Nucleolar Localization of HIV-1 Rev Is Required, Yet Insufficient for Production of Infectious Viral Particles.

Combination antiretroviral therapy fails in complete suppression of HIV-1 due to drug resistance and persistent latency. Novel therapeutic intervention requires knowledge of intracellular pathways responsible for viral replication, specifically those untargeted by antiretroviral drugs. An understudied phenomenon is the nucleolar localization of Rev phosphoprotein, which completes nucleocytoplasmic transport of unspliced/partially spliced HIV mRNA through multimerization with intronic cis-acting targets-the Rev-response element (RRE). Rev contains a nucleolar localization signal (NoLS) comprising the COOH terminus of the arginine-rich motif for accumulation within nucleoli-speculated as the interaction ground for Rev with cellular proteins mediating mRNA-independent nuclear export and splicing. Functionality of Rev nucleolar access during HIV-1 production and infection was investigated in the context of deletion and single-point mutations within Rev-NoLS. Mutations induced upon Rev-NoLS are hypothesized to inactivate the HIV-1 infectious cycle. HIV-1HXB2 replication ceased with Rev mutations lacking nucleolar access due to loss or replacement of multiple arginine residues. Rev mutations missing single arginine residues remained strictly nucleolar in pattern and participated in proviral production, however, with reduced efficiency. Viral RNA packaging also decreased in efficiency after expression of nucleolar-localizing mutations. These results were observed during propagation of variant HIV-1NL4-3 containing nucleolar-localizing mutations within the viral backbone (M4, M5, and M6). Lentiviral particles produced with Rev single-point mutations were transducible at extremely low frequency. Similarly, HIV-1NL4-3 Rev-NoLS variants lost infectivity, unlike virulent WT (wild type) HIV-1NL4-3. HIV-1NL4-3 variants were capable of CD4+ host entry and reverse transcription as WT HIV-1NL4-3, but lacked ability to complete a full infectious cycle. We currently reveal that viral integration is deregulated in the presence of Rev-NoLS mutations

Introduction » au dossier « Méthodologie complexe et plurielle dans la recherche doctorale en sciences sociales

L’hybridation méthodologique au coeur d’une journée d’étude à destination des doctorant.e.s de l’UMR ES

Spontaneous self-ordered states of vortex-antivortex pairs in a Polariton Condensate

Polariton condensates have proved to be model systems to investigate topological defects, as they allow for direct and non-destructive imaging of the condensate complex order parameter. The fundamental topological excitations of such systems are quantized vortices. In specific configurations, further ordering can bring the formation of vortex lattices. In this work we demonstrate the spontaneous formation of ordered vortical states, consisting in geometrically self-arranged vortex-antivortex pairs. A mean-field generalized Gross-Pitaevskii model reproduces and supports the physics of the observed phenomenology

The Network of Online Stolen Data Markets: How Vendor Flows Connect Digital Marketplaces

In the face of market uncertainty, illicit actors on the darkweb mitigate risk by displacing their operations across digital marketplaces. In this study, we reconstruct market networks created by vendor displacement to examine how digital marketplaces are connected on the darkweb and identify the properties that drive vendor flows before and after a law enforcement disruption. Findings show that vendors’ movement across digital marketplaces creates a highly connected ecosystem; nearly all markets are directly or indirectly connected. These network characteristics remain stable following a law enforcement operation; prior vendor flows predict vendor movement before and after the interdiction. The findings inform work on collective patterns in offender decision-making and extend discussions of displacement into digital spaces

Periodic squeezing in a polariton Josephson junction

The use of a Kerr nonlinearity to generate squeezed light is a well-known way to surpass the quantum noise limit along a given field quadrature. Nevertheless, in the most common regime of weak nonlinearity, a single Kerr resonator is unable to provide the proper interrelation between the field amplitude and squeezing required to induce a sizable deviation from Poissonian statistics. We demonstrate experimentally that weakly coupled bosonic modes allow exploration of the interplay between squeezing and displacement, which can give rise to strong deviations from the Poissonian statistics. In particular, we report on the periodic bunching in a Josephson junction formed by two coupled exciton-polariton modes. Quantum modeling traces the bunching back to the presence of quadrature squeezing. Our results, linking the light statistics to squeezing, are a precursor to the study of nonclassical features in semiconductor microcavities and other weakly nonlinear bosonic systems.Comment: 6 pages, 4 figure

Interprétation de mesures de contraintes réalisées avec une cellule doorstopper modifiée en milieu anisotrope

