3,235 research outputs found

    Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation

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    Background: Neuropilin is a transmembrane receptor for vascular endothelial growth factor (VEGF) and is expressed in normal endothelial cells and upregulated in cancer cells. Neuropilin-1 (NRP-1) has been shown to promote tumour cell migration and survival in colon cancer in response to VEGF binding. The expression profiles of neuropilins, associated co-receptors and known ligands have been mapped in three colorectal cell lines: Caco-2, HCT116 & HT29. We have previously shown that butyrate, a naturally occurring histone deacetylase inhibitor (HDACi) produced by fermentation of fibre in the colon, causes apoptosis of colon cancer cell lines. Results: Here we demonstrate that butyrate down-regulates NRP-1 and VEGF at the mRNA and protein level in colorectal cancer cell lines. NRP-1 is a known transcriptional target of Sp1, whose activity is regulated by acetylation. NRP-1 down-regulation by butyrate was associated with decreased binding affinity of Sp1 for canonical Sp-binding sites in the NRP-1 promoter. siRNA-mediated knock-down of Sp1 implied that Sp1 may have strong DNA binding activity but weak transactivation potential. Conclusion: The downregulation of the key apoptotic and angiogenesis regulator NRP-1 by butyrate suggests a novel contributory mechanism to the chemopreventive effect of dietary fibre

    Thermal effects in InGaAs/AlAsSb quantum-cascade lasers

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    A quantum-cascade laser (QCL) thermal model is presented. On the basis of a finite-difference approach, the model is used in conjunction with a self-consistent carrier transport model to calculate the temperature distribution in a near-infrared InGaAs/AlAsSb QCL. The presented model is used to investigate the effects of driving conditions and device geometries on the active-region temperature, which has a major influence on the device performance. A buried heterostructure combined with epilayer-down mounting is found to offer the best performance compared with alternative structures and has thermal time constants up to eight times smaller. The presented model provides a valuable tool for understanding the thermal dynamics inside a QCL and will help to improve operating temperatures

    Double giant resonances in deformed nuclei

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    We report on the first microscopic study of the properties of two-phonon giant resonances in deformed nuclei. The cross sections of the excitation of the giant dipole and the double giant dipole resonances in relativistic heavy ion collisions are calculated. We predict that the double giant dipole resonance has a one-bump structure with a centroid 0.8 MeV higher than twice energy for the single giant dipole resonance in the reaction under consideration. The width of the double resonance equals to 1.33 of that for the single resonance.Comment: 5 pages, 2 postscript figure

    Expanding the Family of Grassmannian Kernels: An Embedding Perspective

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    Modeling videos and image-sets as linear subspaces has proven beneficial for many visual recognition tasks. However, it also incurs challenges arising from the fact that linear subspaces do not obey Euclidean geometry, but lie on a special type of Riemannian manifolds known as Grassmannian. To leverage the techniques developed for Euclidean spaces (e.g, support vector machines) with subspaces, several recent studies have proposed to embed the Grassmannian into a Hilbert space by making use of a positive definite kernel. Unfortunately, only two Grassmannian kernels are known, none of which -as we will show- is universal, which limits their ability to approximate a target function arbitrarily well. Here, we introduce several positive definite Grassmannian kernels, including universal ones, and demonstrate their superiority over previously-known kernels in various tasks, such as classification, clustering, sparse coding and hashing

    A dynamic multi-objective evolutionary algorithm based on polynomial regression and adaptive clustering

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    In this paper, a dynamic multi-objective evolutionary algorithm is proposed based on polynomial regression and adaptive clustering, called DMOEA-PRAC. As the Pareto-optimal solutions and fronts of dynamic multi-objective optimization problems (DMOPs) may dynamically change in the optimization process, two corresponding change response strategies are presented for the decision space and objective space, respectively. In the decision space, the potentially useful information contained in all historical populations is obtained by the proposed predictor based on polynomial regression, which extracts the linear or nonlinear relationship in the historical change. This predictor can generate good initial population for the new environment. In the objective space, in order to quickly adapt to the new environment, an adaptive reference vector regulator is designed in this paper based on K-means clustering for the complex changes of Pareto-optimal fronts, in which the adjusted reference vectors can effectively guide the evolution. Finally, DMOEA-PRAC is compared with some recently proposed dynamic multi-objective evolutionary algorithms and the experimental results verify the effectiveness of DMOEA-PRAC in dealing with a variety of DMOPs

