Europe-wide precipitation projections at convection permitting scale with the Unified Model.

For the first time, we analyze 2.2 km UK Met Office Unified Model convection-permitting model (CPM) projections for a pan-European domain. These new simulations represent a major increase in domain size, allowing us to examine the benefits of CPMs across a range of European climates.

Enhanced future changes in wet and dry extremes over Africa at convection-permitting scale.

African society is particularly vulnerable to climate change. The representation of convection in climate models has so far restricted our ability to accurately simulate African weather extremes, limiting climate change predictions. Here we show results from climate change experiments with a convection-permitting (4.

Onset of optical-phonon cooling in multilayer graphene revealed by RF noise and black-body radiation thermometries.

We report on electron cooling power measurements in few-layer graphene excited by Joule heating by means of a new setup combining electrical and optical probes of the electron and phonon baths temperatures. At low bias, noise thermometry allows us to retrieve the well known acoustic phonon cooling regimes below and above the Bloch-Grüneisen temperature, with additional control over the phonon bath temperature. At high electrical bias, we show the relevance of direct optical investigation of the electronic temperature by means of black-body radiation measurements.

Coupling of mutated Met variants to DNA repair via Abl and Rad51.

Abnormal activation of DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems is a compelling likelihood with significant implications in both cancer biology and treatment. Here, we show that due to a potential substrate switch, mutated variants of the receptor for hepatocyte growth factor Met, but not the wild-type form of the receptor, directly couple to the Abl tyrosine kinase and the Rad51 recombinase, two key signaling elements of homologous recombination-based DNA repair. Treatment of cells that express the mutated receptor variants with the Met inhibitor SU11274 leads, in a mutant-dependent manner, to a reduction of tyrosine phosphorylated levels of Abl and Rad51, impairs radiation-induced nuclear translocation of Rad51, and acts as a radiosensitizer together with the p53 inhibitor pifithrin-alpha by increasing cellular double-strand DNA break levels following exposure to ionizing radiation.

The Met kinase inhibitor SU11274 exhibits a selective inhibition pattern toward different receptor mutated variants.

Point mutations constitute a major mode of oncogenic activation of the Met receptor tyrosine kinase. Met is aberrantly activated in many types of human malignancies and its deregulated activity is correlated with aggressive tumor traits such as abnormal proliferation and survival, leading to tumor growth, local invasion and metastasis. Here we report that the Met kinase inhibitor SU11274 differentially affects the kinase activity and subsequent signaling of various mutant forms of Met.

Prevalence and clinical impact of Met Y1253D-activating point mutation in radiotherapy-treated squamous cell cancer of the oropharynx.

Aberrant signalling through the hepatocyte growth factor/scatter factor receptor Met has been implicated in various aspects of the development of human cancer including the promotion of tumour invasion, angiogenesis and metastasis. Moreover, experimental data indicate that activation of the Met receptor may be involved in cellular resistance towards antineoplastic treatments such as chemotherapy and ionizing radiation. We determined the prevalence and clinical impact of the Met-activating mutation Y1253D in patients with squamous cell cancer of the oropharynx treated by radical radiotherapy.