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Multiplex digital PCR for the simultaneous quantification of a miRNA panel
No full textInternational audienceBackgroundmicroRNAs (miRNAs) are small non-coding RNAs regulating gene expression. They have attracted significant interest as biomarkers for early diagnosis, prediction and monitoring of treatment response in many diseases. As individual miRNAs often lack the required sensitivity and specificity, miRNA signatures are developed for clinical applications. Digital PCR (dPCR) is a sensitive fluorescent-based quantification method, that can be used to detect the expression of miRNAs in patient samples. Our study presents the first proof-of-concept of a multiplexed dPCR assay for the simultaneous analysis and quantification of multiple miRNAs.ResultsAfter reverse transcription (RT) using a pool of miRNA-specific stem-loop primers, dPCR was performed with a universal reverse primer and miRNA-specific forward primers along with fluorescently-labelled hydrolysis probes. Multiple experimental parameters were evaluated and strategies for modulating the observed signals were devised. The optimised assay was applied to the analysis of miRNAs from cell lines and biological samples. Although absolute quantification was lost, due to the reverse transcription step, quantification was linear for the dilution series and results were highly reproducible for independent dPCR and RT reactions. Our results confirmed the high sensitivity of dPCR for patient samples.ConclusionsWe demonstrate the feasibility and reliability of multiplexed detection and quantification of miRNAs by dPCR that can be applied in a clinical setting to evaluate miRNA signatures
Robust plug-and-play methods for highly accelerated non-Cartesian MRI reconstruction
No full textInternational audienceAchieving high-quality Magnetic Resonance Imaging (MRI) reconstruction at accelerated acquisition rates remains challenging due to the inherent ill-posed nature of the inverse problem. Traditional Compressed Sensing (CS) methods, while robust across varying acquisition settings, struggle to maintain good reconstruction quality at high acceleration factors (≥ 8). Recent advances in deep learning have improved reconstruction quality, but purely data-driven methods are prone to overfitting and hallucination effects, notably when the acquisition setting is varying. Plug-and-Play (PnP) approaches have been proposed to mitigate the pitfalls of both frameworks. In a nutshell, PnP algorithms amount to replacing suboptimal handcrafted CS priors with powerful denoising deep neural network (DNNs). However, in MRI reconstruction, existing PnP methods often yield suboptimal results due to instabilities in the proximal gradient descent (PGD) schemes and the lack of curated, noiseless datasets for training robust denoisers. In this work, we propose a fully unsupervised preprocessing pipeline to generate clean, noiseless complex MRI signals from multicoil data, enabling training of a high-performance denoising DNN. Furthermore, we introduce an annealed Half-Quadratic Splitting (HQS) algorithm to address the instability issues, leading to significant improvements over existing PnP algorithms. When combined with preconditioning techniques, our approach achieves state-of-the-art results, providing a robust and efficient solution for high-quality MRI reconstruction.</div
Numerical assessment of ICRF-specific Plasma-Wall Interaction in the new ITER baseline using the SSWICH-SW code
No full textInternational audienceIn 2023, switching the material on the first wall of ITER to tungsten (W) was recommended. In magnetic Fusion devices, waves in the Ion Cyclotron Range of Frequencies (ICRF) interact with the Scrape-Off Layer (SOL) via RF-sheath rectification. This contribution re-assesses this phenomenon close to the ITER ICRF antenna, focusing on the ICRF-specific gross erosion of W from the antenna port sides. Our quantitative estimates rely on predictive multi-2D numerical simulations of the ICRF antenna environment using the SSWICH-SW code. They combine Slow Wave propagation from the antenna mouth to the SOL, the excitation of RF oscillations in the sheath voltages at the antenna port sides and a subsequent DC biasing of the SOL. Maps of the parallel RF electric field at the antenna mouth, from the antenna code TOPICA, excite the system. Our simulations cover more than four decades in the local densities near the antenna. Since both the sputtering and the local heat loads are proportional to the local particle fluxes, the most intense Plasma-Wall Interaction is found for high local density, with or without ICRF waves. In these conditions, larger margins also exist for coupling the ICRF power. We tested several operational trade-offs between these two constraints. The simulated target plasma contains 2% of neon ions. These are efficient at sputtering W, already at low accelerating voltages. Consequently, although the RF-sheath rectification sufficiently amplifies the local sputtering at the antenna port for a detection using visible spectroscopy, the ICRF-induced increment of the gross W production represents at worse 22% of the W source expected from thermal sheaths over the eighteen out-board mid-plane ports. An upper bound, independent of our main assumptions, is proposed for this enhancement factor. This moderate expected global increase questions the ability to detect ICRF-specific W contamination of the plasma core, even at the planned maximal ICRF power
