Dose-Finding Based on Bivariate Efficacy-Toxicity Outcome Using Archimedean Copula

In dose-finding clinical study, it is common that multiple endpoints are of interest. For instance, efficacy and toxicity endpoints are both primary in clinical trials. In this article, we propose a joint model for correlated efficacy-toxicity outcome constructed with Archimedean Copula, and extend the continual reassessment method (CRM) to a bivariate trial design in which the optimal dose for phase III is based on both efficacy and toxicity. Specially, considering numerous cases that continuous and discrete outcomes are observed in drug study, we will extend our joint model to mixed correlated outcomes. We demonstrate through simulations that our algorithm based on Archimedean Copula model has excellent operating characteristics.     

ST6Gal-I通过上调整合素β1的唾液酸化促进绒毛膜癌细胞的迁移

为了研究β-半乳糖α2,6-唾液酸转移酶1(ST6Gal-I)对人绒毛膜癌细胞(JAR)和人绒毛膜外滋养层细胞(HTR-8/SVneo)迁移能力的影响。首先采用Transwell小室的实验方法比较两种细胞的迁移能力,再用PCR和Western blot的方法检测ST6Gal-I mRNA及其蛋白的表达差异,最后通过Transwell检测经siRNA干扰ST6Gal-I的表达后对细胞迁移能力的影响,并通过免疫共沉淀技术检测ST6Gal-I的靶蛋白整合素β1唾液酸化程度的变化。结果表明,JAR细胞的迁移能力强于HTR-8/SVneo细胞;JAR细胞中ST6Gal-I在mRNA及蛋白水平表达均高于HTR-8/SVneo细胞,同时检测到JAR细胞中靶蛋白整合素β1的唾液酸化程度亦高于对照组。用siRNA干扰相对高表达的JAR细胞中ST6Gal-I基因,发现其迁移能力随之下降,且ST6Gal-I的靶蛋白整合素β1的唾液酸化程度也发生降低。表明ST6Gal-I参与了肿瘤细胞的迁移调控。该研究结果对发现新的治疗靶点有重要的启示。     

三峡工程与江汉平原农业持续发展

三峡工程与江汉平原农业持续发展朱俊林（湖北大学生态学研究所,武汉４３００６２）ＩｎｆｌｕｅｎｃｅｓｏｆｔｈｅＴｈｒｅｅ＿ＧｏｒｇｅＰｒｏｊｅｃｔｏｎｔｈｅＡｇｒｉｃｕｌｔｕｒｅｉｎＪｉａｎｇｈａｎＰｌａｉｎＡｒｅａａｎｄｔｈｅＡ┐ｇｒｉｃｕｌｔｕｒａ...     

Genome-Wide Identification and Expression Profiling of the Shaker K⁺ Channel and HAK/KUP/KT Transporter Gene Families in Grape (<i>Vitis vinifera</i> L.)

Potassium (K⁺) is an essential macronutrient for plants to maintain normal growth and development. Shaker-like K⁺ channels and HAK/KUP/KT transporters are critical components in the K⁺ acquisition and translocation. In this study, we identified 9 Shaker-like K⁺ channel (VvK) and 18 HAK/KUP/KT transporter (VvKUP) genes in grape, which were renamed according to their distributions in the genome and relative linear orders among the distinct chromosomes. Similar structure organizations were found within each group according to the exon/intron structure and protein motif analysis. Chromosomal distribution analysis showed that 9 VvK genes and 18 VvKUP genes were unevenly distributed on 7 or 10 putative grape chromosomes. Three pairs of tandem duplicated genes and one pair of segmental duplicated genes were observed in the expansion of the grape VvKUP genes. Gene expression omnibus (GEO) data analysis showed that VvK and VvKUP genes were expressed differentially in distinct tissues. Various cis-acting regulatory elements pertinent to phytohormone responses and abiotic stresses, including K⁺ deficiency response and drought stress, were detected in the promoter region of VvK and VvKUP genes. This study provides valuable information for further functional studies of VvK and VvKUP genes, and lays a foundation to explore K⁺ uptake and utilization in fruit trees.     

Comparative conformational analysis of nucleosides by NMR, X-ray, and semi-empirical (PM3 VS. AM1) methods

The 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl ortho-aza-purine and -pyrimidine nucleosides manifest an unusually rigid sugar N conformation in solution.     

染色质乙酰化相关BRD蛋白家族

Bromodomain结构域首先在果蝇蛋白质Brahma中发现,折叠模式独特且高度保守,是最早也是截至目前公认唯一可与乙酰化赖氨酸结合的结构域。BRD蛋白通过结合不同的蛋白质或者定位蛋白质到细胞核发挥精细调节作用。BRD蛋白复合物常特异性识别并结合到染色质组蛋白H3/H4特定的乙酰化赖氨酸残基,从而影响靶基因的转录翻译;该蛋白复合物功能异常通常与多种疾病的发生相关联,表明对转录翻译调节有重要意义。但迄今为止,BRD蛋白复合物修饰染色质机理不明,现有研究提示BRD蛋白复合物维持染色质乙酰化状态,也可以与染色质组蛋白其它位点结合,从整体水平增强组蛋白乙酰化精度和效率。     

通过接合作用质粒从大肠杆菌到棒状杆菌的转移

构建了可接合转移的穿梭质粒pXZ911、pBZ51和pBZ52。这些质粒中含有具转移功能的Mob片段和在棒状杆菌中复制的复制区。以大肠杆菌S17—1为供体菌,通过接合转移作用,可将这些质粒转移到谷氨酸棒杆菌ATCCl3032、谷氨酸棒杆菌ATCC21543、北京棒杆菌B3、北京棒杆菌1．299、裂氏棒杆菌B43、黄色短杆菌ATCC 14067等棒状杆菌苗株,接合转移频率分别为：9X10^-5,1X10^-4,8．5x10,2．3X10^-4×10^-5,2．9X10^-5。本文还探索了大肠杆菌和几种革兰氏阳性棒状杆菌问基因转移的方法、转移频率、影响转移频率的因素、宿主范围等问题。