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International audience; In this work we investigate the properties of negatively charged nitrogen-vacancy (NV À) centres created during single crystal diamond growth by chemical vapour deposition (CVD) on [113]-oriented substrates and with N 2 O as a dopant gas. The use of spin echo and double electron-electron resonance (DEER) allows us to assess NV À ratio with respect to substitutional nitrogen impurities (N 0 s) incorporated during growth, a critical figure of merit for quantum technologies. We demonstrate that, at moderate growth temperatures (800 C), dense NV À ensembles of several hundreds of ppb (800 ppb for 50 ppm of added N 2 O) and with exceptionally high NV À / N 0 s ratios of up to 25% can be achieved. This NV À creation yield is higher by at least an order of magnitude to that typically obtained on standard [100]-grown diamonds and comparable to the best values reported for electron-irradiated diamonds. The material obtained here thus advantageously combines a high NV À density, high creation yield, long coherence times of several tens of ms together with a partial preferential orientation. These are highly desirable requirements for diamond-based quantum sensors that may spur new developments with this crystalline orientation leading to improved performance and sensitivity.

Efficient humoral responses rely on DNA damage, mutagenesis and error-prone DNA repair. Diversification of B cell receptors through somatic hypermutation and class-switch recombination are initiated by cytidine deamination in DNA mediated by activation-induced cytidine deaminase (AID)1 and by the subsequent excision of the resulting uracils by uracil DNA glycosylase (UNG) and by mismatch repair proteins1–3. Although uracils arising in DNA are accurately repaired1–4, how these pathways are co-opted to generate mutations and double-strand DNA breaks in the context of somatic hypermutation and class-switch recombination is unknown1–3. Here we performed a genome-wide CRISPR–Cas9 knockout screen for genes involved in class-switch recombination and identified FAM72A, a protein that interacts with the nuclear isoform of UNG (UNG2)5 and is overexpressed in several cancers5. We show that the FAM72A–UNG2 interaction controls the levels of UNG2 and that class-switch recombination is defective in Fam72a−/− B cells due to the upregulation of UNG2. Moreover, we show that somatic hypermutation is reduced in Fam72a−/− B cells and that its pattern is skewed upon upregulation of UNG2. Our results are consistent with a model in which FAM72A interacts with UNG2 to control its physiological level by triggering its degradation, regulating the level of uracil excision and thus the balance between error-prone and error-free DNA repair. Our findings have potential implications for tumorigenesis, as reduced levels of UNG2 mediated by overexpression of Fam72a would shift the balance towards mutagenic DNA repair, rendering cells more prone to acquire mutations. FAM72A interacts with UNG2 to regulate the balance between error-prone and error-free DNA repair.

Les conduites addictives s’imposent comme une question de sante au travail. Dans ce cadre, nous posons deux constats. D’une part, les consommations de psychotropes sont conjointement des facteurs et des symptomes de risques professionnels a evaluer. D’autre part, les pratiques de prevention ignorent cette investigation et se focalisent sur une amelioration a priori des savoirs et des conduites. Nous defendons l’idee que pour respecter leur obligation de moyens renforces en sante et securite, les dirigeants doivent creer les conditions de mobiliser leurs savoirs d’experiences et ceux des salaries pour comprendre et ameliorer les interrelations entre leur travail et leurs usages de medicaments, d’alcool ou de drogues. Il s’agit d’ouvrir, ou de renforcer, des espaces de discussion sur le travail qui permettent d’eclairer les strategies de sante, les fonctions professionnelles des usages de psychotropes et leurs regulations dans le travail.

