Évolution récente de la maintenance du matériel roulant à la SNCF (1972-2002)

Cette contribution traite de l’organisation et de la politique générale qui ont structuré la maintenance du matériel roulant à la SNCF entre 1972 et 2002. Après la reconversion technologique exigée après la Seconde Guerre mondiale par la traction thermique et électrique, le domaine fit face à la fois à la réduction de ses moyens et à l’accroissement considérable de la demande, sous-tendue par un trafic en forte augmentation. L’article distingue ainsi cinq grandes phases dans la conception du métier au cours de la période étudiée. D’abord, à partir de 1972 s’établit la « logique industrielle », héritière directe du passé. 1985 initia ensuite l’adoption d’un mode de pensée extérieur, la « démarche qualité ». Puis l’introduction en 1990 d’une décentralisation accrue déstructura partiellement le domaine au nom de l’efficacité. Ce premier stade difficile fut suivi, à partir de 1996, par une politique de « volume » accompagnant la croissance du trafic. Enfin, l’année 2002 introduisit la « logique du service au client » visant à assurer une disponibilité maximum du matériel (jusqu’à penser le « produit train » livré à l’exploitation), quitte à faire évoluer les pratiques et l’organisation historiques du travail des agents du domaine Matériel.This contribution deals with the organization and general policy which have structured maintenance of rolling stock in the SNCF between 1972 and 2002. After the technological conversion required after World War II by thermal and electrical traction, a new challenge emerged in the area, who faced both the reduction of its ressources and the considerable increase in demand (underpinned by a sharp increase in traffic). One must therefore distinguish five major phases in the design of the activity during the period. From 1972 first, is implemented the "industrial logic", direct heir of the past. Then it is 1985 and the adoption of a way of thinking coming from outside, the "quality approach". In 1990, the introduction of increased decentralisation partially undermined the domain in the name of efficiency. This difficult phase was followed, from 1996, by a policy of "volume" accompanying the growth of traffic. Finally, the year 2002 introduced the "logic of customer service" to ensure maximum availability of the equipment (up to think the "product train", delivered to the Operation), even to the price of an evolution of historical practices and organization of work of the « Matériel » agents

Safe selection of genetically manipulated human primary keratinocytes with very high growth potential using CD24

Stable and safe corrective gene transfer in stem keratinocytes is necessary for ensuring success in cutaneous gene therapy. There have been numerous encouraging preclinical approaches to cutaneous gene therapy in the past decade, but it is only recently that a human volunteer suffering from junctional epidermolysis bullosa could be successfully grafted using his own non-selected, genetically corrected epidermal keratinocytes. However, ex vivo correction of cancer-prone genetic disorders necessitates a totally pure population of stably transduced stem keratinocytes for grafting. Antibiotic selection is not compatible with the need for full respect for natural cell fate potential and avoidance of immunogenic response in vivo. In order to surmount these problems, we developed a strategy for selecting genetically modified stem cell keratinocytes. Driving ectopic expression of CD24 (a marker of post-mitotic keratinocytes) at the surface of clonogenic keratinocytes permitted their full selection. Engineered keratinocytes expressing CD24 and the green fluorescent protein (GFP) tracer gene were shown to retain their original growth and differentiation potentials both in vitro and in vivo over 300 generations. Also, they did not exhibit signs of genetic instability. Using ectopic expression of CD24 as a selective marker of genetically modified human epidermal stem cells appears to be the first realistic approach to safe cutaneous gene therapy in cancer-prone disease conditions.We are indebted to Françoise Bernerd (L'Oréal Advanced Research, Clichy, France) and Mathilde Frechet (Centre National de la Recherche Scientifique (CNRS), FRE2939, Villejuif, France) for their expert help with organotypic skin cultures. We thank Yann Lecluse (Institut Gustave Roussy, Villejuif, France) for his expert help with flow cytometry. Françoise Viala (CNRS, Toulouse, France) is gratefully acknowledged for excellent artwork contribution. We thank Claire Marionnet (L'Oréal Advanced Research, Clichy, France) for kindly helping us with statistical analysis and Mandy Schwint for kindly editing the manuscript. Gim Meneguzzi (Institut National de la Santé et de la Recherche Médicale, U634, Nice, France) is acknowledged for the generous gift of the GB3 anti-laminin 5 antibody. James R. Rheinwald and Howard Green (Harvard, Women';s Hospital, Boston, MA) are gratefully acknowledged for the generous gift of 3T3-J2 cells. We thank the Production and Control department of Genethon which is supported by the Association Française contre les Myopathie, within the Gene Vector Production Network (http://www.gvpn.org). This work was supported by funds from CNRS and Centro de Investigación Biomedica en Red de Enfermedades Raras, Spain, and grants SAF-2004-07717 to M.D.R. and FIS OI051577 to F.L. T.M. gratefully acknowledges funding from the Association pour la Recherche sur le Cancer (No. 3590), the Fondation de l'Avenir, the Société Française de Dermatologie, and the Association Française contre les Myopathies

