Showing papers by "École normale supérieure de Cachan published in 2020"

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial

Abstract: Objective: To assess masitinib in the treatment of ALS. Methods: Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.0 m...

A protein assembly mediates Xist localization and gene silencing

Abstract: Nuclear compartments have diverse roles in regulating gene expression, yet the molecular forces and components that drive compartment formation remain largely unclear1. The long non-coding RNA Xist establishes an intra-chromosomal compartment by localizing at a high concentration in a territory spatially close to its transcription locus2 and binding diverse proteins3-5 to achieve X-chromosome inactivation (XCI)6,7. The XCI process therefore serves as a paradigm for understanding how RNA-mediated recruitment of various proteins induces a functional compartment. The properties of the inactive X (Xi)-compartment are known to change over time, because after initial Xist spreading and transcriptional shutoff a state is reached in which gene silencing remains stable even if Xist is turned off8. Here we show that the Xist RNA-binding proteins PTBP19, MATR310, TDP-4311 and CELF112 assemble on the multivalent E-repeat element of Xist7 and, via self-aggregation and heterotypic protein-protein interactions, form a condensate1 in the Xi. This condensate is required for gene silencing and for the anchoring of Xist to the Xi territory, and can be sustained in the absence of Xist. Notably, these E-repeat-binding proteins become essential coincident with transition to the Xist-independent XCI phase8, indicating that the condensate seeded by the E-repeat underlies the developmental switch from Xist-dependence to Xist-independence. Taken together, our data show that Xist forms the Xi compartment by seeding a heteromeric condensate that consists of ubiquitous RNA-binding proteins, revealing an unanticipated mechanism for heritable gene silencing.

Octupolar Plasmonic Nanosensor Based on Ordered Arrays of Triangular Au Nanopillars for Selective Rotavirus Detection

Abstract: Technologies based on plasmonic nanostructures are a rapidly growing field that aims to be a valid alternative to conventional diagnostic tools. One of the main goals in their technological develop...

The direct subordination of universities to the accumulation of capital

Abstract: Universities have historically contributed to the reproduction of capitalism. However, they have been historically conceived as a separate sphere or institution detached from the Market, thus only ...

Immunomodulatory role of Interleukin-33 in large vessel vasculitis

Abstract: The mechanisms regulating inflammation in large vessels vasculitis (LVV) are poorly understood. Interleukin 33 (IL-33) has been shown to license innate and adaptive immunity by enhancing Th2 cytokines production. We aimed to examine the role of IL-33 in the immunomodulation of T cell activation in LVV. T cell homeostasis and cytokines production were determined in peripheral blood from 52 patients with giant cell arteritis (GCA) and 50 healthy donors (HD), using Luminex assay, flow cytometry, quantitative RT-PCR and by immunofluorescence analysis in inflammatory aorta lesions. We found increased level of IL-33 and its receptor ST2/IL-1R4 in the serum of patient with LVV. Endothelial cells were the main source of IL-33, whereas Th2 cells, Tregs and mast cells (MC) express ST2 in LVV vessels. IL-33 had a direct immunomodulatory impact by increasing Th2 and Tregs. IL-33 and MC further enhanced Th2 and regulatory responses by inducing a 6.1 fold increased proportion of Tregs (p = 0.008). Stimulation of MC by IL-33 increased indoleamine 2 3-dioxygenase (IDO) activity and IL-2 secretion. IL-33 mRNA expression was significantly correlated with the expression of IL-10 and TGF-β within aorta inflammatory lesions. To conclude, our findings suggest that IL-33 may exert a critical immunoregulatory role in promoting Tregs and Th2 cells in LVV.

SUGT1 controls susceptibility to HIV-1 infection by stabilizing microtubule plus-ends

Abstract: Understanding the viral-host cell interface during HIV-1 infection is a prerequisite for the development of innovative antiviral therapies. Here we show that the suppressor of G2 allele of skp1 (SUGT1) is a permissive factor for human immunodeficiency virus (HIV)-1 infection. Expression of SUGT1 increases in infected cells on human brain sections and in permissive host cells. We found that SUGT1 determines the permissiveness to infection of lymphocytes and macrophages by modulating the nuclear import of the viral genome. More importantly, SUGT1 stabilizes the microtubule plus-ends (+MTs) of host cells (through the modulation of microtubule acetylation and the formation of end-binding protein 1 (EB1) comets). This effect on microtubules favors HIV-1 retrograde trafficking and replication. SUGT1 depletion impairs the replication of HIV-1 patient primary isolates and mutant virus that is resistant to raltegravir antiretroviral agent. Altogether our results identify SUGT1 as a cellular factor involved in the post-entry steps of HIV-1 infection that may be targeted for new therapeutic approaches.

