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Future fusion reactors like ITER and DEMO will have all-tungsten (W) walls and long pulses. These features will make wall conditioning more difficult than in most of the existing devices. The W Environment Steady-state Tokamak (WEST) is one of the few long pulse (364 s) fusion devices with actively cooled W plasma-facing components in the world. WEST is a unique test bed to study impurity migration and plasma density control via reactor relevant wall conditioning techniques. The phase II of WEST operations began in 2022, after the installation of a new lower divertor, now entirely equipped with actively cooled, ITER grade, W monoblocks. After pump down, we baked WEST between 90 °C and 170 °C for ∼2 weeks. After 82.5 h at 90 °C and 33 h at 170 °C, vacuum conditions were stable with a vessel pressure of 6x10-5 Pa and mass spectra dominated by H2 molecules. While at 170 °C, we performed ∼40 h of D2 glow discharge cleaning (GDC) and ∼5 h of glow discharge boronization (GDB), using a 15 %-85 % B2D6-He mix and a total boron mass of ∼12 g. This was the very first GDB at such high temperature for WEST. The whole wall conditioning sequence led to a ∼10 times reduction of the H2O signal as well as to a ∼3 times reduction of the O2 signal, according to mass spectra. Once back to 70 °C, the vessel pressure was 5.5x10-6 Pa and plasma restart was seamless with ∼30 s cumulated over the very first 5 pulses and an Ohmic radiated power fraction Frad = 0.6, showing successful conditioning of the new ITER grade divertor. The effect of the first, ‘hot’ GDB faded with a characteristic cumulative injected energy of 2.45 GJ and saturation towards Frad ∼0.8. After 1.4 h and 7.5 GJ of cumulative plasma time and injected energy, we carried out a second GDB, this time at 70 °C. This ‘cold’ GDB initially led to a much lower Ohmic Frad = 0.3–0.4 but the effect lasted ∼7 times less, with a characteristic cumulative injected energy of 0.37 GJ. At the end of the campaign, we cumulated ∼3h and ∼30 GJ through repetitive, minute long pulses without any boronization. Throughout this 4-weeks-long experiment, Frad in the 4 MW heating phase evolved only marginally (from 0.5 to 0.55). This increase is mostly due to the build-up of re/co-deposited layers on both lower divertor targets.

Over a series of experiments performed on the WEST device we have demonstrated the ability to perform controlled impurity injections and improve overall wall conditions. Positive changes to overall machine conditions are evidenced by reduced native impurity content after injection as well as decreases in radiated power and reductions in recycling. These results are consistent with the formation of a gettering layer which provides a particle sink and a reduction of source terms. We also observe a reduction in overall Zeff at the conclusion of the powder injection period consistent with a reduced impurity burden within the plasma. Finally, we have demonstrated a minimal injection quantity required to affect a positive change in wall conditions. These results confirm that plasma assisted deposition of conditioning material through particulate injection shows substantial promise as a supplemental wall conditioning technique.

The choice of first wall material is of paramount importance for the plasma start-up conditions in ITER and future fusion power plants. In this context, the present work focuses on the correlations between first wall impurity sources and total radiated power during plasma start-up in the tungsten (W) Environment in Steady-state Tokamak (WEST). The objective is to highlight experimental indications for a preferable combination of start-up plasma scenario and first wall materials. Until 2019, WEST featured a full high Z first wall with all limiters exposing only W surfaces to the plasma. To study the impact of a low Z first wall in WEST, boron nitride tiles were installed in the central part of the inner and outer limiters in 2020. Although visible spectroscopy and bolometry measurements show respectively a strong weakening of the WI line intensity on the limiters and a reduction of radiated power after the changeover, a degradation occurs with the accumulation of plasma exposure. In addition, the different plasma facing elements of the main chamber do not influence equally the radiated power during start-up. In both high Z and low Z environments, a clear non-linear dependence is found between the start-up radiated power and the outer limiter W impurity source. Since W seems to be the main cause for core radiation, correlation between outer limiter W sources and other impurity sources are investigated. Finally, analysis of the legacy of B powder drops on a number of start-up plasmas suggests that it is less effective at reducing radiated power when the first wall is covered with W.

The mission of WEST (tungsten-W Environment in Steady-state Tokamak) is to explore long pulse operation in a full tungsten (W) environment for preparing next-step fusion devices (ITER and DEMO) with a focus on testing the ITER actively cooled W divertor in tokamak conditions. Following the successful completion of phase 1 (2016-2021), phase 2 started in December 2022 with the lower divertor made entirely of actively cooled ITER-grade tungsten mono-blocks. A boronization prior the first plasma attempt allowed for a smooth startup with the new divertor. Despite the reduced operating window due to tungsten, rapid progress has been made in long pulse operation, resulting in discharges with a pulse length of 100 s and an injected energy of around 300 MJ per discharge. Plasma startup studies were carried out with equatorial boron nitride limiters to compare them with tungsten limiters, while Ion Cyclotron Resonance Heating assisted startup was attempted. High fluence operation in attached regime, which was the main thrust of the first campaigns, already showed the progressive build up of deposits and appearance of dust, impacting the plasma operation as the plasma fluence increased. In total, the cumulated injected energy during the first campaigns reached 43 GJ and the cumulated plasma time exceeded 5 h. Demonstration of controlled X-Point Radiator regime is also reported, opening a promising route for investigating plasma exhaust and plasma-wall interaction issues in more detached regime. This paper summarises the lessons learned from the manufacturing and the first operation of the ITER-grade divertor, describing the progress achieved in optimising operation in a full W environment with a focus on long pulse operation and plasma wall interaction.

