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Additional file 2: Graphical abstract.

Quorum sensing systems (QSSs) are genetic systems supporting cell-cell or bacteriophage-bacteriophage communication via the production and the detection of a signal molecule, the extracellular concentration of which reflects the density of the QSS-encoding population. QSSs have a prime importance in the regulation of key biological processes such as virulence, sporulation or biofilm formation in bacteria, conjugation in plasmids or lysogeny in temperate bacteriophages. However, the genetic diversity of QSSs remains largely underexplored and the same holds for the diversity of organisms, plasmids and viruses encoding these systems. Hence, many bacterial and viral density-dependent behaviors likely await to be discovered, some of which could perhaps transform our views of microbial adaptation and of the co-evolution between bacteria and their mobile genetic elements. Specifically, this PhD in evolutionary bioinformatics explores the phylogenetic and functional diversity of quorum sensing using genome and network analysis methods applied to genetic elements traditionally neglected by this research field: genomes of poorly known lineages such as CPRs and DPANNs, environmental metagenomes, viral genomes or plasmids. In particular, this thesis lays the theoretical foundations for the inference of communication networks within environmental microbial communities and includes the development of a new method allowing the identification of QSSs of the RRNPP type (Rap-Rgg-NprR-PlcR-PrgX) that are non-homologous to already known QSSs. This work notably reveals the first bilingual bacteriophages, i.e. encoding two QSSs belonging to different genetic families, as well as the first bacteriophages predicted to manipulate in a density-dependent manner the biology of their bacterial host., Les systèmes de « Quorum Sensing » (QSSs) sont des systèmes génétiques permettant la communication entre cellules ou entre bactériophages. Cette communication est réalisée par l’émission et la détection d’une molécule signal dont la concentration extracellulaire reflète la densité de la population codant le QSS. Les QSSs ont une importance capitale dans la régulation densité-dépendante de processus biologiques clés tels que la virulence, la sporulation ou la formation de biofilms chez les bactéries, la conjugaison chez les plasmides, ou la lysogénie chez les bactériophages tempérés. Néanmoins, la diversité des QSSs demeure largement sous-explorée et il en va de même pour celle des organismes, plasmides et virus codant ces systèmes. Ainsi, beaucoup de comportements microbiens/viraux régulés de façon densité-dépendante restent probablement à découvrir, dont certains pourraient peut-être révolutionner notre vision de l’adaptation microbienne et de la coévolution entre bactéries et leurs éléments génétiques mobiles. Précisément, cette thèse de bioinformatique évolutive explore les diversités phylogénétique et fonctionnelle du processus de détection du quorum par des méthodes d’analyses de génomes et de réseaux appliquées à des éléments génétiques traditionnellement délaissés par ce champ de recherche : génomes de lignées méconnues comme les CPRs et les DPANNs, métagénomes environnementaux, génomes viraux ou encore plasmides. En particulier, cette thèse pose les bases théoriques de l’inférence de réseaux de communication au sein de communautés microbiennes environnementales et inclut le développement d’une nouvelle méthode permettant l’identification de QSSs de type RRNPP (Rap-Rgg-NprR-PlcR-PrgX) non homologues à des QSSs déjà connus. Ce travail révèle notamment les premiers bactériophages bilingues, c’est-à-dire codant deux QSSs appartenant à des familles génétiques différentes ainsi que les premiers bactériophages prédits pour manipuler de façon densité-dépendante la biologie de leur hôte bactérien.

Additional file 1: Supplementary materials.

