Le projet MP5: Gestion de la maintenance assistée par ordinateur

L'année 2000 marque un tournant dans la manière d'appréhender l'activité de maintenance dans la division ST. Les méthodes, jusqu'alors basées sur une approche corporative relayée par des outils informatiques d'ancienne génération, ont évolué vers une approche intégrée. Ce document décrit tous les aspects du projet de migration de l'ancien logiciel RAPIER vers le nouveau logiciel MP5: définition des ressources, identification des contraintes et des facteurs de succès critiques, planification, unification des méthodes et des données, migration informatique, formation du personnel et mise en service. Il présente également les intégrations réalisées avec d'autres logiciels, les possibilités d'évolution pour la division et les perspectives de généralisation pour le CERN

TCR industrial system integration strategy

New turnkey data acquisition systems purchased from industry are being integrated into CERN's Technical Data Server. The short time available for system integration and the large amount of data per system require a standard and modular design. Four different integration layers have been defined in order to easily 'plug in' industrial systems. The first layer allows the integration of the equipment at the digital I/O port or fieldbus (Profibus-DP) level. A second layer permits the integration of PLCs (Siemens S5, S7 and Telemecanique); a third layer integrates equipment drivers. The fourth layer integrates turnkey mimic diagrams in the TCR operator console. The second and third layers use two new event-driven protocols based on TCP/IP. Using this structure, new systems are integrated in the data transmission chain, the layer at which they are integrated depending only on their integration capabilities

CERN LHC Technical Infrastructure Monitoring (TIM)

The CERN Large Hadron Collider (LHC) will start to deliver particles to its experiments in the year 2005. However, all the primary services such as electricity, cooling, ventilation, safety systems and others such as vacuum and cryogenics will be commissioned gradually between 2001 and 2005. This technical infrastructure will be controlled using industrial control systems, which have either already been purchased from specialized companies or are currently being put together for tender. This paper discusses the overall architecture and interfaces that will be used by the CERN Technical Control Room (TCR) to monitor the technical services at CERN and those of the LHC and its experiments. The issue of coherently integrating existing and future control systems over a period of five years with constantly evolving technology is addressed. The paper also summarizes the functionality of all the tools needed by the control room such as alarm reporting, data logging systems, man machine interfaces and the console manager. Particular attention is paid to networking aspects, so that reliable and timely transmission of data can be assured. A pyramidal layered component architecture is compared with a complete SCADA solution

O-GlcNAc transferase associates with the MCM2-7 complex and its silencing destabilizes MCM-MCM interactions

International audienceO-GlcNAcylation of proteins is governed by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). The homeostasis of O-GlcNAc cycling is regulated during cell cycle progression and is essential for proper cellular division. We previously reported the O-GlcNAcylation of the Mini-Chromosome Maintenance proteins MCM2, MCM3, MCM6 and MCM7. These proteins belong to the MCM2-7 complex which is crucial for the initiation of DNA replication through its DNA helicase activity. Here we show that the six subunits of MCM2-7 are O-GlcNAcylated and that O-GlcNAcylation of MCM proteins mainly occurs in the chromatin-bound fraction of synchronized human cells. Moreover, we identify stable interaction between OGT and several MCM subunits. We also show that down-regulation of OGT decreases the chromatin binding of MCM2, MCM6 and MCM7 without affecting their steady-state level. Finally, OGT silencing or OGA inhibition destabilize MCM2/6 and MCM4/7 interactions in the chromatin-enriched fraction. In conclusion, OGT is a new partner of the MCM2-7 complex and O-GlcNAcylation homeostasis might regulate MCM2-7 complex by regulating the chromatin loading of MCM6 and MCM7 and stabilizing MCM/MCM interactions

Cross-Dysregulation of O-GlcNAcylation and PI3K/AKT/mTOR Axis in Human Chronic Diseases

The hexosamine biosynthetic pathway (HBP) and the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathway are considered as nutrient sensors that regulate several essential biological processes. The hexosamine biosynthetic pathway produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the substrate for O-GlcNAc transferase (OGT), the enzyme that O-GlcNAcylates proteins on serine (Ser) and threonine (Thr) residues. O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) and phosphorylation are highly dynamic post-translational modifications occurring at the same or adjacent sites that regulate folding, stability, subcellular localization, partner interaction, or activity of target proteins. Here we review recent evidence of a cross-regulation of PI3K/AKT/mTOR signaling pathway and protein O-GlcNAcylation. Furthermore, we discuss their co-dysregulation in pathological conditions, e.g., cancer, type-2 diabetes (T2D), and cardiovascular, and neurodegenerative diseases

O-GlcNAcylation Is Involved in the Regulation of Stem Cell Markers Expression in Colon Cancer Cells

