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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.

The development of new capillary networks from the normal microvasculature of the host appears to be required for growth of solid tumors. Tumor cells influence this process by producing both inhibitors and positive effectors of angiogenesis. Among the latter, the vascular endothelial growth factor (VEGF) has assumed prime candidacy as a major positive physiological effector. Here, we have directly tested this hypothesis in the brain tumor, glioblastoma multiforme, one of the most highly vascularized human cancers. We introduced an antisense VEGF expression construct into glioblastoma cells and found that (i) VEGF mRNA and protein levels were markedly reduced, (ii) the modified cells did not secrete sufficient factors so as to be chemoattractive for primary human microvascular endothelial cells, (iii) the modified cells were not able to sustain tumor growth in immunodeficient animals, and (iv) the density of in vivo blood vessel formation was reduced in direct relation to the reduction of VEGF secretion and tumor formation. Moreover, revertant cells that recovered the ability to secrete VEGF regained each of these tumorigenic properties. These results suggest that VEGF plays a major angiogenic role in glioblastoma.

Analysis of the influence of exogenous p53 tumor suppressor gene expression in malignant glioma cell lines reveals that p53 gene expression in cells with endogenous p53 mutants induces morphological changes and terminates growth, indicating that genetic lesions of the gene contribute to the development of human astrocytomas. The episomal single cell reporter method developed for monitoring the phenotypic effects of p53 gene is suitable for screening of germ-line p53 gene mutations in patients.

The retroviral transfer method helps examine the biological effects of a mutant epidermal growth factor receptor (EGFR) lacking exons 2-7 (de 2-7 EGFR). This transfer helps the expression of de 2-7 EGFR in glioblastoma cells expressing wild-type endogenous receptors. Western blotting analysis reveals that these cells express endogenous 170-kDa EGFR and exogenous 140-155 kDa de 2-7 EGFR. Implementation of mutant EGFR in mice increases tumorigenic capacity. Tumor-specific alteration of EGFR influences interactions between tumor cells and their microenvironment.

Post-oxidation N2O annealing in the gate oxide N2O anneal step causes a 4- to 10-fold increase in the lifetime of CMOSFETs and reduces boron infiltration from the P-MOSFET p+ poly-Si gate. Charge trapping properties and interface hardness remain unaffected at the cryogenic temperatures. A nitrogen concentration of 2% at the Si/SiO2 interface at a temperature of 900 degrees Celsius or 950 degrees Celsius is responsible for the enhancements in the MOSFET.

Brown planthopper (BPH), white‐backed planthopper (WBPH) and small brown planthopper (SBPH), are the closely related rice pests that perform differentially on wheat plants. Using fecundity as a fitness measure, we found that SBPH well‐adapted on wheat plants, followed by WBPH, while BPH had the worst performance. The transcriptomic responses of SBPH and BPH to wheat plants have been compared previously. To understand the different fitness mechanisms of three planthoppers, this study first investigated the transcriptomic responses of WBPH to rice and wheat plants. Genes involved in detoxification, transportation and proteasome were significantly enriched in WBPH in response to different diets. Moreover, comparative analysis demonstrated that most co‐regulated genes in BPH and SBPH showed different expression changes; whereas most co‐regulated genes in BPH and WBPH exhibited similar expression changes. Subsequently, this study also investigated the influences of host plants on the bacterial community of three planthoppers. The three planthoppers harboured distant diversity of bacterial communities. However, there was no dramatic change in bacterial diversity or relative abundance in planthoppers colonized on different hosts. This study illustrates generic and species‐specific changes of three rice planthoppers in response to different plants, which deepen our understanding towards the host fitness for planthopper species. [ABSTRACT FROM AUTHOR]

The effect of periodic rectangular grooves on vacuum multipactor has been theoretically and experimentally investigated. Dynamic calculation is applied to research the electron trajectory and impact energy under groove surface. Two-dimensional electromagnetic particle-in-cell simulation is used to analyze and compare multipactor scenario, statistic energy, and secondary emission yield on the flat surface with that on the corrugated surface. It has been found by computational and simulative analysis that grooved surface can explicitly suppress multipactor in the developmental stage of multipactor. S-band high power microwave (HPM) dielectric breakdown experiment under vacuum, with microsecond pulse length was conducted. It was confirmed by experiment that periodic grooves perpendicular to the major electric field can effectively increase transmitted power. [ABSTRACT FROM AUTHOR]

