Le Mans – 10 rue des Faloriers

Dans le cadre d’un projet immobilier situé 10 rue des Falotiers, un sondage d’évaluation ainsi qu’une étude documentaire ont été financés par l’aménageur. Ce sondage était destiné à préciser la profondeur d’enfouissement des formations archéologiques et, le cas échéant, leur nature. Les nombreuses découvertes archéologiques faites dans la vallée d’Isaac et à ses abords immédiats, depuis le xixe s., pouvaient laisser présager la présence de vestiges antiques et médiévaux dans ce secteur. Rappe..

Autonomous vehicle fleets for public transport: scenarios and comparisons

Autonomous vehicles (AVs) are becoming a reality and may integrate with existing public transport systems to enable the new generation of autonomous public transport. It is vital to understand what are the alternatives for AV integration from different angles such as costs, emissions, and transport performance. With the aim to support AV integration in public transport, this paper takes a typical European city as a case study for analyzing the impacts of different AV integration alternatives. A transport planning model considering AVs is developed and implemented, with a methodology to estimate the costs of the transport network. Traffic simulations are conducted to derive key variables related to AVs. An optimization process is introduced for identifying the optimal network configuration based on a given AV integration strategy, followed by the design of different AV integration scenarios, simulation, and analyses. With the proposed method, a case study is done for the city of Uppsala with presentation of detailed cost results together with key traffic statistics such as mode share. The results show that integrating AVs into public transport does not necessarily improve the overall cost efficiency. Based on the results and considering the long transition period to fully autonomous vehicles, it is recommended that public transport should consider a gradual introduction of AVs with more detailed analysis on different combination and integration alternatives of bus services and AVs.Peer ReviewedPostprint (published version

The Metallo-β-Lactamase/β-CASP Domain of Artemis Constitutes the Catalytic Core for V(D)J Recombination

The V(D)J recombination/DNA repair factor Artemis belongs to the metallo-β-lactamase (β-Lact) superfamily of enzymes. Three regions can be defined within the Artemis protein sequence: (a) the β-Lact homology domain, to which is appended (b) the β-CASP region, specific of members of the β-Lact superfamily acting on nucleic acids, and (c) the COOH-terminal domain. Using in vitro mutagenesis, here we show that the association of the β-Lact and the β-CASP regions suffices for in vivo V(D)J recombination of chromosome-integrated substrates. Single amino acid mutants point to critical catalytic residues for V(D)J recombination activity. The results presented here define the β-Lact/β-CASP domain of Artemis as the minimal core catalytic domain needed for V(D)J recombination and suggest that Artemis uses one or two Zn(II) ions to exert its catalytic activity, like bacterial class B β-Lact enzymes hydrolyzing β-lactam compounds

New Salivary Biomarkers of Human Exposure to Malaria Vector Bites

International audienc

IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal

<p>Abstract</p> <p>Background</p> <p>Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific <it>Anopheles </it>gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to <it>Anopheles </it>bites. The aim of this study was to use this biomarker to evaluate the human exposure to <it>Anopheles </it>mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where <it>Anopheles </it>biting rates and malaria transmission are supposed to be low.</p> <p>Methods</p> <p>One cross-sectional study concerning 1,010 (505 households) children (n = 505) and adults (n = 505) living in 16 districts of downtown Dakar and its suburbs was performed from October to December 2008. The IgG responses to gSG6-P1 peptide have been assessed and compared to entomological data obtained in or near the same district.</p> <p>Results</p> <p>Considerable individual variations in anti-gSG6-P1 IgG levels were observed between and within districts. In spite of this individual heterogeneity, the median level of specific IgG and the percentage of immune responders differed significantly between districts. A positive and significant association was observed between the exposure levels to <it>Anopheles gambiae </it>bites, estimated by classical entomological methods, and the median IgG levels or the percentage of immune responders measuring the contact between human populations and <it>Anopheles </it>mosquitoes. Interestingly, immunological parameters seemed to better discriminate the exposure level to <it>Anopheles </it>bites between different exposure groups of districts.</p> <p>Conclusions</p> <p>Specific human IgG responses to gSG6-P1 peptide biomarker represent, at the population and individual levels, a credible new alternative tool to assess accurately the heterogeneity of exposure level to <it>Anopheles </it>bites and malaria risk in low urban transmission areas. The development of such biomarker tool would be particularly relevant for mapping and monitoring malaria risk and for measuring the efficiency of vector control strategies in these specific settings.</p

