Mouse p53-deficient cancer models as platforms for obtaining genomic predictors of human cancer clinical outcomes

Mutations in the TP53 gene are very common in human cancers, and are associated with poor clinical outcome. Transgenic mouse models lacking the Trp53 gene or that express mutant Trp53 transgenes produce tumours with malignant features in many organs. We previously showed the transcriptome of a p53-deficient mouse skin carcinoma model to be similar to those of human cancers with TP53 mutations and associated with poor clinical outcomes. This report shows that much of the 682-gene signature of this murine skin carcinoma transcriptome is also present in breast and lung cancer mouse models in which p53 is inhibited. Further, we report validated gene-expression-based tests for predicting the clinical outcome of human breast and lung adenocarcinoma. It was found that human patients with cancer could be stratified based on the similarity of their transcriptome with the mouse skin carcinoma 682-gene signature. The results also provide new targets for the treatment of p53-defective tumours.

Regimes of spray vaporization and combustion in counterflow configurations

This article addresses the problem of spray vaporization and combustion in axisymmetric opposed-jet configurations involving a stream of hot air counterflowing against a stream of nitrogen carrying a spray of fuel droplets. The Reynolds numbers of the jets are assumed to be large, so that mixing of the two streams is restricted to a thin mixing layer that separates the counterflowing streams. The evolution of the droplets in their feed stream from the injection location is seen to depend fundamentally on the value of the droplet Stokes number, St, defined as the ratio of the droplet acceleration time to the mixing layer strain time close to the stagnation point. Two different regimes of spray vaporization and combustion can be identified depending on the value of St. For values of St below a critical value, equal to 1/4 for dilute sprays with small values of the spray liquid mass loading ratio, the droplets decelerate to approach the gas stagnation plane with a vanishing axial velocity. In this case, the droplets located initially near the axis reach the mixing layer, where they can vaporize due to the heat received from the hot air, producing fuel vapor that can burn with the oxygen in a diffusion flame located on the air side of the mixing layer. The character of the spray combustion is different for values of St of order unity, because the droplets cross the stagnation plane and move into the opposing air stream, reaching distances that are much larger than the mixing layer thickness before they turn around. The vaporization of these crossing droplets, and also the combustion of the fuel vapor generated by them, occur in the hot air stream, without significant effects of molecular diffusion, generating a vaporization-assisted nonpremixed flame that stands on the air side outside the mixing layer. Separate formulations will be given below for these two regimes of combustion, with attention restricted to the near-stagnation-point region, where the solution is self-similar and all variables are only dependent on the distance to the stagnation plane. The resulting formulations display a reduced number of controlling parameters that effectively embody dependences of the structure of the spray flame on spray dilution, droplet inertia, and fuel preferential diffusion. Sample solutions are given for the limiting cases of pure vaporization and of infinitely fast chemistry, with the latter limit formulated in terms of chemistry-free coupling functions that allow for general nonunity Lewis numbers of the fuel vapor.