Antiferromagnetic materials are promising platforms for next-generation spintronics owing to their fast dynamics and high robustness against parasitic magnetic fields. However, nanoscale imaging of the magnetic order in such materials with zero net magnetization remains a major experimental challenge. Here we show that non-collinear antiferromagnetic spin textures can be imaged by probing the magnetic noise they locally produce via thermal populations of magnons. To this end, we perform nanoscale, all-optical relaxometry with a scanning quantum sensor based on a single nitrogen-vacancy (NV) defect in diamond. Magnetic noise is detected through an increase of the spin relaxation rate of the NV defect, which results in an overall reduction of its photoluminescence signal under continuous laser illumination. As a proof-of-concept, the efficiency of the method is demonstrated by imaging various spin textures in synthetic antiferromagnets, including domain walls, spin spirals and antiferromagnetic skyrmions. This imaging procedure could be extended to a large class of intrinsic antiferromagnets and opens up new opportunities for studying the physics of localized spin wave modes for magnonics., 7 pages, 5 figures

Controlling the quantum properties of individual fluorescent defects in silicon is a key challenge towards advanced quantum photonic devices prone to scalability. Research efforts have so far focused on extrinsic defects based on impurities incorporated inside the silicon lattice. Here we demonstrate the detection of single intrinsic defects in silicon, which are linked to a tri-interstitial complex called W-center, with a zero-phonon line at 1.218${\mu}$m. Investigating their single-photon emission properties reveals new information about this common radiation damage center, such as its dipolar orientation and its photophysics. We also identify its microscopic structure and show that although this defect does not feature electronic states in the bandgap, Coulomb interactions lead to excitonic radiative recombination below the silicon bandgap. These results could set the stage for numerous quantum perspectives based on intrinsic luminescent defects in silicon, such as quantum integrated photonics, quantum communications and quantum sensing.

Efficient humoral responses rely on DNA damage, mutagenesis and error-prone DNA repair. B cell receptor diversification through somatic hypermutation (SHM) and class switch recombination (CSR) are initiated by cytidine deamination in DNA mediated by activation induced cytidine deaminase (AID)1 and by the subsequent excision of the resulting uracils by Uracil DNA glycosylase (UNG) and by mismatch repair (MMR) proteins2–4. Although uracils arising in DNA are faithfully repaired2–7, it is not known how these pathways are co-opted to generate mutations and double stranded DNA breaks (DSBs) in the context of SHM and CSR2,4,8. Here we have performed a genome-wide CRISPR/Cas9 knockout screen for genes involved in CSR. The screen identified FAM72A, a protein that interacts with the nuclear isoform of UNG (UNG2)9 and that is overexpressed in several cancers9. We show that the FAM72A-UNG2 interaction controls the protein levels of UNG2 and that CSR is defective in Fam72a−/− B cells due to the specific upregulation of UNG2. Moreover, we show that in Fam72a−/− B cells SHM is reduced by 5-fold and that upregulation of UNG2 results in a skewed mutation pattern. Our results are consistent with a model in which FAM72A interacts with UNG2 to control its physiological level by triggering its degradation. Consequently, deficiency in Fam72a leads to supraphysiological levels of UNG2 and enhanced uracil excision, shifting the balance from error-prone to error-free DNA repair. Our findings have potential implications for tumorigenesis, as Fam72a overexpression would lead to reduced UNG2 levels, shifting the balance toward mutagenic DNA repair and rendering cells more prone to acquire mutations.

Alors que l’Insee va lancer la preparation de nouvelles projections de population pour la France, ce dossier thematique est l’occasion de faire le point tant sur les resultats des projections precedentes que sur les methodes utilisees en France et ailleurs.

In this paper we use legitimacy as a lens to explore how sustainable business models (SBMs) develop within and across business ecosystems. We explore legitimacy as a resource that is created through sustainable development projects. We introduce the idea of linked legitimacy as a key driver for developing SBMs both within the business ecosystem of the focal firm, and in the overlapping ecosystems of their stakeholders. Using data from three business cases we explore different ways firms build and exploit linked legitimacy and how this leads to SBM development. We suggest that linked legitimacy can cross firm boundaries as a resource to be exploited broadly by ecosystem stakeholders. Finally, we re-conceptualize the rules of engagement for developing SBMs. In our model of SBM development, each firm then takes advantage of the resource (linked legitimacy) available in the ecosystem and is free to use it opportunistically, which drives SBM development.