Human IgG response to a salivary peptide, gSG6-P1, as a new immuno-epidemiological tool for evaluating low-level exposure to Anopheles bites

<p>Abstract</p> <p>Background</p> <p>Human populations exposed to low malaria transmission present particular severe risks of malaria morbidity and mortality. In addition, in a context of low-level exposure to <it>Anopheles </it>vector, conventional entomological methods used for sampling <it>Anopheles </it>populations are insufficiently sensitive and probably under-estimate the real risk of malaria transmission. The evaluation of antibody (Ab) responses to arthropod salivary proteins constitutes a novel tool for estimating exposure level to insect bites. In the case of malaria, a recent study has shown that human IgG responses to the gSG6-P1 peptide represented a specific biomarker of exposure to <it>Anopheles gambiae </it>bites. The objective of this study was to investigate if this biomarker can be used to estimate low-level exposure of individuals to <it>Anopheles </it>vector.</p> <p>Methods</p> <p>The IgG Ab level to gSG6-P1 was evaluated at the peak and at the end of the <it>An. gambiae </it>exposure season in children living in Senegalese villages, where the <it>Anophele</it>s density was estimated to be very low by classical entomological trapping but where malaria transmission occurred during the studied season.</p> <p>Results</p> <p>Specific IgG responses to gSG6-P1 were observed in children exposed to very low-level of <it>Anopheles </it>bites. In addition, a significant increase in the specific IgG Ab level was observed during the <it>Anopheles </it>exposure season whereas classical entomological data have reported very few or no <it>Anopheles </it>during the studied period. Furthermore, this biomarker may also be applicable to evaluate the heterogeneity of individual exposure.</p> <p>Conclusion</p> <p>The results strengthen the hypothesis that the evaluation of IgG responses to gSG6-P1 during the season of exposure could reflect the real human contact with anthropophilic <it>Anopheles </it>and suggest that this biomarker of low exposure could be used at the individual level. This promising immuno-epidemiological marker could represent a useful tool to assess the risk to very low exposure to malaria vectors as observed in seasonal, urban, altitude or travellers contexts. In addition, this biomarker could be used for the surveillance survey after applying anti-vector strategy.</p

Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability

DNA damage response mechanisms encompass pathways of DNA repair, cell cycle checkpoint arrest and apoptosis. Together, these mechanisms function to maintain genomic stability in the face of exogenous and endogenous DNA damage. ATM is activated in response to double strand breaks and initiates cell cycle checkpoint arrest. Recent studies in human fibroblasts have shown that ATM also regulates a mechanism of end-processing that is required for a component of double strand break repair. Human fibroblasts rarely undergo apoptosis after ionising radiation and, therefore, apoptosis is not considered in our review. The dual function of ATM raises the question as to how the two processes, DNA repair and checkpoint arrest, interplay to maintain genomic stability. In this review, we consider the impact of ATM's repair and checkpoint functions to the maintenance of genomic stability following irradiation in G2. We discuss evidence that ATM's repair function plays little role in the maintenance of genomic stability following exposure to ionising radiation. ATM's checkpoint function has a bigger impact on genomic stability but strikingly the two damage response pathways co-operate in a more than additive manner. In contrast, ATM's repair function is important for survival post irradiation

Novel Peptide Marker Corresponding to Salivary Protein gSG6 Potentially Identifies Exposure to Anopheles Bites

BACKGROUND: In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites. METHODOLOGY/PRINCIPAL FINDINGS: Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1. CONCLUSIONS/SIGNIFICANCE: This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could also represent a direct criterion of efficacy in evaluation of vector control strategies

Chronique de jurisprudence constitutionnelle française 2014

Désormais traditionnelle dans cette revue, la chronique de jurisprudence constitutionnelle vise à faire un état des lieux annuel des décisions rendues par le Conseil constitutionnel. Sous un angle critique, les auteurs présentent les continuités et ruptures de jurisprudence, ainsi que la variabilité du contrôle exercé par le Conseil selon les droits en cause.Now traditional in this journal, the chronicle of constitutional jurisprudence aims to make an annual inventory of the Constitutional Council’s decisions. The authors present, from a critical point of view, the continuity and discontinuity of case law, and the variability of the control exercised by the Council according to the rights in question