107 research outputs found

    Réparations minces de parapets de ponts avec des bétons fibrés à ultra-hautes performances (BFUP)

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    RÉSUMÉ Le Canada possède un vaste réseau d’infrastructures routières. Cependant, dû à leur âge grandissant, un sous-investissement dans les années 89 à 90 et des conditions climatiques agressives, ceux-ci vont nécessiter dans les prochaines années des investissements majeurs pour leur remplacement ou leur réhabilitation. Ainsi, il devient intéressant d’effectuer des réparations durables et performantes pour le reste de la vie utile des ouvrages. Cependant, les réparations minces sont sensibles au problème de retrait restreint, tel que dans les parapets de ponts, ce qui peut mener à une fissuration précoce de la réparation et affecter négativement leur durabilité et leur efficacité à long terme.----------ABSTRACT Canada has a vast network of road infrastructures. However, due to their increasing age, an underinvestment in the eighties and nineties and aggressive climate conditions, many structure are going to require major investments in the upcoming years for their replacement or their rehabilitation. As such, it is important to repair them sustainably and successfully for the reminder of their service life. However, thin repairs are sensitive to restrained shrinkage such as in bridges parapets, which can lead to premature cracking of the concrete repair and can negatively affect their durability and their long-term efficiency

    Next-generation sequencing (NGS) in the microbiological world : how to make the most of your money

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    The Sanger sequencing method produces relatively long DNA sequences of unmatched quality and has been considered for long time as the gold standard for sequencing DNA. Many improvements of the Sanger method that culminated with fluorescent dyes coupled with automated capillary electrophoresis enabled the sequencing of the first genomes. Nevertheless, using this technology to sequence whole genomes was costly, laborious and time consuming even for genomes that are relatively small in size. A major technological advance was the introduction of next-generation sequencing (NGS) pioneered by 454 Life Sciences in the early part of the 21th century. NGS allowed scientists to sequence thousands to millions of DNA molecules in a single machine run. Since then, new NGS technologies have emerged and existing NGS platforms have been improved, enabling the production of genome sequences at an unprecedented rate as well as broadening the spectrum of NGS applications. The current affordability of generating genomic information, especially with microbial samples, has resulted in a false sense of simplicity that belies the fact that many researchers still consider these technologies a black box. In this review, our objective is to identify and discuss four steps that we consider crucial to the success of any NGS-related project. These steps are: (1) the definition of the research objectives beyond sequencing and appropriate experimental planning, (2) library preparation, (3) sequencing and (4) data analysis. The goal of this review is to give an overview of the process, from sample to analysis, and discuss how to optimize your resources to achieve the most from your NGS-based research. Regardless of the evolution and improvement of the sequencing technologies, these four steps will remain relevant

    Salirasib inhibits the growth of hepatocarcinoma cell lines in vitro and tumor growth in vivo through ras and mTOR inhibition

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    <p>Abstract</p> <p>Background</p> <p>Dysregulation of epidermal growth factor and insulin-like growth factor signaling play important roles in human hepatocellular carcinoma (HCC), leading to frequent activation of their downstream targets, the ras/raf/extracellular signal-regulated kinase (ERK) and the phosphoinositide 3-kinase (PI3K)/Akt/mammalian Target of Rapamycin (mTOR) pathways. Salirasib is an S-prenyl-cysteine analog that has been shown to block ras and/or mTOR activation in several non hepatic tumor cell lines. We investigated <it>in vitro </it>the effect of salirasib on cell growth as well as its mechanism of action in human hepatoma cell lines (HepG2, Huh7, and Hep3B) and its <it>in vivo </it>effect in a subcutaneous xenograft model with HepG2 cells.</p> <p>Results</p> <p>Salirasib induced a time and dose dependent growth inhibition in hepatocarcinoma cells through inhibition of proliferation and partially through induction of apoptosis. A 50 percent reduction in cell growth was obtained in all three cell lines at a dose of 150 μM when they were cultured with serum. By contrast, salirasib was more potent at reducing cell growth after stimulation with EGF or IGF2 under serum-free conditions, with an IC<sub>50 </sub>ranging from 60 μM to 85 μM. The drug-induced anti-proliferative effect was associated with downregulation of cyclin A and to a lesser extent of cyclin D1, and upregulation of p21 and p27. Apoptosis induction was related to a global pro-apoptotic balance with caspase 3 activation, cytochrome c release, death receptor upregulation, and a reduced mRNA expression of the apoptosis inhibitors cFLIP and survivin. These effects were associated with ras downregulation and mTOR inhibition, without reduction of ERK and Akt activation. <it>In vivo</it>, salirasib reduced tumour growth from day 5 onwards. After 12 days of treatment, mean tumor weight was diminished by 56 percent in the treated animals.</p> <p>Conclusions</p> <p>Our results show for the first time that salirasib inhibits the growth of human hepatoma cell lines through inhibition of proliferation and induction of apoptosis, which is associated with ras and mTOR inhibition. The therapeutic potential of salirasib in human HCC was further confirmed in a subcutaneous xenograft model.</p