Integration of Myeloblastosis Associated Virus proviral sequences occurs in the vicinity of genes encoding signaling proteins and regulators of cell proliferation

AIMS: Myeloblastosis Associated Virus type 1 (N) [MAV 1(N)] induces specifically nephroblastomas in 8–10 weeks when injected to newborn chicken. The MAV-induced nephroblastomas constitute a unique animal model of the pediatric Wilms' tumor. We have made use of three independent nephroblastomas that represent increasing tumor grades, to identify the host DNA regions in which MAV proviral sequences were integrated. METHODS Cellular sequences localized next to MAV-integration sites in the tumor DNAs were used to screen a Bacterial Artificial Chromosomes (BACs) library and isolate BACs containing about 150 kilobases of normal DNA corresponding to MAV integration regions (MIRs). These BACs were mapped on the chicken chromosomes by Fluorescent In Situ Hybridization (FISH) and used for molecular studies. RESULTS: The different MAV integration sites that were conserved after tumor cell selection identify genes involved in the control of cell signaling and proliferation. Syntenic fragments in human DNA contain genes whose products have been involved in normal and pathological kidney development, and several oncogenes responsible for tumorigenesis in human. CONCLUSION: The identification of putative target genes for MAV provides important clues for the understanding of the MAV pathogenic potential. These studies identified ADAMTS1 as a gene upregulated in MAV-induced nephroblastoma and established that ccn3/nov is not a preferential site of integration for MAV as previously thought. The present results support our hypothesis that the highly efficient and specific MAV-induced tumorigenesis results from the alteration of multiple target genes in differentiating blastemal cells, some of which are required for the progression to highly aggressive stages. This study reinforces our previous conclusions that the MAV-induced nephroblastoma constitutes an excellent model in which to characterize new potential oncogenes and tumor suppressors involved in the establishment and maintenance of tumors

How reliable are left ventricular ejection fraction cut offs assessed by echocardiography for clinical decision making in patients with heart failure?

We aimed to study the potential influence of the variability in the assessment of echocardiographically measured left ventricular ejection fraction (LVEF) on indications for the implantation of internal cardioverter defibrillator and/or cardiac resynchronization devices in heart failure patients. TIME-CHF was a multicenter trial comparing NT-BNP versus symptom-guided therapy in patients aged ≥60years. Patients had their LVEF assessed at the recruiting centre using visual assessment, the area-length or biplane Simpson's method. Echocardiographic data were transferred to the study core-lab for re-assessment. Re-assessment in the core-lab was done with biplane Simpson's method, and included an appraisal of image quality. 413 patients had the LVEF analyzed at the recruiting centre and at the core lab. Image quality was optimal in 191 and suboptimal in 222. Overall, the correlation between LVEF at the recruiting centres and at the core-lab was good, independent of image quality (R²=0.62). However, when a LVEF≤30% or ≥30% was used as a cut-off, about 20% of all patients would have been re-assigned to having either a LVEF above or below the cut-off, this proportion was not significantly influenced by image quality. We conclude that correlation between LVEF assessed by different centres based on the same ultrasound data is good, regardless of image quality. However, one fifth of patients would have been re-assigned to a different category when using the clinically important cut-off of 30

