WD-40 repeat region regulates Apaf-1 self-association and procaspase-9 activation

The casp9 protein plays a critical role in apoptosis induced by a variety of death stimuli. A regulator of apoptosis, Apaf-1, binds to and activates pro-casp9 in the presence of cytochrome c and dATP, a requirement that is bypassed by deletion of the WD-40 repeats located in the C-terminal half of Apaf-1. In this report, we used constitutively active Apaf-1 mutant lacking the WD-40 repeat region to study the mechanism and regulation of pro-casp9 activation. Mutational analysis revealed that only a small portion of the CED-4 homologous region (residues 456-559) could be deleted without destroying the ability of Apaf-1-(1-559) to activate pro-casp9. Apaf-1 can self-associate to form oligomers. Disruption of Apaf-1 self-association by deletion (Delta109-559) or mutation of the P-loop region (K149R) abrogated Apaf-1-mediated pro-casp9 activation. Forced oligomerization of the caspase recruitment domain of Apaf-1 was sufficient for pro-casp9 activation. Dimerization of chimeric Fpk-pro-casp9 protein with the dimerizer drug FK1012 induced pro-casp9 processing and apoptosis in cells. Significantly, the C-terminal region containing WD-40 repeats interacted with its N-terminal CED-4 homologous region, as determined by immunoprecipitation experiments. Importantly, expression of the WD-40 repeat region inhibited Apaf-1 self-association and proteolytic activation of pro-casp9. These studies provide a mechanism by which Apaf-1 promotes autoactivation of pro-casp9 through Apaf-1 self-association, a process that is negatively regulated by the WD-40 repeats.     

基于自组织神经网络的实时统计特征抽取方法

应用人工神经网络讨论统计了特征抽取的原理，提出了相应的抽取方法。该方法具有实时性，容错性，高数据压缩率和良好的特征分辨率。通过计算机仿真和桥梁索力状态的实例计算分析证实了该技术具有广泛的应用价值。     

Angiotensin II stimulates cardiac myocyte hypertrophy via paracrine release of TGF-beta 1 and endothelin-1 from fibroblasts

We examined the effects of different cytokine combinations and culture conditions on the expansion and modulation of cell surface antigens of CD34+ derived dendritic cells (DCs), the most efficient antigen-presenting cells capable of stimulating resting T cells in the primary immune response. Cells with a dendritic morphology and expressing HLA-DR, CD1a, S100 and CD83 were maximally expanded under serum-free conditions with the addition of SCF, GM-CSF, TNF-alpha, TGF-beta and Flt-3 ligand (fold increase of CD1a+ cells = 102 +/- 32 after 2 weeks of culture). CD34+ cells were also grown under continuous flow conditions in an artificial capillary system: after 14d of culture, the expansion in the total cell number was lower than that of the static cultures (3.3 +/- 2 v 18.9 +/- 4) but the percentage of CD1a+/CD83+/ CD80+ cells was considerably higher, whereas the CD14+ cells were significantly reduced (8.9 +/- 2 v 26 +/- 13). In continuous perfusion cultures, low levels of DC precursors and of LTC-IC were still present up to day 14. The DCs generated under flow conditions stimulated the mixed leucocyte reaction (MLR) more than the cells grown in static cultures. By electron microscopy, cells grown in the continuous flow system showed an increased number of large cells with numerous dendritic processes and abundant multilamellar complexes. The cells expanded under these conditions were sorted on the basis of their light-scatter properties into two fractions: one containing a predominance of CD1a+/S100+/ CD8 3+/CD80+/CD14- 'large cells' with great internal complexity (mature DCs); the second including 'small cells' either CD33+/CD14+, CD33+/CD15+ or CD33+/CD13-/CD14. The DCs generated and selected with this method are therefore particularly well suited for immunotherapeutic protocols.     

激光技术推广应用中安全防护问题

论述加强激光安全防护工作的紧迫性,介绍我国激光安全工作的进展,提出下一步工作建议。     

差齿原理在推床同步调整技术中的应用

文章应用差齿原理在冶金设备初轧机推拉床实施转角性微调技术，以达到初轧机机前与机后推拉床同步调整效果．实践证明，效果显著，适用面广，且操作简单、方便经济．     

陶瓷模用α半水石膏的研究

理论上提出了影响陶瓷模用半水石膏常，高温性能的主要因素，即结晶形态．标准稠水度，初凝时间，抗折强度，进行了实验验证，确定了相应的制作技术，获得了性能优良的陶瓷模用α半水石膏。     

光盘的出错率分析和研究

本文通过对光存储系统出错特性的分析，研究了一些描述出错特性的主要参数，并且给出了描述出错特性的Ｇｉｌｂｅｒｔ模型及其改进型模型。     

Effect of hydrogen loading on temperature/electric-field poling ofSiO2-based thin films on Si

Waveguide stacks of GeSiO₂-based glass deposited on Si exhibit a permanent second-order nonlinearity following temperature electric-field poling. High temperature hydrogen loading increases the second harmonic signal under certain conditions     

A method for exploring the effects of attrition in randomized experiments with dichotomous outcomes.

Attrition from conditions in randomized experiments is common. Yet it is difficult to assess the possible effects of attrition because the outcome status of the dropouts is usually unknown. This article develops methods to assess those effects in studies with dichotomous outcomes, illustrating the methods with randomized experiments in drug abuse treatment, smoking cessation treatment, and alcoholism treatment. The methods include computing the lowest and highest possible effect sizes that could have been observed, enumerating the percent of possible study outcomes below a given threshold, estimating the probability that an outcome beyond any given threshold would be observed if all participants were measured, and constructing attrition analysis plots showing the effects of attrition under varied assumptions. For the kind of study to which they apply, these methods should replace the treatment of missing participants as failures in an "intent-to-treat" analysis. A user-friendly personal computer program is available to implement all of these analyses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)