Nitrogen-Vacancy centers in diamond possess an electronic spin resonance that strongly depends on temperature, which makes them efficient temperature sensor with a sensitivity down to a few mK/$\sqrt{\rm Hz}$. However, the high thermal conductivity of the host diamond may strongly damp any temperature variations, leading to invasive measurements when probing local temperature distributions. In view of determining possible and optimal configurations for diamond-based wide-field thermal imaging, we here investigate, both experimentally and numerically, the effect of the presence of diamond on microscale temperature distributions. Three geometrical configurations are studied: a bulk diamond substrate, a thin diamond layer bonded on quartz and diamond nanoparticles dispersed on quartz. We show that the use of bulk diamond substrates for thermal imaging is highly invasive, in the sense that it prevents any substantial temperature increase. Conversely, thin diamond layers partly solve this issue and could provide a possible alternative for microscale thermal imaging. Dispersions of diamond nanoparticles throughout the sample appear as the most relevant approach as they do not affect the temperature distribution, although NV centers in nanodiamonds yield lower temperature sensitivities compared to bulk diamond., Comment: 5 pages, 3 figures

Ce travail s'interesse a la construction d'un nouveau concept, la valeur territoriale, et sa relation a la question du developpement territorial. Il propose dans un premier temps, une approche genealogique du concept de valeur a partir d'une discussion sur l'entreprise et les business models (modeles d’affaires) soutenables. Les nouvelles formes de valeur (valeur client elargie, valeur partenariale, valeur partagee, etc.) privilegient une definition de la valeur tournee vers l'entreprise (valeur pour l'entreprise), le territoire etant alors exogene. Dans un second temps, nous montrons qu'une nouvelle forme de valeur (valeur territoriale) peut emerger par la combinaison d'un projet territorial (une action collective provenant d'acteurs heterogenes reposant sur la captation, la realisation et la redistribution d'externalites sociales positives) et de business models soutenables. La valeur emergente est une valeur pour le territoire. De nouveaux modeles de developpement exploratoires, fondes sur ces nouveaux modeles economiques, sont proposes a partir d’etudes de cas.

Purpose The purpose of this paper is to tackle the issue of store brand equity by considering two store brand’s positioning strategies: those with high perceived added value (the organic store brands), as opposed to economic brands. It takes place in the current environmental considerations showing the important role played by the packaging in determining the store brand equity. Design/methodology/approach A PLS Path model divided into four sub-models enables the authors to make specific predictions about customers’ purchase intentions. It also provides a concise operational calculation of the brand equity of each studied store brand. Findings Results show that economic brands build their equity with reinforced packaging, and organic brands maximise their brand equity by using simple packaging. In general, reinforced packaging improves the perceived quality of economic store brands but destroys that of organic brands. The calculations of overall equity scores for each studied store brand reveal that economic brands could benefit from further development whilst organic brands already maximise their equity. Practical implications Results will enable large retailers to develop effective campaigns focussing on perceived quality and more specifically by designing packaging that are suitable for the positioning of their brands – a simple packaging for organic brands and a reinforced packaging for economic brands to maximise customers’ value. Originality/value This is one of the first studies to deepen the store brand equity, comparing two contrasting types of brands, by studying specifically variations of the levels of customers’ perceived quality depending of two types of packaging.