Gérard Reach,1 Laurent Benarbia,2 Eric Bruckert,3 Jean-Philippe Kevorkian,4 Michel Farnier,5,6 Jean-Jacques Mourad,7 Bernard-Charles Vaisse8 1Health Education and Practices Laboratory (LEPS), Sorbonne Paris-Nord University, Bobigny, France; 2Marketing Studio, Paris, France; 3Department of Endocrinology and Prevention of Cardiovascular Diseases, Institute of Cardiometabolism and Nutrition (ICAN), La Pitié-Salpêtrière Hospital, AP-HP, Sorbonne University, Paris, France; 4Department of Diabetes and Endocrinology, Lariboisière Hospital, Assistance Publique-Hôpitaux de Paris, Paris University, Paris, 75010, France; 5PEC2, EA 7460, University of Bourgogne Franche-Comté, Dijon, France; 6Cardiology Department, University Hospital Centre of Dijon Bourgogne, Dijon, France; 7Department of Internal Medicine and ESH Excellence Centre, Groupe Hospitalier Paris Saint-Joseph, Paris, France; 8Hypertension Unit -Vascular Medicine, Department of Cardiology, CHU Timone, Marseille, FranceCorrespondence: Gérard ReachHealth Education and Practices Laboratory (LEPS), Sorbonne Paris-Nord University, 74 rue Marcel Cachin, Bobigny, 93017, FranceTel +33 6 60 84 53 25Email gerardreach@icloud.comPurpose: Some patients make a rational choice not to follow medical prescriptions; others fail to take their medications for reasons beyond their control, such as mere forgetfulness or a weak medication routine. The aim of this study was to elucidate the functioning of patient intentionality in medication adherence.Patients and Methods: This online study was conducted in metropolitan France in 2019. A cross-sectional survey of 50 questions was conducted with 3001 respondents diagnosed with diabetes, hypertension, and/or hypercholesterolemia identified from a panel of 54,000 people. These questions included a validated six-item questionnaire to detect nonadherence, two questions to detect intentional nonadherence by patients, and three questions on the effects of habit. Our questionnaire also included questions on the feelings of respondents regarding their doctor’s attitude to their problems and needs, their trust in general practitioners (GP) and specialists, their sense of being involved in treatment decisions, and the influence of side effects and habits on patients’ adherence. This study used the strategy of focusing on strictly adherent patients in the hope of finding ways to improve adherence. For this reason, we defined adherence as the absence of a positive response to the 6-item nonadherence screening questionnaire.Results: Of 3001 respondents, 1804 were diagnosed with hypertension, 1458 with hypercholesterolemia, and 774 with diabetes. Of the total number of patients, 72% were afflicted with one disease, 21% with two ailments, and 7% with three simultaneous illnesses. One-third (33%) of the patients did not tender a positive answer to the adherence questionnaire and were deemed adherent. 1) Thirty-two percent of the patients reported occasionally omitting their medication deliberately, and 84% said they had a reason for missing doses. These statements suggesting intentional nonadherence were negatively associated with adherence as identified via multivariate analysis (P = 0.0012 and P < 0.0001, for the first and second statement, respectively). 2) Univariate analyses revealed strong associations (P < 0.0001) between strict adherence on one hand and lack of intentional nonadherence, patient age, absence of drug side effects, taking drugs by habit, feeling involved in treatment decisions, getting information about treatment, and disease, and trust in doctors, on the other hand. 3) Specifically, univariate analysis of the absence of reported side effects revealed strong associations (P < 0.0001) with adequate information about medicines and diseases and trust in GP. These original data were consistent with the concept of the nocebo effect. 4) We observed a strong association between the absence of intentional nonadherence (statement of never deliberately missing medication) and respondent statements about generally sticking to the routine (P < 0.0001), ie, “I take my medication because I am used to taking it.” This important result suggests that patients are strictly adherent in two ways: the absence of intentional nonadherence and reliance on habit, which we term as “unintentional adherence.” 5) Finally, a multiple correspondence analysis illustrated all statistically significant relationships found in this study.Conclusion: We present a new global model of adherence in which patient adherence was improved both by reducing intentional nonadherence and by promoting the abovementioned unintentional adherence by habit. This model highlights the role of shared decision-making and the trust felt by patients in their doctors. These results could exert a major impact on medical practice and education by demonstrating the importance of physicians’ attitudes, involving the patient in decisions (shared decision-making), offering information about medicines and diseases (patient education), understanding the problems of patients, and taking their needs into account (empathy). The development of these attitudes should be an important aspect of the medical curricula.Keywords: adherence; intentionality; intentional; unintentional, doctor-patient relationship, shared medical decision, trust, habit, side effects of drugs

International audience; The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. Upon Bacillus infection, Bacillus phages phi3T rely on the "arbitrium" quorum sensing (QS) system to communicate on their population density in order to orchestrate the lysis-to-lysogeny transition. At high phage densities, where there may be limited host cells to infect, lysogeny is induced to preserve chances of phage survival. Here, we report the presence of an additional, host-derived QS system in the phi3T genome, making it the first known virus with two communication systems. Specifically, this additional system, coined "Rapφ-Phrφ", is predicted to downregulate host defense mechanisms during the viral infection, but only upon stress or high abundance of Bacillus cells and at low density of population of the phi3T phages. Post-lysogenization, Rapφ-Phrφ is also predicted to provide the lysogenized bacteria with an immediate fitness advantage: delaying the costly production of public goods while nonetheless benefiting from the public goods produced by other non-lysogenized Bacillus bacteria. The discovered "Rapφ-Phrφ" QS system hence provides novel mechanistic insights into how phage communication systems could contribute to the phage-host evolutionary stability.

