monkeys695F IGURE 1.HPLC chromatograms.(A )Standards for L,Z (RRZ),meso -Z (RSZ):reversed phase;(B )standards for L,Z (RRZ),meso -Z (RSZ):normal phase;(C )xanthophyll-free animal,4-mm retinal punch:reversed phase;(D )xanthophyll-free,4-mm retinal punch:normal phase;(E )L-fed animal,8-mm retinal punch:reversed phase;(F )L-fed,8-mm retinal punch:normal phase;(G )Z-fed,peripheral punch:reversed phase;(H )Z-fed,peripheral punch:normal phase;(I )Stock-diet control animal,4-mm retinal punch:reversed phase;and (J )stock-diet control,4-mm retinal punch:normal phase.696Johnson et al.IOVS,February 2005,Vol.46,No.2the end of the7ϫ/wk supplementation period did not corre-late significantly with the duration of this period.In addition,final concentrations did not correlate significantly with the total duration of supplementation or the duration of4-week supplementation.Final concentrations also were not signifi-cantly related to sex,body weight,or n-3fatty acid status,and the absence of a difference between the Z-and L-fed groups was not altered by adjusting for any of these factors by ANCOVA.In the L-fed group,all the L was in the all-trans form,and no Z was detected.IN the Z-fed group,81%of the total Z was all-trans,and19%was in the cis form.In addition,3Јdehydro-lutein(presumptive)was detected from12to48weeks in one or two Z-fed monkeys per time point(not always the same monkey)at concentrations of0.04Ϯ0.01nmol/g dry weight (8.1%Ϯ1.2%of the total xanthophyll,9/30adipose tissue samples).Thereafter,3Јdehydrolutein was detected in the two remaining Z-fed monkeys at86to103weeks at similar con-centrations(0.04Ϯ0.01nmol/g dry weight;3.9%Ϯ1.1%of the total xanthophyll content,5/6adipose tissue samples).In the adipose tissue biopsy specimens sampled at time of death, 3Јdehydrolutein was detected in all samples at a concentration of0.06Ϯ0.01nmol/g dry weight(3.2%Ϯ0.3%total xantho-phyll).For the control group,all the L was in the all-trans form and the Z was in the all-trans(79%of total Z)and cis(21%of total Z)forms.Retinal CarotenoidsControl Monkeys.Representative reversed-phase and nor-mal-phase chromatograms from the4-mm macular sample of a stock-diet control monkey are shown in Figures1I and1J.For control monkeys,the amount of total xanthophylls(L,RRZ, RSZ,and cis Z)in the4-mm macular sample was2.91Ϯ0.84 pmol/mg(Table4,bottom two rows).Approximately88%of this was as Z(RRZϩRSZ)with the remainder being L,result-ing in an L-to-Z ratio of0.12.Only one monkey had a small amount of detectable cis Z(0.32pmol/mg,9%of total xantho-phyll).The normal-phase HPLC results demonstrated that the ratio of RRZ to RSZ in the4-mm macular sample of the control monkeys was1.0:0.91Ϯ0.2.In the8-mm annulus samples,the total amount of xantho-phyll in the control monkeys was0.27Ϯ0.04pmol/mg(Table 4),only10%of the concentration in the4-mm macular sam-ples.Approximately63%of this was RRZ with the remainder as L,for an L-to-Z ratio of0.59.Unlike the4-mm punch,no RSZ or cis-Z was detectable in these samples.In the peripheral retina of the control monkeys,the amount of xanthophyll was0.22Ϯ0.04pmol/mg(Table4),very similar to the value for the8-mm sample.Approximately64% of the peripheral xanthophylls was L,and the remainder was RRZ(36%)and cis Z(Ͻ1%),so that the L-to-Z ratio was1.75.Xanthophyll-Free and Supplement-Fed Monkeys.In-corporation of L into the Retina.There was no detectable L or Z in retinal samples from xanthophyll-free,unsupplemented monkeys.Furthermore,there was no L in retinal samples from Z-fed monkeys.These results show that retinal L must be derived from the diet and it is not derived from Z.Supplemen-tation was very successful in inducing the incorporation of L into the retina of animals that previously had no L in the diet. The mean L content of the4-mm macular area from the L-fed animals(2.44Ϯ0.34pmol/mg)was nearly8times the amount found in control monkeys(0.31Ϯ0.08pmol/mg;PϽ0.0001). In the8-mm sample from the L-fed monkeys,the L content (0.81Ϯ0.07pmol/mg)was eight times the amount found in control monkeys(0.10Ϯ0.01pmol/mg;PϽ0.0001),and in the periphery it was nearlyfive times the amount in the control