Pharmacokinetics of sifuvirtide, a novel anti-HIV-1 peptide, in monkeys and its inhibitory concentration in vitro

Aim: To study the pharmacokinetics of sifuvirtide, a novel anti-human immunodeficiency virus (HIV) peptide, in monkeys and to compare the inhibitory concentrations of sifuvirtide and enfuvirtide on HIV-1-infected-cell fusion. Methods: Monkeys received 1.2 mg/kg iv or sc of sifuvirtide. An on-line solid-phase extraction procedure combined with liquid chromatography tandem mass spectrometry (SPELC/MS/MS) was established and applied to determine the concentration of sifuvirtide in monkey plasma. A four-I-127 iodinated peptide was used as an internal standard. Fifty percent inhibitory concentration (IC50) of sifuvirtide on cell fusion was determined by co-cultivation assay. Results: The assay was validated with good precision and accuracy. The calibration curve for sifuvirtide in plasma was linear over a range of 4.88-5000 mu g/L, with correlation coefficients above 0.9923. After iv or sc administration, the observed peak concentrations of sifuvirtide were 10626 +/- 2886 mu g/L and 528 +/- 191 mu g/L, and the terminal elimination half-lives (T,12) were 6.3 +/- 0.9 h and 5.5 +/- 1.0 h, respectively. After sc, T-max was 0.25-2 h, and the absolute bioavailability was 49% +/- 13%. Sifuvirtide inhibited the syncytium formation between HIV-1 chronically infected cells and uninfected cells with an IC50 of 0.33 mu g/L. Conclusion: An on-line SPE-LC/MS/MS approach was established for peptide pharmacokinetic studies. Sifuvirtide was rapidly absorbed subcutaneously into the blood circulation. The T-1/2 of sifuvirtide was remarkably longer than that of its analog, enfuvirtide, reported in healthy monkeys and it conferred a long-term plasma concentration level which was higher than its IC50 in vitro.

广西高原鳅属鱼类一穴居新种记述

2003 年1 月, 在广西壮族自治区天峨县红水河水系地下河采集到一批盲鱼标本。经鉴定, 为高原鳅 属Triplophysa 一未经发表的新种。新种天峨高原鳅Triplophysa tianeensis sp1nov1 与个旧盲高原鳅T. gejiuensis 、 石林盲高原鳅T. shilinensis 、阿庐高原鳅T. aluensis 和南丹高原鳅T. nandanensis 相似; 本新种腹鳍末端不达 肛门, 尾鳍分枝鳍条16 , 可进一步与个旧盲高原鳅和石林盲高原鳅(腹鳍末端达到肛门, 尾鳍分枝鳍条14～ 15) 相区别; 本新种背鳍起点位于体之中点、腹鳍起点之后, 肛门紧靠臀鳍起点, 可进一步与阿庐高原鳅(背 鳍起点靠近吻端、位于腹鳍起点之前, 肛门距臀鳍起点仍有一段距离) 相区别。本新种与同分布于红水河水系 的南丹高原鳅Triplophysa nandanensis Lan et al1 较为相似; 但二者区别明显: 新种背鳍分枝鳍条7 、胸鳍分枝鳍 条9 、腹鳍分枝鳍条6 、背鳍外缘平截、背鳍起点位于腹鳍起点之后, 后者背鳍分枝鳍条8 、胸鳍分枝鳍条10～ 11 、腹鳍分枝鳍条7 、背鳍外缘凹入、背鳍起点位于腹鳍起点之前; 此外, 新种的穴居特征更为显著: 眼极度 退化、头长为眼径1618～3218 (2510) 倍、部分个体无色素斑且各鳍无斑点, 而南丹高原鳅眼小、头长为眼径 417～910 (715) 倍、体和头背侧密布云状斑且各鳍均具点状斑。

香溪河库湾春季水华期间水体光学特征及相关分析

研究了香溪河库湾春季水华期间(2006年3月3日—4月16日)透明度水层可见光衰减系数KSd的时空特征,分析其与表层水叶绿素a浓度、DOC浓度和透明度Sd的相关关系。结果表明:香溪河库湾春季水华可见光衰减系数KSd时空变异很大;除峡口河段(样点X7—X8)外,可见光衰减系数KSd的变化特征取决于叶绿素a浓度和DOC浓度的时空变化,类似于深水湖泊;除峡口河段(样点X7—X8)外,香溪河库湾可见光衰减系数KSd和透明度之间呈反比的关系具有显著的相关,但它们之间的反比关系因水体叶绿素a和无机悬浮颗粒的空间差异而

Delayed control of a Moore-Greitzer axial compressor model

Several feedback control laws have appeared in the literature concerning the stabilization of the nonlinear Moore-Greitzer axial compression model. Motivated by magnitude and rate limitations imposed by the physical implementation of the control law, Larsen et al. studied a dynamic implementation of the S-controller suggested by Sepulchre and Kokotović. They showed the potential benefit of implementing the S-controller through a first-order lag: while the location of the closed-loop equilibrium achieved with the static control law was sensitive to poorly known parameters, the dynamic implementation resulted in a small limit cycle at a very desirable location, insensitive to parameter variations. In this paper, we investigate the more general case when the control is applied with a time delay. This can be seen as an extension of the model with a first-order lag. The delay can either be a result of system constraints or be deliberately implemented to achieve better system behavior. The resulting closed-loop system is a set of parameter-dependent delay differential equations. Numerical bifurcation analysis is used to study this model and investigate whether the positive results obtained for the first-order model persist, even for larger values of the delay.

BACKGATING AND LIGHT SENSITIVITY IN GAAS METAL-SEMICONDUCTOR FIELD-EFFECT TRANSISTORS

Three different types of GaAs metal-semiconductor field effect transistors (MESFET) by employing ion implantation, molecular beam epitaxy (MBE) and low-temperature MBE (LT MBE) techniques respectively were fabricated and studied in detail. The backgating (sidegating) measurement in the dark and in the light were carried out. For the LT MBE-GaAs buffered MESFETs, the output resistance R(d) and the peak transconductance g(m) were measured to be above 50 k Omega and 140 mS/mm, respectively, and the backgating and light sensitivity were eliminated. A theoretical model describing the light sensitivity in these kinds of devices is given. and good agreement with experimental data is reached.

Ag生长温度对Ag/ZnO肖特基接触特性的影响

利用脉冲激光沉积(PLD)方法在Si衬底上制备了ZnO单晶体薄膜,并在不同温度下生长了Ag膜作为肖特基电极,研究了Ag与ZnO的接触特性.利用X射线衍射仪、扫描电子显微镜和Ⅰ-Ⅴ测试方法对样品的晶体质量、结构和电学性质进行了分析.结果表明,ZnO薄膜具有高度的c轴择优取向,Ag膜随生长温度的不同的晶体质量有较大差异.样品在室温下的Ⅰ-Ⅴ测试结果表明Ag电极的生长温度对Ag/ZnO接触性能有重要影响.在150℃和200℃生长的Ag电极实现了Ag与ZnO的肖特基接触,电极生长温度低于150℃和高于200℃的样品Ag与ZnO均为欧姆接触.经过分析,肖特基接触的形成依赖于在Ag与ZnO接触界面处形成的p型反型层.