The heat tolerance of tomato seedlings was significantly enhanced after heat shock treatment at 40°C for 4 h. Compared with the control, the heat-shocked tomato seedlings, on one hand, had a higher net photosynthetic rate (PN), stomatal conductance, intercellular CO2 concentration, water-use efficiency, maximal quantum yield of PSII photochemistry (Fv/Fm), electron transport rate, actual photochemical efficiency of PSII, and activity of antioxidant enzymes, on the other hand, had lower nonphotochemical quenching, relative conductivity, malondialdehyde content (MDA), and accumulation of reactive oxygen species (ROS). In addition, heat shock induced production of heat shock proteins (HSPs) in tomato seedling leaves. HSP70 was significantly negatively correlated with PN, Fv/Fm, catalase, superoxide dismutase, and peroxidase and was significantly positively correlated with MDA and ROS. Overall, short-term heat shock treatments, inducing the production of HSPs, helped improve the thermal tolerance of tomato seedlings. [ABSTRACT FROM AUTHOR]

Wolbachia influence the fitness of their invertebrate hosts. They have effects on reproductive incompatibility and egg production. Although the former are well characterized, the mechanistic basis of the latter is unclear. Here, we investigate whether apoptosis, which has been implicated in fecundity in model insects, influences the interaction between fecundity and Wolbachia in the planthopper Laodelphax striatellus. Wolbachia‐infected females produced about 30% more eggs than uninfected females. We used the terminal deoxyribonucleotidyl transferase (TDT)‐mediated dUTP‐digoxigenin nick end labeling staining to visualize apoptosis. Microscopic observations indicated that the Wolbachia strain wStri increased the number of ovarioles that contained apoptotic nurse cells in both young and aged adult females. The frequency of apoptosis was much higher in the infected females. The increased fecundity appeared to be a result of apoptosis of nurse cells, which provide nutrients to the growing oocytes. In addition, cell apoptosis inhibition by caspase messenger RNA interference in Wolbachia‐infected L. striatellus markedly decreased egg numbers. Together, these data suggest that wStri might enhance fecundity by increasing the number of apoptotic cells in the ovaries in a caspase‐dependent manner. Our findings establish a link between Wolbachia‐induced apoptosis and egg production effects mediated by Wolbachia, although the way in which the endosymbiont influences caspase levels remains to be determined. [ABSTRACT FROM AUTHOR]

Summary: Chicken infectious anaemia (CIA) is a disease with a highly economic impact in the poultry industry. The infected chickens are characterized by aplastic anaemia and extreme immunosuppression, followed by the increased susceptibility to secondary infectious pathogens and suboptimal immune responses for vaccination. Commercially available CIA vaccines are routinely used in the breeders in Taiwan to protect their progeny with maternal‐derived antibodies. However, CIA cases still occur in the field and little is known about the genetic characteristics of Taiwanese chicken anaemia viruses (CAVs). In this study, CAV DNA was detected in 72 of 137 flocks collected during 2010–2015. Among the PCR‐positive samples, the coding regions of 51 CAVs were sequenced. Phylogenetic analysis of the VP1 gene revealed that, although most of Taiwanese CAVs belonged to genotypes II and III, some isolates were clustered into a novel genotype (genotype IV). Moreover, a Taiwanese isolate in this novel genotype IV appeared to be derived from a recombination event between genotypes II and III viruses. Five Taiwanese CAV isolates were highly similar to the vaccine strains, 26P4 or Del‐Ros. Taken together, these results indicate that the sequences of CAVs in Taiwan are variable, and inter‐genotypic recombination had occurred between viruses of different genotypes. Moreover, vaccine‐like strains might induce clinical signs of CIA in chickens. Our findings could be useful for understanding the evolution of CAVs and development of a better control strategy for CIA. [ABSTRACT FROM AUTHOR]

The urokinase plasminogen activator system is involved in angiogenesis and tumor growth of malignant gliomas, which are highly neovascularized and so may be amenable to antiangiogenic therapy. In this paper, we describe the activity of [Angstrom]6, an octamer capped peptide derived from the non-receptor-binding region of urokinase plasminogen activator. [Angstrom]6 inhibited human microvascular endothelial cell migration but had no effect on the proliferation of human microvascular endothelial cells or U87MG glioma cells in vitro. In contrast, [Angstrom]6 or cisplatin (CDDP) alone suppressed subcutaneous tumor growth in vivo by 48% and 53%, respectively, and, more strikingly, the combination of [Angstrom]6 plus CDDP inhibited tumor growth by 92%. Such combination treatment also greatly reduced the volume of intracranial tumor xenografts and increased survival of tumor-bearing animals when compared with CDDP or [Angstrom]6 alone. Tumors from the combination treatment group had significantly reduced neovascularization, suggesting a mechanism involving [Angstrom]6-mediated inhibition of endothelial cell motility, thereby eliciting vascular sensitivity to CDDP-mediated toxicity. These data suggest that the combination of an angiogenesis inhibitor that targets endothelial cells with a cytotoxic agent may be a useful therapeutic approach.

