Pegylated peptides. V. Carboxy-terminal PEGylated analogs of growth hormone-releasing factor (GRF) display enhanced duration of biological activity in vivo

In the present study, human growth hormone-releasing factor (hGRF) and analogs were successfully pegylated at the carboxy-terminus using a novel solid- and solution-phase strategy. Following synthesis, these pegylated hGRF analogs were evaluated for in vitro and in vivo biological activity. Specifically, hGRF (1-29)-NH2, [Ala15]-hGRF (1-29)-NH2, [desNH2Tyr1, D-Ala2, Ala15]-hGRF(1-29)-NH2 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH were each C-terminally extended using a Gly-Gly-Cys-NH2 spacer (previously demonstrated not to alter intrinsic biological activity), and then monopegylated via coupling to an activated dithiopyridyl-PEG reagent. PEG moieties of 750, 2000, 5000 or 10,000 molecular weight (MW) were examined to determine the effect of polymer weight on activity. Initial biological evaluations in vitro revealed that all C-terminally pegylated hGRF analogs retained high growth hormone (GH)-releasing potencies, regardless of the MW of PEG polymer employed. Two of these pegylated hGRF analogs, [desNH2Tyr1, D-Ala2, Ala15]-hGRF (1-29)-Gly-Gly-Cys(NH2)-S-Nle-PEG5000 and [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-Gly-Cys(NH2)-S-Nle-PEG5000, were subsequently evaluated in both pig and mouse models and found to be highly potent (in vivo potency range = 12-55-fold that of native hGRF). Relative to their non-pegylated counterparts, these two pegylated hGRF analogs exhibited enhanced duration of activity.     

Egg handling and storage

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.     

INMARSAT 21世纪工程——全球个人移动卫星通信

本文概述INMARSAT 21世纪工程的规划及为实现这一规划,INMARSAT组织在本世纪末正在进行和即将进行的一系列卫星通信技术工作。着重阐述INMARSAT 21世纪工程的业务性能以及对三种卫星布局方案进行抉择的新动向。     

G~2－连续的保凸插值三次Bezier样条曲线

本文引入曲率参数，描述了分段三次Ｂｅｚｉｅｒ插值样条曲线（开的和闭的）。这些插值曲线是Ｇ~２－连续的和保凸的，并且这些曲线可以作局部修改。最后，用本文的方法解决了一个实际问题。     

Poly(3-octylthiophene) as semiconductor for schottky barrier: Effects of doping and storage time

Schottky diodes of aluminium/poly(3-octylthiophene)(P30T)/indium-tin oxide with large active area are prepared by using the proposed new casting technique. Their rectifying behavior and junction characteristics are dependent on whether the P30T is doped and on the storage time, but independent of the thickness of the P30T layer. The present technique can also be applied in a fabrication of electronic devices with other soluble conjugated polymers.     

环境中氚和碳-14

本文介绍了加拿大恰克河实验室有关氚和碳－14在环境中行为和评价的研究。     

大庆长垣外围油田的开发问题

本文在对大庆长垣外围油田的地质情况、油藏类型综合分析评价的基础上,论述了开发这些油田的一系列有关问题。     

纳米碳酸钙制备过程中添加剂作用机理探讨

采用鼓泡碳化法 ,在最佳反应温度、反应物浓度的条件下 ,考察了添加剂对产物形状及粒径大小的影响 ,得到了直径为 2 0～ 30nm、长径比在 2 0左右且分散性能良好的针状纳米碳酸钙 ,并对添加剂作用机理进行了分析。     

高架桥梁上部结构整体降低施工中的抗风险对策

在高架道路、桥梁改建中,往往遇到需调整桥面标高的情况。以上海市南北高架与内环线高架相连的鲁班路立交SE匝道为例,介绍利用旧桥承台基础,在其上搭设支架和液压系统,然后解除立柱的垂直约束和水平约束,将桥梁上部结构整体分步降低到设计标高。重点介绍针对施工中安全风险点,采取的支撑体系、液压体系、降低顺序原则、上部结构牵拉系统、监测系统等具体措施。