2,586 research outputs found

    Multifractal spectra in homogeneous shear flow

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    Employing numerical simulations of 3-D homogeneous shear flow, the associated multifractal spectra of the energy dissipation, scalar dissipation and vorticity fields were calculated. The results for (128) cubed simulations of this flow, and those obtained in recent experiments that analyzed 1- and 2-D intersections of atmospheric and laboratory flows, are in some agreement. A two-scale Cantor set model of the energy cascade process which describes the experimental results from 1-D intersections quite well, describes the 3-D results only marginally

    Distance, dissimilarity index, and network community structure

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    We address the question of finding the community structure of a complex network. In an earlier effort [H. Zhou, {\em Phys. Rev. E} (2003)], the concept of network random walking is introduced and a distance measure defined. Here we calculate, based on this distance measure, the dissimilarity index between nearest-neighboring vertices of a network and design an algorithm to partition these vertices into communities that are hierarchically organized. Each community is characterized by an upper and a lower dissimilarity threshold. The algorithm is applied to several artificial and real-world networks, and excellent results are obtained. In the case of artificially generated random modular networks, this method outperforms the algorithm based on the concept of edge betweenness centrality. For yeast's protein-protein interaction network, we are able to identify many clusters that have well defined biological functions.Comment: 10 pages, 7 figures, REVTeX4 forma

    Endothelial LRP1 transports amyloid-β1-42 across the blood-brain barrier

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    According to the neurovascular hypothesis, impairment of low-density lipoprotein receptor-related protein-1 (LRP1) in brain capillaries of the blood-brain barrier (BBB) contributes to neurotoxic amyloid-beta (A beta) brain accumulation and drives Alzheimer's disease (AD) pathology. However, due to conflicting reports on the involvement of LRP1 in A beta transport and the expression of LRP1 in brain endothelium, the role of LRP1 at the BBB is uncertain. As global Lrp1 deletion in mice is lethal, appropriate models to study the function of LRP1 are lacking. Moreover, the relevance of systemic A beta clearance to AD pathology remains unclear, as no BBB-specific knockout models have been available. Here, we developed transgenic mouse strains that allow for tamoxifen-inducible deletion of Lrp1 specifically within brain endothelial cells (Slo1c1-CreER(Tz) Lrp1(fl/fl) mice) and used these mice to accurately evaluate LRP1-mediated A beta BBB clearance in vivo. Selective deletion of Lrp1 in the brain endothelium of C57BL/6 mice strongly reduced brain efflux of injected [I-125] A beta(1-42). Additionally, in the 5xFAD mouse model of AD, brain endothelial-specific Lrp1 deletion reduced plasma A beta levels and elevated soluble brain A beta, leading to aggravated spatial learning and memory deficits, thus emphasizing the importance of systemic AD elimination via the BBB. Together, our results suggest that receptor-mediated A beta BBB clearance may be a potential target for treatment and prevention of A beta brain accumulation in AD

    Network Landscape from a Brownian Particle's Perspective

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    Given a complex biological or social network, how many clusters should it be decomposed into? We define the distance di,jd_{i,j} from node ii to node jj as the average number of steps a Brownian particle takes to reach jj from ii. Node jj is a global attractor of ii if di,jdi,kd_{i,j}\leq d_{i,k} for any kk of the graph; it is a local attractor of ii, if jEij\in E_i (the set of nearest-neighbors of ii) and di,jdi,ld_{i,j}\leq d_{i,l} for any lEil\in E_i. Based on the intuition that each node should have a high probability to be in the same community as its global (local) attractor on the global (local) scale, we present a simple method to uncover a network's community structure. This method is applied to several real networks and some discussion on its possible extensions is made.Comment: 5 pages, 4 color-figures. REVTeX 4 format. To appear in PR

    The Transcriptome of Human Endometrial Mesenchymal Stem Cells Under TGFβR Inhibition Reveals Improved Potential for Cell-Based Therapies

