1,243 research outputs found

    Module networks revisited: computational assessment and prioritization of model predictions

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    The solution of high-dimensional inference and prediction problems in computational biology is almost always a compromise between mathematical theory and practical constraints such as limited computational resources. As time progresses, computational power increases but well-established inference methods often remain locked in their initial suboptimal solution. We revisit the approach of Segal et al. (2003) to infer regulatory modules and their condition-specific regulators from gene expression data. In contrast to their direct optimization-based solution we use a more representative centroid-like solution extracted from an ensemble of possible statistical models to explain the data. The ensemble method automatically selects a subset of most informative genes and builds a quantitatively better model for them. Genes which cluster together in the majority of models produce functionally more coherent modules. Regulators which are consistently assigned to a module are more often supported by literature, but a single model always contains many regulator assignments not supported by the ensemble. Reliably detecting condition-specific or combinatorial regulation is particularly hard in a single optimum but can be achieved using ensemble averaging.Comment: 8 pages REVTeX, 6 figure

    Cadmium influences the 5-fluorouracil cytotoxic effects on breast cancer cells

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    The aim of the research was to evaluate a heavy metal, cadmium (Cd), which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-fluorouracil (5-FU), after exposure to different concentrations of cd. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 µM) to the cells treated with Cd (5 µM–20 µM) did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer

    The SFXC software correlator for Very Long Baseline Interferometry: Algorithms and Implementation

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    In this paper a description is given of the SFXC software correlator, developed and maintained at the Joint Institute for VLBI in Europe (JIVE). The software is designed to run on generic Linux-based computing clusters. The correlation algorithm is explained in detail, as are some of the novel modes that software correlation has enabled, such as wide-field VLBI imaging through the use of multiple phase centres and pulsar gating and binning. This is followed by an overview of the software architecture. Finally, the performance of the correlator as a function of number of CPU cores, telescopes and spectral channels is shown.Comment: Accepted by Experimental Astronom

    Solitary coherent structures in viscoelastic shear flow: computation and mechanism

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    Starting from stationary bifurcations in Couette-Dean flow, we compute nontrivial stationary solutions in inertialess viscoelastic circular Couette flow. These solutions are strongly localized vortex pairs, exist at arbitrarily large wavelengths, and show hysteresis in the Weissenberg number, similar to experimentally observed ``diwhirl'' patterns. Based on the computed velocity and stress fields, we elucidate a heuristic, fully nonlinear mechanism for these flows. We propose that these localized, fully nonlinear structures comprise fundamental building blocks for complex spatiotemporal dynamics in the flow of elastic liquids.Comment: 5 pages text and 4 figures. Submitted to Physical Review Letter

    Dynamical percolation on general trees

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    H\"aggstr\"om, Peres, and Steif (1997) have introduced a dynamical version of percolation on a graph GG. When GG is a tree they derived a necessary and sufficient condition for percolation to exist at some time tt. In the case that GG is a spherically symmetric tree, H\"aggstr\"om, Peres, and Steif (1997) derived a necessary and sufficient condition for percolation to exist at some time tt in a given target set DD. The main result of the present paper is a necessary and sufficient condition for the existence of percolation, at some time tDt\in D, in the case that the underlying tree is not necessary spherically symmetric. This answers a question of Yuval Peres (personal communication). We present also a formula for the Hausdorff dimension of the set of exceptional times of percolation.Comment: 24 pages; to appear in Probability Theory and Related Field

    Dynamic contrast-enhanced and diffusion-weighted MRI for early detection of tumoral changes in single-dose and fractionated radiotherapy: evaluation in a rat rhabdomyosarcoma model

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    We aimed to examine different intratumoral changes after single-dose and fractionated radiotherapy, using diffusion-weighted (DW) and dynamic contrast-enhanced (DCE) MRI in a rat rhabdomyosarcoma model. Four WAG/Rij rats with rhabdomyosarcomas in the flanks received single-dose radiotherapy of 8 Gy, and four others underwent fractionated radiotherapy (five times 3 Gy). In rats receiving single-dose radiotherapy, a significant perfusion decrease was found in the first 2 days post-treatment, with slow recuperation afterwards. No substantial diffusion changes could be seen; tumor growth delay was 12 days. The rats undergoing fractionated radiotherapy showed a similar perfusion decrease early after the treatment. However, a very strong increase in apparent diffusion coefficient occurred in the first 10 days; growth delay was 18 days. DW-MRI and DCE-MRI can be used to show early tumoral changes induced by radiotherapy. Single-dose and fractionated radiotherapy induce an immediate perfusion effect, while the latter induces more intratumoral necrosis

    A matrix model for the topological string II: The spectral curve and mirror geometry

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    In a previous paper, we presented a matrix model reproducing the topological string partition function on an arbitrary given toric Calabi-Yau manifold. Here, we study the spectral curve of our matrix model and thus derive, upon imposing certain minimality assumptions on the spectral curve, the large volume limit of the BKMP "remodeling the B-model" conjecture, the claim that Gromov-Witten invariants of any toric Calabi-Yau 3-fold coincide with the spectral invariants of its mirror curve.Comment: 1+37 page

    Morphological population balance modelling of the effect of crystallisation environment on the evolution of crystal size and shape of para-aminobenzoic acid

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    A current morphological population balance (MPB) modelling methodology, which integrates crystal morphology, facet growth kinetics with multi-dimensional population balance, is overviewed and demonstrated, hence providing an attractive approach for modelling crystallisation processes. MPB modelling is applied to simulate the batch crystallisation of the alpha-form of para-aminobenzoic acid from ethanolic solutions as a function of the crystallisation environment including cooling rate, seeding temperature and seed conditions (loading, size and shape). The evolution of crystal shape/size and their distributions revealed that higher loading led to smaller and less needle-like crystals with similar yields, hence potentially being an important parameter for process control. Examination of the development of the fracture surface for broken seeds, mimicking the seed conditions after milling in practice in the simulated processes, demonstrated that these faces grew fast and then rapidly disappeared from the external crystal morphology. Restriction and challenges inherent in the current model are also highlighted
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