A family of oligonucleotides and phosphorothioate oligonucleotide analogues was synthesized with a cholesteryl group tethered at the 3'-terminal internucleoside link. This modification, introduced to enhance interaction of the polyanions with cell membranes, significantly increases the antiviral activity of the oligomers, as judged by inhibition of syncytia formation and expression of viral proteins p17, p24, and reverse transcriptase for human immunodeficiency virus 1 in Molt-3 cells. In the most favorable case, with a 20-mer cholesteryl-phosphorothioate derivative, complete inhibition by all assays was obtained with an oligomer concentration of 0.2 jIM. Even decamers were active, and some antiviral activity was observed for a heptanucleotide cholesteryl-phosphorothioate derivative, which binds very poorly to complementary oligonucleotides. These facts, and the finding that the activity of the phosphorothioate decamers does not correlate with a specific sequence., suggests that a mechanism other than "antisense inhibition" may be operative in these systems.

A procedure is described for linking nucleosides covalently to controlled pore glass or cross-linked polystyrene supports by means of an oxalyl anchor. Though stable to triethylamine and diisopropylamine, the nucleoside-oxalyl link can be cleaved within a few minutes at room temperature with ammonium hydroxide in methanol. This new anchor can be used in automated synthesis of conventional oligonucleotides. The primary value, however, is that it enables one to employ solid support methodology to synthesize a variety of base-sensitive oligonucleotide derivatives, as illustrated here by synthesis of oligomers with base protecting groups intact and with methyl phosphotriester groups at the internucleoside links.

The big success in marine shale gas exploration and production made China the third country worldwide to commercialize shale gas development. However, the Upper Ordovician Wufeng Formation and the Lower Silurian Longmaxi Formation in and around the Sichuan Basin are currently the only targets that have realized shale gas industrial development. Great challenges are emerging since tremendous shale gas resources of marine facies, continental facies, and transitional facies that are trapped in new areas and multiple other formations are yet to be successfully developed. Thus, we find it a great necessity to provide suggestions on shale gas exploration and development in China, which hopefully can be helpful for global shale gas exploitation. To meet this goal, this work provides a critical review on the history and current status of China’s shale gas exploration and development and summarizes key practical experiences. In the light of characteristic analysis of typical industrial gas fields and wells, research status, problems and challenges, along with suggestions on pivotal scientific issues are addressed including the development of organic-rich shales, reservoir types and characteristics, shale gas content, and the main controlling factors on shale gas enrichment. Further, future directions of shale gas exploration and development are nailed down, incorporating three levels: areas to improve development technology, areas to seek exploration breakthrough, and areas to conduct preliminary studies. The normal-pressure and deep shale gas retained in the Wufeng and Longmaxi Formations in and around the Sichuan Basin are the first level, which are the most realistic resources that can be commercially developed. For the normal-pressure shale gas, detailed research on the sweet spot selection, drilling–encounter ratio enhancement, and cost minimization by advanced technologies are most imperative; for the deep shale gas, state-of-the-art technology to maximize the stimulated reservoir volume of lateral wells is the key. Gas resources in other shale formations in the Sichuan Basin and its periphery such as the Cambrian marine shales, Permian transitional shales, and Jurassic continental shales are the second level, which have the greatest prospective to claim exploration breakthroughs, while shale gas resources in other basins or regions still demand grand scientific and technological tasks for exploration and development preparation. All in all, as a country with diverse shale gas types and such intricate geological and surface conditions, the summary of China’s shale gas exploration and development practices is of vital significance that will not only shed light on China’s shale gas development directions but also provide references for the shale gas industry in other countries and regions.

No abstract

The cushion rockjasmine, Androsace tapete (Primulaceae), is among the angiosperms with highest altitudal distribution in the world. Cushion rockjasmine is a prominent pioneer species in alpine deserts and alpine flowstone slope habitats up to 5,300 m on Qinghai-Tibetan Plateau. In this study, we use inter simple sequence repeat (ISSR) markers to investigate the spatial genetic structure of A. tapete at both fine-scale and landscape-scale, with emphasis on testing the hypothesis that the low-altitude valley of the Brahmaputra River, running from west to east across Qinghai-Tibetan Plateau, has significant effects on the spatial population structure of A. tapete. A total of 235 individuals were collected from five populations in disjunct ridges (i.e. two populations located in the north, and three in the south of the Brahmaputra River), including 158 individuals that were spatial explicitly sampled from a 30 m x 90 m plot. At fine scale, spatial autocorrelation analysis indicates a significant genetic structure within a short distance (less than 10 m), which is probably due to limited gene dispersal via pollen and/or seeds. At landscape scale, however, AMOVA suggests that most of the total genetic variation (85%) is among individuals within populations; and the Brahmaputra River plays a weak role in shaping the spatial population structure of A. tapete. In addition, the results of PCA and STRUCTURE assignment show significant genetic associations between the populations across the Brahmaputra River. The historical gene exchanges and slow genetic drift may be responsible for the lack of deep genetic differentiation among topographically separated populations in A. tapete.