Migration, trapping, and venting of gas in a soft granular material

Abstract: Gas migration through a soft, liquid-saturated granular material involves a strong coupling between the motion of the gas and the deformation of the material. This process is central to many natural and industrial systems, such as the generation and venting of gases from lake beds and waste ponds. Using high-resolution experiments and a simple mechanistic model, grain-scale fluid and solid mechanics are linked with macroscopic migration, trapping, and venting. The largest amount of trapping and the largest venting events are found to occur at intermediate confining stress.

Thermal Stability of Superconductors

Abstract: A stability criterion is worked out for the superconducting phase. The validity of a prerequisite, established previously for persistent currents, is thereby confirmed. Temperature dependence is given for the specific heat and concentration of superconducting electrons in the vicinity of the critical temperature $T_c$. The isotope effect, mediated by electron-phonon interaction and hyperfine coupling, is analyzed. Several experiments, intended at validating this analysis, are presented, including one giving access to the specific heat of high-$T_c$ compounds.

Apprenticeship Learning for a Predictive State Representation of Anesthesia

Abstract: Objective: In this paper, we present an original decision support algorithm to assist the anesthesiologists delivery of drugs to maintain the optimal Depth of Anesthesia (DoA). Methods: Derived from a Transform Predictive State Representation algorithm (TPSR), our model learned by observing anesthesiologists in practice. This framework, known as apprenticeship learning, is particularly useful in the medical field as it is not based on an exploratory process – a prohibitive behavior in healthcare. The model only relied on the four commonly monitored variables: Heart Rate (HR), the Mean Blood Pressure (MBP), the Respiratory Rate (RR) and the concentration of anesthetic drug (AAFi). Results: Thirty-one patients have been included. The performances of the model is analyzed with metrics derived from the Hamming distance and cross entropy. They demonstrated that low rank dynamical system had the best performances on both predictions and simulations. Then, a confrontation of our agent to a panel of six real anesthesiologists demonstrated that $\boldsymbol{95.7}$ % of the actions were valid. Conclusion: These results strongly support the hypothesis that TPSR based models convincingly embed the behavior of anesthesiologists including only four variables that are commonly assessed to predict the DoA. Significance: The proposed novel approach could be of great help for clinicians by improving the fine tuning of the DoA. Furthermore, the possibility to predict the evolutions of the variables would help preventing side effects such as low blood pressure. A tool that could autonomously help the anesthesiologist would thus improve safety-level in the surgical room.

Th1-Polarized, Dengue Virus-Activated Human Mast Cells Induce Endothelial Transcriptional Activation and Permeability.

Abstract: Dengue virus (DENV), an arbovirus, strongly activates mast cells (MCs), which are key immune cells for pathogen immune surveillance. In animal models, MCs promote clearance of local peripheral DENV infections but, conversely, also promote pathological vascular leakage when widely activated during systemic DENV infection. Since DENV is a human pathogen, we sought to ascertain whether a similar phenomenon could occur in humans by characterizing the products released by human MCs (huMCs) upon direct (antibody-independent) DENV exposure, using the phenotypically mature huMC line, ROSA. DENV did not productively infect huMCs but prompted huMC release of proteases and eicosanoids and induced a Th1-polarized transcriptional profile. In co-culture and trans-well systems, huMC products activated human microvascular endothelial cells, involving transcription of vasoactive mediators and increased monolayer permeability. This permeability was blocked by MC-stabilizing drugs, or limited by drugs targeting certain MC products. Thus, MC stabilizers are a viable strategy to limit MC-promoted vascular leakage during DENV infection in humans.

