A Convex-Nonconvex variational method for the additive decomposition of functions on surfaces

We present a Convex-NonConvex variational approach for the additive decomposition of noisy scalar f ields defined over triangulated surfaces into piecewise constant and smooth components. The energy functional to be minimized is defined by the weighted sum of three terms, namely an L2 fidelity term for the noise component, a Tikhonov regularization term for the smooth component and a Total Variation (TV)-like non-convex term for the piecewise constant component. The last term is parametrized such that the free scalar parameter allows to tune its degree of non- convexity and, hence, to separate the piecewise constant component more effectively than by using a classical convex TV regularizer without renouncing to convexity of the total energy functional. A method is also presented for selecting the two regularization parameters. The unique solution of the proposed variational model is determined by means of an efficient ADMM-based minimization algorithm. Numerical experiments show a nearly perfect separation of the different components

A Unified Surface Geometric Framework for Feature-Aware Denoising, Hole Filling and Context-Aware Completion

Technologies for 3D data acquisition and 3D printing have enormously developed in the past few years, and, consequently, the demand for 3D virtual twins of the original scanned objects has increased. In this context, feature-aware denoising, hole filling and context-aware completion are three essential (but far from trivial) tasks. In this work, they are integrated within a geometric framework and realized through a unified variational model aiming at recovering triangulated surfaces from scanned, damaged and possibly incomplete noisy observations. The underlying non-convex optimization problem incorporates two regularisation terms: a discrete approximation of the Willmore energy forcing local sphericity and suited for the recovery of rounded features, and an approximation of the l(0) pseudo-norm penalty favouring sparsity in the normal variation. The proposed numerical method solving the model is parameterization-free, avoids expensive implicit volumebased computations and based on the efficient use of the Alternating Direction Method of Multipliers. Experiments show how the proposed framework can provide a robust and elegant solution suited for accurate restorations even in the presence of severe random noise and large damaged areas

PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs

The regulation of intragenic miRNAs by their own intronic promoters is one of the open problems of miRNA biogenesis. Here, we describe PROmiRNA, a new approach for miRNA promoter annotation based on a semi-supervised statistical model trained on deepCAGE data and sequence features. We validate our results with existing annotation, PolII occupancy data and read coverage from RNA-seq data. Compared to previous methods PROmiRNA increases the detection rate of intronic promoters by 30%, allowing us to perform a large-scale analysis of their genomic features, as well as elucidate their contribution to tissue-specific regulation. PROmiRNA can be downloaded from http://promirna.molgen.mpg.de

Recent developments in StemBase: a tool to study gene expression in human and murine stem cells

<p>Abstract</p> <p>Background</p> <p>Currently one of the largest online repositories for human and mouse stem cell gene expression data, StemBase was first designed as a simple web-interface to DNA microarray data generated by the Canadian Stem Cell Network to facilitate the discovery of gene functions relevant to stem cell control and differentiation.</p> <p>Findings</p> <p>Since its creation, StemBase has grown in both size and scope into a system with analysis tools that examine either the whole database at once, or slices of data, based on tissue type, cell type or gene of interest. As of September 1, 2008, StemBase contains gene expression data (microarray and Serial Analysis of Gene Expression) from 210 stem cell samples in 60 different experiments.</p> <p>Conclusion</p> <p>StemBase can be used to study gene expression in human and murine stem cells and is available at <url>http://www.stembase.ca</url>.</p

The response of invertebrate communities to a moisture gradient in artificial soils of Ukrainian steppe arid zone

Animals were sampled within the experimental area using traps to investigate the spatial and temporal variation in abundance, species richness, and species composition of invertebrate communities. A total of 60 traps were operated simultaneously during each sampling period. Traps were emptied 26 times every 7-9 days each year. Plant water availability, precipitation, wind speed, air temperature (minimum, maximum, daily mean), air humidity, and atmospheric pressure were used as ecological predictors of invertebrate community status and structure. Two-dimensional geographic coordinates of sampling locations were used to create a set of orthogonal spatial variables based on eigenvectors. We used time series of sampling dates to produce a set of orthogonal eigenvector time variables. The moisture content in technosols was the most important factor determining the terrestrial invertebrate community's temporal dynamics under semi-arid climate and reclaimed ecosystem conditions. Each ecological group of terrestrial invertebrates is homogeneous in terms of moisture gradient (xerophilic, xerozoophilic, mesophilic) and has a specific set of patterns best explain the species response to water content in technosols. However, one should consider the fact that the species response to soil water content is influenced not only by soil water content but also by a complex of other environmental, temporal and spatial factors. That is why the effect of other factors on the species response must be extracted previously to find real estimations of the species optima and tolerance. This task can be solved using the constrained correspondence analysis (CCA) or constrained redundancy analysis (RDA) depending on the type of response to ecological factors prevailing in the community – monotone or unimodal. We found that in more dry conditions, the prevalent species responses are unimodal asymmetric, in moister – bimodal, and in moderate conditions, the distributions are symmetric unimodal. The asymmetric species response to soil moisture in different parts of the soil humidity range may be assumed as predominantly due to the abiotic factors in the gradient's aridest margin and due predominantly to the biotic factors in the most humid margin of the gradient. Keywords: species response, niche, optima, tolerance, reclamation, gradient, temporal dynami