PARP3 has been shown to be a key driver of TGFβ-induced epithelial-to-mesenchymal transition (EMT) and stemness in breast cancer cells, emerging as an attractive therapeutic target. Nevertheless, the therapeutic value of PARP3 inhibition has not yet been assessed. Here we investigated the impact of the absence of PARP3 or its inhibition on the tumorigenicity of BRCA1-proficient versus BRCA1-deficient breast cancer cell lines, focusing on the triple-negative breast cancer subtype (TNBC). We show that PARP3 knockdown exacerbates centrosome amplification and genome instability and reduces survival of BRCA1-deficient TNBC cells. Furthermore, we engineered PARP3(−/−) BRCA1-deficient or BRCA1-proficient TNBC cell lines using the CRISPR/nCas9(D10A) gene editing technology and demonstrate that the absence of PARP3 selectively suppresses the growth, survival and in vivo tumorigenicity of BRCA1-deficient TNBC cells, mechanistically via effects associated with an altered Rictor/mTORC2 signaling complex resulting from enhanced ubiquitination of Rictor. Accordingly, PARP3 interacts with and ADP-ribosylates GSK3β, a positive regulator of Rictor ubiquitination and degradation. Importantly, these phenotypes were rescued by re-expression of a wild-type PARP3 but not by a catalytic mutant, demonstrating the importance of PARP3’s catalytic activity. Accordingly, reduced survival and compromised Rictor/mTORC2 signaling were also observed using a cell-permeable PARP3-specific inhibitor. We conclude that PARP3 and BRCA1 are synthetic lethal and that targeting PARP3’s catalytic activity is a promising therapeutic strategy for BRCA1-associated cancers via the Rictor/mTORC2 signaling pathway.

Des enquêtes spécifiques sur la famille sont adossées au Recensement de la population depuis 1954. Le changement de méthode du recensement, avec un passage à des enquêtes par sondage chaque année, a nécessité de revoir la méthodologie des enquêtes associées. L’enquête sur la famille et les logements de 2011 est la première enquête couplée au nouveau recensement. Elle a permis de tester la faisabilité d’un tel couplage et de mettre en place le protocole de collecte associé, sans impact négatif sur le recensement. Cette enquête apporte, comme les enquêtes Famille précédentes, des informations complémentaires (dénombrement des personnes pacsées ou des familles recomposées par exemple) et une meilleure compréhension des résultats du recensement (comparaison des réponses des mêmes personnes dans les deux sources)., Breuil-Genier Pascale, Buisson Guillemette, Robert- Bobée Isabelle, Trabut Loïc. Enquête Famille et Logements adossée au Recensement de 2011 : comment s’adapter à la nouvelle méthodologie des enquêtes annuelles et quels apports ?. In: Economie et statistique, n°483-485, 2016. Le Recensement rénové : avancées méthodologiques et apports à la connaissance. pp. 205-226.

Thomas-Claudepierre et al. report that mediator facilitates the long-range contacts between acceptor switch regions and the IgH locus enhancers during class switch recombination and their transcriptional activation., Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1-deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation.

Control of the crystalline orientation of nitrogen-vacancy (NV) defects in diamond is here demonstrated by tuning the temperature of chemical vapor deposition (CVD) growth on a (113)-oriented diamond substrate. We show that preferential alignment of NV defects along the [111] axis is significantly improved when the CVD growth temperature is decreased. This effect is then combined with temperature-dependent incorporation of NV defects during the CVD growth to obtain preferential alignment over dense ensembles of NV defects spatially localized in thin diamond layers. These results demonstrate that growth temperature can be exploited as an additional degree of freedom to engineer optimized diamond samples for quantum sensing applications., 6 pages, 3 figures

The Mediator complex is known to orchestrate transcription. Here we show that B cell conditional deficient mice for the Med1 subunit display robust somatic hypermutation. Nevertheless, the mutation frequency at A residues is decreased and the expected A/T ratio is abolished, implicating Mediator in the second phase of somatic hypermutation.

By calling the present condition of the French food retail industry an interregnum, this research considers the impact of liquid modernity on this sector and looks for signs of a new order at a designing stage. Nine experts representing large retailers and entrepreneurs using alternative modes of food retailing were interviewed. An interpretive analysis reveals a wide diversity of changes. Following Bauman’s liquid metaphor, we identify shock, transformations, and crisis in food retailing, which we describe as phases that mark the dynamics in the shift from solid to liquid retailing. We discuss how retailers are adapting and deploying tactics both to respond and belong to these liquid times and how retailers can regain some legitimacy by claiming a role in territorial sovereignty.

