New energy carriers in vehicles and their impact on confined infrastructures Overview of previous research and research needs

International audienceThe global warming debate forces the vehicle industry to come up with new environmentally friendly solutions. In 10 years time, or even faster depending on the pressure from different governments in particular in Europe, vehicles will not only use gasoline, diesel and LPG, but also CNG, Hydrogen, ethanol, DME and other bio-fuels, as well as batteries and fuel cells. This quick development and the diversity of new energy carriers can jeopardize the safety in underground infrastructures such as tunnels or car parks. This can cause a major drawback in the adoption of new energy carriers as regulators or operators may prohibit use of these vehicles in underground systems if no new relevant measures will be taken. Unclear situation will also affect the implementation of international policies aiming at reducing the environmental footprint and especially CO2 emission in road traffic. The problem became clear after a workshop with the vehicle industry, tunnel operators, authorities, and safety experts organised in November 2008 by L-surF Services with the support of ITA-COSUF, ECTP and HYSAFE. This workshop demonstrated that the construction sector lacks appropriate design data and tools as well as knowledge to build safe underground infrastructure compatible with a diversity of new and alternative energy carriers. Vehicle industry, infrastructure operators and regulators have not yet addressed this problem. In a first part, an overview of the regulatory situation regarding safety and security of the admission of new energy carriers for vehicles in underground infrastructures is presented. Then, a detailed review of previous relevant research projects performed makes it possible to formulate recommendations in terms of a strategic research & development agenda. The overview shows that it is necessary to develop an integrated risk assessment and management method specific for underground transport systems, metros and hubs in confined spaces taking into account the "emerging risk" aspects

The SWR1 Histone Replacement Complex Causes Genetic Instability and Genome-Wide Transcription Misregulation in the Absence of H2A.Z

The SWR1 complex replaces the canonical histone H2A with the variant H2A.Z (Htz1 in yeast) at specific chromatin regions. This dynamic alteration in nucleosome structure provides a molecular mechanism to regulate transcription, gene silencing, chromosome segregation and DNA repair. Here we show that genetic instability, sensitivity to drugs impairing different cellular processes and genome-wide transcriptional misregulation in htz1Δ can be partially or totally suppressed if SWR1 is not formed (swr1Δ), if it forms but cannot bind to chromatin (swc2Δ) or if it binds to chromatin but lacks histone replacement activity (swc5Δ and the ATPase-dead swr1-K727G). These results suggest that in htz1Δ the nucleosome remodelling activity of SWR1 affects chromatin integrity because of an attempt to replace H2A with Htz1 in the absence of the latter. This would impair transcription and, either directly or indirectly, other cellular processes. Specifically, we show that in htz1Δ, the SWR1 complex causes an accumulation of recombinogenic DNA damage by a mechanism dependent on phosphorylation of H2A at Ser129, a modification that occurs in response to DNA damage, suggesting that the SWR1 complex impairs the repair of spontaneous DNA damage in htz1Δ. In addition, SWR1 causes DSBs sensitivity in htz1Δ; consistently, in the absence of Htz1 the SWR1 complex bound near an endonuclease HO-induced DSB at the mating-type (MAT) locus impairs DSB-induced checkpoint activation. Our results support a stepwise mechanism for the replacement of H2A with Htz1 and demonstrate that a tight control of this mechanism is essential to regulate chromatin dynamics but also to prevent the deleterious consequences of an incomplete nucleosome remodelling

Histone H3K56 Acetylation, CAF1, and Rtt106 Coordinate Nucleosome Assembly and Stability of Advancing Replication Forks

Chromatin assembly mutants accumulate recombinogenic DNA damage and are sensitive to genotoxic agents. Here we have analyzed why impairment of the H3K56 acetylation-dependent CAF1 and Rtt106 chromatin assembly pathways, which have redundant roles in H3/H4 deposition during DNA replication, leads to genetic instability. We show that the absence of H3K56 acetylation or the simultaneous knock out of CAF1 and Rtt106 increases homologous recombination by affecting the integrity of advancing replication forks, while they have a minor effect on stalled replication fork stability in response to the replication inhibitor hydroxyurea. This defect in replication fork integrity is not due to defective checkpoints. In contrast, H3K56 acetylation protects against replicative DNA damaging agents by DNA repair/tolerance mechanisms that do not require CAF1/Rtt106 and are likely subsequent to the process of replication-coupled nucleosome deposition. We propose that the tight connection between DNA synthesis and histone deposition during DNA replication mediated by H3K56ac/CAF1/Rtt106 provides a mechanism for the stabilization of advancing replication forks and the maintenance of genome integrity, while H3K56 acetylation has an additional, CAF1/Rtt106-independent function in the response to replicative DNA damage

Large scale experiments for safety and security in tunnels and underground constructions : L-surf project

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