The Great Pyramid or Khufu's Pyramid was built on the Giza Plateau (Egypt) during the IVth dynasty by the pharaoh Khufu (Cheops), who reigned from 2509 to 2483 BC. Despite being one of the oldest and largest monuments on Earth, there is no consensus about how it was built. To better understand its internal structure, we imaged the pyramid using muons, which are by-products of cosmic rays that are only partially absorbed by stone. The resulting cosmic-ray muon radiography allows us to visualize the known and potentially unknown voids in the pyramid in a non-invasive way. Here we report the discovery of a large void (with a cross section similar to the Grand Gallery and a length of 30 m minimum) above the Grand Gallery, which constitutes the first major inner structure found in the Great Pyramid since the 19th century. This void, named ScanPyramids Big Void, was first observed with nuclear emulsion films installed in the Queen's chamber (University of Nagoya), then confirmed with scintillator hodoscopes set up in the same chamber (KEK) and re-confirmed with gas detectors outside of the pyramid (CEA). This large void has therefore been detected with a high confidence by three different muon detection technologies and three independent analyses. These results constitute a breakthrough for the understanding of Khufu's Pyramid and its internal structure. While there is currently no information about the role of this void, these findings show how modern particle physics can shed new light on the world's archaeological heritage., Comment: Nature (2017)

Éclectique, revanchard, réactif sont tous des traits associés à Trump, mais est-ce que sa politique commerciale raconte la même histoire ? Pour répondre à cette interrogation, nous proposons de déconstruire l’agenda de Trump selon les zones économiques concernées par les grandes décisions exécutives du président. Par exemple, la doctrine « America First » s’articule, s’applique et s’interprète différemment face au Canada que face à un opposant hégémonique comme la Chine. Cette méthode permet d’élaguer le discours de Donald Trump et ainsi d’en analyser les tendances et les incohérences. Nous en concluons que la diplomatie commerciale américaine sous Trump est structurée autour d’une ambition idéologique visant à dévaloriser progressivement l’ordre libéral et le multilatéralisme qui le sous-tend. Conjointement à notre hypothèse, nous notons aussi que les politiques commerciales détonnant avec la rhétorique du président résultent plutôt d’une structure institutionnelle, économique et politique antérieure à Trump que d’un changement d’approche., Eclectic, vindictive, reactive are all traits associated with Trump and his attitude towards commerce, but does his trade policy tell the same story ? To answer this question, we propose to deconstruct Trump’s agenda according to the economic zones affected by the President’s major executive decisions. For example, the America First doctrine is articulated, applied and interpreted differently regarding Canada than in relation to a hegemonic opponent such as China. This method makes it possible to prune Donald Trump’s speech and thus to analyze trends and inconsistencies. We conclude that American commercial diplomacy under Trump is structured around an ideological ambition aimed at gradually delegitimizing the liberal order and the multilateralism that underlies it. In conjunction with our hypothesis, we also note that trade policies that are in contradiction with the president’s rhetoric are more the result of a pre-Trump institutional, economic and political structure rather than a change of approach.

This paper focuses on the impacts of Positive Behavior Intervention Supports (PBIS/PBI/PBS) on the progression of positive student behavior traits. Specifically, there will be a focus on the ways that PBIS impact student behaviors in the classroom. The research will focus on: the benefits and detriments of enacting PBIS into the classroom, the role PBIS can have on the academic outcomes of students, and the role technology can have in promoting student self-regulation in the 21st century. In conducting this study, the goal is to connect my desired research with that of prior analysis to support my argument that PBIS is essential to positive classroom and school culture that fosters educational success in all learning environments.

