Étude de la production inclusive de J/ dans les collisions Pb-Pb à sNN=2,76 TeV avec le spectromètre à muons de l'expérience ALICE au LHC

La théorie de la chromodynamique quantique prédit l existence d un état déconfiné de la matière appelé Plasma de Quarks et de Gluons (PQG). Expérimentalement, la formation d un PQG est attendue sous les conditions extrêmes de température et de densité atteintes lors de collisions d ions lourds ultra-relativistes. Afin d observer et de caractériser de manière indirecte un tel état de la matière, de nombreuses observables ont été proposées. En particulier, les phénomènes de suppression et de(re)combinaison du meson J/ dans le PQG sont intensément étudiés. Cette thèse présente l analyse de la production inclusive de J/ dans les collisions Pb-Pb, à une énergie dans le centre de masse sNN = 2,76 TeV, détectés avec le spectromètre à muons de l expérience ALICE au LHC. A partir de la statistique élevée d événements collectés lors de la prise de données de 2011, le facteur de modification nucléaire du J/ a été mesuré en fonction de son impulsion transverse, de sa rapidité et de la centralité de la collision. L impulsion transverse moyenne du J/ a également été mesurée en fonction de la centralité. Les prédictions des modèles théoriques, incluant tous une contribution de (re)combinaison, présentent un bon accord avec les données. Enfin, un excès de J/ de très faible impulsion transverse (<300 MeV/c) par rapport à la production hadronique attendue a été observé pour la première fois.The quantum chromodynamics theory predicts the existence of a deconfined state of matter called Quark Gluon Plasma (QGP). Experimentally, the formation of a QGP is expected under the extreme conditions of temperature and density reached in ultra-relativisticheavy-ion collisions. Many observables were proposed to observe and characterize indirectly such a state of matter. In particular, the phenomena of suppression and (re)combination of the J/ meson in the QGP are extensively studied. This thesis presents the analysis of the inclusive production of J/ in Pb-Pb collisions, at a center of mass energy sNN = 2.76 TeV, detected with the ALICE muon spectrometer at the LHC. From the high statistics of events collected during 2011 datataking, the J/ nuclear modification factor was measured as a function of transverse momentum, rapidity and collision centrality. The J/ mean transverse momentum was also measured as a function of centrality. The predictions of theoretical models, all including a (re)combination contribution, are in good agreement with data. Finally, an excess of J/ yield at very low transverse momentum (<300 MeV/c) with respect to the expected hadronic production was observed fort he first time.NANTES-ENS Mines (441092314) / SudocSudocFranceF

The Muon Spectrometer of the ALICE experiment

The main goal of the Muon Spectrometer of the ALICE experiment is the measurement of heavy quarks in pp, pA and AA collisions at LHC energies, via the muonic channel. Physics motivations, the apparatus and its physics performances are presented in this talk.Comment: 5 pages, 4 figures. Talk presented in Phase transitions in strongly interacting matter Prague, 23.8.-29.8. 2004 18th Nuclear Physics Division Conference of the EPS (NPDC18) Europhysics Conferenc

Construct validation of the Narcissistic Admiration and Rivalry Questionnaire in Spanish‐speaking countries: Assessment of the reliability, structural and external validity and cross‐cultural equivalence

A recent re-operationalisation of grandiose narcissism has resulted in the distinction of two narcissistic strategies based on the cognitive, affective-motivational, and behavioural dynamics: admiration (assertive self-enhancement) and rivalry (antagonistic self-protection). The Narcissistic Admiration and Rivalry Questionnaire (NARQ) was developed to assess this model with two higher-order dimensions. However, cross-validations of the NARQ have not been extensively conducted across diverse population groups and languages. This study aimed to test the internal and external validity (through the relation with envy and self-esteem), reliability, and cross-cultural equivalence of the Spanish version of the NARQ. The psychometric properties were evaluated in a Spanish sample (N = 310), and cross-cultural equivalence was tested in participants from Chile (N = 234) and Colombia (N = 256). The results supported the reliability and validity of the Spanish NARQ, as well as the cross-cultural equivalence across Spanish-speaking countries. In addition, we discuss obtained differences across Spanish, Chilean, and Colombian sample within two narcissistic strategies.The work of Maria M. Kwiatkowska is supportedby the research program for young scientists and PhDstudents funded by the Cardinal Stefan Wyszy´nskiUniversity in Warsaw, Poland (project number:UmoBMF-14/18). The work of R. Rogoza was sup-ported by National Science Centre, Poland (projectnumber 2015/19/N/HS6/00685)

