Fast acoustic streaming in standing waves : Generation of an additional outer streaming cell

Rayleigh streaming in a cylindrical acoustic standing waveguide is studied both experimentally and numerically for nonlinear Reynolds numbers from 1 to 30. Streaming velocity is measured by means of laser Doppler velocimetry in a cylindrical resonator filled with air at atmospheric pressure at high intensity sound levels. The compressible Navier-Stokes equations are solved numerically with high resolution finite difference schemes. The resonator is excited by shaking it along the axis at imposed frequency. Results of measurements and of numerical calculation are compared with results given in the literature and with each other. As expected, the axial streaming velocity measured and calculated agrees reasonably well with the slow streaming theory for small ReNL but deviates significantly from such predictions for fast streaming (ReNL > 1). Both experimental and numerical results show that when ReNL is increased, the center of the outer streaming cells are pushed toward the acoustic velocity nodes until counter-rotating additional vortices are generated near the acoustic velocity antinodes

Synthesis and biological evaluation of novel substituted pyrrolo[1,2-a]quinoxaline derivatives as inhibitors of the human protein kinase CK2

Herein we describe the synthesis and properties of substituted phenylaminopyrrolo[1,2-a]quinoxaline-carboxylic acid derivatives as a novel class of potent inhibitors of the human protein kinase CK2. A set of 15 compounds was designed and synthesized using convenient and straightforward synthesis protocols. The compounds were tested for inhibition of human protein kinase CK2, which is a potential drug target for many diseases including inflammatory disorders and cancer. New inhibitors with IC50 in the micro- and sub-micromolar range were identified. The most promising compound, the 4-[(3-chlorophenyl)amino]pyrrolo[1,2-a]quinoxaline-3-carboxylic acid 1c inhibited human CK2 with an IC50 of 49 nM. Our findings indicate that pyrrolo[1,2-a]quinoxalines are a promising starting scaffold for further development and optimization of human protein kinase CK2 inhibitorsFil: Guillon, Jean. Universite de Bordeaux; Francia;Fil: Le Borgne, Marc. Université de Lyon; Francia;Fil: Rimbault, Charlotte. Universite de Bordeaux; Francia;Fil: Moreau, Stéphane. Universite de Bordeaux; Francia;Fil: Savrimoutou, Solène. Universite de Bordeaux; Francia;Fil: Pinaud, Noël. Universite de Bordeaux; Francia;Fil: Baratin, Sophie. Universite de Bordeaux; Francia;Fil: Marchivie, Mathieu. Universite de Bordeaux; Francia;Fil: Roche, Séverine. Universite de Bordeaux; Francia;Fil: Bollacke, Andre. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania;Fil: Pecci, Adali. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Fisiol., Biol.molecular y Neurociencias; Argentina;Fil: Alvarez, Lautaro Damian. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Unid.microanal.y Met.fisicos En Quim.org.(i); Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Departamento de Quimica Organica;Fil: Desplat, Vanessa. Universite de Bordeaux; Francia;Fil: Joachim, Jose. Institut für Pharmazeutische und Medizinische Chemie. Westfälische Wilhelms-Universität Münster; Alemania

Development of an innovative adenovirus-inspired self-assembling vaccine platform rapidly adaptable to coronaviruses and other emergent viruses

The COVID-19 pandemic clearly shows how emergent diseases can cause severe global health and economic problems. We must be prepared to react swiftly against new pathogenic agents and this requires the development of vaccines that are safe, efficient in the long-term and easily adaptable with a short revision time. To this end, the COVID-19 mRNA and adenoviral vector vaccines have been spectacular successes, permitting rapid vaccination across the world in an unprecedented manner. Here we report the design of a new adenovirus-derived vaccine technology based on non-infectious pseudo-viral nanoparticles from the serotype 3 human adenovirus. Each nanoparticle comprises sixty identical proteins that assemble to form a 30 nm diameter spherical particle. A sequence has been engineered into the surface of this protein that enables the display of a covalently-bound target antigens. To demonstrate the efficiency of this approach, we added the SARS-CoV 2 spike protein receptor binding domain (RBD), that interacts with host cell ACE2 receptors, to the surface of the nanoparticles. We first showed that the glycosylated RBD retained its ACE2-binding function when displayed on nanoparticles. We then measured the in vivo humoral response of our vaccine candidate in mice and observed a strong antibody response after the prime injection; further levels were achieved following a second booster injection. In mice preimmunized with underivatized adenoviral nanoparticles, we tested if adenovirus seroprevalence, as frequently observed in humans, was detrimental to the RBD-mediated protection provided by our vaccine candidate. Interestingly, a strong anti-coronaviral response was still observed suggesting that existing circulating anti-adenovirus antibodies are not deleterious to our vaccine platform. We then performed pseudo-CoV 2 neutralization assays and obtained higher ID50 values than observed with COVID-19 convalescent sera, thus showing the high potential efficacy of our vaccine platform. This new vaccine technology is a tool that is easily adaptable to future SARS-CoV 2 variants and, more generally, to future emergent viruses and pathogens

Neurology

The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery). We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up). We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [-0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93-1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate. Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias.Observatoire Français de la Sclérose en Plaque

Vérification formelle de la non-traçabilité pour les protocoles à état : entre modèles symboliques et calculatoires

