Safety Analysis of Parameterised Networks with Non-Blocking Rendez-Vous

We consider networks of processes that all execute the same finite-state protocol and communicate via a rendez-vous mechanism. When a process requests a rendez-vous, another process can respond to it and they both change their control states accordingly. We focus here on a specific semantics, called non-blocking, where the process requesting a rendez-vous can change its state even if no process can respond to it. In this context, we study the parameterised coverability problem of a configuration, which consists in determining whether there is an initial number of processes and an execution allowing to reach a configuration bigger than a given one. We show that this problem is EXPSPACE-complete and can be solved in polynomial time if the protocol is partitioned into two sets of states, the states from which a process can request a rendez-vous and the ones from which it can answer one. We also prove that the problem of the existence of an execution bringing all the processes in a final state is undecidable in our context. These two problems can be solved in polynomial time with the classical rendez-vous semantics

Détermination de la constante de Boltzmann au plus haut niveau d'exactitude par spectroscopie acoustique dans un résonateur quasi sphérique (Vers une nouvelle définition de l'unité internationale de température.)

Depuis 2005, il existe un intérêt important dans la communauté internationale de métrologiepour de nouvelles déterminations précises de la constante de Boltzmann kB ; lebut étant de redéfinir en 2015 l unité internationale de température, le kelvin. Actuellement,cinq techniques sont utilisées pour déterminer kB avec comme objectif d atteindreune incertitude relative inférieure à 1 . 10 6. La méthode retenue pour cette thèse est latechnique acoustique.La constante de Boltzmann est liée à la vitesse du son u dans un gaz parfait par l équationdu viriel acoustique. La méthode décrite dans cette thèse consiste à mesurer u en utilisantun résonateur de forme quasi sphérique et de volume intérieur de 0,5 L, rempli d argon.Ces mesures sont effectuées lors d un isotherme à la température du point triple de l eau,T = 273,16 K, pour des pressions statiques P allant de 0,05 MPa à 0,7 MPa. La constantede Boltzmann est ensuite déterminée en estimant u à pression nulle par une régressionpolynomiale.Dans cette thèse, un modèle de propagation des ondes acoustiques dans un résonateur quasisphérique est défini. Aussi, les moyens techniques utilisés pour contrôler soigneusement lesparamètres de l expérience qui ont un effet sur les mesures de u (comme la température,la pression statique, la composition du gaz, etc) sont présentés. De nouvelles techniquesexpérimentales et des nouveaux moyens d analyse des données sont proposés, comme lamesure du rayon du résonateur par spectroscopie électromagnétique, mais aussi l utilisationde l écart-type d Allan comme un outil efficace pour étudier la présence d impuretélors d une expérience de longue durée. Les effets systématiques sont analysés puis corrigés.Pour certains, la correction est estimée grâce à un modèle analytique, comme l effet lié auxcouches limites thermiques. Pour d autres, des corrections basées sur des fonctions empiriquessont proposées ; c est le cas pour l effet du débit de gaz continu sur les mesures deu, effet qui est caractérisé expérimentalement dans cette thèse.Enfin, l analyse des données acquises en 2009 au LCM/LNE-CNAM lors de deux isothermeseffectuées avec de l argon est présentée. Celle-ci a permis d obtenir la valeur kB =1, 3806475 (16) . 10 23 J · K 1, c est à dire avec une incertitude relative de 1, 14 . 10 6.Since 2005, there is an important interest in the international metrology community fornew accurate determinations of the Boltzmann constant kB ; the purpose is to redefine in2015 the unit of thermodynamic temperature, the kelvin. Currently, five techniques areimplemented for determining kB with the objective to achieve a relative uncertainty below1 . 10 6. The method used in the present work is based on acoustic measurements.The Boltzmann constant is linked to the speed of sound u in a noble gas by the virial acousticalequation. The method described here consists in measuring u inside a quasi-sphericalacoustic resonator of inner volume of 0.5 L filled with argon. Measurements are performedduring an isotherm process at the temperature of the triple point of water, T = 273.16 K,at static pressures P from 0.05 MPa to 0.7 MPa. The Boltzmann constant is then determinedby estimating u at zero pressure limit with a polynomial regression.In the present work an acoustic wave propagation model within a quasi-spherical resonatoris defined. Also, the technical means used to carefully control the parameters of theexperiment with an effect on the measurement of u (like temperature, static pressure, gascomposition, etc.) are presented. New exprimental methods and data analyses are described,like the measurement of the radius of the resonator by electromagnetic spectroscopy,as well as the use of the Allan deviation as an efficient tool to study the gas impuritypresence during a long-term experience. Systematic effects are analyzed and corrected. Insome cases the corrections are based on analytical models like the thermal layer boundaryeffect. In other cases, empirical correction functions are proposed, as for the case of changesin the measurements of u related to the continuous gas flow, which was experimentally characterizedin the present work.Finally, the analysis of the data acquiered in 2009 at LCM/LNE-CNAM during two isothermprocesses using argon is presented. This leads to the value kB = 1.3806475 (16) .10 23 J · K 1, i.e. with a relative uncertainty of 1.14 . 10 6.PARIS-CNAM (751032301) / SudocSudocFranceF

