La légitimité des parties prenantes dans l'aménagement des villes : éthique de la conduite des projets urbains

Les projets urbains – appelés aussi projets d’aménagement urbain ou opérations d’aménagement – sont largement tributaires de la participation accrue d’une multitude de parties prenantes, dont les atouts pour le projet et les revendications vis-à-vis de celui-ci peuvent être complémentaires et/ou contradictoires. Dans ce contexte quel degré de priorité accorder à telle ou telle partie prenante ? Pour y parvenir, les porteurs d’un projet sont appelés à évaluer la légitimité de ces parties prenantes. Afin d’examiner ce concept, l’étude fait appel au croisement de textes issus de corpus théoriques autres que les corpus classiques de l’urbanisme et des études urbaines : ceux de la théorie des stakeholders dans le domaine du management organisationnel et de l’éthique des affaires ; du modèle des cités, ancré dans la sociologie pragmatique ; et des théories de la justice. Puis elle confronte les enseignements de ces théories à l’analyse empirique d’un cas pratique virtuel, créé pour les besoins de cette recherche. L’aller-retour entre la théorie et des mises en situation concrètes, mettant souvent en avant des tensions entre légitimités concurrentes, permet d’affiner les principes éthiques à la base de ces légitimités, selon une méthode inspirée de celle de l’équilibre réflexif. L’analyse montre que la légitimité d’une partie prenante résulte d’un raisonnement s’appuyant sur une norme d’efficacité ou sur une norme éthique, idéalement compatibles dans le cadre d’une éthique de responsabilité. Dans la première approche (l’efficacité) le porteur du projet sera principalement attentif aux capacités d’action des parties prenantes sur le projet, incluant la capacité de représentativité, les capacités légales (titres, droits, liens contractuels), les savoirs et savoir-faire (expertise, compétences), la créativité, les ressources matérielles et financières, et la capacité à engager. Dans la deuxième approche (éthique) le porteur de projet sera principalement attentif aux revendications légitimes des parties prenantes vis-à-vis du projet : les revendications de bien-être global, de capabilités (autonomie, libertés, possibilités offertes aux individus, avantages socio-économiques), de liens communautaires (valeurs et traditions), de bien-être d’autrui et les revendications environnementales. La recherche permet alors de faire émerger six principes éthiques pour l’évaluation de la légitimité : l’utilité globale, le respect de la liberté, l’équité, la solidarité (et la tolérance), le care et la responsabilité environnementale. Alors que les théories de l’urbanisme – dont l’un des objets principaux est pourtant l’analyse critique des processus de fabrication des villes – se sont peu intéressées aux principes normatifs à la base de ces processus, cette recherche propose un cadre conceptuel utile aux chercheurs et aux professionnels pour porter un jugement, notamment en termes éthiques, sur les décisions relatives à la prise en compte des parties prenantes dans les projets urbains. En faisant cela, elle contribue à jeter les bases d’une éthique de la conduite des projets urbains.Urban projects - also referred to as urban development projects - are largely dependent on the increased involvement of a multitude of stakeholders, whose assets for, and demands on, the project may be complementary and / or contradictory. In this context, how much priority should be given to different stakeholders? To answer this question, project leaders are called upon to assess the legitimacy of these stakeholders. To examine this concept, the study calls upon the crossing of texts from theoretical corpuses other than the classic corpus of urban planning and urban studies: those of stakeholder theory in the field of organizational management and business ethics; the model of the « cités », anchored in pragmatic sociology; and theories of justice. Then it confronts the lessons of these theories with the empirical analysis of a virtual practical case created for the purpose of this research. The round-trip between theory and concrete situations, often emphasizing tensions between competing legitimacies, makes it possible to refine the ethical principles underlying these legitimacies, through a method inspired by that of reflexive equilibrium. The analysis shows that the legitimacy of a stakeholder results from reasoning based on an efficiency standard or on an ethical standard, ideally compatible in the context of an ethics of responsibility. In the first approach (effectiveness) the proponent will be mainly attentive to the stakeholders' capacities for action on the project, including representativeness, legal capacities (titles, rights, contractual links), knowledge and know-how (expertise, skills), creativity, material and financial resources, and the ability to engage other stakeholders into the project. In the second (ethical) approach, the project proponent will be mainly attentive to the legitimate demands of stakeholders on the project: demands for global well-being, capability building (autonomy, freedoms, opportunities for individuals, socio-economic benefits), community ties (values ​​and traditions of large and small communities), well-being of others and environmental claims. The research then enables the emergence of six ethical principles for the assessment of legitimacies: global utility, respect for freedom, equity, solidarity (and tolerance), care and environmental responsibility. While the theories of planning and urban studies - one of the main objects of which is the critical analysis of the manufacturing processes of cities - have paid little attention to the normative principles underlying these processes, this research proposes a conceptual framework that is useful for researchers and professionals to make a judgment, especially in terms of ethics, on decisions concerning the consideration of stakeholders in urban projects. In doing so, it helps to lay the foundations for an ethic of the conduct of urban projects