animals(0.69Ϯ0.07vs.0.14Ϯ0.03pmol/mg,Pϭ0.0001).Formation of RSZ(meso-Z)in the Retina.In the4-mm macular samples of the L-fed group,Z was present entirely in the form of RSZ.RSZ was not found outside the4mm sample in the L-fed animals,and it was not present in any samples from the Z-fed animals.Thus,in rhesus monkeys,RSZ appears to be formed from dietary L,and only in the macular region.Deriving Retinal Z Concentrations.Quantitative analysis of retinal Z data from the experimental monkeys was more complex,because an unknown peak overlapping with Z ap-peared in the reversed-phase HPLC system in all retinal extracts from animals fed the semipurified diet,including animals that were not supplemented(Fig.1C).This was unexpected be-cause no xanthophyll was detected in the diet,serum,orT ABLE3.Serum and Adipose Tissue Xanthophyll ConcentrationsControlZeaxanthin-Fed Lutein-Fed7؋/wk End Study End P7؋/wkEnd Study End PSerum(nmol/L)Lutein74Ϯ90Ϯ0*0Ϯ0*NS838Ϯ38*529Ϯ73*0.015 Zeaxanthintrans59Ϯ9391Ϯ44*†577Ϯ125*†NS0Ϯ00Ϯ0NS cis22Ϯ4263Ϯ32*†213Ϯ60*†NS0Ϯ00Ϯ0NS Total zeaxanthin81Ϯ12654Ϯ68*†791Ϯ178*†NS0Ϯ00Ϯ0NS 3ЈDehydrolutein ND10Ϯ2*†11Ϯ4*†NS ND ND NS Total xanthophyll154Ϯ20665Ϯ69*801Ϯ180*NS838Ϯ38*529Ϯ73*0.015 Adipose tissues(nmol/g dry wt)Lutein 1.18Ϯ0.440Ϯ0*0Ϯ0*NS0.44Ϯ0.17 1.89Ϯ0.820.087 Zeaxanthintrans0.57Ϯ0.130.33Ϯ0.04† 1.33Ϯ0.30*†0.0400Ϯ00Ϯ0NS cis0.15Ϯ0.040.06Ϯ0.02†0.32Ϯ0.07*†0.0380Ϯ00Ϯ0NS Total zeaxanthin0.72Ϯ0.160.39Ϯ0.06† 1.64Ϯ0.37*†0.0400Ϯ00Ϯ0NS 3ЈDehydrolutein ND0.02Ϯ0.010.06Ϯ0.000.093ND NDTotal xanthophyll 1.90Ϯ0.570.41Ϯ0.06 1.70Ϯ0.390.0380.44Ϯ0.06 1.89Ϯ0.820.087 *For each row:significantly different from control(PϽ0.05).†For each timepoint(7ϫ/wk,study end):significantly different from lutein-fed(PϽ0.05).ND,not detectable.Data were recorded at the end of the7ϫ/wk supplementation period and at time of death(study end)for lutein-fed and zeaxanthin-fed monkeys and at single time point for control monkeys fed stock diets.P is7ϫ/wk versus end of study.For control,serum groups nϭ17;For adipose tissue control group nϭ10.For adipose groups at study’s end nϭ4(Z-fed).For all other nϭ6.IOVS,February2005,Vol.46,No.2Xanthophyll Accumulation and Transformation in Monkeys697。
网路银行消费者行为之研究--创新扩散理论

網路銀行消費者行為之研究--創新擴散理論王文弘Wen-Hung Wang國立臺灣海洋大學、航運管理學系、助理教授林獻堂Hsien-Tang Lin國立臺灣海洋大學、航運管理學系、研究生摘要研究調查顯示,未來使用網路銀行人口有越來越多的趨勢。
本研究以創新擴散理論為基礎,並納入使用經驗與安全性等因素,探討消費者使用網路銀行的行為。
透過便利抽樣法發放網路問卷,本研究共蒐集有效問卷1030份。
本研究以結構方程模式為主要研究方法,採用LISREL8.80進行驗證性因素分析和結構模式分析。
研究結果顯示:「相對優勢」、「相容性」、「可試用性」、「可觀察性」、「安全性」及「使用經驗」均會顯著影響「態度」;「態度」和「使用經驗」會顯著影響「行為意圖」;「使用經驗」和「行為意圖」會顯著影響「實際使用行為」。
因此,銀行管理者可透過強化消費者使用網路銀行的相對優勢、相容性、可試用性、可觀察性、安全性及使用經驗等,進而影響消費者實際使用網路銀行之行為,並可作為推廣網路銀行及制定行銷策略時的依據。
關鍵詞:網路銀行、創新擴散、安全性、使用經驗A n E m p i r i c a l R e s e a r c h o f C u s t o m e rB e h a v i o r o f We b-B a n k i n g S e r v i c e,I n n o v a t i o n o f D i f f u s i o n T h e o r yAbstractWith the rapid growth internet users, the demand of web-banking is eager. Based on innovation of diffusion theory, this research wants to discuss the factors that influence consumer web-bank using behavior. Data collected from online survey and got 1030 usable samples.With the analysis of SEM, the analytic results showed that “Relative Advantage,” “Compatibility,” “Trialibility,” “Observability,” “Security,” and “Experience,” have positive significant effect on “Attitude;”in the meanwhile, both “Attitude,” and “E xperience” have positive significant on “Behavioral Intention;” furthermore, both “E xperience” and “Behavioral Intention” have positive significant effect on “Usage.”Based on the analytic results,suggestions are the managers of banks should enhance the attributes of web-bank by “Relative Advantage,”“Compatibility,”“Trialibility,” “Observability,” “Security” and “Experience,”in order to achieve both elevation of using behavior of web-bank and financial performance.Keywords: Web-Bank, Innovation of Diffusion, Security, Experience緒論現今台灣的金融環境,正面臨著一系列的改革與挑戰。
人类基因组概况ppt课件

2.91Gbp
54% 38% 9% 35% 26588 42% Titin(234) 约300万个 1/12500 bp
最长的染色体 最短的染色体 基因最多的染色体 基因最少的染色体 基因密度最大的染色体 基因密度最小的染色体 重复序列含量最高的染色体
It is essentially immoral not to get it (the human genome sequence) done as fast as possible.
James Watson
人类基因组计划的完成,使得我们今天有可能来探 讨基因组的概,但我们仍然无法来谈论细节。
重复序列含量最低的染色体
编码外显子序列的比例 基因的平均长度
2(240 Mbp) Y(19 Mbp) 1(2453) Y(104) 19(23/Mb) 13,Y(5/Mb) 19(57%)
2,8,10,13,18(36%)
1.1~1.4% 27 Kb
女 平均 男
染色体上距着丝粒越远,重组率越高
4. Francis S. Collins, Eric D. Green, Alan E. Guttmacher, Mark S. Guyer :A Vision for the Future of Genomics Research. A blueprint for the genomic era. Nature Apr 24 2003: 835.
而 Celera 的测序样本来自5个人:分别属于西班牙裔、 亚洲裔、非洲裔、美洲裔和高加索裔(2男3女),是从21个志 愿者样本中挑选的。
生物科技创业者:伊丽莎白·伊霍尔姆(23andMe创始人)人物简介

• 加大对研发和创新的投资 • 拓展新的业务领域,如药物研发和疾病预防
未来发展方向
• 成为一个全面的个性化医疗平台 • 为客户提供更丰富的基因检测和健康管理服务
伊丽莎白·伊霍尔姆对生物科技产业的展望和预测
展望
• 生物科技将继续快速发展,成为全球经济增长的重要驱 动力 • 个性化医疗将成为未来医疗领域的重要趋势
对科技产业的贡献
• 23andMe公司的创新产品和服务推动了个性化医疗的发 展 • 为生物科技领域树立了成功的创业典范
伊丽莎白·伊霍尔姆的社会影响和荣誉奖项
社会影响
• 被评为全球最具影响力的女性企业家之一 • 为个性化医疗的普及和推广做出了巨大贡献
荣誉奖项
• 获得多项生物科技领域的奖项和荣誉 • 被《时代》杂志评为全球最具影响力的100位人物之一
02 童年时期对科学和技术的兴趣
• 喜欢参观科学博物馆 • 对遗传学和生物学有浓厚兴趣
03 家庭环境对她的影响
• 父母鼓励她追求自己的梦想 • 培养了她独立思考和解决问题的能力
伊丽莎白·伊霍尔姆的教育经历和学术成就
进入斯坦福大学学习生物学
• 主修生物学,辅修计算机科学 • 成绩优异,获得学术奖学金
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生物科技创业者:伊丽莎白·伊霍尔姆 (23andMe创始人)人物简介
01
伊丽莎白·伊霍尔姆的早期生活与教育背景
伊丽莎白·伊霍尔姆的童年经历和家庭背景
01 出生于美国加利福尼亚州
• 父亲是一位知名的企业家 • 母亲是一位海洋生物学家
伊丽莎白·伊霍尔姆的领导风格和管理哲学
领导风格
经济社会学理论传统嵌入性等当代理论

Selected Publications
1973. "The Strength of Weak Ties." American Journal of Sociology, 78 (May): 1360-1380.
1978. "Threshold Models of Collective Behavior." American Journal of Sociology, 83 (May): 1420-1443.
格拉诺维特当前的经济社会学研究
经济制度的社会建构
Professor Mark Granovetter is currently concentrating on three main projects. The first is a general treatment of economic sociology with the preliminary title Society and Economy: The Social Construction of Economic Institutions, to be published by Harvard University Press. The theoretical scheme that will inform the book is laid out in his 1985 American Journal of Sociology paper, "Economic Action and Social Structure: The Problem of Embeddedness".
