A recombinant immunotoxin consisting of two antibody variable domains fused to Pseudomonas exotoxin

Antibodies and growth factors have been chemically coupled to different toxins to produce cytotoxic molecules that selectively kill cells bearing appropriate antigens or receptors. Antibody-toxin conjugates (immunotoxins) produced using conventional chemical coupling techniques have several undesirable characteristics. The smallest binding unit of an antibody is an Fv fragment which consists of a light and heavy chain variable domain. Recently, active single chain Fv fragments of antibodies have been produced in Escherichia coli by attaching the light and heavy chain variable domains together with a peptide linker. Here we describe the construction and expression in E. coli of a single chain antibody toxin fusion protein, anti-Tac(Fv)-PE40, in which the variable regions of anti-Tac, a monoclonal antibody to the p55 subunit of the human interleukin-2 receptor, are joined in peptide linkage to PE40, a modified form of Pseudomonas exotoxin lacking its binding domain. Anti-Tac(Fv)-PE40 was very cytotoxic to two interleukin-2 receptor-bearing human cell lines but was not cytotoxic to receptor-negative cells.     

Humanized antibodies for therapy

Protein engineering has made it possible to combine the binding sites of murine antibodies with human antibody regions. Antibodies constructed in this way have important advantages for therapy.     

裂缝诱导的多次散射波边界元法模拟

提出了一种研究二维弹性动力学散射问题的边界元法，其中，散射体或侵入体散场以Ｈｕｙｇｅｎｓ原理积分形式表达，虚拟场源以适配边界条件来求取，该间接边界元法可以高精度计算包括多次散射在内的全波场。通过对不同空间与尺度分布裂缝所诱导的地震波散射数值计算表明：该方法具有计算多次散射波场的能力，尾波（多次散射波）频率及延续长度受控于裂缝位置及尺度；等效介质弹性参数受控于散射体不同的统计分布。     

Modelling a traffic network with missing data

Whitlock and Queen (1998) developed a dynamic graphical model for forecasting traffic flows at a number of sites at a busy traffic junction in Kent, UK. Some of the data collection sites at this junction have been faulty over the data collection period and so there are missing series in the multivariate problem. Here we adapt the model developed in Whitlock and Queen ( 1998 ) to accommodate these missing data. Markov chain Monte Carlo methods are used to provide forecasts of the missing series, which in turn are used to produce forecasts for some of the other series. The methods are used on part of the network and shown to be very promising. Copyright © 2000 John Wiley & Sons, Ltd.     

Forecast covariances in the linear multiregression dynamic model

The linear multiregression dynamic model (LMDM) is a Bayesian dynamic model which preserves any conditional independence and causal structure across a multivariate time series. The conditional independence structure is used to model the multivariate series by separate (conditional) univariate dynamic linear models, where each series has contemporaneous variables as regressors in its model. Calculating the forecast covariance matrix (which is required for calculating forecast variances in the LMDM) is not always straightforward in its current formulation. In this paper we introduce a simple algebraic form for calculating LMDM forecast covariances. Calculation of the covariance between model regression components can also be useful and we shall present a simple algebraic method for calculating these component covariances. In the LMDM formulation, certain pairs of series are constrained to have zero forecast covariance. We shall also introduce a possible method to relax this restriction. Copyright © 2008 John Wiley & Sons, Ltd.     

β-Adrenergic receptors and nitric oxide generation in the cardiovascular system

Nitric oxide plays a crucial role in cardiovascular homeostasis, with important vasodilatory, anti-thrombotic and anti-atherogenic properties. β-Adrenergic receptors (βARs), present on a wide variety of cardiovascular cells, including vascular endothelial cells, platelets, cardiac myocytes and leukocytes, have long been established as key players in maintaining cardiovascular homeostatic control. During the last few years a wealth of evidence has emerged which directly links stimulation of these cardiovascular βARs to nitric oxide (NO) generation, suggesting a new and important mechanism of adrenergic control of cardiovascular function. This review explores the cardiovascular cell systems in which this coupling of βARs and NO occurs, the intracellular signalling and regulatory mechanisms involved and the abnormalities in βAR-NO oxide coupling found in cardiovascular disease states. Received 30 September 2005; received after revision 24 November 2005; accepted 24 January 2006     

Optical detection of meteoroidal impacts on the Moon

Impacts of meteoroids on the Moon should cause detectable optical flashes, but the population of objects that are big enough is very low, and hitherto no unambiguous impact flashes have been recorded. The flux of meteoroids associated with the Leonid meteor shower of 18 November 1999 was predicted to produce observable flashes on the night side of the Moon. Here we report the unambiguous detection of five such impact flashes, three of which were seen simultaneously by other observers. We also observed a possible impact flash on 16 July 1999. All of the flashes were of very brief duration (<0.02 s), as expected for high-speed impacts.