Determining the position of a single spin relative to a metallic nanowire

Abstract: The nanoscale localization of individual paramagnetic defects near an electrical circuit is an important step for realizing hybrid quantum devices with strong spin-microwave photon coupling. Here, we demonstrate the fabrication of an array of individual NV centers in diamond near a metallic nanowire deposited on top of the substrate. We determine the relative position of each NV center with $\sim$10\,nm accuracy, using it as a vector magnetometer to measure the field generated by passing a dc current through the wire.

Optimization of fiber to resonator coupling

Abstract: In this poster we are interested in knowing how multi-physic optimization can simulate and be helpful to find an optimal design for resonator coupling. It is based on COMSOL multi-physics software.

3D PCB package for GaN inverter leg with low EMC feature

Abstract: This paper presents the adaptation of a 3D integration concept previously used with vertical devices to lateral GaN devices. This 3D integration allows to reduce loop inductance, to ensure more symmetrical design with especially limited Common Mode emission, thanks to a low middle point stray capacitance. This reduction has been achieved by both working on the power layout and including a specific shield between the devices and the heatsink. The performances of this 3D layout have been verified in comparison with a more conventional 2D implementation, using both simulations and measurements.

Learning the piece-wise constant graph structure of a varying Ising model

Abstract: This work focuses on the estimation of multiple change-points in a time-varying Ising model that evolves piece-wise constantly. The aim is to identify both the moments at which significant changes occur in the Ising model, as well as the underlying graph structures. For this purpose, we propose to estimate the neighborhood of each node by maximizing a penalized version of its conditional log-likelihood. The objective of the penalization is twofold: it imposes sparsity in the learned graphs and, thanks to a fused-type penalty, it also enforces them to evolve piece-wise constantly. Using few assumptions, we provide two change-points consistency theorems. Those are the first in the context of unknown number of change-points detection in time-varying Ising model. Finally, experimental results on several synthetic datasets and a real-world dataset demonstrate the performance of our method.

Enumerating Answers to First-Order Queries over Databases of Low Degree

Abstract: A class of relational databases has low degree if for all $\delta>0$, all but finitely many databases in the class have degree at most $n^{\delta}$, where $n$ is the size of the database. Typical examples are databases of bounded degree or of degree bounded by $\log n$. It is known that over a class of databases having low degree, first-order boolean queries can be checked in pseudo-linear time, i.e. for all $\epsilon>0$ in time bounded by $n^{1+\epsilon}$. We generalize this result by considering query evaluation. We show that counting the number of answers to a query can be done in pseudo-linear time and that after a pseudo-linear time preprocessing we can test in constant time whether a given tuple is a solution to a query or enumerate the answers to a query ith constant delay.

Supplement to 'The Inverse Product Differentiation Logit Model'

Abstract: Full paper available at https://ssrn.com/abstract=3141041 We first present simulations investigating some properties of the Inverse Product Differentiation Logit (IPDL) model. Next, we provide a range of general methods for building Generalized Logit (GL) models along with illustrative examples that go beyond the IPDL model.

Unsupervised Variational Bayesian Kalman Filtering For Large-Dimensional Gaussian Systems

Abstract: This paper considers the unsupervised filtering problem for large-dimensional linear and Gaussian systems, a setup in which the optimal Kalman filter (KF) might not be usable due to the exorbitant computational cost and storage requirements. For this problem, we propose two efficient algorithms based on the variational Bayesian (VB) approach. The first algorithm is an extension of a recent VBKF algorithm to the unsupervised framework, whereas the second algorithm is an accelerated version of the first one, derived based on the adaptation of subspace optimization methods in Hilbert spaces into the space of probability density functions. Furthermore, both algorithms account for the sparsity in the state and observations through heavy-tailed Student-t priors. Results of numerical experiments conducted on a dynamical tomography problem to assess the performances of the proposed schemes are presented.

The Inverse Product Differentiation Logit Model

Abstract: We propose the Inverse Product Differentiation Logit (IPDL) model, a structural (inverse) demand model for differentiated products that captures market segmentation along several possibly overlapping dimensions. It generalizes the nested logit model to allow richer substitution patterns, including complementarity in demand, and can be estimated by linear instrumental variable regression using aggregate data. We use the IPDL model to estimate the demand for cereals in Chicago. We then extend it to a general demand model that is consistent with a utility model of heterogeneous and utility-maximizing consumers.