A cross-machine comparison of global parameters that determine the runaway electron (RE) generation and loss process during tokamak start-up was carried out with the aim to extrapolate these to ITER. The study found that all considered discharges, also those that do not show signs of RE, are non-thermal at the start, i.e. have a streaming parameter larger than 0.1. During the current ramp-up the electric field, E , remains above the critical value, E _c , that allows RE in the plasma. The distinction to be made is not if RE can form but, if sufficient RE can form fast enough such that they are detected or start to dominate the dynamics of the tokamak discharge. The dynamics of the value of E , density and temperature during tokamak are key to the formation of RE. It was found that larger devices operate with E closer to E _c , due to their higher temperatures, hence the RE generation is relatively slower. The slower time scales for the formation of RE, estimated to be of the order of 100s of ms in ITER simplifies the development of avoidance schemes. The RE confinement time is also an important determinant of the entire process and is found to increase with the device size. The study also revealed that drift orbit losses, a mechanism often attributed as the main RE loss mechanism during the early tokamak discharge, are actually more difficult to achieve. RE losses might be more likely attributed to RE diffusion due to magnetic turbulence.

Boron (B) powder injection is a potential alternative to glow discharge boronization as a wall conditioning method for tokamaks. This technique is currently being studied in WEST experiments, during which B powder is injected by an Impurity Powder Dropper developed by PPPL. In order to interpret and analyse experimental trends, and to help develop future experiments, a modelling workflow using a boundary plasma simulation (SOLEDGE-EIRENE) and powder ablation simulation (Dust Injection Simulator) was developed and tested. The effect of adding a B neutral source to simulated deuterium + oxygen (D + O) plasmas was compared to experimental data from the WEST C5 campaign, where B powder was injected in a dedicated experiment. While the impact of B injection on radiated power ${P_{{\text{rad}}}}$ measurements at the upper divertor was similar, there were significant differences in measurements of ${P_{{\text{rad}}}}$ , outer strike point electron temperature $T_{\text{e}}^{{\text{OSP}}}$ and O-II line intensity at the lower divertor between experiment and simulation. This discrepancy suggests that those parameters were affected by phenomena not present in the simulations, with the most likely candidates being reduced D recycling and a reduced O sourcing from the divertor.

The paper deals with radiation resistant sensors and their associated measuring instrumentation developed in the course of R and D activities carried out in the framework of an international collaboration. The first trial tests of three-dimensional (3D) probes with Hall sensors have been performed in European tokamaks TORE SUPRA (2004) and JET (2005). Later in 2009 six sets of 3D probes were installed in JET and now continue to operate. The statistical analysis performed in 2014 on the basis of the JET database have demonstrated stable long term operation of all 18 sensors of 3D probes. The results of measurements conducted at the neutron fluxes of nuclear reactors have demonstrated the operability of the sensors up to high neutron fluences of F  >  1018n ∙ cm−2 that exceeds the maximum one for the locations of steady state sensors in ITER over its total lifetime. [ABSTRACT FROM AUTHOR]

Stargardt disease is a currently untreatable, inherited neurodegenerative disease that leads to macular degeneration and blindness due to loss-of-function mutations in the ABCA4 gene. We have designed a dual adeno-associated viral vector encoding a split-intein adenine base editor to correct the most common mutation in ABCA4 (c.5882G>A, p.Gly1961Glu). We optimized ABCA4 base editing in human models, including retinal organoids, induced pluripotent stem cell-derived retinal pigment epithelial (RPE) cells, as well as adult human retinal explants and RPE/choroid explants in vitro. The resulting gene therapy vectors achieved high levels of gene correction in mutation-carrying mice and in female nonhuman primates, with average editing of 75% of cones and 87% of RPE cells in vivo, which has the potential to translate to a clinical benefit. No off-target editing was detectable in human retinal explants and RPE/choroid explants. The high editing rates in primates show promise for efficient gene editing in other ocular diseases that are targetable by base editing., Competing Interests: Competing interests: J.S., C.P-W., T.V., L.A.B., L.Y., A.K., D.B. and G.C. are employees and/or shareholders of Beam Therapeutics. Beam Therapeutics has filed a patent based on some of this work. H.P.N.S. is member of the Scientific Advisory Board of: Boehringer Ingelheim, Droia NV, Janssen Research & Development (Johnson & Johnson) and Okuvision and Tenpoint Therapeutics. H.P.N.S. is a member of the Data Monitoring and Safety Board/Committee of Belite Bio (DRAGON trial, NCT05244304 ; LBS-008-CT02, NCT05266014 ), F. Hoffmann-La Roche (VELODROME trial, NCT04657289 ; DIAGRID trial, NCT05126966 ; HUTONG trial) and ViGeneron (protocol no. VG901-2021-A) and a member of the Steering Committee of Novo Nordisk (FOCUS trial; NCT03811561 ). B.R. is a consultant of SpliceBio. All other authors declare no competing interests., (© 2025. The Author(s).)