High frequency trans-splicing in a cell line producing spliced and polyadenylated RNA polymerase I transcripts from an rDNA-myc chimeric gene

The 2G1MycP2Tu1 cell line was obtained following transfection of human colon carcinoma cells from the SW613-S cell line with a plasmid carrying a genomic copy of the human MYC gene. 2G1MycP2Tu1 cells produce MYC mRNAs and proteins of abnormal size. In order to analyze the structure of these abnormal products, a cDNA library constructed using RNA isolated from these cells was screened with a MYC probe. Fifty clones were studied by DNA sequencing. The results indicated that a truncated copy of the MYC gene had integrated into an rDNA transcription unit in 2G1MycP2Tu1 cells. This was confirmed by northern blot analysis, PCR amplification on genomic DNA and fluorescent in situ hybridization (FISH) experiments on metaphase chromosomes. 2G1MycP2Tu1 cells produce hybrid rRNA-MYC RNA molecules that are polyadenylated and processed by splicing reactions involving natural and cryptic splice sites. These transcripts are synthesized by RNA polymerase I, as confirmed by actinomycin D sensitivity experiments, suggesting that 3′ end processing and splicing are uncoupled from transcription in this case. 2G1MycP2Tu1 cells also produce another type of chimeric mRNAs consisting of correctly spliced exons 2 and 3 of the MYC gene fused to one or more extraneous 5′ exons by proper splicing to the acceptor sites of MYC exon 2. These foreign exons belong to 33 different genes, which are located on 14 different chromosomes. These observations and the results of FISH and Southern blotting experiments lead us to conclude that trans-splicing events occur at high frequency in 2G1MycP2Tu1 cells

High Resolution Genome-Wide Analysis of Chromosomal Alterations in Burkitt's Lymphoma

Additional chromosomal abnormalities are currently detected in Burkitt's lymphoma. They play major roles in the progression of BL and in prognosis. The genes involved remain elusive. A whole-genome oligonucleotide array CGH analysis correlated with karyotype and FISH was performed in a set of 27 Burkitt's lymphoma-derived cell lines and primary tumors. More than half of the 145 CNAs<2 Mb were mapped to Mendelian CNVs, including GSTT1, glutathione s-transferase and BIRC6, an anti-apoptotic protein, possibly predisposing to some cancers. Somatic cell line-specific CNVs localized to the IG locus were consistently observed with the 244 K aCGH platform. Among 136 CNAs >2 Mb, gains were found in 1q (12/27), 13q (7/27), 7q (6/27), 8q(4/27), 2p (3/27), 11q (2/27) and 15q (2/27). Losses were found in 3p (5/27), 4p (4/27), 4q (4/27), 9p (4/27), 13q (4/27), 6p (3/27), 17p (3/27), 6q (2/27),11pterp13 (2/27) and 14q12q21.3 (2/27). Twenty one minimal critical regions (MCR), (range 0.04–71.36 Mb), were delineated in tumors and cell lines. Three MCRs were localized to 1q. The proximal one was mapped to 1q21.1q25.2 with a 6.3 Mb amplicon (1q21.1q21.3) harboring BCA2 and PIAS3. In the other 2 MCRs, 1q32.1 and 1q44, MDM4 and AKT3 appeared as possible drivers of these gains respectively. The 13q31.3q32.1 <89.58–96.81> MCR contained an amplicon and ABCC4 might be the driver of this amplicon. The 40 Kb 2p16.1 <60.96–61> MCR was the smallest gained MCR and specifically encompassed the REL oncogene which is already implicated in B cell lymphomas. The most frequently deleted MCR was 3p14.1 <60.43–60.53> that removed the fifth exon of FHIT. Further investigations which combined gene expression and functional studies are essential to understand the lymphomagenesis mechanism and for the development of more effective, targeted therapeutic strategies

Les règlements généraux de 1743 et les statuts de 1755

Bernheim Alain. Les règlements généraux de 1743 et les statuts de 1755 . In: Annales historiques de la Révolution française, n°197, 1969. La Franc-Maçonnerie et la Révolution française. pp. 379-392