Operational framework based on modeling languages to support product repository implementation.

Part 3: Tools and MethodologiesInternational audienceEmbracing Product Lifecycle Management approach involves integrating a product repository in the company information system. From customer's needs to disposal stage, several product representations exist. The product repository purpose is to secure consistency of one product representation with the others. This paper presents an operational modeling framework that supports product repository implementation. In order to ensure consistency, this framework identifies correspondences between entities of languages (“trade” languages and standard languages). The presented concepts are illustrated with correspondences between language entities of product designed and productplanned to be built Bills of Materials

Targeting the Replication Initiator of the Second Vibrio Chromosome: Towards Generation of Vibrionaceae-Specific Antimicrobial Agents

The Vibrionaceae is comprised of numerous aquatic species and includes several human pathogens, such as Vibrio cholerae, the cause of cholera. All organisms in this family have two chromosomes, and replication of the smaller one depends on rctB, a gene that is restricted to the Vibrionaceae. Given the increasing prevalence of multi-drug resistance in pathogenic vibrios, there is a need for new targets and drugs to combat these pathogens. Here, we carried out a high throughput cell-based screen to find small molecule inhibitors of RctB. We identified a compound that blocked growth of an E. coli strain bearing an rctB-dependent plasmid but did not influence growth of E. coli lacking this plasmid. This compound, designated vibrepin, had potent cidal activity against V. cholerae and inhibited the growth of all vibrio species tested. Vibrepin blocked RctB oriCII unwinding, apparently by promoting formation of large non-functional RctB complexes. Although vibrepin also appears to have targets other than RctB, our findings suggest that RctB is an attractive target for generation of novel antibiotics that only block growth of vibrios. Vibrio-specific agents, unlike antibiotics currently used in clinical practice, will not engender resistance in the normal human flora or in non-vibrio environmental microorganisms

SPI observations of the diffuse 60Fe emission in the Galaxy

Gamma-ray line emission from radioactive decay of 60Fe provides constraints on nucleosynthesis in massive stars and supernovae. The spectrometer SPI on board INTEGRAL has accumulated nearly three years of data on gamma-ray emission from the Galactic plane. We have analyzed these data with suitable instrumental-background models and sky distributions to produce high-resolution spectra of Galactic emission. We detect the gamma-ray lines from 60Fe decay at 1173 and 1333 keV, obtaining an improvement over our earlier measurement of both lines with now 4.9 sigma significance for the combination of the two lines. The average flux per line is (4.4 \pm 0.9) \times 10^{-5} ph cm^{-2} s^{-1} rad^{-1} for the inner Galaxy region. Deriving the Galactic 26Al gamma-ray line flux with using the same set of observations and analysis method, we determine the flux ratio of 60Fe/26Al gamma-rays as 0.148 \pm 0.06. The current theoretical predictions are still consistent with our result.Comment: 10 pages, 7 figures, 2 tables, A&A in pres

Fragmentation and mass segregation in the massive dense cores of Cygnus X

We present Plateau de Bure interferometer observations obtained in continuum at 1.3 and 3.5 mm towards the six most massive and young (IR-quiet) dense cores in Cygnus X. Located at only 1.7 kpc, the Cygnus X region offers the opportunity of reaching small enough scales (of the order of 1700 AU at 1.3 mm) to separate individual collapsing objects. The cores are sub-fragmented with a total of 23 fragments inside 5 cores. Only the most compact core, CygX-N63, could actually be a single massive protostar with an envelope mass as large as 60 Msun. The fragments in the other cores have sizes and separations similar to low-mass pre-stellar and proto-stellar condensations in nearby protoclusters, and are probably of the same nature. A total of 9 out of these 23 protostellar objects are found to be probable precursors of OB stars with envelope masses ranging from 6 to 23 Msun. The level of fragmentation is globally higher than in the turbulence regulated, monolithic collapse scenario, but is not as high as expected in a pure gravo-turbulent scenario where the distribution of mass is dominated by low-mass protostars/stars. Here, the fractions of the total core masses in the high-mass fragments are reaching values as high as 28, 44, and 100 % in CygX-N12, CygX-N53, and CygX-N63, respectively, much higher than what an IMF-like mass distribution would predict. The increase of the fragmentation efficiency as a function of density in the cores is proposed to be due to the increasing importance of self-gravity leading to gravitational collapse at the scale of the dense cores. At the same time, the cores tend to fragment into a few massive protostars within their central regions. We are therefore probably witnessing here the primordial mass segregation of clusters in formation.Comment: 14 pages, 16 figures, submitted for publication in A&

The Scientific Performance of the Microchannel X-ray Telescope on board the SVOM Mission