The dynamic O-linked-N-acetylglucosamine posttranslational modification of nucleocytoplasmic proteins has emerged as a key regulator of diverse cellular processes including several hallmarks of cancer. However, the role played by this modification in the establishment of CSC phenotype has been poorly studied so far and remains unclear. In this study we confirmed the previous reports showing that colon cancer cells exhibit higher O-GlcNAc basal levels than non-malignant cells, and investigated the role played by O-GlcNAcylation in the regulation of CSC phenotype. We found that the modification of O-GlcNAcylation levels by pharmacological inhibition of the O-GlcNAc-transferase enzyme that adds O-GlcNAc (OGT), but not of the enzyme that removes it (OGA), increased the expression of all stem cell markers tested in our colon malignant cell lines, and induced the appearance of a double positive (CD44+/CD133+) small stem cell-like subpopulation (which corresponded to 1–10%) that displayed very aggressive malignant phenotype such as increased clonogenicity and spheroid formation abilities in 3D culture. We reasoned that OGT inhibition would mimic in the tumor the presence of severe nutritional stress, and indeed, we demonstrated that nutritional stress reproduced in colon cancer cells the effects obtained with OGT inhibition. Thus, our data strongly suggests that stemness is regulated by HBP/O-GlcNAcylation nutrient sensing pathway, and that O-GlcNAc nutrient sensor represents an important survival mechanism in cancer cells under nutritional stressful conditions

Cyclin D1 Stability Is Partly Controlled by O-GlcNAcylation

Cyclin D1 is the regulatory partner of the cyclin-dependent kinases (CDKs) CDK4 or CDK6. Once associated and activated, the cyclin D1/CDK complexes drive the cell cycle entry and G1 phase progression in response to extracellular signals. To ensure their timely and accurate activation during cell cycle progression, cyclin D1 turnover is finely controlled by phosphorylation and ubiquitination. Here we show that the dynamic and reversible O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) regulates also cyclin D1 half-life. High O-GlcNAc levels increase the stability of cyclin D1, while reduction of O-GlcNAcylation strongly decreases it. Moreover, elevation of O-GlcNAc levels through O-GlcNAcase (OGA) inhibition significantly slows down the ubiquitination of cyclin D1. Finally, biochemical and cell imaging experiments in human cancer cells reveal that the O-GlcNAc transferase (OGT) binds to and glycosylates cyclin D1. We conclude that O-GlcNAcylation promotes the stability of cyclin D1 through modulating its ubiquitination

Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer.

The early detection of breast cancer is the best means to minimise disease-related mortality. Current screening techniques have limited sensitivity and specificity. Breast nipple aspirate fluid can be obtained noninvasively and contains proteins secreted from ductal and lobular epithelia. Nipple aspirate fluid proteins are breast specific and generally more concentrated than corresponding blood levels. Proteomic analysis of 1 microl of diluted nipple aspirate fluid over a 5-40 kDa range from 20 subjects with breast cancer and 13 with nondiseased breasts identified five differentially expressed proteins. The most sensitive and specific proteins were 6500 and 15 940 Da, found in 75-84% of samples from women with cancer but in only 0-9% of samples from normal women. These findings suggest that (1) differential expression of nipple aspirate fluid proteins exists between women with normal and diseased breasts, and (2) analysis of these proteins may predict the presence of breast cancer

Transcription profiles of non-immortalized breast cancer cell lines

BACKGROUND: Searches for differentially expressed genes in tumours have made extensive use of array technology. Most samples have been obtained from tumour biopsies or from established tumour-derived cell lines. Here we compare cultures of non-immortalized breast cancer cells, normal non-immortalized breast cells and immortalized normal and breast cancer cells to identify which elements of a defined set of well-known cancer-related genes are differentially expressed. METHODS: Cultures of cells from pleural effusions or ascitic fluids from breast cancer patients (MSSMs) were used in addition to commercially-available normal breast epithelial cells (HMECs), established breast cancer cell lines (T-est) and established normal breast cells (N-est). The Atlas Human Cancer 1.2 cDNA expression array was employed. The data obtained were analysed using widely-available statistical and clustering software and further validated through real-time PCR. RESULTS: According to Significance Analysis of Microarray (SAM) and AtlasImage software, 48 genes differed at least 2-fold in adjusted intensities between HMECs and MSSMs (p < 0.01). Some of these genes have already been directly linked with breast cancer, metastasis and malignant progression, whilst others encode receptors linked to signal transduction pathways or are otherwise related to cell proliferation. Fifty genes showed at least a 2.5-fold difference between MSSMs and T-est cells according to AtlasImage, 2-fold according to SAM. Most of these classified as genes related to metabolism and cell communication. CONCLUSION: The expression profiles of 1176 genes were determined in finite life-span cultures of metastatic breast cancer cells and of normal breast cells. Significant differences were detected between the finite life-span breast cancer cell cultures and the established breast cancer cell lines. These data suggest caution in extrapolating information from established lines for application to clinical cancer research