[reaction--see text] An efficient Grignard- and organolithium-induced regio- and chemoselective anionic acylation is reported. A number of tricyclic ketones are prepared in good to excellent yields via this method. This method is complementary to the Frieldel-Crafts acylation for electron-deficient substrates. A novel anisole-based Grignard reagent was developed to effect the cyclization of sterically hindered substrates. This novel reagent has been successfully applied to the synthesis of Sch 66336, a candidate for oncologic treatment.

Charles Bernard. Découvrir la Corse ou interpeller la République ?. In: Autres Temps. Cahiers d'éthique sociale et politique. N°65, 2000. pp. 80-92.

Resume Soient E′ et E″ deux espaces vectoriels complexes de dimension finie. Etant donne les operateurs lineaires A′ sur E″ et A″ sur E″ sous leurs formes de Jordan respectives, nous montrons que l'etude de la forme de Jordan des operateurs A sur E′ ⋯ E″ dont les matrices sont de la forme A= A′ B O A″ avec B un operateur lineaire de E″ dans E′ peut-etre abordee a partir de la description des sous-espaces reduisants minimaux contenant un sous-espace donne. Comme application, nous donnons une nouvelle methode pour la determination explicite de la forme de Jordan de A dans le cas ou A″ est cyclique.

Two methods for the stereospecific synthesis of the title compound are described. These short and efficient syntheses provide rapid access to this key intermediate in the construction of 2′-Deoxy Carbocyclic Nucleosides.

Charles Bernard. Rétrospective et prospective, 1993-1995. In: Autres Temps. Cahiers d'éthique sociale et politique. N°43, 1994. pp. 111-115.

Resume Soit A un operateur algebrique p -primaire sur un espace vectoriel E. Nous donnons une description complete de l'algebre des operateurs qui laissent invariants les sous-espaces invariants pour A et nous etudions le comportement de la reflexivite algebrique par extension du corps de base.

[reaction--see text] An efficient Grignard- and organolithium-induced regio- and chemoselective anionic acylation is reported. A number of tricyclic ketones are prepared in good to excellent yields via this method. This method is complementary to the Frieldel-Crafts acylation for electron-deficient substrates. A novel anisole-based Grignard reagent was developed to effect the cyclization of sterically hindered substrates. This novel reagent has been successfully applied to the synthesis of Sch 66336, a candidate for oncologic treatment.

Motived by an intrinisic necessary condition for the purifiability of subgroups of primary abelian groups due to K. Benabdallah and T. Okuyama we introduce new functors on the category of pairs (G, A),where A is a subgroup of G,to the category of Z/pZ-vector spaces. The vanishing of these functors leads to the notion of vertical subgroup which is a weakening of purity but also an essential component of the latter. In fact, a vertical subgroup is pure if and only if it is neat. We establish various facts about vertical subgroups and “maximal” vertical subgroups and apply the resulting theory to the problem of purifiability. We show that the class of quasi-complete groups is precisely the class of reduced groups in which every subgroup satisfying the intrinsic necessary condition for purifiability is in fact purifiable. This is also the class of reduced p-groups in which the maximal vertical subgroups are precisely the pure subgroups.

Resume Soit A un operateur nilpotent sur un espace de Banach E . Nous demontrons que l'orbite de E par l'action du commutant de A contient les F ϵ Lat A qui sont de dimension finie.

Surface Tilt Mapping (STM) has been successfully applied to stimulation treatments, disposal projects and in numerous steam floods to provide information on fluid movements in the reservoir. This proven technology has now been applied to a waterflood in the San Andres formation at a depth of 5600 feet to analyze preferential flow. Since typical water injection rates in the San Andres range from 100 to 300 BWPD, a novel flowback method was developed to maximize the STM response when testing injection wells under normal operating conditions. An analysis technique that allows the removal of earth tides was also applied to further enhance the quality of the data. The STM results showed conclusive preferential flow direction in the seven wells tested. In most wells, multiple tests were performed with good agreement on the flow trend.

A novel enantioselective alkylation of double benzylic substrates with secondary electrophiles is reported. A simple norephedrine-based chiral ligand was synthesized that gives alkylation product in 95% yield and 95% ee. A unique water effect on the enantioselectivity was unveiled. Good to excellent ee values were obtained with a number of double benzylic substrates and secondary electrophiles. This novel reaction has been applied to the synthesis of a promising anticancer agent.

Charles Bernard. La mémoire vivante. Des témoins du siècle à venir. In: Autres Temps. Les cahiers du christianisme social. N°37, 1993. pp. 95-97.