Module networks revisited: computational assessment and prioritization of model predictions

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

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

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

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

H\"aggstr\"om, Peres, and Steif (1997) have introduced a dynamical version of percolation on a graph $G$. When $G$ is a tree they derived a necessary and sufficient condition for percolation to exist at some time $t$. In the case that $G$ 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 $t$ in a given target set $D$. The main result of the present paper is a necessary and sufficient condition for the existence of percolation, at some time $t\in D$, 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

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

Transfer of Communication Skills to the Workplace during Clinical Rounds : Impact of a Program for Residents

peer reviewe

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

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

Analysis of the symmetry of electrodes for Electropalatography with Cone Beam CT Scanning

The process of compression of air and vibration of activity in the larynx through which speech is produced is of great interest in phonetics, phonology, psychology and is related to various areas of biomedical engineering as it has a strong relationship with cochlear implants, Parkinson’s disease and Stroke. One technique by means of which speech production is analysed is the use of electropalatography, in which an artificial palate, moulded to the speakers’ hard palate is introduced in the mouth. The palate contains a series of electrodes, which monitor contact between the tongue and the palate during speech production. There is interest in the symmetry or asymmetry of the movement of the tongue as this may be related to languages or right- or left-handedness, however this has never been thoroughly studied. A specific limitation of electropalatography for symmetry studies is that palates are hand-crafted and the position of the electrodes themselves may be asymmetric. In this work, we analyse the positioning of electrodes of one electropalatography setting. The symmetry was analysed by locating the electrodes of the palate through the observation of the palate with Computed Tomography. An algorithm to segment the electrodes and find the symmetry of left and right sides of the palates is described. No significant asymmetry was found for one specific palate. The methodology presented should allow the analysis of palates to be used in larger studies of speech production

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

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