The ever-increasing dependency on computer systems justifies significant concerns over privacy, and notably calls for communication protocols that ensure some security properties such as unlinkability. Formally specifying this property is difficult and context-dependent, and verifying it is complex. Therefore, providing solid mathematical foundations and computer-assisted methods is becoming crucial, but current techniques are not sufficient to analyze unlinkability for stateful protocols. In this manuscript, we address both the modelling issue and the verification issue. We first propose a precise definition of unlinkability and discuss how existing notions are inadequate for our class of stateful protocols. Then, we address the issue of computer-assisted verification. We develop two approaches, both illustrated with case studies. Our first approach is a verification method based on sufficient conditions in the symbolic model. Our second approach is a framework and an interactive prover allowing us to mechanize proofs of security protocols for an arbitrary number of sessions in the computational model.La dépendance de plus en plus grande à l'égard des systèmes informatiques soulève d'importantes questions en terme de vie privée, et nécessite notamment des protocoles de communication garantissant des propriétés de sécurité telles que la non-traçabilité. Spécifier formellement cette propriété est difficile et dépendant du contexte, et la vérifier est d'autant plus complexe. Fournir des bases mathématiques solides et des méthodes assistées par ordinateur devient donc crucial, mais les techniques actuelles ne sont pas satisfaisantes pour analyser la non-traçabilité des protocoles à état. Dans ce manuscrit de thèse, nous abordons à la fois la question de la modélisation et de la vérification. Tout d'abord, nous proposons une définition précise de non-traçabilité et expliquons pourquoi les notions actuelles ne sont pas adaptées à notre classe de protocoles à état. Ensuite, nous abordons la question de la vérification assistée par ordinateur. Nous développons deux approches, illustrées par des études de cas. Notre première approche est une méthode de vérification basée sur des conditions suffisantes dans le modèle symbolique. Notre deuxième approche est un cadre théorique et un assistant de preuve interactif permettant de mécaniser des preuves de protocoles cryptographiques pour un nombre arbitraire de sessions dans le modèle calculatoire

A Method for Proving Unlinkability of Stateful Protocols

International audienceThe rise of contactless and wireless devices such as mobile phones and RFID chips justifies significant concerns over privacy, and calls for communication protocols that ensure some form of unlinkability. Formally specifying this property is difficult and context-dependent, and analysing it is very complex; as is common with security protocols, several incorrect unlinkability claims can be found in the literature. Formal verification is therefore desirable, but current techniques are not sufficient to directly analyse unlinkability. In [Hirschi et al., S&P'19], two conditions have been identified that imply unlinkability and can be automatically verified. This work, however, only considers a restricted class of protocols. We adapt their formal definition as well as their proof method to the common setting of RFID authentication protocols, where readers access a central database of authorised users. Moreover, we also consider protocols where readers may update their database, and tags may also carry a mutable state. We propose sufficient conditions to ensure unlinkability, find new attacks, and obtain new proofs of unlinkability using Tamarin to establish our sufficient conditions

Post-Linear Pottery cultural boundary and repopulation of the German Rhineland:Revisiting the Western contacts hypothesis

International audienceThe lack of consensus surrounding the macroscopic determination of high-quality black flint discovered at the Aldenhoven Plateau sites (Rhineland, NorthWestern Germany) from the beginning of the Middle Neolithic has far-reaching consequences for the anthropological understanding of the socio-cultural dynamics involved in the neolithization of NorthWestern Europe. This flint has been assigned to Western Belgian 'Obourg' flint type and is used as a key indicator of strong links between populations from West Belgium (Mons Basin) and the German Rhineland at the beginning of the 5th millennium BC. Here, we present an integrated study of this flint using geochemical and lithic technological approaches. This work rules out attribution of the analysed flint artefacts to the Upper Cretaceous flint sources of the Mons Basin; however, the exact origin of the black flint used in the Rhineland remains unanswered. Our results do not support the hypothesis of intensive contact between populations from West Belgium and the German Rhineland and highlights the urgent need for further combined petrographic and geochemical analyses in the region, particularly on geological samples, in order to build up an extensive and reliable comparative reference collection

Test of single degree of freedom acoustic treatment impedance models for multimodal acoustic propagation in duct with flow

International audiencePassive acoustic treatments, also called liners, are the main solution to noise problems. The Single Degree Of Freedom (SDOF) acoustic treatment, composed of a thin material (perforated plate) affixed to air cavities with a rigid bottom, constitutes a solution. Predicting sound level reduction by an SDOF treatment requires reliable acoustic impedance models. An experimental/numerical method has been developed for a duct with an acoustic treatment to test acoustic impedance models of SDOF treatment with a multimodal propagation in the presence of a mean flow. This method is based on the comparison of experimental results from an aeroacoustic bench composed of a circular duct with a treated area, and numerical results from an FEM-PML axisymmetric model based on Galbrun's equation. The numerical results are confronted with experimental results to test impedance models up to M 0 ¼ 60:25

Cracking the Stateful Nut: Computational Proofs of Stateful Security Protocols using the Squirrel Proof Assistant

International audienceBana and Comon have proposed a logical approach to proving protocols in the computational model, which they call the Computationally Complete Symbolic Attacker (CCSA). The proof assistant Squirrel implements a verification technique that elaborates on this approach, building on a meta-logic over the CCSA base logic. In this paper, we show that this meta-logic can naturally be extended to handle protocols with mutable states (key updates, counters, etc.) and we extend \Squirrel's proof system to be able to express the complex proof arguments that are sometimes required for these protocols. Our theoretical contributions have been implemented in Squirrel and validated on a number of case studies, including a proof of the YubiKey and YubiHSM protocols