PICOSEC Micromegas Precise-timing Detectors: Development towards Large-Area and Integration
No full textInternational audiencePICOSEC Micromegas (MM) is a precise timing gaseous detector based on a Cherenkov radiator coupled with a semi-transparent photocathode and an MM amplifying structure. The detector conceprt was successfully demonstrated through a single-channel prototype, achieving sub-25 ps time resolution with Minimum Ionizing Particles (MIPs). A series of studies followed, aimed at developing robust, large-area, and scalable detectors with high time resolution, complemented by specialized fast-response readout electronics. This work presents recent advancements towards large-area resistive PICOSEC MM, including 10 10 area prototypes and a 20 20 prototype, which features the jointing of four photocathodes. The time resolution of these detector prototypes was tested during the test beam, achieved a timing performance of around 25 ps for individual pads in MIPs. Meanwhile, customized electronics have been developed dedicated to the high-precision time measurement of the large-area PICOSEC MM. The performance of the entire system was evaluated during the test beam, demonstrating its capability for large-area integration. These advancements highlight the potential of PICOSEC MM to meet the stringent requirements of future particle physics experiments
Using multiomic integration to improve blood biomarkers of major depressive disorder: a case-control study
No full textInternational audienceBackground Major depressive disorder (MDD) is a leading cause of disability, with a twofold increase in prevalence in women compared to men. Over the last few years, identifying molecular biomarkers of MDD has proven challenging, reflecting interactions among multiple environmental and genetic factors. Recently, epigenetic processes have been proposed as mediators of such interactions, with the potential for biomarker development.Methods We characterised gene expression and two mechanisms of epigenomic regulation, DNA methylation (DNAm) and microRNAs (miRNAs), in blood samples from a cohort of individuals with MDD and healthy controls (n = 169). Case-control comparisons were conducted for each omic layer. We also defined gene coexpression networks, followed by step-by-step annotations across omic layers. Third, we implemented an advanced multiomic integration strategy, with covariate correction and feature selection embedded in a cross-validation procedure. Performance of MDD prediction was systematically compared across 6 methods for dimensionality reduction, and for every combination of 1, 2 or 3 types of molecular data. Feature stability was further assessed by bootstrapping.Findings Results showed that molecular and coexpression changes associated with MDD were highly sex-specific and that the performance of MDD prediction was greater when the female and male cohorts were analysed separately, rather than combined. Importantly, they also demonstrated that performance progressively increased with the number of molecular datasets considered.Interpretation Informational gain from multiomic integration had already been documented in other medical fields. Our results pave the way toward similar advances in molecular psychiatry, and have practical implications for developing clinically useful MDD biomarkers.</div
Near-infrared study of radiation damage in ion-irradiated cerium dioxide and cerium-gadolinium dioxide
No full textInternational audienceRadiation damage is studied in ion-irradiated sintered CeO2 and (Ce, Gd)O2-x samples. Near Infra-red (NIR) spectra were recorded at room temperature for wavenumbers between 2800 and 11,000 cm−1 (i.e. ∼0.9–3.57 µm in wavelength and ∼0.35–1.36 eV in photon energy). Measurements were carried out by using the diffuse reflectivity mode for all of these sintered samples. Samples were irradiated with 100-MeV Kr, 200-MeV Xe, and 36-MeV W ions up to 1 × 1014 cm−2. A sintered (Ce, Gd)O2-x sample for 5 mol% Gd2O3 was also irradiated with 12-MeV Ar ions at 2 × 1014 cm−2. Four broad absorption bands centered at 3700, 4100, 6000, and 7600 cm−1 (i.e. ∼0.46, 0.51, 0.74, and 0.94 eV) are deduced from fits of the FTIR spectra for the ion-irradiated sintered CeO2 and (Ce, Gd)O2-x samples accompanied by a change in color from ivory to green. No such bands are recorded for the virgin (Ce, Gd)O2-x samples with 5, 10, and 15 mol% Gd2O3 with an increasing amount of oxygen vacancies. Absorption bands are tentatively assigned to electronic transitions involving cerium vacancy levels in the band gap, also observed under high-energy electron irradiation. The possible effects of either electronic excitations or nuclear collisions in this damage process are discussed