☆功利主义传统:理性较少受到社会关系影响 [例]霍布斯:自然状态(state of nature) 罗尔斯:原初位置(original position)
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Carlos Gonzalez-Buxton and Kevin Ingersent∗
Department of Physics, University of Florida, P. O. Box 118440, Gainesville, Florida 32611 (January 6, 1998) Thermodynamic properties are presented for four magnetic impurity models describing delocalized fermions scattering from a localized orbital at an energy-dependent rate Γ(ǫ) which vanishes precisely at the Fermi level, ǫ = 0. Specifically, it is assumed that for small |ǫ|, Γ(ǫ) ∝ |ǫ|r with r > 0. The cases r = 1 and r = 2 describe dilute magnetic impurities in unconventional (d- and p-wave) superconductors, “flux phases” of the two-dimensional electron gas, and certain zero-gap semiconductors. For the nondegenerate Anderson model, the main effects of the depression of the low-energy scattering rate are the suppression of mixed valence in favor of local-moment behavior, and a marked reduction in the exchange coupling on entry to the local-moment regime, with a consequent narrowing of the range of parameters within which the impurity spin becomes Kondo-screened. The precise relationship between the Anderson model and the exactly screened Kondo model with power-law exchange is examined. The intermediate-coupling fixed point identified in the latter model by Withoff and Fradkin (WF) is shown to have clear signatures both in the thermodynamic properties and in the local magnetic response of the impurity. The underscreened, impurity-spin-one Kondo model and the overscreened, two-channel Kondo model both exhibit a conditionally stable intermediatecoupling fixed point in addition to unstable fixed points of the WF type. In all four models, the presence or absence of particle-hole symmetry plays a crucial role in determining the physics both at strong coupling and in the vicinity of the WF transition. These results are obtained using an extension of Wilson’s numerical renormalization-group technique to treat energy-dependent scattering. The strong- and weak-coupling fixed points of each model are identified and their stability is analyzed. Algebraic expressions are derived for the fixed-point thermodynamic properties, and for low-temperature corrections about the stable fixed points. Numerical data are presented confirming the algebraic results, identifying and characterizing intermediate-coupling (non-Fermi-liquid) fixed points, and exploring temperature-driven crossovers between different physical regimes. PACS numbers: 72.15.Qm, 75.20.Hr I. INTRODUCTION
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unconventional superconductor can vary like |ǫ| or |ǫ|2 near line or point nodes in the gap.11 Heavy-fermion and cuprate superconductors are strong candidates for this behavior. (2) The valence and conduction bands of certain semiconductors touch in such a way that, for small |ǫ|, ρ(ǫ) is proportional to |ǫ|d−1 in d spatial dimensions. Examples include PbTe-SnTe heterojunctions,12 and the ternary compounds Pb1−x Snx Se, Pb1−x Snx Te, and Hg1−x Cdx Te, each at a temperature-dependent critical composition.13 (Zero-gap mercury cadmium telluride has been proposed as the basis for a giant magnetoresistance read-head for high-density storage.14 ) (3) Various two-dimensional electron systems — including graphite sheets,15 “flux phases” in a strong magnetic field,16 and exotic phases of the Hubbard model17 — are predicted to exhibit a linear pseudogap. It is a matter of ongoing debate whether this pseudogap survives the presence of disorder.18 (4) The single-particle density of states in the one-dimensional Luttinger model varies like |ǫ|2α , where α changes continuously with the strength of the bulk interactions.19 In all these examples, the effective density of states can be approximated near the Fermi level by a power law, ρ(ǫ) ∝ |ǫ|r with r > 0. The first theoretical study of magnetic impurities in gapless Fermi systems was carried out by Withoff and
arXiv:cond-mat/9803256v2 [cond-mat.str-el] 23 Mar 1998
In conventional metallic systems, it is well understood how many-body correlations induced by dilute magnetic impurities in an otherwise noninteracting conduction band can at low temperatures effectively quench all spin fluctuations on each impurity site.1 This, the Kondo effect, depends critically on the presence of fermionic excitations down to arbitrarily small energy scales. The impurity properties are sensitive to the density of electronic states ρ(ǫ) only through its value at the Fermi level, ǫ = 0. Other details of the band shape have negligible effect on the low-temperature physics. A growing body2–10 of theoretical work shows that the standard picture of the Kondo effect must be fundamentally revised in order to treat “gapless” systems, in which the effective density of states vanishes precisely at ǫ = 0 but is nonzero everywhere else in the vicinity of the Fermi energy. The goal of the present paper is to extend the understanding of this issue through a comprehensive account of the different physical regimes exhibited by magnetic impurities in gapless host materials, including detailed calculations of thermodynamic properties. Gaplessness may be realized in a number of physical systems: (1) The quasiparticle density of states in an