54 research outputs found

    Comparison between two packages for pectoral muscle removal on mammographic images

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    Background: Pectoral muscle removal is a fundamental preliminary step in computer-aided diagnosis systems for full-field digital mammography (FFDM). Currently, two open-source publicly available packages (LIBRA and OpenBreast) provide algorithms for pectoral muscle removal within Matlab environment. Purpose: To compare performance of the two packages on a single database of FFDM images. Methods: Only mediolateral oblique (MLO) FFDM was considered because of large presence of pectoral muscle on this type of projection. For obtaining ground truth, pectoral muscle has been manually segmented by two radiologists in consensus. Both LIBRA’s and OpenBreast’s removal performance with respect to ground truth were compared using Dice similarity coefficient and Cohen-kappa reliability coefficient; Wilcoxon signed-rank test has been used for assessing differences in performances; Kruskal–Wallis test has been used to verify possible dependence of the performance from the breast density or image laterality. Results: FFDMs from 168 consecutive women at our institution have been included in the study. Both LIBRA’s Dice-index and Cohen-kappa were significantly higher than OpenBreast (Wilcoxon signed-rank test P < 0.05). No dependence on breast density or laterality has been found (Kruskal–Wallis test P > 0.05). Conclusion: Libra has a better performance than OpenBreast in pectoral muscle delineation so that, although our study has not a direct clinical application, these results are useful in the choice of packages for the development of complex systems for computer-aided breast evaluation

    Pur-alpha functionally interacts with FUS carrying ALS-associated mutations

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to motor neuron loss. Fused in sarcoma (FUS) protein carrying ALS-associated mutations localizes to stress granules and causes their coalescence into larger aggregates. Here we show that Pur-alpha physically interacts with mutated FUS in an RNA-dependent manner. Pur-alpha colocalizes with FUS carrying mutations in stress granules of motoneuronal cells differentiated from induced pluripotent stem cells and that are derived from ALS patients. We observe that both Pur-alpha and mutated FUS upregulate phosphorylation of the translation initiation factor eukaryotic translation initiation factor 2 alpha and consistently inhibit global protein synthesis. In vivo expression of Pur-alpha in different Drosophila tissues significatively exacerbates the neurodegeneration caused by mutated FUS. Conversely, the downregulation of Pur-alpha in neurons expressing mutated FUS significatively improves fly climbing activity. All these findings suggest that Pur-alpha, through the control of mRNA translation, might be involved in the pathogenesis of ALS associated with the mutation of FUS, and that an alteration of protein synthesis may be directly implicated in the disease. Finally, in vivo RNAi-mediated ablation of Pur-alpha produced locomotion defects in Drosophila, indicating a pivotal role for this protein in the motoneuronal function

    Functional interaction between FUS and SMN underlies SMA-like splicing changes in wild-type hFUS mice

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    Several of the identified genetic factors in Amyotrophic Lateral Sclerosis (ALS) are deeply associated to RNA metabolism, thus implying dysfunction in RNA processing as a major pathogenic mechanism. However, whether a precise RNA pathway is particularly affected remains so far unknown. Evidence suggests that FUS, that is mutated in familial ALS, and SMN, the causative factor in Spinal Muscular Atrophy (SMA), cooperate to the same molecular pathway, i.e. alternative splicing regulation, and that disturbances in SMN-regulated functions, either caused by depletion of SMN protein (as in the case of SMA) or by pathogenic interactions between FUS and SMN (as in the case of ALS) might be a common theme in both diseases. In this work, we followed these leads and tested their pathogenic relevance in vivo on motor neuron survival/degeneration. FUS-associated ALS recapitulates, in transgenic mice, crucial molecular features that characterise mouse models of SMA, including defects in snRNPs distribution and alteration in the alternative splicing of genes that have important roles in motor neuron function. Interestingly, decreasing SMN expression in these mice does not modify the disease course nor the molecular phenotypes analysed. Similarly, altering SMN levels by either transgenic overexpression or RNAi-mediated downregulation of SMN does not affect eye degeneration caused by FUS expression in Drosophila. Overall, these findings support the concept that FUS and SMN functionally interact and that FUS acts downstream of SMN-regulated snRNP assembly in the regulation of alternative splicing and gene expression

    A megaxion at 750 GeV as a first hint of low scale string theory

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    Journal of High Energy Physics 2016.7 (2016): 021 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Low scale string models naturally have axion-like pseudoscalars which couple directly to gluons and photons (but not W’s) at tree level. We show how they typically get tree level masses in the presence of closed string fluxes, consistent with the axion discrete gauge symmetry, in a way akin of the axion monodromy of string inflation and relaxion models. We discuss the possibility that the hints for a resonance at 750 GeV recently reported at ATLAS and CMS could correspond to such a heavy axion state (megaxion). Adjusting the production rate and branching ratios suggest the string scale to be of order Ms ≈ 7–104 TeV, depending on the compactification geometry. If this interpretation was correct, one extra Z’ gauge boson could be produced before reaching the string threshold at LHC and future collidersThis work is partially supported by the grants FPA2012-32828 and FPA2015-65929-P from the MINECO, the ERC Advanced Grant SPLE under contract ERC-2012-ADG-20120216-320421, the Consolider-Ingenio 2010 programme under grant MULTIDARK CSD2009-00064 and the grant SEV-2012-0249 of the “Centro de Excelencia Severo Ochoa” Programm

    Bioaccumulation and Toxicity of Organic Chemicals in Terrestrial Invertebrates

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    Terrestrial invertebrates are key components in ecosystems, with crucial roles in soil structure, functioning, and ecosystem services. The present chapter covers how terrestrial invertebrates are impacted by organic chemicals, focusing on up-to-date information regarding bioavailability, exposure routes and general concepts on bioaccumulation, toxicity, and existing models. Terrestrial invertebrates are exposed to organic chemicals through different routes, which are dependent on both the organismal traits and nature of exposure, including chemical properties and media characteristics. Bioaccumulation and toxicity data for several groups of organic chemicals are presented and discussed, attempting to cover plant protection products (herbicides, insecticides, fungicides, and molluscicides), veterinary and human pharmaceuticals, polycyclic aromatic compounds, polychlorinated biphenyls, flame retardants, and personal care products. Chemical mixtures are also discussed bearing in mind that chemicals appear simultaneously in the environment. The biomagnification of organic chemicals is considered in light of the consumption of terrestrial invertebrates as novel feed and food sources. This chapter highlights how science has contributed with data from the last 5 years, providing evidence on bioavailability, bioaccumulation, and toxicity derived from exposure to organic chemicals, including insights into the main challenges and shortcomings to extrapolate results to real exposure scenarios

    QCD and strongly coupled gauge theories : challenges and perspectives

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    We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe
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