The tumor-suppressor activity of p53 is closely related to its DNA-binding properties. It binds a number of DNA response-elements and it is likely that these share a common structural feature. Here, we present a new, general method to determine the absolute twist of exible DNA promoter sequences based on direct imaging of the topology of microcircles containing the sequences. We have used magnetically driven dynamic force microscopy ("MacMode" AFM) to observe, in solution, the conformation of 168 base-pair DNA microcircles, each containing four equally spaced copies of the waf1/cip1/p21 p53 response-element. Analysis of the images showed that the microcircles are markedly puckered with a small excess of negatively writhed molecules. The average measured values of writhe are 0.109 0.013 (for 60 positively writhed molecules) and 0.098 0.011 (for 65 negatively writhed molecules). These values lead directly to a difference in linking number for the positively and negatively writhed molecules prior to ligation, from which we derive a twist mismatch of 178 (overtwist). This is 44.5 for each 42-mer precursor containing a single waf1/cip1/p21 p53 response-element, in good agreement with the range of values deduced by indirect biochemical techniques. The two values of writhe may also be used to determine the ratio of the bending (B) to twisting (C) rigidity, yielding B/C 0.23. This is about one-third of the value for long, random-sequence DNA, suggesting that the waf1/cip1/p21 p53 response-element is extremely exible, a result that is also consistent with indirect biochemical experiments. These results support the idea, proposed by us earlier, that torsional stress may play a role in the regulation of p53 binding through modulation of twist at the binding site.

微流控芯片最初起源于分析化学领域，是一种采用精细加工技术，在数平方厘米的基片，制作出微通道网络结构及其它功能单元，以实现集微量样品制备、进样、反应、分离及检测于一体的快速、高效、低耗的微型分析实验装置。随着微电子及微机械制作技术的不断进步，近年来微流控芯片技术发展迅猛，并开始在化学、生命科学及医学器件等领域发挥重要作用。本文首先简单介绍了微流控芯片制作材料和工艺，然后主要阐述了其在蛋白质分离、免疫分析、NDA分析和测序、细胞培养及检测等方面的应用进展。

The contour length of DNA fragments, deposited and imaged on mica under buffer, was measured as a function of deposition temperature. Extended DNA molecules (on Ni-and silane-treated surfaces) contract rapidly with falling temperature, approaching the contour length of A-DNA at 2℃. The contraction is not unique to a specific sequence and does not occur in solution at 2℃ or on a surface at 25℃, indicating that it arises from a combination of low temperature and surface contact. It is probably a consequence of reduced water activity at a cold surface.

This article reviews the current and future applications of micro reactors in the field of chemistry, biochemistry and drug discovery. The fabrication and physical characterisation of micro reactors, together with details of their use and operation is described. Liquid and gas phase reactions have been used to illustrate the advantages of performing chemical reactions in micro reactors. A brief evaluation of the possible advantages that micro fabrication could offer in developing biological applications, based on miniaturized devices is also presented.

Received 26 January 1998; received in revised form 19 May 1998; accepted 20 May 1998 The results from the measurement of the fluorescence spectrum showing the binding characteristics of acridine orange (AO) and bovine serum albumin (BSA) are reported. It was found that the equilibrium constant k-4848.64 lmol1, and the number of binding sites n-0.82. Based on the mechanism of the Forster energy transference, the transfer efficiency of energy and distance between the acceptor AO and BSA were found. The interaction between AO and BSA have been verified as consistent with the static quenching procedure and the quenching mechanism is related to the energy transfer.