International audience; Stochastic resonance is a general phenomenon usually observed in one-dimensional, amplitude modulated, bistable systems. We show experimentally the emergence of phase stochastic resonance in the bidimensional response of a forced nanoelectromechanical membrane by evidencing the enhancement of a weak phase modulated signal thanks to the addition of phase noise. Based on a general forced Duffing oscillator model, we demonstrate experimentally and theoretically that phase noise acts multiplicatively, inducing important physical consequences. These results may open interesting prospects for phase noise metrology or coherent signal transmission applications in nanomechanical oscillators. Moreover, our approach, due to its general character, may apply to various systems.

International audience; Solid papillary carcinoma with reverse polarity is a rare breast cancer of favorable prognosis that can be difficult to diagnose. We report here nine additional cases of this tumor, and we describe its morphologic, immunohistochemical and molecular profile in comparison to other types of papillary and micropapillary lesions of the breast that are intraductal papilloma with usual ductal hyperplasia, encapsulated papillary carcinoma, solid papillary carcinoma and invasive micropapillary carcinoma. We studied nine cases of this special papillary tumor and six of each other types mentioned above. We found that solid papillary carcinoma with reverse polarity harbor specific morphologic features as cuboid or tall cells with abundant eosinophilic cytoplasms located at the basal pole giving the impression of reverse nuclear polarity. Nuclei were sometimes grooved. Immunohistochemistry demonstrated the lack of myoepithelial cells, as in encapsulated papillary carcinoma and solid papillary carcinoma, questioning their invasive nature. Seven of nine solid papillary carcinoma with reverse polarity showed a low Ki67 proliferative index (Ki67

In a large number of experiments or devices, noise is usually viewed as an undesirable disturbance, hindering the measurement sensitivity or device performances. In some circumstances however, noise-induced phenomena can help, as in the case of stochastic resonance whereby a small coherent signal gets amplified resonantly by application of external noise. Stochastic resonance occurs in a wide class of nonlinear systems, in neurobiology [1], mesoscopic physics [2], photonics [3], atomic physics [4], mechanics [5, 6]… Stochastic resonance is a kind of synchronization of the switching events. If a weak periodic forcing is applied to the oscillator, the initially symmetrical double-well potential gets tilted asymmetrically up and down, periodically raising and lowering the potential barrier. Although the periodic forcing is too weak to let the membrane switch periodically from one potential well into the other one, noise-induced hopping between the potential wells can become synchronized with the weak period forcing. This time coincidence takes place when the average waiting time between noise-induced interwell transitions is comparable with half the period of the periodic forcing. Thus stochastic resonance corresponds to the noise-assisted amplification of a weak coherent input that is too feeble to induce hopping between the two stable states.

The motion of a micromechanical resonator coupled simultaneously to a high-finesse optical cavity and a microwave resonator can be used to transduce the fragile quantum states generated in the realm of microwave superconducting circuits into optical photons that can transport quantum information over large distances in telecom optical fibers at room temperature. We have engineered the optical and mechanical properties of thin membranes patterned in a suspended high-stress Si3N4 film to realize such a hybrid opto-electro-mechanical system. An optical Fabry-Perot cavity with a finesse exceeding 12 000 was realized between a highly reflective photonic crystal patch realized on the suspended membrane and a conventional high-reflectivity mirror. The electromechanical coupling with a nearby planar superconducting circuit is achieved by approaching the membrane at a sub-micron distance from an on-chip interdigitated capacitor. By operating the hybrid opto-electro-mechanical system in a cryogenic environment, the photon-phonon swap rates between microwave, mechanical, and optical degrees of freedom is expected to overcome the mechanical decoherence rate. An artist view of the device envisioned is depicted on Figure 1.