Physics of the Muon Spectrometer of the ALICE Experiment

The main goal of the Muon spectrometer of the ALICE experiment at LHC is the measurement of heavy quark production in p+p, p+A and A+A collisions at LHC energies, via the muonic channel. Physics motivations and expected performances have been presented in this talk.Comment: 10 pages and 4 figures. Talk presented in the ICPAQGP Conference, February 8-12, 2005, Salt Lake City, Kolkata, India. Web page of the conference : http://www.veccal.ernet.in/~icpaqgp

Risk factors for recurrence after robot-assisted radical hysterectomy for early-stage cervical cancer: a multicenter retrospective study

This retrospective analysis aimed to assess the risk factors for recurrence in patients diagnosed with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) undergoing robot-assisted radical hysterectomy in Spain and Portugal between 2009 and 2018. A second primary objective was to audit the oncological outcomes according to quality indicators (QI) proposed by the European Society of Gynecology Oncology (ESGO). The study population included 239 women. After a median follow-up of 51 months, recurrence occurred in 26 patients (10.9%). Independent factors for recurrence were clinical tumor size > 20 mm (hazard ratio (HR) 2.37), adenocarcinoma as histological type (HR 2.51), positive pelvic lymph nodes (HR 4.83), tumor grade 2 (HR 4.99), tumor grade 3 (HR 8.06), and having not performed sentinel lymph node biopsy (SLNB) (HR 4.08). All 5 QI selected were surpassed by our results. In patients with early-stage cervical cancer undergoing robotic radical hysterectomy, clinicians should be aware that tumor grade 2 and 3, tumor size > 20 mm, adenocarcinoma, positive pelvic nodes, and lack of performance of SLNB are risk factors for recurrence. Fulfillment of QI targets of the ESGO might be considered as an objective oncological outcome indicator supporting the minimally invasive approach for early-stage cervical cancer treatment. KEYWORDS: early-stage cervical cancer; oncological outcome; radical hysterectomy; recurrence; robotic surgery

UGT1A and TYMS genetic variants predict toxicity and response of colorectal cancer patients treated with first-line irinotecan and fluorouracil combination therapy

BACKGROUND: The impact of thymidylate synthase (TYMS) and UDP-glucoronosyltransferase 1A (UGT1A) germline polymorphisms on the outcome of colorectal cancer (CRC) patients treated with irinotecan plus 5-fluorouracil (irinotecan/5FU) is still controversial. Our objective was to define a genetic-based algorithm to select patients to be treated with irinotecan/5FU. METHODS: Genotyping of TYMS (5'TRP and 3'UTR), UGT1A1*28, UGT1A9*22 and UGT1A7*3 was performed in 149 metastatic CRC patients treated with irinotecan/5FU as first-line chemotherapy enrolled in a randomised phase 3 study. Their association with response, toxicity and survival was investigated by univariate and multivariate statistical analysis. RESULTS: TYMS 3TRP/3TRP genotype was the only independent predictor of tumour response (OR=5.87, 95% confidence interval (CI)=1.68-20.45; P=0.005). UGT1A1*28/*28 was predictive for haematologic toxicity (OR=6.27, 95% CI=1.09-36.12; P=0.04), specifically for neutropenia alone (OR=6.40, 95% CI=1.11-37.03; P=0.038) or together with diarrhoea (OR=18.87, 95% CI=2.14-166.67; P=0.008). UGT1A9*1/*1 was associated with non-haematologic toxicity (OR=2.70, 95% CI=1.07-6.82; P=0.035). Haplotype VII (all non-favourable alleles) was associated with non-haematologic toxicity (OR=2.11, 95% CI-1.12-3.98; P-0.02). CONCLUSION: TYMS and UGT1A polymorphisms influence on tumour response and toxicities derived from irinotecan/5FU treatment in CRC patients. A genetic-based algorithm to optimise treatment individualisation is proposed. British Journal of Cancer (2010) 103, 581-589. doi:10.1038/sj.bjc.6605776 www.bjcancer.com Published online 13 July 2010 (C) 2010 Cancer Research U