    Whole genome sequencing of a Canadian Bovine gammaherpesvirus 4 strain and possible link between the viral infection and respiratory and reproductive clinical manifestations in dairy cattle

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    Bovine gammaherpesvirus 4 (BoHV-4) is a herpesvirus widespread in cattle populations, and with no clear disease association. Its genome contains a long unique coding region (LUR) flanked by polyrepetitive DNA and 79 open reading frames (ORFs), with unique 17 ORFs, named Bo1 to Bo17. In 2009, a BoHV-4 strain was isolated (FMV09-1180503: BoHV-4-FMV) from cattle with respiratory disease from Quebec, Canada, and its LUR was sequenced. Despite the overall high similarity, BoHV-4-FMV had the most divergent LUR sequence compared to the two known BoHV-4 reference strain genomes; most of the divergences were in the Bo genes and in the repeat regions. Our phylogenetic analysis based on DNA polymerase and thymidine kinase genes revealed that virus isolate was BoHV-4 gammaherpesvirus and clustered it together with European BoHV-4 strains. Because BoHV-4-FMV was isolated from animals presenting respiratory signs, we have updated the BoHV-4 Canadian cattle seroprevalence data and tried to find out whether there is a link between clinical manifestation and BoHV-4 seropositivity. An indirect immunofluorescence assay (IFA) was performed with nearly 200 randomized sera of dairy cattle from two Canadian provinces, Quebec (n = 100) and Ontario (n = 91). An additional set of sera obtained from Quebec, from the healthy (n = 48) cows or from the animals experiencing respiratory or reproductive problems (n = 75), was also analyzed by IFA. BoHV-4 seroprevalence in Canadian dairy cattle was 7.9% (Quebec: 6% and Ontario: 9.9%). Among animals from the Quebec-based farms, diseased animals showed higher BoHV-4 seropositivity than healthy animals (P < 0.05), with a significant 2.494 odds ratio of being seropositive in sick compared to healthy animals. Although there is no established direct link between BoHV-4 and specific diseases, these seroprevalence data suggest the possible involvement of BoHV-4 in dairy cattle diseases

    Kinetics of angiogenic changes in a new mouse model for hepatocellular carcinoma

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    <p>Abstract</p> <p>Background</p> <p>The increasing incidence of hepatocellular carcinoma in Western countries has led to an expanding interest of scientific research in this field. Therefore, a vast need of experimental models that mimic the natural pathogenesis of hepatocellular carcinoma (HCC) in a short time period is present. The goal of our study was (1) to develop an efficient mouse model for HCC research, in which tumours develop in a natural background of fibrosis and (2) to assess the time-dependent angiogenic changes in the pathogenesis of HCC.</p> <p>Methods</p> <p>Weekly intraperitoneal injections with the hepatocarcinogenic compound N-nitrosodiethylamine was applied as induction method and samples were taken at several time points to assess the angiogenic changes during the progression of HCC.</p> <p>Results</p> <p>The N-nitrosodiethylamine-induced mouse model provides well vascularised orthotopic tumours after 25 weeks. It is a representative model for human HCC and can serve as an excellent platform for the development of new therapeutic targets.</p

    Variants of a genomic island in Aeromonas salmonicida subsp. salmonicida link isolates with their geographical origins

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    Aeromonas salmonicida subsp. salmonicida is a fish pathogen. Analysis of its genomic characteristics is required to determine the worldwide distribution of the various populations of this bacterium. Genomic alignments between the 01-B526 pathogenic strain and the A449 reference strain have revealed a 51-kb chromosomal insertion in 01-B526. This insertion (AsaGEI1a) has been identified as a new genomic island (GEI) bearing prophage genes. PCR assays were used to detect this GEI in a collection of 139 A. salmonicida subsp. salmonicida isolates. Three forms of this GEI (AsaGEI1a, AsaGEI1b, AsaGEI2a) are now known based on this analysis and the sequencing of the genomes of seven additional isolates. A new prophage (prophage 3) associated with AsaGEI2a was also discovered. Each GEI appeared to be strongly associated with a specific geographic region. AsaGEI1a and AsaGEI2a were exclusively found in North American isolates, except for one European isolate bearing AsaGEI2a. The majority of the isolates bearing AsaGEI1b or no GEI were from Europe. Prophage 3 has also a particular geographic distribution and was found only in North American isolates. We demonstrated that A. salmonicida subsp. salmonicida possesses unsuspected elements of genomic heterogeneity that could be used as indicators to determine the geographic origins of isolates of this bacterium.Keywords : Bacteria, Genomics-functional genomics-comparative genomics; Furunculosis; Aeromonas salmonicida; Fish pathogen; Genomic island; Geographical distributio

