279 research outputs found

    Visible Photoluminescence from Low Temperature deposited hydrogenated amorphous silicon nitride

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    Cataloged from PDF version of article.Hydrogenated amorphous silicon nitride (a-SiNx:H) samples have been prepared by plasma enhanced chemical vapor deposition (PECVD) using a mixture of silane (Sill4), nitrogen and ammonia (NH3). Most films exhibit visible photoluminescence (PL) and some emit strong PL after annealing. While films grown without NH 3 exhibit PL in the deep red, those grown with NH 3 show PL in the green. The PL properties of these films with no oxygen (O) content are similar to those of silicon oxide (SiO x) films and porous Si. Using infrared and X-ray Photoelectron Spectroscopy, we suggest that PL from a-SiNx:H films originate from Si clusters which form during PECVD and crystallize upon annealing. We propose that the presence of O is not necessary for efficient PL

    The progestin receptor interactome in the female mouse hypothalamus: Interactions with synaptic proteins are isoform specific and ligand dependent

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    Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase–tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I–positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease

    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 Îą-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

    Understanding the roles of gingival beta-defensins

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    Gingival epithelium produces β-defensins, small cationic peptides, as part of its contribution to the innate host defense against the bacterial challenge that is constantly present in the oral cavity. Besides their functions in healthy gingival tissues, β-defensins are involved in the initiation and progression, as well as restriction of periodontal tissue destruction, by acting as antimicrobial, chemotactic, and anti-inflammatory agents. In this article, we review the common knowledge about β-defensins, coming from in vivo and in vitro monolayer studies, and present new aspects, based on the experience on three-dimensional organotypic culture models, to the important role of gingival β-defensins in homeostasis of the periodontium

    Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alvolar bone resorption by mitochondrial-related mechanisms

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    Background/Objectives: Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats.Methods/Findings: Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations.Conclusions: The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.This study was supported by I+D grants from the Spanish Ministry of Education and Science (AGL2008-01057) and the Autonomous Government of Andalusia (AGR832)

    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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