1,012 research outputs found

    Wnt-11 expression promotes invasiveness and correlates with survival in human pancreatic ductal adeno carcinoma

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    Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest forms of cancer, proving difficult to manage clinically. Wnt-11, a developmentally regulated gene producing a secreted protein, has been associated with various carcinomas but has not previously been studied in PDAC. The present study aimed to elucidate these aspects first in vitro and then in a clinical setting in vivo. Molecular analyses of Wnt-11 expression as well as other biomarkers involved qRT-PCR, RNA-seq and siRNA. Proliferation was measured by MTT; invasiveness was quantified by Boyden chamber (Matrigel) assay. Wnt-11 mRNA was present in three different human PDAC cell lines. Wnt-11 loss affected epithelial-mesenchymal transition and expression of neuronal and stemness biomarkers associated with metastasis. Indeed, silencing Wnt-11 in Panc-1 cells significantly inhibited their Matrigel invasiveness without affecting their proliferative activity. Consistently with the in vitro data, human biopsies of PDAC showed significantly higher Wnt-11 mRNA levels compared with matched adjacent tissues. Expression was significantly upregulated during PDAC progression (TNM stage I to II) and maintained (TNM stages III and IV). Wnt-11 is expressed in PDAC in vitro and in vivo and plays a significant role in the pathophysiology of the disease; this evidence leads to the conclusion that Wnt-11 could serve as a novel, functional biomarker PDA

    Optimal filtering of the LISA data

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    The LISA time-delay-interferometry responses to a gravitational-wave signal are rewritten in a form that accounts for the motion of the LISA constellation around the Sun; the responses are given in closed analytic forms valid for any frequency in the band accessible to LISA. We then present a complete procedure, based on the principle of maximum likelihood, to search for stellar-mass binary systems in the LISA data. We define the required optimal filters, the amplitude-maximized detection statistic (analogous to the F statistic used in pulsar searches with ground-based interferometers), and discuss the false-alarm and detection probabilities. We test the procedure in numerical simulations of gravitational-wave detection.Comment: RevTeX4, 28 pages, 9 EPS figures. Minus signs fixed in Eq. (46) and Table II. Corrected discussion of F-statistic distribution in Sec. IV

    Critical currents in Josephson junctions, with unconventional pairing symmetry: dx2y2+isd_{x^2-y^2}+is versus dx2y2+idxyd_{x^2-y^2}+id_{xy}

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    Phenomenological Ginzburg-Landau theory is used to calculate the possible spontaneous vortex states that may exist at corner junctions of dx2y2+ixd_{x^2-y^2}+ix-wave, (where x=sx=s or x=dxyx=d_{xy}) and s-wave superconductors. We study the magnetic flux and the critical current modulation with the junction orientation angle θ\theta, the magnitude of the order parameter, and the magnetic field HH. It is seen that the critical current IcI_c versus the magnetic flux Φ\Phi relation is symmetric / asymmetric for x=dxy/sx=d_{xy}/s when the orientation is exactly such that the lobes of the dominant dx2y2d_{x^2-y^2}-wave order parameter points towards the two junctions, which are at right angles for the corner junction. The conclusion is that a measurement of the Ic(Φ)I_c(\Phi) relation may distinguish which symmetry (dx2y2+isd_{x^2-y^2}+is or dx2y2+idxyd_{x^2-y^2}+id_{xy}) the order parameter has.Comment: 11 pages with 11 figures, Changed conten

    Magnetic-interference patterns in Josephson junctions with d+is symmetry

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    The magnetic interference pattern and the spontaneous flux in unconventional Josephson junctions of superconductors with d+is symmetry are calculated for different reduced junction lengths and the relative factor of the d and s wave components. This is a time reversal broken symmetry state. We study the stability of the fractional vortex and antivortex which are spontaneously formed and examine their evolution as we change the length and the relative factor of d and s wave components. The asymmetry in the field modulated diffraction pattern exists for lengths as long as L=10\lambda_J.Comment: 8 pages, 6 eps files, submitted to PR

    A Mathematical Model of Liver Cell Aggregation In Vitro

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    The behavior of mammalian cells within three-dimensional structures is an area of intense biological research and underpins the efforts of tissue engineers to regenerate human tissues for clinical applications. In the particular case of hepatocytes (liver cells), the formation of spheroidal multicellular aggregates has been shown to improve cell viability and functionality compared to traditional monolayer culture techniques. We propose a simple mathematical model for the early stages of this aggregation process, when cell clusters form on the surface of the extracellular matrix (ECM) layer on which they are seeded. We focus on interactions between the cells and the viscoelastic ECM substrate. Governing equations for the cells, culture medium, and ECM are derived using the principles of mass and momentum balance. The model is then reduced to a system of four partial differential equations, which are investigated analytically and numerically. The model predicts that provided cells are seeded at a suitable density, aggregates with clearly defined boundaries and a spatially uniform cell density on the interior will form. While the mechanical properties of the ECM do not appear to have a significant effect, strong cell-ECM interactions can inhibit, or possibly prevent, the formation of aggregates. The paper concludes with a discussion of our key findings and suggestions for future work

