排序方式: 共有65条查询结果,搜索用时 15 毫秒
51.
Raghavan S Lu Z Beeson T Chapman KT Schleif WA Olsen DB Stahlhut M Rutkowski CA Gabryelski L Emini E Tata JR 《Bioorganic & medicinal chemistry letters》2007,17(19):5432-5436
A series of HIV protease inhibitors with modifications on the P3 position have been designed and synthesized. These compounds exhibit excellent antiviral activity against both the wild type enzyme and PI-resistant clinical viral isolates. The synthesis and biological activity of the compounds are described. 相似文献
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LJ Melchers MJAM Clausen MF Mastik L Slagter-Menkema JE van der Wal GBA Wisman JLN Roodenburg E Schuuring 《Epigenetics》2015,10(9):850-860
Hypermethylation is an important mechanism for the dynamic regulation of gene expression, necessary for metastasizing tumour cells. Our aim is to identify methylation tumour markers that have a predictive value for the presence of regional lymph node metastases in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Significantly differentially expressed genes were retrieved from four reported microarray expression profiles comparing pN0 and pN+ head-neck tumours, and one expression array identifying functionally hypermethylated genes. Additional metastasis-associated genes were included from the literature. Thus genes were selected that influence the development of nodal metastases and might be regulated by methylation. Methylation-specific PCR (MSP) primers were designed and tested on 8 head-neck squamous cell carcinoma cell lines and technically validated on 10 formalin-fixed paraffin-embedded (FFPE) OOSCC cases. Predictive value was assessed in a clinical series of 70 FFPE OOSCC with pathologically determined nodal status. Five out of 28 methylation markers (OCLN, CDKN2A, MGMT,
MLH1 and DAPK1) were frequently differentially methylated in OOSCC. Of these, MGMT methylation was associated with pN0 status (P = 0.02) and with lower immunoexpression (P = 0.02). DAPK1 methylation was associated with pN+ status (P = 0.008) but did not associate with protein expression. In conclusion, out of 28 candidate genes, two (7%) showed a predictive value for the pN status. Both genes, DAPK1 and MGMT, have predictive value for nodal metastasis in a clinical group of OOSCC. Therefore DNA methylation markers are capable of contributing to diagnosis and treatment selection in OOSCC. To efficiently identify additional new methylation markers, genome-wide methods are needed. 相似文献
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Combinatorial diversification of indinavir: in vivo mixture dosing of an HIV protease inhibitor library 总被引:2,自引:0,他引:2
Rano TA Cheng Y Huening TT Zhang F Schleif WA Gabryelski L Olsen DB Kuo LC Lin JH Xu X Olah TV McLoughlin DA King R Chapman KT Tata JR 《Bioorganic & medicinal chemistry letters》2000,10(14):1527-1530
An efficient combination solution-phase/solid-phase route enabling the diversification of the P1', P2', and P3 subsites of indinavir has been established. The synthetic sequence can facilitate the rapid generation of HIV protease inhibitors possessing more favorable pharmacokinetic properties as well as enhanced potencies. Multiple compound dosing in vivo may also accelerate the identification of potential drug candidates. 相似文献
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Design and synthesis of highly potent HIV protease inhibitors with activity against resistant virus 总被引:1,自引:0,他引:1
Lu Z Raghavan S Bohn J Charest M Stahlhut MW Rutkowski CA Simcoe AL Olsen DB Schleif WA Carella A Gabryelski L Jin L Lin JH Emini E Chapman K Tata JR 《Bioorganic & medicinal chemistry letters》2003,13(10):1821-1824
A series of highly potent HIV protease inhibitors have been designed and synthesized. These compounds are active against various clinical viral isolates as well as wild-type virus. The synthesis and biological activity of these HIV protease inhibitors are discussed. 相似文献
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Danyel GJ Jennen Addie LJ Vereijken Henk Bovenhuis Richard MPA Crooijmans Jan J van der Poel Martien AM Groenen 《遗传、选种与进化》2005,37(3):215-228
In this report we describe the analysis of an advanced intercross line (AIL) to confirm the quantitative trait locus (QTL) regions found for fatness traits in a previous study. QTL analysis was performed on chromosomes 1, 3, 4, 15, 18, and 27. The AIL was created by random intercrossing in each generation from generation 2 (G2) onwards until generation 9 (G9) was reached. QTL for abdominal fat weight (AFW) and/or percentage abdominal fat (AF%) on chromosomes 1, 3 and 27 were confirmed in the G9 population. In addition, evidence for QTL for body weight at the age of 5 (BW5) and 7 (BW7) weeks and for the percentage of intramuscular fat (IF%) were found on chromosomes 1, 3, 15, and 27. Significant evidence for QTL was detected on chromosome 1 for BW5 and BW7. Suggestive evidence was found on chromosome 1 for AFW, AF% and IF%, on chromosome 15 for BW5, and on chromosome 27 for AF% and IF%. Furthermore, evidence on the chromosome-wise level was found on chromosome 3 for AFW, AF%, and BW7 and on chromosome 27 for BW5. For chromosomes 4 and 18, test statistics did not exceed the significance threshold. 相似文献
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广义隐Markov模型(GHMM)是基因识别的一种重要模型,但是其计算量比传统的隐Markov模型大得多,以至于不能直 接在基因识别中使用。根据原核生物基因的结构特点,提出了一种高效的简化算法,其计算量是序列长度的线性函数。在此 基础上,构建了针对原核生物基因的识别程序GeneMiner,对实际数据的测试表明,此算法是有效的。 相似文献