    PKCθ Is Required For Alloreactivity And GVHD But Not For Immune Responses Toward Leukemia And Infection In Mice

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    Mean-field analysis of collapsing and exploding Bose-Einstein condensates

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    The dynamics of collapsing and exploding trapped Bose-Einstein condensat es caused by a sudden switch of interactions from repulsive to attractive a re studied by numerically integrating the Gross-Pitaevskii equation with atomic loss for an axially symmetric trap. We investigate the decay rate of condensates and the phenomena of bursts and jets of atoms, and compare our results with those of the experiments performed by E. A. Donley {\it et al.} [Nature {\bf 412}, 295 (2001)]. Our study suggests that the condensate decay and the burst production is due to local intermittent implosions in the condensate, and that atomic clouds of bursts and jets are coherent. We also predict nonlinear pattern formation caused by the density instability of attractive condensates.Comment: 7 pages, 8 figures, axi-symmetric results are adde

    Measure representation and multifractal analysis of complete genomes

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    This paper introduces the notion of measure representation of DNA sequences. Spectral analysis and multifractal analysis are then performed on the measure representations of a large number of complete genomes. The main aim of this paper is to discuss the multifractal property of the measure representation and the classification of bacteria. From the measure representations and the values of the DqD_{q} spectra and related CqC_{q} curves, it is concluded that these complete genomes are not random sequences. In fact, spectral analyses performed indicate that these measure representations considered as time series, exhibit strong long-range correlation. For substrings with length K=8, the DqD_{q} spectra of all organisms studied are multifractal-like and sufficiently smooth for the CqC_{q} curves to be meaningful. The CqC_{q} curves of all bacteria resemble a classical phase transition at a critical point. But the 'analogous' phase transitions of chromosomes of non-bacteria organisms are different. Apart from Chromosome 1 of {\it C. elegans}, they exhibit the shape of double-peaked specific heat function.Comment: 12 pages with 9 figures and 1 tabl

    CD20-targeting immunotherapy promotes cellular senescence in B-cell lymphoma

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    The CD20-targeting monoclonal antibody Rituximab is an established component of immunochemotherapeutic regimens against B-cell lymphomas, where its co-administration with conventional anti-cancer agents has significantly improved long-term outcome. However, the cellular mechanisms by which Rituximab exerts its anti-lymphoma activity are only partially understood. We show here that Rituximab induces typical features of cellular senescence, a long-term growth arrest of viable cells with distinct biological properties, in established B-cell lymphoma cell lines as well as primary transformed B-cells. In addition, Rituximab-based immunotherapy sensitized lymphoma cells to senescence induction by the chemotherapeutic compound Adriamycin (a.k.a. Doxorubicin), and, to a lesser extent, by the antimicrotubule agent Vincristine. Anti-CD20 treatment further enhanced secretion of senescence-associated cytokines, and augmented the DNA damage response (DDR) signaling cascade triggered by Adriamycin. As the underlying pro-senescence mechanism, we found intracellular reactive oxygen species (ROS) levels to be elevated in response to Rituximab, and, in turn, the ROS scavenger N-acetylcysteine (NAC) to largely abrogate Rituximab-mediated senescence. Our results, further supported by gene set enrichment analyses in a clinical data set of chronic lymphocytic leukemia patient samples exposed to a Rituximab-containing treatment regimen, provide important mechanistic insights into the biological complexity of anti-CD20-evoked tumor responses, and unveil cellular senescence as a hitherto unrecognized effector principle of the antibody component in lymphoma immunochemotherapy

    Electron-acoustic plasma waves: oblique modulation and envelope solitons

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    Theoretical and numerical studies are presented of the amplitude modulation of electron-acoustic waves (EAWs) propagating in space plasmas whose constituents are inertial cold electrons, Boltzmann distributed hot electrons and stationary ions. Perturbations oblique to the carrier EAW propagation direction have been considered. The stability analysis, based on a nonlinear Schroedinger equation (NLSE), reveals that the EAW may become unstable; the stability criteria depend on the angle θ\theta between the modulation and propagation directions. Different types of localized EA excitations are shown to exist.Comment: 10 pages, 5 figures; to appear in Phys. Rev.
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