137 research outputs found

    Mechanism of periodic height variations along self-aligned VLS-grown planar nanostructures

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    In this study we report in-plane nanotracks produced by molecular-beam-epitaxy (MBE) exhibiting lateral self-assembly and unusual periodic and out-of-phase height variations across their growth axes. The nanotracks are synthesized using bismuth segregation on the GaAsBi epitaxial surface, which results in metallic liquid droplets capable of catalyzing GaAsBi nanotrack growth via the vapor–liquid–solid (VLS) mechanism. A detailed examination of the nanotrack morphologies is carried out employing a combination of scanning electron and atomic force microscopy and, based on the findings, a geometric model of nanotrack growth during MBE is developed. Our results indicate diffusion and shadowing effects play significant roles in defining the interesting nanotrack shape. The unique periodicity of our lateral nanotracks originates from a rotating nucleation “hot spot” at the edge of the liquid–solid interface, a feature caused by the relative periodic circling of the non-normal ion beam flux incident on the sample surface, inside the MBE chamber. We point out that such a concept is divergent from current models of crawling mode growth kinetics and conclude that these effects may be utilized in the design and assembly of planar nanostructures with controlled non-monotonous structure

    Atomic picture of ligand migration in toluene 4-monooxygenase

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    Computational modeling combined with mutational and activity assays was used to underline the substrate migration pathways in toluene 4-monooxygenase, a member of the important family of bacterial multicomponent monooxygenases (BMMs). In all structurally defined BMM hydroxylases, several hydrophobic cavities in the α-subunit map a preserved path from the protein surface to the diiron active site. Our results confirm the presence of two pathways by which different aromatic molecules can enter/escape the active site. While the substrate is observed to enter from both channels, the more hydrophilic product is withdrawn mainly from the shorter channel ending at residues D285 and E214. The long channel ends in the vicinity of S395, whose variants have been seen to affect activity and specificity. These mutational effects are clearly reproduced and rationalized by the in silico studies. Furthermore, the combined computational and experimental results highlight the importance of residue F269, which is located at the intersection of the two channels.This work has been funded by the EU projects INDOX (KBBE20137613549) and ERC 2009Adg25027PELE (to V.G) and the Spanish Ministry of Education and Science project CTQ201348287 (to V.G).Peer ReviewedPostprint (author's final draft

    European experts consensus: BRCA/homologous recombination deficiency testing in first-line ovarian cancer

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    Background: Homologous recombination repair (HRR) enables fault-free repair of double-stranded DNA breaks. HRR deficiency is predicted to occur in around half of high-grade serous ovarian carcinomas. Ovarian cancers harbouring HRR deficiency typically exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi). Current guidelines recommend a range of approaches for genetic testing to identify predictors of sensitivity to PARPi in ovarian cancer and to identify genetic predisposition. Design: To establish a European-wide consensus for genetic testing (including the genetic care pathway), decision making and clinical management of patients with recently diagnosed advanced ovarian cancer, and the validity of biomarkers to predict the effectiveness of PARPi in the first-line setting. The collaborative European experts’ consensus group consisted of a steering committee (n = 14) and contributors (n = 84). A (modified) Delphi process was used to establish consensus statements based on a systematic literature search, conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Results: A consensus was reached on 34 statements amongst 98 caregivers (including oncologists, pathologists, clinical geneticists, genetic researchers, and patient advocates). The statements concentrated on (i) the value of testing for BRCA1/2 mutations and HRR deficiency testing, including when and whom to test; (ii) the importance of developing new and better HRR deficiency tests; (iii) the importance of germline non-BRCA HRR and mismatch repair gene mutations for predicting familial risk, but not for predicting sensitivity to PARPi, in the first-line setting; (iv) who should be able to inform patients about genetic testing, and what training and education should these caregivers receive. Conclusion: These consensus recommendations, from a multidisciplinary panel of experts from across Europe, provide clear guidance on the use of BRCA and HRR deficiency testing for recently diagnosed patients with advanced ovarian cancer

    Searches for new physics using the t(t)over-bar invariant mass distribution in pp collisions at √s=8 TeV

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    This is the pre-print version of the final published paper that is available from the link belowSearches for anomalous top quark-antiquark production are presented, based on pp collisions at √s=8  TeV . The data, corresponding to an integrated luminosity of 19:7 fb^-1, were collected with the CMS detector at the LHC. The observed tt invariant mass spectrum is found to be compatible with the standard model prediction. Limits on the production cross section times branching fraction probe, for the first time, a region of parameter space for certain models of new physics not yet constrained by precision measurements
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