Two-dimensional photonic crystal slabs (PCS) offer an appealing alternative to distributed Bragg reflectors or filters for various applications. Indeed, their scattering properties, governed by Fano-resonances, have been used in areas as diverse as optical wavelength and polarization filters, reflectors, semiconductor lasers, photodetectors, bio-sensors, or non-linear optical components. Suspended PCSs also find natural applications in the field of optomechanics, where the mechanical modes of a suspended slab interact via radiation pressure with the optical field of a high finesse cavity. The reflectivity and transmission properties of a defect-free suspended PCS around normal incidence can be used to couple out-of-plane mechanical modes to an optical field by integrating it in a free space cavity. We have demonstrated the successful implementation of a PCS reflector on a high-tensile stress Si3N4 nanomembrane. We could measure the photonic crystal band diagram with a spectrally, angular, and polarization resolved setup. Moreover, a cavity with a finesse as high as 12 000 was formed using the suspended membrane as end-mirror of a Fabry-Perot cavity. These achievements allow us to operate in the resolved sideband regime where the optical storage time exceeds the mechanical period of low-order mechanical drum modes. This condition is a prerequisite to achieve quantum control of the mechanical resonator with light.

To mount highly specific and adapted immune responses, B lymphocytes assemble and diversify their antibody repertoire through mechanisms involving the formation of programmed DNA damage. Immunoglobulin class switch recombination (CSR) is triggered by DNA lesions induced by activation-induced cytidine deaminase, which are processed to double-stranded DNA break (DSB) intermediates. These DSBs activate the cellular DNA damage response and enroll numerous DNA repair factors, involving poly(ADP-ribose) polymerases Parp1, Parp2, and Parp3 to promote appropriate DNA repair and efficient long-range recombination. The macroParp Parp9, which is overexpressed in certain lymphomas, has been recently implicated in DSB repair, acting together with Parp1. Here, we examine the contribution of Parp9 to the resolution of physiological DSBs incurred during V(D)J recombination and CSR by generating Parp9-/- mice. We find that Parp9-deficient mice are viable, fertile, and do not show any overt phenotype. Moreover, we find that Parp9 is dispensable for B-cell development. Finally, we show that CSR and DNA end-joining are robust in the absence of Parp9, indicating that Parp9 is not essential in vivo to achieve physiological DSB repair, or that strong compensatory mechanisms exist.

This article introduces the concept of sufficiency, its specific dual nature (voluntary and obligatory), and its collective implications to the literature on sustainability. Sufficiency implies a reorganization of consumption priorities and is introduced by a discussion of consumerism and the dominant social paradigm. Long interviews with sufficient people show the complexity of the construct, which creates semantic oppositions around the notion of having (everything vs. nothing and not nothing vs. not everything). After a semiotic analysis of people’s interpretation of sufficiency, we propose a reflection about the use of macromarketing tools to better enhance and enact sufficiency in a collective way.

This research, based on the French macro-context, explains sustainable discourses in advertising from 2007 to 2012, during which time the concept of sustainability developed significantly and became institutionalized at a national level. This article defines sustainability broadly and explains the issue of inequality, particularly gender inequality, as originating in various forms of ascendancy over nature. Next, using a socio-semiotic reading, it identifies and deciphers five types of brand narratives on sustainability – Prometheus, Gaia, the Labyrinth, an automated world, and a sublimated nature – and their corresponding gender ideologies. Finally, the article discusses how feminist thought helps interpret major issues within sustainable communication, which reproduces both the dominant sustainable paradigm and conservative gender representations despite the national institutionalization of sustainability and a rich tradition of French feminist thought.

To cope with the devastating insults constantly inflicted to their genome by intrinsic and extrinsic DNA damaging sources, cells have evolved a sophisticated network of interconnected DNA caretaking mechanisms that will detect, signal and repair the lesions. Among the underlying molecular mechanisms that regulate these events, PARylation catalyzed by Poly(ADP-ribose) polymerases (PARPs), appears as one of the earliest post-translational modification at the site of the lesion that is known to elicit recruitment and regulation of many DNA damage response proteins. In this review we discuss how the complex PAR molecule operates in stress-induced DNA damage signaling and genome maintenance but also in various physiological settings initiated by developmentally programmed DNA breakage. To illustrate the latter, particular emphasis will be placed on the emerging contribution of PARPs to B cell receptor assembly and diversification.

