-We estimate the cosmological variation of the proton-to-electron mass ratio µ = m p /m e by measuring the wavelengths of molecular hydrogen transitions in the early universe. The analysis is performed using high spectral resolution observations (F W HM ≈ 7 km/s) of two damped Lyman-α systems at z abs = 2.3377 and 3.0249 observed along the lines of sight to the quasars Q 1232+082 and Q 0347−382 respectively.The most conservative result of the analysis is a possible variation of µ over the last ∼10 Gyrs, with an amplitude ∆µ/µ = (5.7 ± 3.8) × 10 −5 .The result is significant at the 1.5σ level only and should be confirmed by further observations. This is the most stringent estimate of a possible cosmological variation of µ obtained up to now.

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We investigated abundance ratios along the profiles of six high-redshift Damped Lyman-α systems, three of them associated with H 2 absorption, and derived optical depths in each velocity pixel. The variations of the pixel abundance ratios were found to be remarkably small and usually smaller than a factor of two within a profile. This result holds even when considering independent sub-clumps in the same system. The depletion factor is significantly enhanced only in those components where H 2 is detected. There is a strong correlation between [Fe/S] and [Si/S] abundances ratios, showing that the abundance ratio patterns are definitely related to the presence of dust. The depletion pattern is usually close to the one seen in the warm halo gas of our Galaxy.

Genetically engineered mouse (GEM) models of cancer currently comprise the most accurate way to experimentally recapitulate the human disease in the laboratory. Given recent advances in genomics and genetic screens, however, as well as an increasing urgency for the translation of effective preclinical treatments into the clinic, there is a pressing need to make these models easier and more efficient to work with. Accordingly, we have developed a versatile lentivirus-based approach to induce tumours from somatic cells of GEMs, add or subtract gene expression and render the tumours imageable from a simple breeding stock. The vectors deliver a tamoxifen-inducible and self-inactivating Cre recombinase, conditional bioluminescent and fluorescent proteins and an shRNA component. Following the transduction of somatic cells, tumours are initiated by Cre-mediated recombination of the inherited floxed alleles. Self-inactivation of Cre expression switches on the expression of luciferase, thereby rendering the recombined cells and resulting tumours bioluminescent. We demonstrate proof of concept of this approach by inducing bioluminescent lung tumours in conditional Kras and p53 mice. We also show that a variant vector expressing shRNA alters tumour growth dynamics and the histological grade associated with the inherited genotype. This approach comprises a versatile means to induce imageable and spontaneous tumour burden in mice. The vectors can be readily customized at the bench to modify reporter readout or tumour phenotype without additional transgenic strain development or breeding. They should also be useful for inducing imageable tumours in organs other than the lung, provided that the inherited conditional genotype is sufficiently penetrant. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.