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    Mesenchymal stem/stromal cells (MSCs) are multipotent cells with favorable properties for cell therapies and regenerative medicine. Human endometrium harbors a small population of perivascular, clonogenic MSCs (eMSCs) identified by the SUSD2 marker. As for other MSCs, eMSCs require extensive in vitro expansion to generate clinically relevant numbers of cells, resulting in spontaneous differentiation, replicative senescence and cell death, decreasing therapeutic potency. We previously demonstrated that A83-01, a TGF-β receptor inhibitor, maintained eMSC clonogenicity, promoted proliferation, prevented apoptosis and maintained MSC function in vitro. Here we compare the transcriptome of passaged eMSCs from six women cultured with and without A83-01 for 7 days. We identified 1206 differentially expressed genes (DEG) using a false discovery rate cut-off at 0.01 and fold change >2. Significant enrichment of genes involved in anti-inflammatory responses, angiogenesis, cell migration and proliferation, and collagen fibril and extracellular matrix organization were revealed. TGF-β, Wnt and Akt signaling pathways were decreased. Anti-fibrotic and anti-apoptotic genes were induced, and fibroblast proliferation and myofibroblast related genes were downregulated. We found increased MSC potency genes (TWIST1, TWIST2, JAG1, LIFR, and SLIT2) validating the enhanced potency of A83-01-treated eMSCs, and importantly no pluripotency gene expression. We also identified eMSCs’ potential for secreting exosomes, possibly explaining their paracrine properties. Angiogenic and cytokine protein arrays confirmed the angiogenic, anti-fibrotic and immunomodulatory phenotype of A83-01-treated eMSCs, and increased angiogenic activity was functionally demonstrated in vitro. eMSCs culture expanded with A83-01 have enhanced clinically relevant properties, suggesting their potential for cell-therapies and regenerative medicine applications

    MESMER: MeerKAT Search for Molecules in the Epoch of Reionization

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    [Abridged] Observations of molecular gas at all redshifts are critical for measuring the cosmic evolution in molecular gas density and understanding the star-formation history of the Universe. The 12CO molecule (J=1-0 transition = 115.27 GHz) is the best proxy for extragalactic H2, which is the gas reservoir from which star formation occurs, and has been detected out to z~6. Typically, redshifted high-J lines are observed at mm-wavelengths, the most commonly targeted systems exhibiting high SFRs (e.g. submm galaxies), and far-IR-bright QSOs. While the most luminous objects are the most readily observed, detections of more typical galaxies with modest SFRs are essential for completing the picture. ALMA will be revolutionary in terms of increasing the detection rate and pushing the sensitivity limit down to include such galaxies, however the limited FoV when observing at such high frequencies makes it difficult to use ALMA for studies of the large-scale structure traced out by molecular gas in galaxies. This article introduces a strategy for a systematic search for molecular gas during the EoR (z~7 and above), capitalizing on the fact that the J=1-0 transition of 12CO enters the upper bands of cm-wave instruments at high-z. The FoV advantage gained by observing at such frequencies, coupled with modern broadband correlators allows significant cosmological volumes to be probed on reasonable timescales. In this article we present an overview of our future observing programme which has been awarded 6,500 hours as one of the Large Survey Projects for MeerKAT, the forthcoming South African SKA pathfinder instrument. Its large FoV and correlator bandwidth, and high-sensitivity provide unprecedented survey speed for such work. An existing astrophysical simulation is coupled with instrumental considerations to demonstrate the feasibility of such observations and predict detection rates.Comment: 7 pages, 4 figures, to appear in the proceedings of "Astronomy with megastructures: Joint science with the E-ELT and SKA", 10-14 May 2010, Crete, Greece (Eds: Isobel Hook, Dimitra Rigopoulou, Steve Rawlings and Aris Karastergiou

    Attractiveness of periodic orbits in parametrically forced systemswith time-increasing friction

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    We consider dissipative one-dimensional systems subject to a periodic force and study numerically how a time-varying friction affects the dynamics. As a model system, particularly suited for numerical analysis, we investigate the driven cubic oscillator in the presence of friction. We find that, if the damping coefficient increases in time up to a final constant value, then the basins of attraction of the leading resonances are larger than they would have been if the coefficient had been fixed at that value since the beginning. From a quantitative point of view, the scenario depends both on the final value and the growth rate of the damping coefficient. The relevance of the results for the spin-orbit model are discussed in some detail.Comment: 30 pages, 6 figure
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