Une chaîne d'applications intégrées

Dans leurs phases d'étude, d'installation, de maintenance et de suivi technico-financier des contrats d'appui, les activités du groupe électricité sont largement basées sur l'utilisation d'applications informatiques. Couplées à des bases de données, ces applications CERN étroitement interconnectées, sont développées autour de noyaux informatiques industriels. Toutes les phases d'un projet, tel que le LHC, bénéficient de ces bases de données enrichies par le personnel du CERN et par ses partenaires industriels. Ce document présente le maquettage virtuel des ouvrages du génie-civil et des équipements du CERN. Il traite également de la gestion de ces équipements, de leur câblage, de leur maintenance et du suivi des contrats de sous-traitance

Cisplatin resistant spheroids model clinically relevant survival mechanisms in ovarian tumors

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS 11 (2016): e0151089, doi: 10.1371/journal.pone.0151089 .The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05) (S2 Table). Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.This work was funded by the NIH NCRR supplement grant P41 RR001395-27S1 (J.W.H.), NSF DBI-1005378 “REU Site: Biological Discovery in Woods Hole”, faculty startup funds from the Office of Research at Oklahoma State University (W.C.), and the Mary Kay Foundation (A.S.B.)

Reduced incidence of atrial fibrillation after cardiac surgery by continuous wireless monitoring of oxygen saturation on the normal ward and resultant oxygen therapy for hypoxia

Objective: Monitoring of cardiac surgical patients after transfer from the intensive care unit to the normal ward is incomplete. Undetected hypoxia, however, is known to be a risk factor for occurrence of atrial fibrillation. We have utilized Auricall® for continuous wireless monitoring of oxygen saturation and heart rate until discharge. The object of the study was to analyze if oxygen therapy as a result of Auricall® alerts of hypoxia can decrease the incidence of postoperative atrial fibrillation. Methods: Auricall® is a wireless portable pulse oximeter. An alert is generated depending on preset threshold values (heart rate, oxygen saturation). Over a period of 6 months, 119 patients were monitored with the Auricall® following coronary artery bypass graft and/or valve surgery. Oxygen therapy was started subsequent to an oxygen saturation below 90%. These patients were compared with a cohort of 238 patients from the time period before availability of Auricall®. The patient characteristics were comparable in both groups. In a retrospective study, the incidence of atrial fibrillation was measured in both groups. Results: The postoperative AF was observed in 22/119 patients (18%) in group I and in 66/238 patients (28%) in group II. This difference between the two groups approached significance (p=0.056). In the subgroup of patients with coronary artery bypass graft with our without simultaneous valve surgery (n=312), Auricall® monitoring resulted in a significantly reduced incidence of atrial fibrillation (14% vs 26%, p=0.016). Conclusions: Continuous monitoring of oxygen saturation on the normal ward and subsequent oxygen therapy for hypoxia can reduce the incidence of atrial fibrillation in a subgroup of patients after cardiac surgery. Prospective randomized trials are warranted to confirm these dat

A Virtual CAD Model of the LHC

Integrating the large and complex LHC machine into the existing LEP tunnel is a major challenge. Space was not really a problem to fit the LEP machine into its tunnel, but LHC cryostats are much larger than the LEP quadrupoles and the external cryogenic line fills even more the tunnel. Space problems lead to small clearances. Possible conflicts, or at least the most penalising ones, between installed equipment or with transport, must be solved beforehand in order to avoid unacceptable delays and extra costs during the installation. Experience gained with LEP has already shown the help that Computer-Aided Engineering tools could provide for the integration. A virtual model of the LHC is presently prepared. The actual LEP tunnel, known with a quite good accuracy (centimetre level), has been modelled and all the elements of the machine constructed as 3D objects with the CAD system are positioned accurately on the basis of data generated from the theoretical definition. These layouts are used to generate the reference sections and to check the clearances. Examples of this powerful approach applied to engineering for accelerators are given

Human Wharton’s jelly mesenchymal stromal cell-derived small extracellular vesicles drive oligodendroglial maturation by restraining MAPK/ERK and Notch signaling pathways.