Somatic hypermutation in variable heavy chain rearranged regions is abrogated in the absence of the 3′ regulatory region enhancer, whereas transcription rate in the Ig heavy chain is only partially reduced., Interactions with cognate antigens recruit activated B cells into germinal centers where they undergo somatic hypermutation (SHM) in V(D)J exons for the generation of high-affinity antibodies. The contribution of IgH transcriptional enhancers in SHM is unclear. The Eμ enhancer upstream of Cμ has a marginal role, whereas the influence of the IgH 3′ regulatory region (3′RR) enhancers (hs3a, hs1,2, hs3b, and hs4) is controversial. To clarify the latter issue, we analyzed mice lacking the whole 30-kb extent of the IgH 3′RR. We show that SHM in VH rearranged regions is almost totally abrogated in 3′RR-deficient mice, whereas the simultaneous Ig heavy chain transcription rate is only partially reduced. In contrast, SHM in κ light chain genes remains unaltered, acquitting for any global SHM defect in our model. Beyond class switch recombination, the IgH 3′RR is a central element that controls heavy chain accessibility to activation-induced deaminase modifications including SHM.

International audience; Cavity optomechanical systems with an enhanced coupling between mechanical motion and electromagnetic radiation have permitted the investigation of many novel physical effects. The optomechanical coupling in the majority of these systems is of dispersive nature: the cavity resonance frequency is modulated by the vibrations of the mechanical oscillator. Dissipative optomechanical interaction, where the photon lifetime in the cavity is modulated by the mechanical motion, has recently attracted considerable interest and opens new avenues in optomechanical control and sensing. In this work we demonstrate an external optical control over the dissipative optomechanical coupling strength mediated by the modulation of the absorption of a quantum dot layer in a hybrid optomechanical system. Such control enhances the capability of tailoring the optomechanical coupling of our platform, which can be used in complement to the previously demonstrated control of the relative (dispersive to dissipative) coupling strength via the geometry of the integrated access waveguide.

Light scattering by a two-dimensional photonic-crystal slab (PCS) can result in marked interference effects associated with Fano resonances. Such devices offer appealing alternatives to distributed Bragg reflectors and filters for various applications, such as optical wavelength and polarization filters, reflectors, semiconductor lasers, photodetectors, bio-sensors and non-linear optical components. Suspended PCS also have natural applications in the field of optomechanics, where the mechanical modes of a suspended slab interact via radiation pressure with the optical field of a high-finesse cavity. The reflectivity and transmission properties of a defect-free suspended PCS around normal incidence can be used to couple out-of-plane mechanical modes to an optical field by integrating it in a free-space cavity. Here we demonstrate the successful implementation of a PCS reflector on a high-tensile stress Si3N4 nanomembrane. We illustrate the physical process underlying the high reflectivity by measuring the photonic-crystal band diagram. Moreover, we introduce a clear theoretical description of the membrane scattering properties in the presence of optical losses. By embedding the PCS inside a high-finesse cavity, we fully characterize its optical properties. The spectrally, angular- and polarization-resolved measurements demonstrate the wide tunability of the membrane’s reflectivity, from nearly 0 to 99.9470±0.0025%, and show that material absorption is not the main source of optical loss. Moreover, the cavity storage time demonstrated in this work exceeds the mechanical period of low-order mechanical drum modes. This so-called resolved-sideband condition is a prerequisite to achieve quantum control of the mechanical resonator with light.

