Dicer and Drosha expression and response to Bevacizumab-based therapy in advanced colorectal cancer patients

PURPOSE: The miRNA-regulating enzymes Dicer and Drosha exhibit aberrant expression in several cancer types. Dicer and Drosha play a crucial role during the angiogenetic process in vitro and, for Dicer, in vivo. We aimed to investigate the potential role of Dicer and Drosha in predicting response to Bevacizumab-based therapy in advanced colorectal cancer (CRC) patients. METHODS: Dicer and Drosha mRNA levels were analysed in formalin-fixed paraffin-embedded specimens from patients affected by advanced CRC treated with or without Bevacizumab-containing regimens (n=116 and n=50, respectively) and from patients with diverticulosis as control group (n=20). The experimental data were obtained using qRT-PCR, analysed comparing Dicer and Drosha expression levels in tumour samples versus normal mucosa and then compared to clinical outcome. RESULTS: The tumour samples from Bevacizumab-treated patients showed a significantly higher Drosha expression (P<.001) versus normal mucosa, while Dicer levels did not differ. Intriguingly, we found that low Dicer levels predicted a longer progression-free survival (PFS) (P<.0001) and overall survival (OS) (P=.009). In addition, low Dicer levels were associated with better response to Bevacizumab-based treatments versus high Dicer levels (1.7% complete responses and 53.4% partial responses versus 0% and 32.7%, respectively; P=.0067). Multivariate analysis identified three independent predictors of improved OS: high performance status (PS) (relative risk (RR) 1.45; P=.011), lower organs involvement (RR 0.79; P=.034) and low Dicer expression (RR 0.71; P=.008). Conversely, Drosha levels were not associated with prognosis and outcome associated with treatment. In non-Bevacizumab-treated patients, Dicer and Drosha expression did not correlate with outcome. CONCLUSION: These findings suggest that low Dicer mRNA levels seem to be independent predictors of favourable outcome and response in patients affected by advanced CRCs treated with Bevacizumab-based therapy

On the Classification of Residues of the Grassmannian

We study leading singularities of scattering amplitudes which are obtained as residues of an integral over a Grassmannian manifold. We recursively do the transformation from twistors to momentum twistors and obtain an iterative formula for Yangian invariants that involves a succession of dualized twistor variables. This turns out to be useful in addressing the problem of classifying the residues of the Grassmannian. The iterative formula leads naturally to new coordinates on the Grassmannian in terms of which both composite and non-composite residues appear on an equal footing. We write down residue theorems in these new variables and classify the independent residues for some simple examples. These variables also explicitly exhibit the distinct solutions one expects to find for a given set of vanishing minors from Schubert calculus.Comment: 20 page

Phenomenology of the Higgs effective Lagrangian via FeynRules

The Higgs discovery and the lack of any other hint for new physics favor a description of non-standard Higgs physics in terms of an effective field theory. We present an implementation of a general Higgs effective Lagrangian containing operators up to dimension six in the framework of FeynRules and provide details on the translation between the mass and interaction bases, in particular for three- and four-point interaction vertices involving Higgs and gauge bosons. We illustrate the strengths of this implementation by using the UFO interface of FeynRules capable to generate model files that can be understood by the MadGraph 5 event generator and that have the specificity to contain all interaction vertices, without any restriction on the number of external legs or on the complexity of the Lorentz structures. We then investigate several new physics effects in total rates and differential distributions for different Higgs production modes, including gluon fusion, associated production with a gauge boson and di-Higgs production. We finally study contact interactions of gauge and Higgs bosons to fermions

Precision branching-ratio measurements in 18 O

Abstract: An experiment has been performed utilising the 12C(7Li,p)18O reaction to populate high-energy states in 18O. Using the Munich Q3D magnetic spectrograph in conjunction with the Birmingham large-angular-coverage DSSD array, branching ratios have been measured for over fifty states in 18O, investigating the α-decay, n-decay, 2n-decay and γ-decay branches. In tandem, Monte-Carlo techniques have been used to identify and separate features

State recognition for ‘contested languages’: a comparative study of Sardinian and Asturian, 1992–2010

While the idea of a named language as a separate and discrete identity is a political and social construct, in the cases of Sardinian and Asturian doubts over their respective ‘languageness’ have real material consequences, particularly in relation to language policy decisions at the state level. The Asturian example highlights how its lack of official status means that it is either ignored or subjected to repeated challenges to its status as a language variety deserving of recognition and support, reflecting how ‘official language’ in the Spanish context is often understood in practice as synonymous with the theoretically broader category of ‘language’. In contrast, the recent state recognition of Sardinian speakers as a linguistic minority in Italy (Law 482/1999) illustrates how legal recognition served to overcome existing obstacles to the implementation of regional language policy measures. At the same time, the limited subsequent effects of this Law, particularly in the sphere of education, are a reminder of the shortcomings of top-down policies which fail to engage with the local language practices and attitudes of the communities of speakers recognized. The contrastive focus of this article thus acknowledges the continued material consequences of top-down language classification, while highlighting its inadequacies as a language policy mechanism which reinforces artificial distinctions between speech varieties and speakers deserving of recognition