Covalent grafting onto self-adhesive surfaces based on aryldiazonium salt seed layers

International audienceThe chemistry of aryldiazonium salts has been thoroughly used in recent years to graft in a very simple and robust way ultrathin polyphenylene-like films on a broad range of surfaces. We show here that the same chemistry can be used to obtain self-adhesive surfaces. This target was reached in a simple way by coating various surfaces with chemisorbed organic films containing active aryldiazonium salts. These self-adhesive surfaces are then put into contact with various species (molecules, polymers, nanoparticles, nanotubes, graphene flakes, etc.) that react either spontaneously or under activation with the immobilized aryldiazonium salts. Our self-adhesive surfaces were synthesized following a simple aqueous two-step protocol based on p-phenylenediamine diazotisation. The first diazotisation step results in the robust grafting of thin polyaminophenylene (PAP) layers onto the surface. The second diazotisation step changed the grafted PAP film into a poly-aryldiazonium polymer (PDP) film. The covalent grafting between those self-adhesive surfaces and the target species was achieved by direct contact or by immersion of the self-adhesive surfaces in solution. We present in this preliminary work the grafting of multi-wall carbon nanotubes (MWCNTs), flakes of highly oriented pyrolytic graphite (HOPG), various organic compounds and copper nanoparticles. We also tested these immobilized aryldiazonium salts as electropolymerization initiators for the grafting-to process

Dark matter as a heavy thermal hot relic

If, during the early Universe epoch, the dark matter particle thermalizes in a hidden sector which does not thermalize with the Standard Model thermal bath, its relativistic thermal decoupling can easily lead to the observed relic density, even if the dark matter particle mass is many orders of magnitude heavier than the usual $\sim$ eV hot relic mass scale. This straightforward scenario simply requires that the temperature of the hidden sector thermal bath is one to five orders of magnitude cooler than the temperature of the Standard Model thermal bath. In this way the resulting relic density turns out to be determined only by the dark matter mass scale and the ratio of the temperatures of both sectors. In a model independent way we determine that this can work for a dark matter mass all the way from $\sim 1$ keV to $\sim 30$ PeV. We also show how this scenario works explicitly in the framework of two illustrative models. One of them can lead to a PeV neutrino flux from dark matter decay of the order of the one needed to account for the high energy neutrinos observed by IceCube.Comment: 6 pages with 2 figures, published versio

Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection

Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells

The mutational impact of culturing human pluripotent and adult stem cells

Genetic changes acquired during in vitro culture pose a risk for the successful application of stem cells in regenerative medicine. To assess the genetic risks induced by culturing, we determined all mutations in individual human stem cells by whole genome sequencing. Individual pluripotent, intestinal, and liver stem cells accumulate 3.5 ± 0.5, 7.2 ± 1.1 and 8.3 ± 3.6 base substitutions per population doubling, respectively. The annual in vitro mutation accumulation rate of adult stem cells is nearly 40-fold higher than the in vivo mutation accumulation rate. Mutational signature analysis reveals that in vitro induced mutations are caused by oxidative stress. Reducing oxygen tension in culture lowers the mutational load. We use the mutation rates, spectra, and genomic distribution to model the accumulation of oncogenic mutations during typical in vitro expansion, manipulation or screening experiments using human stem cells. Our study provides empirically defined parameters to assess the mutational risk of stem cell based therapies

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors