1,156 research outputs found

    The Coming Resolution of the European Crisis

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    The economic and financial problems in the euro area are clearly serious and plentiful. An increasing number of commentators and economists have begun to question whether the euro can survive. There are only two alternatives. Europe can jettison the monetary union or it can adopt a complementary economic union. Every policymaker in Europe knows that the collapse of the euro would be a political and economic disaster for all and thus totally unacceptable. Europe's overriding political imperative to preserve the integration project will surely drive its leaders to ultimately secure the euro and restore the economic health of the continent.

    Ras/Raf-1/MAPK pathway mediates response to tamoxifen but not chemotherapy in breast cancer patients

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    <b>Purpose</b>: The expression and activation of the Ras/Raf-1/mitogen-activated protein kinase (MAPK) pathway plays an important role in the development and progression of cancer, and may influence response to treatments such as tamoxifen and chemotherapy. In this study we investigated whether the expression and activation of the key components of this pathway influenced clinical outcome, to test the hypothesis that activation of the MAPK pathway drives resistance to tamoxifen and chemotherapy in women with breast cancer. <b>Experimental Design</b>: Breast tumors from patients at the Glasgow Royal Infirmary and others treated within the BR9601 trial were analyzed for expression of the three Ras isoforms, total Raf-1, active and inactive forms of Raf-1 [pRaf(ser338) and pRaf(ser259), respectively], MAPK, and phospho-MAPK using an immunohistochemical approach. Analyses were done with respect to disease free-survival and overall survival. <b>Results</b>: Expression and activation of the Ras pathway was associated with loss of benefit from treatment with tamoxifen but not chemotherapy. Overexpression of pRaf(ser338) was associated with shortened disease-free and overall survival time in univariate analyses. Multivariate analysis suggested pRaf(ser338) was independent of known prognostic markers in predicting outcome following tamoxifen treatment (<i>P</i>=0.03). <b>Conclusion</b>: This study suggests that activation of the Ras pathway predicts for poor outcome on tamoxifen but not chemotherapy, and identifies pRaf(ser338) as a potential marker of resistance to estrogen receptor–targeted therapy. In addition, it suggests that expression of pRaf(ser338) could identify patients for whom tamoxifen alone is insufficient adjuvant systemic therapy, but for whom the addition of chemotherapy may be of benefit

    Filter-feeding, near-field flows, and the morphologies of colonial choanoflagellates

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    Efficient uptake of prey and nutrients from the environment is an important component in the fitness of all microorganisms, and its dependence on size may reveal clues to the origins of evolutionary transitions to multicellularity. Because potential benefits in uptake rates must be viewed in the context of other costs and benefits of size, such as varying predation rates and the increased metabolic costs associated with larger and more complex body plans, the uptake rate itself is not necessarily that which is optimized by evolution. Uptake rates can be strongly dependent on local organism geometry and its swimming speed, providing selective pressure for particular arrangements. Here we examine these issues for choanoflagellates, filter-feeding microorganisms that are the closest relatives of the animals. We explore the different morphological variations of the choanoflagellate Salpingoeca rosetta\textit{Salpingoeca rosetta}, which can exist as a swimming cell, as a sessile thecate cell, and as colonies of cells in various shapes. In the absence of other requirements and in a homogeneously nutritious environment, we find that the optimal strategy to maximize filter-feeding by the collar of microvilli is to swim fast, which favors swimming unicells. In large external flows, the sessile thecate cell becomes advantageous. Effects of prey diffusion are discussed and also found to be to the advantage of the swimming unicell.This work was supported in part by the Engineering and Physical Sciences Research Council and St. Johns College (J.B.K.) and Wellcome Trust Senior Investigator Award 097855MA (R.E.G.)

    Construction of Time-Dependent Spectra Using Wavelet Analysis for Determination of Global Damage

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    Positron lifetime measurements on neutron‐irradiated InP crystals

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    Neutron‐irradiated InP single crystals have been investigated by positron‐lifetime measurements. The samples were irradiated with thermal neutrons at different fluences yielding concentrations for Sn‐transmuted atoms between 2×1015 and 2×1018 cm−3. The lifetime spectra have been analyzed into one exponential decay component. The mean lifetimes show a monotonous increase with the irradiation dose from 246 to 282 ps. The increase in the lifetime has been associated to a defect containing an Indium vacancy. Thermal annealing at 550 °C reduces the lifetime until values closed to those obtained for the as‐grown and conventionally doped InP [email protected] ; [email protected]

    An efficient 2D inversion scheme for airborne frequency domain data

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    In many cases, inversion in 2D gives a better description of the subsurface compared with 1D inversion, but, computationally, 2D inversion is expensive, and it can be hard to use for large-scale surveys. We have developed an efficient hybrid 2D airborne frequency-domain electromagnetic inversion algorithm. Our hybrid scheme combines 1D and 2D inversions in a three-stage process, in which each step is progressively more accurate and computationally more expensive than the previous one. This results in an approximately 2x - 6x speedup compared with full 2D inversions, and with only minor changes to the inversion results. Our inversion structure is based on a regular grid, in which each sounding is discretized individually. The 1D modeling code uses layered models with derivatives derived through the finite-difference method, whereas our 2D modeling code uses an adaptive finite-element mesh, and it uses the adjoint-state method to calculate the derivatives. By incorporating the inversion grid structure into the 2D finite-element mesh, interpolation between the different meshes becomes trivial. Large surveys are handled by using local meshing to split large surveys into small sections, which retains the 2D information. The algorithm is heavily optimized and parallelized over the frequencies and sections, with good scalability even on nonuniform memory architecture systems, on which it is generally hard to achieve a satisfactory scaling. The algorithm has been tested successfully with various synthetic studies as well as field examples, of which results from two synthetic studies and a field example are shown
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