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Although waling has been considered as an important transport mode, pedestrian modelling has received little attention in either academic or practising circles. There is an increasing need for methods that can be used to help the planning, design and management of pedestrian traffic systems. This paper presents a nonlinear programming formulation of the dynamic pedestrian equilibrium assignment problem based on the following assumptions. The pedestrian traffic system in a congested urban area can be modelled as a capacitated network with alternative walkway sections. People in this pedestrian network make such decisions as selecting departure time and walking path between origins and destinations (OD). The study horizon is divided equally into shorter time intervals of 5-10 minutes each, for which the pedestrian departure time matrices are given by a logit formula. It is dependent on the predetermined departure time costs and the equilibrium OD walking costs. In the proposed model, a `quasi-continuous' technique is adopted to smooth out the transitions of various variables between time intervals and to satisfy the first-in-first-out discipline. A heuristic algorithm that generates approximate solutions to the model is presented. The numerical results in a real network shows that the model and algorithm proposed in this paper are able to capture the main characteristics of the departure time and route choices in congested unidirectional pedestrian traffic systems. Journal of the Operational Research Society (2002) 53, 97-107. DOI: 10.1057/palgrave/jors/2601267 Keywords: transport; non-linear programming; pedestrian network; dynamic equilibrium assignment; logit-based departure time choice

Alterations of the epidermal growth factor receptor (EGFR) gene occur frequently in human malignant gliomas. The most common of these is deletion of exons 2-7, resulting in truncation of the extracellular domain ([Delta]EGFR or EGFRvIII), which occurs in a large fraction of de novo malignant gliomas (but not in progressive tumors or those lacking p53 function) and enhances tumorigenicity, in part by decreasing apoptosis through up-regulation of Bcl-[X.sub.L]. Here, we demonstrate that the [Delta]EGFR concomitantly confers resistance to the chemotherapeutic drug cisplatin (CDDP) by suppression of CDDP-induced apoptosis. Expression of Bcl-[X.sub.L] was elevated in U87MG.[Delta]EGFR cells prior to and during CDDP treatment, whereas it decreased considerably in CDDP-treated parental cells. CDDP-induced activation of caspase-3-like proteases was suppressed significantly in U87MG.[Delta]EGFR cells. These responses were highly specific to constitutively kinase-active [Delta]EGFR, because overexpression of kinase-deficient [Delta]EGFR (DK) or wild-type EGFR had no such effects. Correspondingly, [Delta]EGFR specific tyrosine kinase inhibitors reduced Bcl-[X.sub.L] expression and potentiated CDDP-induced apoptosis in U87MG.[Delta]EGFR cells. Ectopic overexpression of Bcl-[X.sub.L] in parental U87MG cells also resulted in suppression of both caspase activation and apoptosis induced by CDDP. These results may have important clinical implications for the use of CDDP in the treatment of those malignant gliomas expressing [Delta]EGFR.

Deletions of all or part of chromosome 10 are the most common genetic alterations in high-grade gliomas. The PTEN gene (also called MMAC1 and TEP1) maps to chromosome region 10q23 and has been implicated as a target of alteration in gliomas and also in other cancers such as those of the breast, prostate, and kidney. Here we sought to provide a functional test of its candidacy as a growth suppressor in glioma cells. We used a combination of Northern blot analysis, protein truncation assays, and sequence analysis to determine the types and frequency of PTEN mutations in glioma cell lines so that we could define appropriate recipients to assess the growth suppressive function of PTEN by gene transfer. Introduction of wild-type PTEN into glioma cells containing endogenous mutant alleles caused growth suppression, but was without effect in cells containing endogenous wild-type PTEN. The ectopic expression of PTEN alleles, which carried mutations found in primary tumors and have been shown or are expected to inactivate its phosphatase activity, caused little growth suppression. These data strongly suggest that PTEN is a protein phosphatase that exhibits functional and specific growth-suppressing activity.