525 research outputs found

    Estimating changes in temperature extremes from millennial scale climate simulations using generalized extreme value (GEV) distributions

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    Changes in extreme weather may produce some of the largest societal impacts of anthropogenic climate change. However, it is intrinsically difficult to estimate changes in extreme events from the short observational record. In this work we use millennial runs from the CCSM3 in equilibrated pre-industrial and possible future conditions to examine both how extremes change in this model and how well these changes can be estimated as a function of run length. We estimate changes to distributions of future temperature extremes (annual minima and annual maxima) in the contiguous United States by fitting generalized extreme value (GEV) distributions. Using 1000-year pre-industrial and future time series, we show that the magnitude of warm extremes largely shifts in accordance with mean shifts in summertime temperatures. In contrast, cold extremes warm more than mean shifts in wintertime temperatures, but changes in GEV location parameters are largely explainable by mean shifts combined with reduced wintertime temperature variability. In addition, changes in the spread and shape of the GEV distributions of cold extremes at inland locations can lead to discernible changes in tail behavior. We then examine uncertainties that result from using shorter model runs. In principle, the GEV distribution provides theoretical justification to predict infrequent events using time series shorter than the recurrence frequency of those events. To investigate how well this approach works in practice, we estimate 20-, 50-, and 100-year extreme events using segments of varying lengths. We find that even using GEV distributions, time series that are of comparable or shorter length than the return period of interest can lead to very poor estimates. These results suggest caution when attempting to use short observational time series or model runs to infer infrequent extremes.Comment: 33 pages, 22 figures, 1 tabl

    Nowhere minimal CR submanifolds and Levi-flat hypersurfaces

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    A local uniqueness property of holomorphic functions on real-analytic nowhere minimal CR submanifolds of higher codimension is investigated. A sufficient condition called almost minimality is given and studied. A weaker necessary condition, being contained a possibly singular real-analytic Levi-flat hypersurface is studied and characterized. This question is completely resolved for algebraic submanifolds of codimension 2 and a sufficient condition for noncontainment is given for non algebraic submanifolds. As a consequence, an example of a submanifold of codimension 2, not biholomorphically equivalent to an algebraic one, is given. We also investigate the structure of singularities of Levi-flat hypersurfaces.Comment: 21 pages; conjecture 2.8 was removed in proof; to appear in J. Geom. Ana

    Preconditioning of mesenchymal stromal cells with low-intensity ultrasound: influence on chondrogenesis and directed SOX9 signaling pathways

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    Background: Continuous low-intensity ultrasound (cLIUS) facilitates the chondrogenic differentiation of human mesenchymal stromal cells (MSCs) in the absence of exogenously added transforming growth factor-beta (TGFĪ²) by upregulating the expression of transcription factor SOX9, a master regulator of chondrogenesis. The present study evaluated the molecular events associated with the signaling pathways impacting SOX9 gene and protein expression under cLIUS. Methods: Human bone marrow-derived MSCs were exposed to cLIUS stimulation at 14 kPa (5 MHz, 2.5 Vpp) for 5 min. The gene and protein expression of SOX9 was evaluated. The specificity of SOX9 upregulation under cLIUS was determined by treating the MSCs with small molecule inhibitors of select signaling molecules, followed by cLIUS treatment. Signaling events regulating SOX9 expression under cLIUS were analyzed by gene expression, immunofluorescence staining, and western blotting. Results: cLIUS upregulated the gene expression of SOX9 and enhanced the nuclear localization of SOX9 protein when compared to non-cLIUS-stimulated control. cLIUS was noted to enhance the phosphorylation of the signaling molecule ERK1/2. Inhibition of MEK/ERK1/2 by PD98059 resulted in the effective abrogation of cLIUS-induced SOX9 expression, indicating that cLIUS-induced SOX9 upregulation was dependent on the phosphorylation of ERK1/2. Inhibition of integrin and TRPV4, the upstream cell-surface effectors of ERK1/2, did not inhibit the phosphorylation of ERK1/2 and therefore did not abrogate cLIUS-induced SOX9 expression, thereby suggesting the involvement of other mechanoreceptors. Consequently, the effect of cLIUS on the actin cytoskeleton, a mechanosensitive receptor regulating SOX9, was evaluated. Diffused and disrupted actin fibers observed in MSCs under cLIUS closely resembled actin disruption by treatment with cytoskeletal drug Y27632, which is known to increase the gene expression of SOX9. The upregulation of SOX9 under cLIUS was, therefore, related to cLIUS-induced actin reorganization. SOX9 upregulation induced by actin reorganization was also found to be dependent on the phosphorylation of ERK1/2. Conclusions: Collectively, preconditioning of MSCs by cLIUS resulted in the nuclear localization of SOX9, phosphorylation of ERK1/2 and disruption of actin filaments, and the expression of SOX9 was dependent on the phosphorylation of ERK1/2 under cLIUS

    The effects of degree correlations on network topologies and robustness

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    Complex networks have been applied to model numerous interactive nonlinear systems in the real world. Knowledge about network topology is crucial for understanding the function, performance and evolution of complex systems. In the last few years, many network metrics and models have been proposed to illuminate the network topology, dynamics and evolution. Since these network metrics and models derive from a wide range of studies, a systematic study is required to investigate the correlations between them. The present paper explores the effect of degree correlation on the other network metrics through studying an ensemble of graphs where the degree sequence (set of degrees) is fixed. We show that to some extent, the characteristic path length, clustering coefficient, modular extent and robustness of networks are directly influenced by the degree correlation.Comment: 13 pages, 6 figure

    Gene Expression Signatures That Predict Radiation Exposure in Mice and Humans

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    BACKGROUND: The capacity to assess environmental inputs to biological phenotypes is limited by methods that can accurately and quantitatively measure these contributions. One such example can be seen in the context of exposure to ionizing radiation. METHODS AND FINDINGS: We have made use of gene expression analysis of peripheral blood (PB) mononuclear cells to develop expression profiles that accurately reflect prior radiation exposure. We demonstrate that expression profiles can be developed that not only predict radiation exposure in mice but also distinguish the level of radiation exposure, ranging from 50 cGy to 1,000 cGy. Likewise, a molecular signature of radiation response developed solely from irradiated human patient samples can predict and distinguish irradiated human PB samples from nonirradiated samples with an accuracy of 90%, sensitivity of 85%, and specificity of 94%. We further demonstrate that a radiation profile developed in the mouse can correctly distinguish PB samples from irradiated and nonirradiated human patients with an accuracy of 77%, sensitivity of 82%, and specificity of 75%. Taken together, these data demonstrate that molecular profiles can be generated that are highly predictive of different levels of radiation exposure in mice and humans. CONCLUSIONS: We suggest that this approach, with additional refinement, could provide a method to assess the effects of various environmental inputs into biological phenotypes as well as providing a more practical application of a rapid molecular screening test for the diagnosis of radiation exposure
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