An Optimized Workflow for the Discovery of New Antimicrobial Compounds Targeting Bacterial RNA Polymerase Complex Formation

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein-protein interaction between the beta' subunit and the sigma(70) initiation factor of bacterial RNA polymerase, which is essential for transcription. As a follow-up to such work, we have improved the discovery strategy to make it less time-consuming and more cost-effective. This involves three sequential assays, easily scalable to a high-throughput format, and a subsequent in-depth characterization only limited to hits that passed the three tests. This optimized workflow, applied to the screening of 5360 small molecules from three synthetic and natural compound libraries, led to the identification of six compounds interfering with the beta'-sigma(70) interaction, and thus was capable of inhibiting promoter-specific RNA transcription and bacterial growth. Upon supplementation with a permeability adjuvant, the two most potent transcription-inhibiting compounds displayed a strong antibacterial activity against Escherichia coli with minimum inhibitory concentration (MIC) values among the lowest (0.87-1.56 mu M) thus far reported for beta'-sigma PPI inhibitors. The newly identified hit compounds share structural feature similarities with those of a pharmacophore model previously developed from known inhibitors

Obesity promotes fumonisin B1 hepatotoxicity

Obesity, which is a worldwide public health issue, is associated with chronic inflammation that contribute to long-term complications, including insulin resistance, type 2 diabetes and non-alcoholic fatty liver disease. We hypothesized that obesity may also influence the sensitivity to food contaminants, such as fumonisin B1 (FB1), a mycotoxin produced mainly by the Fusarium verticillioides. FB1, a common contaminant of corn, is the most abundant and best characterized member of the fumonisins family. We investigated whether diet-induced obesity could modulate the sensitivity to oral FB1 exposure, with emphasis on gut health and hepatotoxicity. Thus, metabolic effects of FB1 were assessed in obese and non-obese male C57BL/6J mice. Mice received a high-fat diet (HFD) or normal chow diet (CHOW) for 15 weeks. Then, during the last three weeks, mice were exposed to these diets in combination or not with FB1 (10 mg/kg body weight/day) through drinking water. As expected, HFD feeding induced significant body weight gain, increased fasting glycemia, and hepatic steatosis. Combined exposure to HFD and FB1 resulted in body weight loss and a decrease in fasting blood glucose level. This co-exposition also induces gut dysbiosis, an increase in plasma FB1 level, a decrease in liver weight and hepatic steatosis. Moreover, plasma transaminase levels were significantly increased and associated with liver inflammation in HFD/FB1-treated mice. Liver gene expression analysis revealed that the combined exposure to HFD and FB1 was associated with reduced expression of genes involved in lipogenesis and increased expression of immune response and cell cycle-associated genes. These results suggest that, in the context of obesity, FB1 exposure promotes gut dysbiosis and severe liver inflammation. To our knowledge, this study provides the first example of obesity-induced hepatitis in response to a food contaminant.L.D. PhD was supported by the INRAE Animal Health department. This work was also supported by grants from the French National Research Agency (ANR) Fumolip (ANR-16-CE21-0003) and the Hepatomics FEDER program of Région Occitanie. We thank Prof Wentzel C. Gelderblom for generously providing the FB1 and for his interest and support in our project. B.C. laboratory is supported by a Starting Grant from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. ERC-2018-StG- 804135), a Chaire d'Excellence from IdEx Université de Paris - ANR-18-IDEX-0001, an Innovator Award from the Kenneth Rainin Foundation, an ANR grant EMULBIONT ANR-21-CE15-0042-01 and the national program “Microbiote” from INSERM. We thank Anexplo (Genotoul, Toulouse) for their excellent work on plasma biochemistry. Neutral Lipids MS and NMR experiments were performed with instruments in the Metatoul-AXIOM platform. Sphingolipid MS analysis were performed with instruments in the RUBAM platform. The FB1 plasma levels were determined using an UPLC-MS/MS instrument part of the Ghent University MSsmall expertise centre for advanced mass spectrometry analysis of small organic molecules. We thank Elodie Rousseau-Bacquié and all members of the EZOP staff for their assistance in the animal facility. We are very grateful to Talal al Saati for histology analyses and review, and we thank all members of the US006/CREFRE staff at the histology facility and the Genom'IC platforms (INSERM U1016, Paris, France) for their expertise.Peer reviewe

Supplement: "Localization and broadband follow-up of the gravitational-wave transient GW150914" (2016, ApJL, 826, L13)

This Supplement provides supporting material for Abbott et al. (2016a). We briefly summarize past electromagnetic (EM) follow-up efforts as well as the organization and policy of the current EM follow-up program. We compare the four probability sky maps produced for the gravitational-wave transient GW150914, and provide additional details of the EM follow-up observations that were performed in the different bands

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams

Localization and Broadband Follow-up of the Gravitational-wave Transient GW150914

A gravitational-wave (GW) transient was identified in data recorded by the Advanced Laser Interferometer Gravitational-wave Observatory (LIGO) detectors on 2015 September 14. The event, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the GW data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network circulars, giving an overview of the participating facilities, the GW sky localization coverage, the timeline, and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic (EM) signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the EM data and results of the EM follow-up campaign are being disseminated in papers by the individual teams. </p

Localization and broadband follow-up of the gravitational-wave transient GW150914

A gravitational-wave transient was identified in data recorded by the Advanced LIGO detectors on 2015 September 14. The event candidate, initially designated G184098 and later given the name GW150914, is described in detail elsewhere. By prior arrangement, preliminary estimates of the time, significance, and sky location of the event were shared with 63 teams of observers covering radio, optical, near-infrared, X-ray, and gamma-ray wavelengths with ground- and space-based facilities. In this Letter we describe the low-latency analysis of the gravitational wave data and present the sky localization of the first observed compact binary merger. We summarize the follow-up observations reported by 25 teams via private Gamma-ray Coordinates Network Circulars, giving an overview of the participating facilities, the gravitational wave sky localization coverage, the timeline and depth of the observations. As this event turned out to be a binary black hole merger, there is little expectation of a detectable electromagnetic signature. Nevertheless, this first broadband campaign to search for a counterpart of an Advanced LIGO source represents a milestone and highlights the broad capabilities of the transient astronomy community and the observing strategies that have been developed to pursue neutron star binary merger events. Detailed investigations of the electromagnetic data and results of the electromagnetic follow-up campaign will be disseminated in the papers of the individual teams