Peripartum cerebral hypoxia and ischemia, and intrauterine infection and inflammation, are detrimental for the precursor cells of the myelin-forming oligodendrocytes in the prematurely newborn, potentially leading to white matter injury (WMI) with long-term neurodevelopmental sequelae. Previous data show that hypomyelination observed in WMI is caused by arrested oligodendroglial maturation rather than oligodendrocyte-specific cell death. In a rat model of premature WMI, we have recently shown that small extracellular vesicles (sEV) derived from Wharton's jelly mesenchymal stromal cells (WJ-MSC) protect from myelination deficits. Thus, we hypothesized that sEV derived from WJ-MSC directly promote oligodendroglial maturation in oligodendrocyte precursor cells. To test this assumption, sEV were isolated from culture supernatants of human WJ-MSC by ultracentrifugation and co-cultured with the human immortalized oligodendrocyte precursor cell line MO3.13. As many regulatory functions in WMI have been ascribed to microRNA (miR) and as sEV are carriers of functional miR which can be delivered to target cells, we characterized and quantified the miR content of WJ-MSC-derived sEV by next-generation sequencing. We found that WJ-MSC-derived sEV co-localized with MO3.13 cells within 4 h. After 5 days of co-culture, the expression of myelin basic protein (MBP), a marker for mature oligodendrocytes, was significantly increased, while the oligodendrocyte precursor marker platelet-derived growth factor alpha (PDGFRα) was decreased. Notch and MAPK/ERK pathways known to inhibit oligodendrocyte maturation and differentiation were significantly reduced. The pathway enrichment analysis showed that the miR present in WJ-MSC-derived sEV target genes having key roles in the MAPK pathway. Our data strongly suggest that sEV from WJ-MSC directly drive the maturation of oligodendrocyte precursor cells by repressing Notch and MAPK/ERK signaling

Calibration and evaluation of a high-resolution surface mass-balance model for Paakitsoq, West Greenland

Modelling the hydrology of the Greenland ice sheet, including the filling and drainage of supraglacial lakes, requires melt inputs generated at high spatial and temporal resolution. Here we apply a high spatial (100 m) and temporal (1 hour) mass-balance model to a 450 km2 subset of the Paakitsoq region, West Greenland. The model is calibrated by adjusting the values for parameters of fresh snow density, threshold temperature for solid/liquid precipitation and elevation-dependent precipitation gradient to minimize the error between modelled output and surface height and albedo measurements from three Greenland Climate Network stations for the mass-balance years 2000/01 and 2004/05. Bestfit parameter values are consistent between the two years at 400 kg m–3, 2° C and +14% (100 m)–1, respectively. Model performance is evaluated, first, by comparing modelled snow and ice distribution with that derived from Landsat-7 ETM+ satellite imagery using normalized-difference snow index classification and supervised image thresholding; and second, by comparing modelled albedo with that retrieved from the MODIS sensor MOD10A1 product. Calculation of mass-balance components indicates that 6% of surface meltwater and rainwater refreezes in the snowpack and does not become runoff, such that refreezing accounts for 31% of the net accumulation

The Lausanne Infant Crying Stress Paradigm: Validation of an Early Postpartum Stress Paradigm with Women at Low vs. High Risk of Childbirth-Related Posttraumatic Stress Disorder.

Stress reactivity is typically investigated in laboratory settings, which is inadequate for mothers in maternity settings. This study aimed at validating the Lausanne Infant Crying Stress Paradigm (LICSP) as a new psychosocial stress paradigm eliciting psychophysiological stress reactivity in early postpartum mothers (n = 52) and to compare stress reactivity in women at low (n = 28) vs. high risk (n = 24) of childbirth-related posttraumatic stress disorder (CB-PTSD). Stress reactivity was assessed at pre-, peri-, and post-stress levels through salivary cortisol, heart rate variability (high-frequency (HF) power, low-frequency (LF) power, and LF/HF ratio), and perceived stress via a visual analog scale. Significant time effects were observed for all stress reactivity outcomes in the total sample (all p &lt; 0.01). When adjusting for perceived life threat for the infant during childbirth, high-risk mothers reported higher perceived stress (p &lt; 0.001, d = 0.91) and had lower salivary cortisol release (p = 0.023, d = 0.53), lower LF/HF ratio (p &lt; 0.001, d = 0.93), and marginally higher HF power (p = 0.07, d = 0.53) than low-risk women. In conclusion, the LICSP induces subjective stress and autonomic nervous system (ANS) reactivity in maternity settings. High-risk mothers showed higher perceived stress and altered ANS and hypothalamic-pituitary-adrenal reactivity when adjusting for infant life threat. Ultimately, the LICSP could stimulate (CB-)PTSD research

Childcare Correlates of Physical Activity, Sedentary Behavior, and Adiposity in Preschool Children: A Cross-Sectional Analysis of the SPLASHY Study.

