368 research outputs found

    Chaperone-Mediated Autophagy Markers LAMP2A and HSPA8 in Advanced Non-Small Cell Lung Cancer after Neoadjuvant Therapy.

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    In recent years autophagy has attracted the attention of researchers from many medical fields, including cancer research, and certain anti-macroautophagy drugs in combination with cytotoxic or targeted therapies have entered clinical trials. In the present study, we focused on a less explored subtype of autophagy, i.e., chaperone-mediated autophagy (CMA), with the key proteins LAMP2A and HSPA8 (HSC70), and their immunohistochemical evaluation with previously extensively validated antibodies. We were interested in whether the marker expression is influenced by the antecedent therapy, and its correlation with survival on a cohort of patients with non-small cell lung cancer (NSCLC) after neoadjuvant therapy and matched primary resected tumors. In concordance with our previous study, we did not find any intratumoral heterogeneity, nor correlation between the two parameters, nor correlation between the markers and any included pathological parameters. Surprisingly, the expression of both markers was also independent to tumor response or administered neoadjuvant treatment. In the survival analysis, the results were only significant for LAMP2A, where higher levels were associated with longer 5-year overall survival and disease-free survival for the mixed group of adenocarcinomas and squamous cell carcinomas (p < 0.0001 and p = 0.0019 respectively) as well as the squamous cell carcinoma subgroup (p = 0.0001 and p = 0.0001 respectively). LAMP2A was also an independent prognostic marker in univariate and multivariate analysis

    Surface tension of the isotropic-nematic interface

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    We present the first calculations of the pressure tensor profile in the vicinity of the planar interface between isotropic liquid and nematic liquid crystal, using Onsager's density functional theory and computer simulation. When the liquid crystal director is aligned parallel to the interface, the situation of lowest free energy, there is a large tension on the nematic side of the interface and a small compressive region on the isotropic side. By contrast, for perpendicular alignment, the tension is on the isotropic side. There is excellent agreement between theory and simulation both in the forms of the pressure tensor profiles, and the values of the surface tension.Comment: Minor changes; to appear in Phys. Rev.

    Self-consistent Ginzburg-Landau theory for transport currents in superconductors

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    We elaborate on boundary conditions for Ginzburg-Landau (GL) theory in the case of external currents. We implement a self-consistent theory within the finite element method (FEM) and present numerical results for a two-dimensional rectangular geometry. We emphasize that our approach can in principle also be used for general geometries in three-dimensional superconductors.Comment: 4 pages, 2 figures, to be published in Physica

    The splicing landscape is globally reprogrammed during male meiosis

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    Meiosis requires conserved transcriptional changes, but it is not known whether there is a corresponding set of RNA splicing switches. Here, we used RNAseq of mouse testis to identify changes associated with the progression from mitotic spermatogonia to meiotic spermatocytes. We identified ∌150 splicing switches, most of which affect conserved protein-coding exons. The expression of many key splicing regulators changed in the course of meiosis, including downregulation of polypyrimidine tract binding protein (PTBP1) and heterogeneous nuclear RNP A1, and upregulation of nPTB, Tra2ÎČ, muscleblind, CELF proteins, Sam68 and T-STAR. The sequences near the regulated exons were significantly enriched in target sites for PTB, Tra2ÎČ and STAR proteins. Reporter minigene experiments investigating representative exons in transfected cells showed that PTB binding sites were critical for splicing of a cassette exon in the Ralgps2 mRNA and a shift in alternative 5â€Č splice site usage in the Bptf mRNA. We speculate that nPTB might functionally replace PTBP1 during meiosis for some target exons, with changes in the expression of other splicing factors helping to establish meiotic splicing patterns. Our data suggest that there are substantial changes in the determinants and patterns of alternative splicing in the mitotic-to-meiotic transition of the germ cell cycle

    Generation of Bianchi type V cosmological models with varying Λ\Lambda-term

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    Bianchi type V perfect fluid cosmological models are investigated with cosmological term Λ\Lambda varying with time. Using a generation technique (Camci {\it et al.}, 2001), it is shown that the Einstein's field equations are solvable for any arbitrary cosmic scale function. Solutions for particular forms of cosmic scale functions are also obtained. The cosmological constant is found to be decreasing function of time, which is supported by results from recent type Ia supernovae observations. Some physical aspects of the models are also discussed.Comment: 16 pages, 3 figures, submitted to CJ

    Measurement of Atmospheric Neutrino Oscillations with the ANTARES Neutrino Telescope

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    The data taken with the ANTARES neutrino telescope from 2007 to 2010, a total live time of 863 days, are used to measure the oscillation parameters of atmospheric neutrinos. Muon tracks are reconstructed with energies as low as 20 GeV. Neutrino oscillations will cause a suppression of vertical upgoing muon neutrinos of such energies crossing the Earth. The parameters determining the oscillation of atmospheric neutrinos are extracted by fitting the event rate as a function of the ratio of the estimated neutrino energy and reconstructed flight path through the Earth. Measurement contours of the oscillation parameters in a two-flavour approximation are derived. Assuming maximum mixing, a mass difference of Δm322=(3.1±0.9)⋅10−3\Delta m_{32}^2=(3.1\pm 0.9)\cdot 10^{-3} eV2^2 is obtained, in good agreement with the world average value.Comment: 9 pages, 5 figure

    Biodiversity increases the resistance of ecosystem productivity to climate extremes

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    It remains unclear whether biodiversity buffers ecosystems against climate extremes, which are becoming increasingly frequent worldwide1. Early results suggested that the ecosystem productivity of diverse grassland plant communities was more resistant, changing less during drought, and more resilient, recovering more quickly after drought, than that of depauperate communities2. However, subsequent experimental tests produced mixed results3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13. Here we use data from 46 experiments that manipulated grassland plant diversity to test whether biodiversity provides resistance during and resilience after climate events. We show that biodiversity increased ecosystem resistance for a broad range of climate events, including wet or dry, moderate or extreme, and brief or prolonged events. Across all studies and climate events, the productivity of low-diversity communities with one or two species changed by approximately 50% during climate events, whereas that of high-diversity communities with 16–32 species was more resistant, changing by only approximately 25%. By a year after each climate event, ecosystem productivity had often fully recovered, or overshot, normal levels of productivity in both high- and low-diversity communities, leading to no detectable dependence of ecosystem resilience on biodiversity. Our results suggest that biodiversity mainly stabilizes ecosystem productivity, and productivity-dependent ecosystem services, by increasing resistance to climate events. Anthropogenic environmental changes that drive biodiversity loss thus seem likely to decrease ecosystem stability14, and restoration of biodiversity to increase it, mainly by changing the resistance of ecosystem productivity to climate events

    Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

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    This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio
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