Combined hepatocellular-cholangiocarcinomas exhibit progenitor features and activation of Wnt and TGFβ signaling pathways

Intrahepatic malignant tumours include hepatocellular carcinomas (HCC), cholangiocarcinomas (CC) and combined hepatocholangiocarcinomas (cHCC-CC), a group of rare and poorly characterized tumours that exhibit both biliary and hepatocytic differentiation. The aim of the study was to characterize the molecular pathways specifically associated with cHCC-CC pathogenesis. We performed a genome-wide transcriptional analysis of 20 histologically defined cHCC-CC and compared them with a series of typical HCC and of CC. Data were analysed by gene set enrichment and integrative genomics and results were further validated in situ by tissue microarray using an independent series of 152 tumours. We report that cHCC-CC exhibit stem/progenitor features, a down-regulation of the hepatocyte differentiation program and a commitment to the biliary lineage. TGFβ and Wnt/β-catenin were identified as the two major signalling pathways activated in cHCC-CC. A β-catenin signature distinct from that observed in well-differentiated HCC with mutant β-catenin was found in cHCC-CC. This signature was associated with microenvironment remodelling and TGFβ activation. Furthermore, integrative genomics revealed that cHCC-CC share characteristics of poorly differentiated HCC with stem cell traits and poor prognosis. The common traits displayed by CC, cHCC-CC and some HCC suggest that these tumours could originate from stem/progenitor cell(s) and raised the hypothesis of a potential continuum between intrahepatic CC, cHCC-CC and poorly differentiated HC

DORIS: a diffusion MRI-based 10 tissue class deep learning segmentation algorithm tailored to improve anatomically-constrained tractography

International audienceModern tractography algorithms such as anatomically-constrained tractography (ACT) are based on segmentation maps of white matter (WM), gray matter (GM) and cerebrospinal fluid (CSF). These maps are generally estimated from a T1-weighted (T1w) image and then registered in diffusion weighted images (DWI) space. Registration of T1w to diffusion space and partial volume estimation are challenging and rarely voxel-perfect. Diffusion-based segmentation would thus potentially allow not to have higher quality anatomical priors injected in the tractography process. On the other hand, even if FA-based tractography is possible without T1 registration, the literature shows that this technique suffers from multiple issues such as holes in the tracking mask and a high proportion of generated broken and anatomically implausible streamlines. Therefore, there is an important need for a tissue segmentation algorithm that works directly in native diffusion space. We propose DORIS, a DWI-based deep learning segmentation algorithm. DORIS outputs 10 different tissue classes including WM, GM, CSF, ventricles and 6 other subcortical structures (putamen, pallidum, hippocampus, caudate, amygdala, thalamus). DORIS was trained and validated on a wide range of sujects, including 1000 individuals from 22 to 90 years old from clinical and research DWI acquisitions, from 5 public databases. In the absence of a "true" * Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.ed

Substitution Patterns Are Under Different Influences in Primates and Rodents

There are large-scale variations of the GC-content along mammalian chromosomes that have been called isochore structures. Primates and rodents have different isochore structures, which suggests that these lineages exhibit different modes of GC-content evolution. It has been shown that, in the human lineage, GC-biased gene conversion (gBGC), a neutral process associated with meiotic recombination, acts on GC-content evolution by influencing A or T to G or C substitution rates. We computed genome-wide substitution patterns in the mouse lineage from multiple alignments and compared them with substitution patterns in the human lineage. We found that in the mouse lineage, gBGC is active but weaker than in the human lineage and that male-specific recombination better predicts GC-content evolution than female-specific recombination. Furthermore, we were able to show that G or C to A or T substitution rates are predicted by a combination of different factors in both lineages. A or T to G or C substitution rates are most strongly predicted by meiotic recombination in the human lineage but by CpG odds ratio (the observed CpG frequency normalized by the expected CpG frequency) in the mouse lineage, suggesting that substitution patterns are under different influences in primates and rodents

Bibliothèques et sciences de l\u27information : quel dialogue ? - Programme

Face aux évolutions technologiques, scientifiques, économiques, sociales, culturelles et politiques de leur environnement, les bibliothèques en tant qu\u27organismes culturels et scientifiques doivent repenser leurs pratiques, leur positionnement économique, politique et institutionnel, et leur rôle social, culturel et scientifique. Dans ce contexte, qu\u27attendent les bibliothèques de la recherche ? Quels thématiques et projets de recherche répondraient à leurs besoins ? Les sciences de l\u27information peuvent-elles apporter des réponses aux enjeux actuels ? Pour répondre aux interrogations posées par ces nouveaux défis, le colloque croise les approches et expériences de bibliothécaires et chercheurs en sciences de l\u27information de nombreux pays ( France, Canada, Etats-Unis, Allemagne, Royaume-Uni...