The childcare (CC) environment can influence young children's physical activity (PA), sedentary behavior (SB), and adiposity. The aim of the study was to identify a broad range of CC correlates of PA, SB, and adiposity in a large sample of preschoolers. 476 preschool children (mean age 3.9 yrs; 47% girls) participated in the Swiss Preschoolers' Health Study (SPLASHY). PA and SB were measured by accelerometry. Outcome measures included total PA (TPA), moderate-to-vigorous PA (MVPA), SB, body mass index (BMI), and skinfold thickness (SF). PA measures consisted of both daily PA during CC attendance days and overall daily PA (CC and non-CC days). We identified the following CC correlates for higher TPA and/or higher MVPA or lower SB during CC attendance days: older age, sex (boys), more frequent child-initiated interactions during CC, mixing different ages within a group, and the presence of a written PA policy in the CC (all p ≤ 0.02). The CC correlates for overall TPA and/or MVPA or lower overall SB including both CC and non-CC days were the following: older age, sex (boys), more frequent child-initiated interactions during CC, mixing different ages within a group, less parental PA involvement in the CC, and having a larger surface area in CC (all p ≤ 0.046). Correlates for lower SF were sex (boys) and parental PA involvement in the CC (all p ≤ 0.02), and, for lower BMI, only increased age (p=0.001) was a correlate. More frequent child-initiated interactions and mixing different ages in CC, the presence of a written PA policy, and a larger CC surface are correlates of PA and SB during CC attendance days and/or of overall PA. Parental involvement in CC PA projects was a correlate for reduced body fat. These novel factors are mostly modifiable and can be tackled/addressed in future interventions

Correlates of preschool children's objectively measured physical activity and sedentary behavior: a cross-sectional analysis of the SPLASHY study.

Identifying ways to promote physical activity and decrease sedentary time during childhood is a key public health issue. Research on the putative influences on preschool children's physical activity (PA) and sedentary behavior (SB) is limited and has yielded inconsistent results. Our aim was to identify correlates of PA and SB in preschool children. Cross-sectional data were drawn from the Swiss Preschoolers' Health Study (SPLASHY), a Swiss population-based cohort study. Of 476 two to six year old children, 394 (54% boys) had valid PA data assessed by accelerometry. Information on exposure data was directly measured or extracted from parental questionnaires. Multilevel linear regression modeling was used to separately assess associations between 35 potential correlates and total PA (TPA), moderate-to-vigorous PA (MVPA) and SB. In total, 12 correlates from different domains were identified. TPA and MVPA were greater in boys than girls, increased with age and were positively associated with gross motor skills. Children from single parent families had a higher level of TPA and spent less time sedentary than those living with two parents. Time spent outdoors was positively associated with TPA and negatively with SB. The child's activity temperament was related all three outcomes, whereas parental sports club membership, living area per person and neighborhood safety were associated with SB only. Fixed and random factors in the final models accounted for 28%, 32% and 22% of the total variance in TPA, MVPA and SB, respectively. Variance decomposition revealed that age, sex and activity temperament were the most influential correlates of both, TPA and MVPA, whereas the child's activity temperament, time outdoors and neighborhood safety were identified as the most important correlates of SB. A multidimensional set of correlates of young children's activity behavior has been identified. Personal factors had the greatest influence on PA, whereas environmental-level factors had the greatest influence on SB. Moreover, we identified a number of previously unreported, potentially modifiable correlates of young children's PA and SB. These factors could serve to define target groups or become valuable targets for change in future interventions. Current Controlled Trials ISRCTN41045021 (date of registration: 21.03.14)