Adding 5-hydroxytryptamine receptor type 3 antagonists may reduce drug-induced nausea in poor insight obsessive-compulsive patients taking off-label doses of selective serotonin reuptake inhibitors: a 52-week follow-up case report

Poor-insight obsessive-compulsive disorder (PI-OCD) is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI), fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3) blockers, making them preferred choices especially in cases of drug-induced nausea

Ellipticine cytotoxicity to cancer cell lines — a comparative study

Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts. Ellipticine can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. Here, a comparison of the toxicity of ellipticine to human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cells and U87MG glioblastoma cells and mechanisms of its action to these cells were evaluated. Treatment of all cells tested with ellipticine resulted in inhibition of cell growth and proliferation. This effect was associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes, in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4 and U87MG cells, but not in neuroblastoma UKF-NB-3 cells. Therefore, DNA adduct formation in most cancer cell lines tested in this comparative study might be the predominant cause of their sensitivity to ellipticine treatment, whereas other mechanisms of ellipticine action also contribute to its cytotoxicity to neuroblastoma UKF-NB-3 cells

MedlineRanker: flexible ranking of biomedical literature

The biomedical literature is represented by millions of abstracts available in the Medline database. These abstracts can be queried with the PubMed interface, which provides a keyword-based Boolean search engine. This approach shows limitations in the retrieval of abstracts related to very specific topics, as it is difficult for a non-expert user to find all of the most relevant keywords related to a biomedical topic. Additionally, when searching for more general topics, the same approach may return hundreds of unranked references. To address these issues, text mining tools have been developed to help scientists focus on relevant abstracts. We have implemented the MedlineRanker webserver, which allows a flexible ranking of Medline for a topic of interest without expert knowledge. Given some abstracts related to a topic, the program deduces automatically the most discriminative words in comparison to a random selection. These words are used to score other abstracts, including those from not yet annotated recent publications, which can be then ranked by relevance. We show that our tool can be highly accurate and that it is able to process millions of abstracts in a practical amount of time. MedlineRanker is free for use and is available at http://cbdm.mdc-berlin.de/tools/medlineranker

Detection of Alpha-Rod Protein Repeats Using a Neural Network and Application to Huntingtin

A growing number of solved protein structures display an elongated structural domain, denoted here as alpha-rod, composed of stacked pairs of anti-parallel alpha-helices. Alpha-rods are flexible and expose a large surface, which makes them suitable for protein interaction. Although most likely originating by tandem duplication of a two-helix unit, their detection using sequence similarity between repeats is poor. Here, we show that alpha-rod repeats can be detected using a neural network. The network detects more repeats than are identified by domain databases using multiple profiles, with a low level of false positives (<10%). We identify alpha-rod repeats in approximately 0.4% of proteins in eukaryotic genomes. We then investigate the results for all human proteins, identifying alpha-rod repeats for the first time in six protein families, including proteins STAG1-3, SERAC1, and PSMD1-2 & 5. We also characterize a short version of these repeats in eight protein families of Archaeal, Bacterial, and Fungal species. Finally, we demonstrate the utility of these predictions in directing experimental work to demarcate three alpha-rods in huntingtin, a protein mutated in Huntington's disease. Using yeast two hybrid analysis and an immunoprecipitation technique, we show that the huntingtin fragments containing alpha-rods associate with each other. This is the first definition of domains in huntingtin and the first validation of predicted interactions between fragments of huntingtin, which sets up directions toward functional characterization of this protein. An implementation of the repeat detection algorithm is available as a Web server with a simple graphical output: http://www.ogic.ca/projects/ard. This can be further visualized using BiasViz, a graphic tool for representation of multiple sequence alignments