New insights into the distribution of the topmost gap in random walks and Lévy flights
No full text20 pages, 4 figuresBuilding upon the knowledge of the distribution of the first positive position reached by a random walker starting from the origin, one can derive new results on the statistics of the gap between the largest and second-largest positions of the walk, and recover known ones in a more direct manner
Refinement of the primate corticospinal pathway during prenatal development
No full textAbstract Perturbation of the developmental refinement of the corticospinal pathway leads to motor disorders. In non-primates developmental refinement is well documented, however in primates invasive investigations of the developing corticospinal pathway have been confined to neonatal and postnatal stages when refinement is relatively modest. Here, we investigated the developmental changes in the distribution of corticospinal projection neurons in cynomolgus monkey. Injections of retrograde tracer at the cervical levels of the spinal cord at embryonic day (E) 95 and E105 show that (i) areal distribution of back-labeled neurons is more extensive than in the neonate and dense labeling is found in prefrontal, limbic, temporal and occipital cortex; (ii) distributions of contra- and ipsilateral projecting corticospinal neurons are comparable in terms of location and numbers of labeled neurons, in contrast to the adult where the contralateral projection is an order of magnitude higher than the ipsilateral projection. Findings from one largely restricted injection suggest a hitherto unsuspected early innervation of the gray matter. In the fetus there was in addition dense labeling in the central nucleus of the amygdala, the hypothalamus, the subthalamic nucleus and the adjacent region of the zona incerta, subcortical structures with only minor projections in the adult control
Core/shell 1T/2H-MoS2 nanoparticle induced synergistic effects for enhanced hydrogen evolution reaction
No full textInternational audienceGreen hydrogen is a highly sought-after clean fuel for the next generation of engines aimed at achieving net-zero emissions. Herein, we design and fabricate a mixed-phase core/shell nanoparticles consisting of a semiconducting 2H-MoS2 core and a metallic 1T-MoS2 coating. The core/shell exhibits spherical morphology with an average diameter of 60 nm. To leverage this unique structure, we develop a photocathode device composed of 1T/2H-MoS2 core/shell integrated with p-type silicon to catalyze hydrogen evolution reaction via water splitting driven by solar energy. The core/shell device demonstrates, at zero bias, a remarkable current density of −13.5 ± 1 mA/cm2 and an onset potential of 110 mV. Additionally, the device exhibited a rapid photoresponse time and a high incident photon-to-current efficiency reaching 80 % at 450 nm. Our findings highlight the synergistic effect of 1T/2H-MoS2 mixed-phase core/shell structure in developing the next generation of high-efficient photocatalysts for green hydrogen generation
Sensitivity analysis of Gagge’s Standard Effective Temperature for fan-first cooling control strategy in tropical mixed-mode buildings
No full textInternational audienceMixed-mode (MM) cooling solutions integrate ceiling fans (CF) and traditional air conditioning (AC) simultaneously in a “Fan-first” scenario, enhancing comfort while reducing energy use. However, this dual approach complicates system sizing and consumption assessment due to the added layer of comfort control. To address this, we advocate using Gagge's Standard Effective Temperature (SET) for MM cooling control in the tropics. We also evaluate its sensitivity to air velocity, clothing, and temperature, emphasising its applicability for control algorithms in Building Energy Models (BEM). BEM cooling algorithm should leverage fans' air velocity and clothing flexibility as adaptive opportunities. This study first highlights the relevance of SET over alternative models found in the literature for tropical applications. Second, we use environmental datasets to assess air velocity and clothing contributions alongside temperature setpoints through two Sensitivity Analysis (SA) techniques. Traditional Sobol's indices, assuming input independence, confirm that temperature is not the sole parameter influencing SET. More advanced Shapley Effect techniques, accommodating representative input distributions, reveal that air velocity and clothing outweigh temperature within an airspeed range of [0–2 m.s-1]. This work provides new insights for designing actionable and adaptive control strategies for comfort in tropical indoor conditions to simulate and size MM-coupled cooling systems effectively. It also underscores the benefits of advanced SA techniques in evaluating comfort models