Discrete Choice and Rational Inattention: A General Equivalence Result

Abstract: This note establishes a general equivalence between discrete choice and rational inattention models. We exploit convex-analytic properties of these models to show that the choice probabilities emerging from any additive random utility discrete choice model can be rationalized from a class of suitably generalized rational inattention models, and vice versa. Thus any discrete choice model can be given an interpretation in terms of boundedly rational behavior.

Pomset bisimulation and unfolding for reset Petri nets

Abstract: Reset Petri nets are a particular class of Petri nets where transition firings can remove all tokens from a place without checking if this place actually holds tokens or not. In this paper we look at partial order semantics of reset Petri nets. In particular, we propose a pomset bisimulation for comparing their concurrent behaviours. Building on this pomset bisimulation we then propose a generalization of the standard finite complete prefixes of unfolding for this class of Petri nets.

Modeling and Study of Hydrodynamic flow within the Preneutralizer Reactor using CFD Approach

Abstract: Mathematical modelling and numerical simulations are widely used in the petrochemical industries for operator training, design, and process optimization. However, there is a lack of rigorous numerical modelling and simulations in the phosphate fertilizer industry. There exist many challenges in the production systems of phosphate fertilizers including (i) multiphase flows in the system involving liquids, solids or gases, (ii) particles with different size distributions, and (iii) dynamic variations in the physical properties including rheology and thermodynamic behavior. In the current study, using well-established techniques from computational fluid dynamics, we develop a model for the numerical simulation of multiphase flows in a conditioner operation unit used in the phosphate fertilizers facilities. The proposed model deals with the first step in the process, consisting on the preneutralizer, and it uses the Reynolds-averaged Navier-Stokes equations for modeling turbulent flow in the system. The preneutralization consist on a partial reaction between ammonia and phosphoric acid. Numerical results are presented for several scenarios and we particularly show the importance of the baffles on eliminating vortices, and also their effect on the different hydrodynamic performance criteria. This approach can be used to describe the behavior of reaction systems within this type of industrial plants and the analysis of the other sub-process of the fertilizer plant is an ongoing work.

On flat lossy channel machines

Abstract: We show that reachability, repeated reachability, nontermination and unboundedness are NP-complete for Lossy Channel Machines that are flat, i.e., with no nested cycles in the control graph. The upper complexity bound relies on a fine analysis of iterations of lossy channel actions and uses compressed word techniques for efficiently reasoning with paths of exponential lengths. The lower bounds already apply to acyclic or single-path machines.

Migrants’ Access to Social Protection in Luxembourg

Abstract: For over 100 years, Luxembourg has been an immigration country. In 2019, 93% of the resident population are European citizens. Luxembourg nationals represent 53% of the entire population, nationals from other European Union (EU) Member States 40% and non-EU foreigners 7%. These three groups have different rights regarding residence and access to work in Luxembourg. All persons engaged in a professional activity in Luxembourg, whatever their nationality or residence, are covered by a compulsory social security system. The essence of the Welfare State, whose origins date back to the Customs Union with Germany, is Bismarckian. It protects workers against the following social risks: unemployment, sickness and maternity, long-term care needs, family, invalidity and old age. Family members are entitled to derived rights. Regarding health-care and old age pensions, it is possible to subscribe a voluntary insurance under specific conditions. A guaranteed minimum income, recently reformed, is accessible to everybody residing legally in Luxembourg under specific conditions. For non-EU foreigners, a residence for at least 5 years during the last 20 years or the possession of a long-term resident status is required.

Method for detecting icing and de-icing

Abstract: The invention relates to a device for detecting icing and de-icing of a wind turbine blade, characterized in that it comprises: a sensor, placed on the surface of a blade, and comprising a first so-called “receiving” antenna, a second so-called “emitting” antenna, and a frequency divider inserted between said first and second antennas; and an interrogator, configured to emit an electromagnetic wave towards the receiving antenna of said sensor, and to receive an electromagnetic wave from the emitting antenna of said sensor.

Apparatus And Method For Alarm Management

Abstract: A Petri net that corresponds to the mathematical model is determined and the Petri net includes the domination relationships and mutual dependency relationships between individual alarms. The Petri net is analyzed to determine a set of construction rules. The construction rules define an approach to reduce the number of alarms presented to an operator or a computer program.