    An assessment of particulate organic carbon to thorium-234 ratios in the ocean and their impact on the application of 234Th as a POC flux proxy

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    Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Chemistry 100 (2006): 213-233, doi:10.1016/j.marchem.2005.10.013.Thorium-234 is increasingly used as a tracer of ocean particle flux, primarily as a means to estimate particulate organic carbon export from the surface ocean. This requires determination of both the 234Th activity distribution (in order to calculate 234Th fluxes) and an estimate of the C/234Th ratio on sinking particles, to empirically derive C fluxes. In reviewing C/234Th variability, results obtained using a single sampling method show the most predictable behavior. For example, in most studies that employ in situ pumps to collect size fractionated particles, C/234Th either increases or is relatively invariant with increasing particle size (size classes >1 to 100’s μm). Observations also suggest that C/234Th decreases with depth and can vary significantly between regions (highest in blooms of large diatoms and highly productive coastal settings). Comparisons of C fluxes derived from 234Th show good agreement with independent estimates of C flux, including mass balances of C and nutrients over appropriate space and time scales (within factors of 2-3). We recommend sampling for C/234Th from a standard depth of 100 m, or at least one depth below the mixed layer using either large volume size fractionated filtration to capture the rarer large particles, or a sediment trap or other device to collect sinking particles. We also recommend collection of multiple 234Th profiles and C/234Th samples during the course of longer observation periods to better sample temporal variations in both 234Th flux and the characteristic of sinking particles. We are encouraged by new technologies which are optimized to more reliably sample truly settling particles, and expect the utility of this tracer to increase, not just for upper ocean C fluxes but for other elements and processes deeper in the water column.Individuals and science efforts discussed herein were supported by many national science programs, including the U.S. National Science Foundation and U.S. Department of Energy. S.F. and J.C.M. acknowledge the support provided to the International Atomic Energy Agency (IAEA) Marine Environment Laboratory by the Government of the Principality of Monaco. T.T. acknowledges support from the Australian Antarctic Science Program. K.B. was supported in part by a WHOI Ocean Life Institute Fellowship

    Je suis tombée

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    The effect of S-farnesyl-thiosalicylic acid (FTS, salirasib) on proliferation, apoptosis and signalling pathways in human hepatocarcinoma cell lines

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    Hepatocarcinoma is a frequent and lethal cancer with limited treatment options at an advanced stage. Ras activation seems to be a constant and early event in human hepatocarcinogenesis. Previous work of our team showed that inhibition of Ras by salirasib – an S-prenylcysteine analogue that inhibits Ras by competing with its membrane docking sites – prevents the development of hepatocarcinomas in a rat model of chemically-induced hepatocarcinogenesis. In the present work, we evaluated the anti-tumour activity of salirasib in human hepatocarcinoma cell lines in vitro and in vivo in a subcutaneous xenograft model. We showed that salirasib reduces the growth of HepG2, Huh7 and Hep3B cells, essentially through inhibition of cell proliferation. The effect on cell growth was associated with Ras inhibition, although ERK and Akt phosphorylation was not affected. Furthermore, we found that salirasib directly interfered with mTOR activation. Salirasib also induced a pro-apoptotic phenotype with upregulation of death receptors and downregulation of endogenous apoptosis inhibitors, while true induction of apoptosis was inconstant. Finally, we showed that salirasib reduces tumour growth in a subcutaneous HepG2 xenograft model. Taking advantage of these results indicating that hepatocarcinoma cell lines are possibly primed for apoptosis, we next showed that pre-treatment with salirasib sensitizes hepatocarcinoma cells to TRAIL-induced apoptosis involving both the intrinsic and the extrinsic pathways. Salirasib elicited a significant downregulation of survivin that was associated with apoptosis induction. Using the survivin inhibitor YM155, we further demonstrated that inhibition of survivin is sufficient to sensitize hepatocarcinoma cells to TRAIL-induced apoptosis. In addition, the action of TRAIL was dependent on DR5. Importantly, neither salirasib, TRAIL, nor the combination of both of them induced apoptosis in normal human hepatocytes.(MED - Sciences médicales) -- UCL, 201

    J’étais un garçon normal : [Le chemin de campagne]

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