1,721,087 research outputs found
An accident prediction model for urban road networks
No full textFor several years now increasingly analytical prediction models have been developed that are able to correlate accident frequency with infrastructure characteristics to support the planning and design of measures for enhancing road safety. The models developed so far, though useful in the context for which they have been calibrated, are limited by the fact that they are not transferable to other contexts because of different traffic regulations. The present work aims to develop a predictive model for urban roads that is able to estimate the number of accidents for three situations in an urban road network, a roundabout, a three- or four-way junction, and a straight stretch of road. The models constructed are based on Poisson's and negative binomial algorithms and can be readily applied for accident prediction or identification of black spots
Activation of p53/p21waf1 pathway is associated with senescence during v-Ha-ras transformation of immortal C2C12 myoblasts.
No full textIt has recently been shown that tumor cells can retain the ability to undergo senescence, while the capacity of bypassing senescence has been associated with tumor progression. In this report, we showed that v-Ha-ras-mediated transformation of already immortal C2C12 myoblasts can be associated with senesence, in a low amount during in vitro passages and, to a higher extent, affer cellular stress (cell culture alkalinkation), or DNA damage (doxorubicin treatment). The capacity to undergo replicative senescence is associated with a strong increase of wt-p53 transcriptional activity and p21WAF1 up-regulation. These biochemical activities are down-modulated in the cells that evade the massive replicative senescence after stressing stimuli. Altogether, these findings show that active ras can cause senescence during the transformation of already immortal cells in associaton with p53/p21WAF1 pathway activation and support the hypothesis that p53/p21WAF1 functional activity is important in maintaining the integrity of the senescence pathway during cellular transformation
Exogenous wt-p53 protein is active in transformed cells but not in their non-transformed counterparts: implications for cancer gene therapy without tumor targeting
Full text linkBACKGROUND: Expression of exogenous wild-type p53 (wt-p53) protein in tumor cells can suppress the transformed phenotype whereas it does not apparently induce detrimental effects in non-transformed cells. This observation may provide a molecular basis for p53-mediated gene therapy of p53-sensitive cancers without the need for tumor targeting.
METHODS: To understand the molecular mechanisms responsible for this different behavior in tumor versus normal cells, biochemical and functional analyses of exogenous wt-p53 protein were performed on non-transformed C2C12 myoblasts and their transformed counterparts, the C2-ras cells.
RESULTS: The exogenous wt-p53 protein, which induced persistent growth arrest only in transformed C2-ras cells, was shown to be significantly more stable in transformed than in non-transformed cells. This different stability was due to different p53 proteolytic degradation. Moreover, constitutively, exogenous wt-p53 protein was found to be transcriptionally active only in C2-ras cells but it could also be activated in C2C12 cells by genotoxic damage.
CONCLUSIONS: Non-transformed C2C12 cells present regulatory system(s) which control the expression and the activity of exogenously expressed wt-p53 protein probably through degradation and maintenance in a latent form. This regulatory system is lost/inactivated upon transformation
Exogenous wt-p53 expression is not detrimental for normal cells: implications for tumor gene therapy
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p53 is involved in the differentiation but not in the differentiation-associated apoptosis of C2C12 myoblasts
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