The Microchannel X-ray Telescope (MXT) will be the first focusing X-ray telescope based on a "Lobster-Eye" optical design to be flown on Sino-French mission SVOM. SVOM will be dedicated to the study of Gamma-Ray Bursts and more generally time-domain astrophysics. The MXT telescope is a compact (focal length ~ 1.15 m) and light (< 42 kg) instrument, sensitive in the 0.2--10 keV energy range. It is composed of an optical system, based on micro-pore optics (MPOs) of 40 micron pore size, coupled to a low-noise pnCDD X-ray detector. In this paper we describe the expected scientific performance of the MXT telescope, based on the End-to-End calibration campaign performed in fall 2021, before the integration of the SVOM payload on the satellite.Comment: 22 pages, 12 figures, accepted for publication in Experimental Astronom

FtsK-Dependent Dimer Resolution on Multiple Chromosomes in the Pathogen Vibrio cholerae

Unlike most bacteria, Vibrio cholerae harbors two distinct, nonhomologous circular chromosomes (chromosome I and II). Many features of chromosome II are plasmid-like, which raised questions concerning its chromosomal nature. Plasmid replication and segregation are generally not coordinated with the bacterial cell cycle, further calling into question the mechanisms ensuring the synchronous management of chromosome I and II. Maintenance of circular replicons requires the resolution of dimers created by homologous recombination events. In Escherichia coli, chromosome dimers are resolved by the addition of a crossover at a specific site, dif, by two tyrosine recombinases, XerC and XerD. The process is coordinated with cell division through the activity of a DNA translocase, FtsK. Many E. coli plasmids also use XerCD for dimer resolution. However, the process is FtsK-independent. The two chromosomes of the V. cholerae N16961 strain carry divergent dimer resolution sites, dif1 and dif2. Here, we show that V. cholerae FtsK controls the addition of a crossover at dif1 and dif2 by a common pair of Xer recombinases. In addition, we show that specific DNA motifs dictate its orientation of translocation, the distribution of these motifs on chromosome I and chromosome II supporting the idea that FtsK translocation serves to bring together the resolution sites carried by a dimer at the time of cell division. Taken together, these results suggest that the same FtsK-dependent mechanism coordinates dimer resolution with cell division for each of the two V. cholerae chromosomes. Chromosome II dimer resolution thus stands as a bona fide chromosomal process

Unexpected Role for Helicobacter pylori DNA Polymerase I As a Source of Genetic Variability

Helicobacter pylori, a human pathogen infecting about half of the world population, is characterised by its large intraspecies variability. Its genome plasticity has been invoked as the basis for its high adaptation capacity. Consistent with its small genome, H. pylori possesses only two bona fide DNA polymerases, Pol I and the replicative Pol III, lacking homologues of translesion synthesis DNA polymerases. Bacterial DNA polymerases I are implicated both in normal DNA replication and in DNA repair. We report that H. pylori DNA Pol I 5′- 3′ exonuclease domain is essential for viability, probably through its involvement in DNA replication. We show here that, despite the fact that it also plays crucial roles in DNA repair, Pol I contributes to genomic instability. Indeed, strains defective in the DNA polymerase activity of the protein, although sensitive to genotoxic agents, display reduced mutation frequencies. Conversely, overexpression of Pol I leads to a hypermutator phenotype. Although the purified protein displays an intrinsic fidelity during replication of undamaged DNA, it lacks a proofreading activity, allowing it to efficiently elongate mismatched primers and perform mutagenic translesion synthesis. In agreement with this finding, we show that the spontaneous mutator phenotype of a strain deficient in the removal of oxidised pyrimidines from the genome is in part dependent on the presence of an active DNA Pol I. This study provides evidence for an unexpected role of DNA polymerase I in generating genomic plasticity

DNA Adenine Methylation Is Required to Replicate Both Vibrio cholerae Chromosomes Once per Cell Cycle

DNA adenine methylation is widely used to control many DNA transactions, including replication. In Escherichia coli, methylation serves to silence newly synthesized (hemimethylated) sister origins. SeqA, a protein that binds to hemimethylated DNA, mediates the silencing, and this is necessary to restrict replication to once per cell cycle. The methylation, however, is not essential for replication initiation per se but appeared so when the origins (oriI and oriII) of the two Vibrio cholerae chromosomes were used to drive plasmid replication in E. coli. Here we show that, as in the case of E. coli, methylation is not essential for oriI when it drives chromosomal replication and is needed for once-per-cell-cycle replication in a SeqA-dependent fashion. We found that oriII also needs SeqA for once-per-cell-cycle replication and, additionally, full methylation for efficient initiator binding. The requirement for initiator binding might suffice to make methylation an essential function in V. cholerae. The structure of oriII suggests that it originated from a plasmid, but unlike plasmids, oriII makes use of methylation for once-per-cell-cycle replication, the norm for chromosomal but not plasmid replication