Synthetic analogues of fumagillin that inhibit angiogenesis and suppress tumour growth.

Neovascularization is critical for the growth of tumours and is a dominant feature in a variety of angiogenic diseases such as diabetic retinopathy, haemangiomas, arthritis and psoriasis. Recognition of the potential therapeutic benefit of controlling unabated capillary growth has led to a search for safe and effective angiogenesis inhibitors. We report here the synthesis of a family of novel inhibitors that are analogues of fumagillin, a naturally secreted antibiotic of Aspergillus fumigatus fresenius. We first isolated this fungus from a contaminated culture of capillary endothelial cells. Purified fumagillin inhibited endothelial cell proliferation in vitro and tumour-induced angiogenesis in vivo; it also inhibited tumour growth in mice, but prolonged administration was limited because it caused severe weight loss. Synthesis of fumagillin analogues yielded potent angiogenesis inhibitors ('angioinhibins') which suppress the growth of a wide variety of tumours with relatively few side-effects.     

Cloning of a cDNA encoding a non-isopeptide-selective subtype of the endothelin receptor

Endothelin-1 was initially identified as a 21-residue potent vasoconstrictor peptide produced by vascular endothelial cells, but was subsequently found to have many effects on both vascular and non-vascular tissues. The discovery of three isopeptides of the endothelin family, ET-1, ET-2 and ET-3, each possessing a diverse set of pharmacological activities of different potency, suggested the existence of several different endothelin receptor subtypes. Endothelins may elicit biological responses by various signal-transduction mechanisms, including the G protein-coupled activation of phospholipase C and the activation of voltage-dependent Ca2+ channels. Thus, different subtypes of the endothelin receptor may use different signal-transduction mechanisms. Here we report the cloning of a complementary DNA encoding one subtype belonging to the superfamily of G protein-coupled receptors. COS-7 cells transfected with the cDNA express specific and high-affinity binding sites for endothelins, responding to binding by the production of inositol phosphates and a transient increase in the concentration of intracellular free Ca2+. The three endothelin isopeptides are roughly equipotent in displacing 125I-labelled ET-1 binding and causing Ca2+ mobilization. A messenger RNA corresponding to the cDNA is detected in many rat tissues including the brain, kidney and lung but not in vascular smooth muscle cells. These results indicate that this cDNA encodes a 'nonselective' subtype of the receptor which is different from the vascular smooth muscle receptor.     

溅射用铁电陶瓷靶的烧结与显微结构分析

探讨了溅射用铁电陶瓷靶（ＰＺＴ，ＰＬＺＴ）的烧结工艺，并对其显微结构进行了分析。结果表明，采用新的烧结工艺（含保护措施），可以有效地抑制ＰｂＯ的挥发，制备出组织结构及成分均匀、ＰｂＯ含量正常、致密度较高、不变形的符合磁控溅射要求的铁电陶瓷烧结靶。     

时间序列AR模型参数的积分求解法

基于对时间序列实质的分析，提出了旨在减少序列的随机误差影响以及提高拟合精度的ＡＲ模型参数的积分求解法．重点讨论了ＡＲ（１）模型及ＡＲ（ｐ）模型参数的积分求解法，并与最小二乘法在计算机上进行了仿真比较．结果表明，采用积分求解法所得的ＡＲ模型参数的估计精度比最小二乘法的高．     

剩余静校正的小波包预处理方法

强反射层追踪与相对时差拾取中的“多值”现象严重影响剩余静校正的效果，为此提出的小波包预处理方法，可以实现地震道噪声与信号及不同强反射层的分离，从而能自动识别并提取“纯”的强反射层，提高强反射层追踪的可靠性和相对时差的拾取精度．     

凸曲面平头立铣刀刀位轨迹的计算方法

采用球面刀在三坐标数控机床上加工具有凸曲面工位的零部件时，往往会导致几何形状误差，对此，运用点涉法原理，推导出在凸曲面上确定平头立铣刀五轴和三轴数控联动加工刀位轨迹的计算方法。     

高容量温盘驱动器伺服码同步时钟录写技术

提出了可变频时钟写入方法和锁相环倍频时钟写入方法，给出了这两种写入法的读／写电路，并分析了其性能。结果证明，可变频时钟写入方法电路简单，刻写时钟周期短；锁相环倍频时钟写入过程较前者长，但其频率范围容易调整。两者均适合高密度小型温盘的时钟录写。     

二值点阵图像的放大与缩小方法研究

着重研究了二值点阵图像的放大、缩小方法，针对二值点阵灰度图和工程图现有的缩小和放大算法及存在的问题，提出了基于区域特征的图像变换思想，以图块为单位进行图像的放大、缩小．据此，提出了对二值灰度图和工程图进行放大、缩小的改进算法并进行分析。     

ELNF归约演算

ＥＬＮＦ演算是在ＬＮＦ演算的基础上扩充而成的函数／逻辑归约演算系统，扩充的主要工作包括逻辑变量、谓词名的引进。提出并描述了逻辑函子ＳＯＬＵＴＩＯＮ和ＰＲＯＶＥ及其归约规则．讨论了ＥＬＮＦ演算的基本概念。为表征ＨＯＲＮ子句提供了一种有效方式。     

嵌套式建模支持

阐述了人的建模思维机制。引入等价关系和划分作为问题粒度研究的基础，定义了逆商集，使之与商集一起，构成了对问题不同粒度的完整描述，并讨论了粒度的性质，借助拓扑分析，给出了问题可分解、可细化和粗化、细化等一系列定义，在问题簇和模型簇概念的基础上，提出了嵌套式建模（支持）作为面向复杂系统的建模支持方法论，具体给出了其实施步骤，这是一个人机交互的启发式过程，将嵌套式建模与传统式建模作了比较，此外还作了若干说明。