Global hyperactivation of enhancers stabilizes human and mouse naïve pluripotency through inhibition of CDK8/19 Mediator kinases

Pluripotent stem cells (PSCs) transition between cell states in vitro and reflect developmental changes in the early embryo. PSCs can be stabilized in the naïve state by blocking extracellular differentiation stimuli, particularly FGF-MEK signaling. Here, we report that multiple features of the naïve state in human and mouse PSCs can be recapitulated without affecting FGF-MEK-signaling or global DNA methylation. Mechanistically, chemical inhibition of CDK8 and CDK19 kinases removes their ability to repress the Mediator complex at enhancers. Thus CDK8/19 inhibition increases Mediator-driven recruitment of RNA Pol II to promoters and enhancers. This efficiently stabilizes the naïve transcriptional program and confers resistance to enhancer perturbation by BRD4 inhibition. Moreover, naïve pluripotency during embryonic development coincides with a reduction in CDK8/19. We conclude that global hyperactivation of enhancers drives naïve pluripotency, and this can be achieved in vitro by inhibiting CDK8/19 kinase activity. These principles may apply to other contexts of cellular plasticity

Climate anxiety, wellbeing and pro-environmental action: correlates of negative emotional responses to climate change in 32 countries

This study explored the correlates of climate anxiety in a diverse range of national contexts. We analysed cross-sectional data gathered in 32 countries (N = 12,246). Our results show that climate anxiety is positively related to rate of exposure to information about climate change impacts, the amount of attention people pay to climate change information, and perceived descriptive norms about emotional responding to climate change. Climate anxiety was also positively linked to pro-environmental behaviours and negatively linked to mental wellbeing. Notably, climate anxiety had a significant inverse association with mental wellbeing in 31 out of 32 countries. In contrast, it had a significant association with pro-environmental behaviour in 24 countries, and with environmental activism in 12 countries. Our findings highlight contextual boundaries to engagement in environmental action as an antidote to climate anxiety, and the broad international significance of considering negative climate-related emotions as a plausible threat to wellbeing.publishedVersio

Molecular evidence of adenosine deaminase linking adenosine A2A receptor and CD26 proteins

Adenosine is an endogenous purine nucleoside that acts in all living systems as a homeostatic network regulator through many pathways, which are adenosine receptor (AR)-dependent and -independent. From a metabolic point of view, adenosine deaminase (ADA) is an essential protein in the regulation of the total intracellular and extracellular adenosine in a tissue. In addition to its cytosolic localization, ADA is also expressed as an ecto-enzyme on the surface of different cells. Dipeptidyl peptidase IV (CD26) and some ARs act as binding proteins for extracellular ADA in humans. Since CD26 and ARs interact with ADA at opposite sites, we have investigated if ADA can function as a cell-to-cell communication molecule by bridging the anchoring molecules CD26 and A2AR present on the surfaces of the interacting cells. By combining site-directed mutagenesis of ADA amino acids involved in binding to A2AR and a modification of the bioluminescence resonance energy transfer (BRET) technique that allows detection of interactions between two proteins expressed in different cell populations with low steric hindrance (NanoBRET), we show direct evidence of the specific formation of trimeric complexes CD26-ADA-A2AR involving two cells. By dynamic mass redistribution assays and ligand binding experiments, we also demonstrate that A2AR-NanoLuc fusion proteins are functional. The existence of this ternary complex is in good agreement with the hypothesis that ADA could bridge T-cells (expressing CD26) and dendritic cells (expressing A2AR). This is a new metabolic function for ecto-ADA that, being a single chain protein, it has been considered as an example of moonlighting protein, because it performs more than one functional role (as a catalyst, a costimulator, an allosteric modulator and a cell-to-cell connector) without partitioning these functions in different subunits