RÉSUMÉ Cette étude vise à généraliser aux matériaux transversalement isotropes l’interprétation de mesures réalisées avec une cellule doorstopper modifiée pour la détermination du tenseur des contraintes in situ. Les principales sources d’erreurs à différentes étapes de calculs sont discutées. Dans un premier temps, la justesse des contraintes en fond de trou est évaluée. Celles-ci sont calculées à partir des déformations relevées par la cellule doorstopper et des paramètres de déformabilité déterminés selon la procédure proposée par Corthésy et al. (1993). Des mesures de contraintes par surcarottage ainsi que des essais en laboratoire pour différents matériaux anisotropes sont simulés par éléments finis. L’erreur observée sur les contraintes en fond de trou calculées est jugée acceptable; elle s’avère être principalement due à l’interprétation de l’essai de compression diamétrale.Dans un deuxième temps, des simulations numériques sont réalisées pour déterminer le tenseur des contraintes avec trois forages dans un matériau transversalement isotrope. Suivant une hypothèse fréquemment posée en pratique, les plans d’isotropie des matériaux testés sont supposés parallèles au forage. Cette hypothèse simplificatrice entraîne un biais sur le tenseur des contraintes obtenu; le biais observé demeure toutefois acceptable. Les simulations numériques confirment que l’adaptation de la méthode conventionnelle d’obtention du tenseur des contraintes in situ aux matériaux transversalement isotropes permet une amélioration notable de la justesse du tenseur des contraintes déterminé dans de tels matériaux.Dans un troisième temps, les simulations numériques sont réinterprétées à l’aide de la méthode RPR. La généralisation de cette méthode aux matériaux transversalement isotropes est validée dans son ensemble; des cas déviants sont toutefois observés, puis expliqués. L’avantage de la méthode RPR quant à l’indépendance des points de mesure est conservé uniquement sous l’hypothèse selon laquelle les plans d’isotropie du matériau sont parallèles au forage; cette conclusion devrait être vérifiée à l’aide d’un modèle présentant des hétérogénéités d’anisotropie.----------ABSTRACT The goal of this study is to generalize to transversely isotropic materials the interpretation of modified doorstopper measurements for the determination of the ground stress tensor. Main sources of errors at different computation stages are discussed. Firstly, the accuracy of the stresses at the borehole bottom is assessed. These are calculated from the strains measured by the modified doorstopper cell and from the deformability parameters obtained according to the procedure proposed by Corthésy et al. (1993). Overcoring stress measurements and laboratory tests on different anisotropic materials are simulated using the finite element method. The error observed on the computed stresses at the borehole bottom is satisfactory; it proves to be mainly due to the interpretation of the diametrical compression test. Secondly, numerical simulations are conducted to obtain the ground stress tensor with three boreholes in a transversely isotropic material. Following an assumption frequently done in practice, the isotropy planes of the tested materials are taken parallel to the borehole. The computed stress tensor is biased because of this simplifying assumption; the observed bias remains however satisfactory. Numerical simulations confirm that adapting to transversely isotropic materials the conventional method for obtaining the ground stress tensor allows a significant improvement in the accuracy of the stress tensor determined in such materials. Thirdly, numerical simulations are reinterpreted using the RPR method. The generalization of this method to transversely isotropic materials is validated as a whole; outliers are however observed, and then explained. The advantage of the RPR method regarding the independence of measuring points is maintained only under the assumption the isotropy planes of the material are parallel to the borehole; this conclusion should be verified using a model with heterogeneous anisotropic materials

Network structure and dynamics of effective models of non-equilibrium quantum transport

Across all scales of the physical world, dynamical systems can often be usefully represented as abstract networks that encode the system's units and inter-unit interactions. Understanding how physical rules shape the topological structure of those networks can clarify a system's function and enhance our ability to design, guide, or control its behavior. In the emerging area of quantum network science, a key challenge lies in distinguishing between the topological properties that reflect a system's underlying physics and those that reflect the assumptions of the employed conceptual model. To elucidate and address this challenge, we study networks that represent non-equilibrium quantum-electronic transport through quantum antidot devices -- an example of an open, mesoscopic quantum system. The network representations correspond to two different models of internal antidot states: a single-particle, non-interacting model and an effective model for collective excitations including Coulomb interactions. In these networks, nodes represent accessible energy states and edges represent allowed transitions. We find that both models reflect spin conservation rules in the network topology through bipartiteness and the presence of only even-length cycles. The models diverge, however, in the minimum length of cycle basis elements, in a manner that depends on whether electrons are considered to be distinguishable. Furthermore, the two models reflect spin-conserving relaxation effects differently, as evident in both the degree distribution and the cycle-basis length distribution. Collectively, these observations serve to elucidate the relationship between network structure and physical constraints in quantum-mechanical models. More generally, our approach underscores the utility of network science in understanding the dynamics and control of quantum systems.Comment: 37 pages, including supplementary materia

The CUORE Cryostat: A 1-Ton Scale Setup for Bolometric Detectors

The cryogenic underground observatory for rare events (CUORE) is a 1-ton scale bolometric experiment whose detector consists of an array of 988 TeO2 crystals arranged in a cylindrical compact structure of 19 towers. This will be the largest bolometric mass ever operated. The experiment will work at a temperature around or below 10 mK. CUORE cryostat consists of a cryogen-free system based on pulse tubes and a custom high power dilution refrigerator, designed to match these specifications. The cryostat has been commissioned in 2014 at the Gran Sasso National Laboratories and reached a record temperature of 6 mK on a cubic meter scale. In this paper, we present results of CUORE commissioning runs. Details on the thermal characteristics and cryogenic performances of the system will be also given.Comment: 7 pages, 2 figures, LTD16 conference proceedin