Late Replicating Domains Are Highly Recombining in Females but Have Low Male Recombination Rates: Implications for Isochore Evolution

In mammals sequences that are either late replicating or highly recombining have high rates of evolution at putatively neutral sites. As early replicating domains and highly recombining domains both tend to be GC rich we a priori expect these two variables to covary. If so, the relative contribution of either of these variables to the local neutral substitution rate might have been wrongly estimated owing to covariance with the other. Against our expectations, we find that sex-averaged recombination rates show little or no correlation with replication timing, suggesting that they are independent determinants of substitution rates. However, this result masks significant sex-specific complexity: late replicating domains tend to have high recombination rates in females but low recombination rates in males. That these trends are antagonistic explains why sex-averaged recombination is not correlated with replication timing. This unexpected result has several important implications. First, although both male and female recombination rates covary significantly with intronic substitution rates, the magnitude of this correlation is moderately underestimated for male recombination and slightly overestimated for female recombination, owing to covariance with replicating timing. Second, the result could explain why male recombination is strongly correlated with GC content but female recombination is not. If to explain the correlation between GC content and replication timing we suppose that late replication forces reduced GC content, then GC promotion by biased gene conversion during female recombination is partly countered by the antagonistic effect of later replicating sequence tending increase AT content. Indeed, the strength of the correlation between female recombination rate and local GC content is more than doubled by control for replication timing. Our results underpin the need to consider sex-specific recombination rates and potential covariates in analysis of GC content and rates of evolution

Performance of the ATLAS Electromagnetic Calorimeter End-cap Module 0

The construction and beam test results of the ATLAS electromagnetic end-cap calorimeter pre-production module 0 are presented. The stochastic term of the energy resolution is between 10% GeV^1/2 and 12.5% GeV^1/2 over the full pseudorapidity range. Position and angular resolutions are found to be in agreement with simulation. A global constant term of 0.6% is obtained in the pseudorapidity range 2.5 < eta < 3.2 (inner wheel)

Modelling human choices: MADeM and decision‑making

Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

Experimental characterization of the photon source for small field dosimetry in the context of stereotactic radiosurgery

Adaptation d'une méthode de mesure directe des sources de rayons X pour la mesure de la source de l'Elekta Infinity.Master [120] : ingénieur civil biomédical, Université catholique de Louvain, 201

Catalytic functionalizations of kraft lignin

Les bioraffineries lignocellulosiques sont en plein essor car elles offrent des alternatives innovantes et économiquement viables aux produits issus des industries pétrolières. La lignine, un des trois constituants majoritaires de la structure cellulaire végétale, pose des problématiques de valorisation en raison de sa structure complexe et diversifiée. Ce biopolymère, constitué de polyphénols, représente pourtant la plus grande ressource naturelle et renouvelable de molécules aromatiques. De nombreuses recherches visent à fonctionnaliser cette lignine pour en améliorer ses propriétés. La très grande majorité des modifications de la lignine présente l’inconvénient de générer des sels et sous-produits en quantités stœchiométriques. Des méthodes de fonctionnalisation plus propres sont donc recherchées. Ce manuscrit de thèse présente de nouvelles méthodes de greffage catalytiques s’appuyant sur l’utilisation de butadiène, monoxyde de carbone et alcool allylique comme réactifs d’alkylation/acylation propres. Ces fonctionnalisations influent significativement sur les propriétés physico-chimiques de la lignine. De plus l’insertion d’insaturations au sein de la lignine ouvre de nouvelles voies de fonctionnalisation et de réticulation pour la synthèse de nouveaux matériaux biosourcés.Lignocellulosic biorefineries are rapidely developing as they offer alternatives to petroleum industries’s products. Lignin, one of the three main constituent of plant cell, is hardly valorized due to its complex and diversified structure. This biopolymer, made of polyphenols, is the largest natural and renewable resource of aromatic molecules. Many researches aim at functionalizing lignin in order to improve its properties. Most of lignin modifications have the disadvantage of generating salts and by-products in stoichiometric amounts. Cleaner functionalization methods are consequently needed. This thesis manuscript presents new catalytic grafting methods based on the use of butadiene, carbon monoxide and allylic alcohol as clean, efficient and economic alkylation/acylation reagents. These functionalizations have a significant impact on the physicochemical properties of lignin. In addition, the presence of new unsaturations in the material opens the way to further functionalization and crosslinking pathways