International audience; Light scattering by a two-dimensional photonic-crystal slab (PCS) can result in marked interference effects associated with Fano resonances. Such devices offer appealing alternatives to distributed Bragg reflectors and filters for various applications, such as optical wavelength and polarization filters, reflectors, semiconductor lasers, photodetectors, bio-sensors and non-linear optical components. Suspended PCS also have natural applications in the field of optomechanics, where the mechanical modes of a suspended slab interact via radiation pressure with the optical field of a high-finesse cavity. The reflectivity and transmission properties of a defect-free suspended PCS around normal incidence can be used to couple out-of-plane mechanical modes to an optical field by integrating it in a free-space cavity. Here we demonstrate the successful implementation of a PCS reflector on a high-tensile stress Si3N4 nanomembrane. We illustrate the physical process underlying the high reflectivity by measuring the photonic-crystal band diagram. Moreover, we introduce a clear theoretical description of the membrane scattering properties in the presence of optical losses. By embedding the PCS inside a high-finesse cavity, we fully characterize its optical properties. The spectrally, angular- and polarization-resolved measurements demonstrate the wide tunability of the membrane’s reflectivity, from nearly 0 to 99.9470±0.0025%, and show that material absorption is not the main source of optical loss. Moreover, the cavity storage time demonstrated in this work exceeds the mechanical period of low-order mechanical drum modes. This so-called resolved-sideband condition is a prerequisite to achieve quantum control of the mechanical resonator with light.

Antibody diversification requires the DNA deaminase AID to induce DNA instability at immunoglobulin (Ig) loci upon B cell stimulation. For efficient cytosine deamination, AID requires single-stranded DNA and needs to gain access to Ig loci, with RNA pol II transcription possibly providing both aspects. To understand these mechanisms, we isolated and characterized endogenous AID-containing protein complexes from the chromatin of diversifying B cells. The majority of proteins associated with AID belonged to RNA polymerase II elongation and chromatin modification complexes. Besides the two core polymerase subunits, members of the PAF complex, SUPT5H, SUPT6H, and FACT complex associated with AID. We show that AID associates with RNA polymerase-associated factor 1 (PAF1) through its N-terminal domain, that depletion of PAF complex members inhibits AID-induced immune diversification, and that the PAF complex can serve as a binding platform for AID on chromatin. A model is emerging of how RNA polymerase II elongation and pausing induce and resolve AID lesions.

Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cancer development. HBV encodes the hepatitis B virus X (HBx) protein that promotes transcription of the viral episomal DNA genome by the host cell RNA polymerase II. Here we provide evidence that HBx accomplishes this task by a conserved and unusual mechanism. Thus, HBx strongly stimulates expression of transiently transfected reporter constructs, regardless of the enhancer and promoter sequences. This activity invariably requires HBx binding to the cellular UV-damaged DDB1 E3 ubiquitin ligase, suggesting a common mechanism. Unexpectedly, none of the reporters tested is stimulated by HBx when integrated into the chromosome, despite remaining responsive to their cognate activators. Likewise, HBx promotes gene expression from the natural HBV episomal template but not from a chromosomally integrated HBV construct. The same was observed with the HBx protein of woodchuck HBV. HBx does not affect nuclear plasmid copy number and functions independently of CpG dinucleotide methylation. Conclusion: We propose that HBx supports HBV gene expression by a conserved mechanism that acts specifically on episomal DNA templates independently of the nature of the cis-regulatory sequences. Because of its uncommon property and key role in viral transcription, HBx represents an attractive target for new antiviral therapies. (HEPATOLOGY 2012;56:2116–2124)

Resume Alors que les pratiques manageriales de la responsabilite sociale des entreprises (RSE) s’institutionnalisent et se generalisent, le consommateur est aujourd’hui la cible de nombreuses actions RSE. L’objet de notre article est de mieux apprehender la perception de la RSE par les consommateurs dans une perspective globale et un contexte de crise. Les resultats de cette etude conduisent a proposer des pistes de reflexion sur les nouveaux enjeux qui s’offrent a la fonction marketing, nous inscrivant dans le courant de la « stakeholder marketing theory ».