    An assessment of the resolution limitation due to radiation-damage in x-ray diffraction microscopy

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    X-ray diffraction microscopy (XDM) is a new form of x-ray imaging that is being practiced at several third-generation synchrotron-radiation x-ray facilities. Although only five years have elapsed since the technique was first introduced, it has made rapid progress in demonstrating high-resolution threedimensional imaging and promises few-nm resolution with much larger samples than can be imaged in the transmission electron microscope. Both life- and materials-science applications of XDM are intended, and it is expected that the principal limitation to resolution will be radiation damage for life science and the coherent power of available x-ray sources for material science. In this paper we address the question of the role of radiation damage. We use a statistical analysis based on the so-called "dose fractionation theorem" of Hegerl and Hoppe to calculate the dose needed to make an image of a lifescience sample by XDM with a given resolution. We conclude that the needed dose scales with the inverse fourth power of the resolution and present experimental evidence to support this finding. To determine the maximum tolerable dose we have assembled a number of data taken from the literature plus some measurements of our own which cover ranges of resolution that are not well covered by reports in the literature. The tentative conclusion of this study is that XDM should be able to image frozen-hydrated protein samples at a resolution of about 10 nm with "Rose-criterion" image quality.Comment: 9 pages, 4 figure

    Multimessenger astronomy with the Einstein Telescope

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    Gravitational waves (GWs) are expected to play a crucial role in the development of multimessenger astrophysics. The combination of GW observations with other astrophysical triggers, such as from gamma-ray and X-ray satellites, optical/radio telescopes, and neutrino detectors allows us to decipher science that would otherwise be inaccessible. In this paper, we provide a broad review from the multimessenger perspective of the science reach offered by the third generation interferometric GW detectors and by the Einstein Telescope (ET) in particular. We focus on cosmic transients, and base our estimates on the results obtained by ET's predecessors GEO, LIGO, and Virgo.Comment: 26 pages. 3 figures. Special issue of GRG on the Einstein Telescope. Minor corrections include

    The Physics of Cluster Mergers

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    Clusters of galaxies generally form by the gravitational merger of smaller clusters and groups. Major cluster mergers are the most energetic events in the Universe since the Big Bang. Some of the basic physical properties of mergers will be discussed, with an emphasis on simple analytic arguments rather than numerical simulations. Semi-analytic estimates of merger rates are reviewed, and a simple treatment of the kinematics of binary mergers is given. Mergers drive shocks into the intracluster medium, and these shocks heat the gas and should also accelerate nonthermal relativistic particles. X-ray observations of shocks can be used to determine the geometry and kinematics of the merger. Many clusters contain cooling flow cores; the hydrodynamical interactions of these cores with the hotter, less dense gas during mergers are discussed. As a result of particle acceleration in shocks, clusters of galaxies should contain very large populations of relativistic electrons and ions. Electrons with Lorentz factors gamma~300 (energies E = gamma m_e c^2 ~ 150 MeV) are expected to be particularly common. Observations and models for the radio, extreme ultraviolet, hard X-ray, and gamma-ray emission from nonthermal particles accelerated in these mergers are described.Comment: 38 pages with 9 embedded Postscript figures. To appear in Merging Processes in Clusters of Galaxies, edited by L. Feretti, I. M. Gioia, and G. Giovannini (Dordrecht: Kluwer), in press (2001

    Observations of metals in the intra-cluster medium

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    Because of their deep gravitational potential wells, clusters of galaxies retain all the metals produced by the stellar populations of the member galaxies. Most of these metals reside in the hot plasma which dominates the baryon content of clusters. This makes them excellent laboratories for the study of the nucleosynthesis and chemical enrichment history of the Universe. Here we review the history, current possibilities and limitations of the abundance studies, and the present observational status of X-ray measurements of the chemical composition of the intra-cluster medium. We summarise the latest progress in using the abundance patterns in clusters to put constraints on theoretical models of supernovae and we show how cluster abundances provide new insights into the star-formation history of the Universe.Comment: 28 pages, 12 figures, accepted for publication in Space Science Reviews, special issue "Clusters of galaxies: beyond the thermal view", Editor J.S. Kaastra, Chapter 16; work done by an international team at the International Space Science Institute (ISSI), Bern, organised by J.S. Kaastra, A.M. Bykov, S. Schindler & J.A.M. Bleeke
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