2,283 research outputs found

    Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models

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    Melanomas are highly lethal skin tumours that are frequently treated by surgical resection. However, the efficacy of such procedures is often limited by tumour recurrence and metastasis. Caveolin-1 (CAV1) has been attributed roles as a tumour suppressor, although in late-stage tumours, its presence is associated with enhanced metastasis. The expression of this protein in human melanoma development and particularly how the presence of CAV1 affects metastasis after surgery has not been defined. CAV1 expression in human melanocytes and melanomas increases with disease progression and is highest in metastatic melanomas. The effect of increased CAV1 expression can then be evaluated using B16F10 murine melanoma cells injected into syngenic immunocompetent C57BL/6 mice or human A375 melanoma cells injected into immunodeficient B6Rag1−/− mice. Augmented CAV1 expression suppresses tumour formation upon a subcutaneous injection, but enhances lung metastasis of cells injected into the tail vein in both models. A procedure was initially developed using B16F10 melanoma cells in C57BL/6 mice to mimic better the situation in patients undergoing surgery. Subcutaneous tumours of a defined size were removed surgically and local tumour recurrence and lung metastasis were evaluated after another 14 days. In this postsurgery setting, CAV1 presence in B16F10 melanomas favoured metastasis to the lung, although tumour suppression at the initial site was still evident. Similar results were obtained when evaluating A375 cells in B6Rag1−/− mice. These results implicate CAV1 expression in melanomas as a marker of poor prognosis for patients undergoing surgery as CAV1 expression promotes experimental lung metastasis in two different preclinical models

    Adjoint-based sensitivity analysis of low-order thermoacoustic networks using a wave-based approach

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    Strict pollutant emission regulations are pushing gas turbine manufacturers to develop devices that operate in lean conditions, with the downside that combustion instabilities are more likely to occur. Methods to predict and control unstable modes inside combustion chambers have been developed in the last decades but, in some cases, they are computationally expensive. Sensitivity analysis aided by adjoint methods provides valuable sensitivity information at a low computational cost. This paper introduces adjoint methods and their application in wave-based low order network models, which are used as industrial tools, to predict and control thermoacoustic oscillations. Two thermoacoustic models of interest are analyzed. First, in the zero Mach number limit, a nonlinear eigenvalue problem is derived, and continuous and discrete adjoint methods are used to obtain the sensitivities of the system to small modifications. Sensitivities to base-state modification and feedback devices are presented. Second, a more general case with non-zero Mach number, a moving flame front and choked outlet, is presented. The influence of the entropy waves on the computed sensitivities is shown.J.G.A. is grateful to Alessandro Orchini for fruitful discussions and comments on this paper, and thankfully acknowledges CONACyT and Cambridge Trust for funding this project. L.M. gratefully acknowledges the financial support from the Royal Academy of Engineering Research Fellowships scheme

    A new CP violating observable for the LHC

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    We study a new type of CP violating observable that arises in three body decays that are dominated by an intermediate resonance. If two interfering diagrams exist with different orderings of final state particles, the required CP-even phase arises due to the different virtualities of the resonance in each of the two diagrams. This method can be an important tool for accessing new CP phases at the LHC and future colliders.Comment: 22 pages, v2: discussion of charged particle decays and a few references added v3: typos corrected, matches published versio

    Flavor conversion of cosmic neutrinos from hidden jets

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    High energy cosmic neutrino fluxes can be produced inside relativistic jets under the envelopes of collapsing stars. In the energy range E ~ (0.3 - 1e5) GeV, flavor conversion of these neutrinos is modified by various matter effects inside the star and the Earth. We present a comprehensive (both analytic and numerical) description of the flavor conversion of these neutrinos which includes: (i) oscillations inside jets, (ii) flavor-to-mass state transitions in an envelope, (iii) loss of coherence on the way to observer, and (iv) oscillations of the mass states inside the Earth. We show that conversion has several new features which are not realized in other objects, in particular interference effects ("L- and H- wiggles") induced by the adiabaticity violation. The neutrino-neutrino scattering inside jet and inelastic neutrino interactions in the envelope may produce some additional features at E > 1e4 GeV. We study dependence of the probabilities and flavor ratios in the matter-affected region on angles theta13 and theta23, on the CP-phase delta, as well as on the initial flavor content and density profile of the star. We show that measurements of the energy dependence of the flavor ratios will, in principle, allow to determine independently the neutrino and astrophysical parameters.Comment: 56 pages, 19 figures. Minor changes. Accepted by JHEP

    Concurrent Outbreak of Norovirus Genotype I and Enterotoxigenic Escherichia coli on a U.S. Navy Ship following a Visit to Lima, Peru

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    An outbreak of norovirus (NoV) genotype I and Enterotoxigenic Escherichia coli (ETEC) occurred among US Navy Ship personnel following a visit to Lima, Peru, in June 2008. Visiting a specific area in Lima was significantly associated with illness. While ETEC and NoV are commonly recognized as causative agents of outbreaks, co-circulation of both pathogens has been rarely observed in shipboard outbreaks

    Positive and negative well-being and objectively measured sedentary behaviour in older adults: evidence from three cohorts

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    Background: Sedentary behaviour is related to poorer health independently of time spent in moderate to vigorous physical activity. The aim of this study was to investigate whether wellbeing or symptoms of anxiety or depression predict sedentary behaviour in older adults. Method: Participants were drawn from the Lothian Birth Cohort 1936 (LBC1936) (n = 271), and the West of Scotland Twenty-07 1950s (n = 309) and 1930s (n = 118) cohorts. Sedentary outcomes, sedentary time, and number of sit-to-stand transitions, were measured with a three-dimensional accelerometer (activPAL activity monitor) worn for 7 days. In the Twenty-07 cohorts, symptoms of anxiety and depression were assessed in 2008 and sedentary outcomes were assessed ~ 8 years later in 2015 and 2016. In the LBC1936 cohort, wellbeing and symptoms of anxiety and depression were assessed concurrently with sedentary behaviour in 2015 and 2016. We tested for an association between wellbeing, anxiety or depression and the sedentary outcomes using multivariate regression analysis. Results: We observed no association between wellbeing or symptoms of anxiety and the sedentary outcomes. Symptoms of depression were positively associated with sedentary time in the LBC1936 and Twenty-07 1950s cohort, and negatively associated with number of sit-to-stand transitions in the LBC1936. Meta-analytic estimates of the association between depressive symptoms and sedentary time or number of sit-to-stand transitions, adjusted for age, sex, BMI, long-standing illness, and education, were β = 0.11 (95% CI = 0.03, 0.18) and β = − 0.11 (95% CI = − 0.19, −0.03) respectively. Conclusion: Our findings indicate that depressive symptoms are positively associated with sedentary behavior. Future studies should investigate the causal direction of this association

    Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

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    Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review
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