In this study, we identified a pancreatic lipase-related protein 2 ( PLRP2) gene through searching the transcriptome data of the brown planthopper, Nilaparvata lugens, a monophagous rice pest. PLRP2 mRNAs were first isolated in the human pancreas and play an important role in hydrolysis of galactolipids from the diet. Although homologous PLRP2 genes have been identified in many insect species, their physiological functions remain unknown. The present study for the first time reports the functional role of PLRP2 in an insect species. Differing from mammal PLRP2s, N. lugens PLRP2 was highly expressed in developing oocytes of the ovaries of female adults and little expressed in laid eggs. Suppression of N. lugens PLRP2 expression using RNA interference significantly inhibited egg hatching in rice seedlings, implying that N. lugens PLRP2 was important for oocyte maturation and development. This novel finding will improve our understanding of the reproductive strategies in insects and provides a potential target for future management of crop pests. [ABSTRACT FROM AUTHOR]

Background: Cell-free DNA (cfDNA) from plasma offers easily obtainable material for KRAS mutation analysis. Novel, multiplex, and accurate diagnostic systems using small amounts of DNA are needed to further the use of plasma cfDNA testing in personalized therapy. Patients and methods: Samples of 16 ng of unamplified plasma cfDNA from 121 patients with diverse progressing advanced cancers were tested with a KRAS G12/G13 multiplex assay to detect the seven most common mutations in the hotspot of exon 2 using droplet digital polymerase chain reaction (ddPCR). The results were retrospectively compared to mutation analysis of archival primary or metastatic tumor tissue obtained at different points of clinical care. Results: Eighty-eight patients (73%) had KRASG12/G13 mutations in archival tumor specimens collected on average 18.5 months before plasma analysis, and 78 patients (64%) had KRASG12/G13 mutations in plasma cfDNA samples. The two methods had initial overall agreement in 103 (85%) patients (kappa, 0.66; ddPCR sensitivity, 84%; ddPCR specificity, 88%). Of the 18 discordant cases, 12 (67%) were resolved by increasing the amount of cfDNA, using mutation-specific probes, or re-testing the tumor tissue, yielding overall agreement in 115 patients (95%; kappa 0.87; ddPCR sensitivity, 96%; ddPCR specificity, 94%). The presence of≥6.2% of KRASG12/G13 cfDNA in the wild-type background was associated with shorter survival (P=0.001). Conclusion(s): Multiplex detection of KRASG12/G13 mutations in a small amount of unamplified plasma cfDNA using ddPCR has good sensitivity and specificity and good concordance with conventional clinical mutation testing of archival specimens. A higher percentage of mutant KRASG12/G13 in cfDNA corresponded with shorter survival. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We investigated the interactions among the dysregulated genes in hepatocellular carcinoma (HCC) and identified the hub genes in the protein-protein interaction (PPI) network. Also, we also investigated the regulative effect of miR-379 on the IGF1/IGF1R signaling pathway and chemoresistance in HCC. MATERIALS AND METHODS: Raw data of a microarray that compared transcriptional gene profile between 3-paired HCC tissue samples and adjacent normal tissues were downloaded from Expression Atlas (E-GEOD-33006). The raw data was reanalyzed to identify the significantly dysregulated genes, which were further used for PPI network and KEGG pathway analysis. The regulative effect of miR-379 on IGF1R expression was studied by dual luciferase assay and Western blotting. The functional role of miR-379 in chemosensitivity of HCC cells was studied by drug sensitivity and flow cytometric assay. RESULTS: IGF1 is a hub gene that is mostly upregulated in HCC and it is an important player in the p53 signaling pathway. Knockdown of IGF1R significantly decreased IC50 of 5-FU, paclitaxel (PTX) and Doxorubicin (DOX) in Huh7 and HepG2 cells. MiR-379 could directly bind to the 3'UTR of IGF1R and suppress IGF1R expression. MiR-379 overexpression sensitized Huh7 and HepG2 cells to 5-FU, PTX and DOX and also enhanced DOX-induced cell apoptosis. CONCLUSIONS: IGF1 is a hub gene in HCC and is also one of the most upregulated genes in HCC tissues compared to normal tissues. It is involved in the p53 signaling pathway regulation. MiR-379 can sensitize HCC cells to chemother apeutic reagents via targeting IGF1R and suppressing its expression. [ABSTRACT FROM AUTHOR]