Pathogenic New World arenaviruses (NWAs) cause haemorrhagic fevers and can have high mortality rates, as shown in outbreaks in South America. Neutralizing antibodies (Abs) are critical for protection from NWAs. Having shown that the MOPEVAC vaccine, based on a hyperattenuated arenavirus, induces neutralizing Abs against Lassa fever, we hypothesized that expression of NWA glycoproteins in this platform might protect against NWAs. Cynomolgus monkeys immunized with MOPEVAC MAC , targeting Machupo virus, prevented the lethality of this virus and induced partially NWA cross-reactive neutralizing Abs. We then developed the pentavalent MOPEVAC NEW vaccine, expressing glycoproteins from all pathogenic South American NWAs. Immunization of cynomolgus monkeys with MOPEVAC NEW induced neutralizing Abs against five NWAs, strong innate followed by adaptive immune responses as detected by transcriptomics and provided sterile protection against Machupo virus and the genetically distant Guanarito virus. MOPEVAC NEW may thus be efficient to protect against existing and potentially emerging NWAs., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Amblyopia is a major public health concern. Its screening and management require reliable methods of visual acuity assessment. New technologies offer nowadays many tests available on different app stores for smartphone or tablet but most of them often lack of scientific validation for a medical use. The aim of our study was to attempt validating a tablet-based near visual acuity test adapted to the pediatric population: the eMOVA test (electronic Measurement Of Visual Acuity) by comparing visual acuity measured with more conventional test., Methods: A cohort of 100 children aged 3 to 8 attending the ophthalmic-pediatric for eye examination between September 2016 and June 2017 were included in the study. Near visual acuity was assessed on participants using both the eMOVA test and a Standard test (Rossano-Weiss test). Duration of each test, its comprehension, its acceptability and the attention of the child during the test was also investigated., Results: The eMOVA test overestimated near visual acuity by 0.06 logMAR. This difference, statistically significant, was not clinically relevant. The duration of the eMOVA test was longer than the reference test, but less discomfort and preferred by children and their parents compared to standard tests., Conclusion: The eMOVA test appears as a reliable test to assess near visual acuity in children. By its portability and efficiency, this application proved to be a relevant tool to be used for children eye examination in daily routine at the hospital., (© 2022. The Author(s).)

A safe and protective Lassa virus vaccine is crucially needed in Western Africa to stem the recurrent outbreaks of Lassa virus infections in Nigeria and the emergence of Lassa virus in previously unaffected countries, such as Benin and Togo. Major challenges in developing a Lassa virus vaccine include the high diversity of circulating strains and their reemergence from 1 year to another. To address each of these challenges, we immunized cynomolgus monkeys with a measles virus vector expressing the Lassa virus glycoprotein and nucleoprotein of the prototypic Lassa virus strain Josiah (MeV-NP). To evaluate vaccine efficacy against heterologous strains of Lassa virus, we challenged the monkeys a month later with heterologous strains from lineage II or lineage VII, finding that the vaccine was protective against these strains. A second cohort of monkeys was challenged 1 year later with the homologous Josiah strain, finding that a single dose of MeV-NP was sufficient to protect all vaccinated monkeys. These studies demonstrate that MeV-NP can generate both long-lasting immune responses and responses that are able to protect against diverse strains of Lassa virus., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Aim: To validate a visual acuity (VA) test application on touchpad in the screening of pediatric population by comparing VA results obtained with conventional tests., Methods: A cohort of 101 patients, 44 girls and 57 boys with a median of 6.5 years old (3-10 years of age), presenting for eye examinations in Ophthalmology Department (Strasbourg, France) between November 1 st , 2018, and February 1 st , 2019 were enrolled. Monocular and binocular VA testing was performed on the subject using both a standard test and the touchpad application (Monoyer, "E" or, Pigassou depending of children's capacities). Patients were excluded if they were physically or mentally unable to use the touchpad. The duration of each tests, the painfulness, the comprehension, the attention of children during the test and test's preferences were also evaluated., Results: There was a good linear correlation and intra-class correlation coefficient [ICC=0.50 (0.34, 0.64) for binocular acuity, 0.74 (0.64, 0.82) for right eyes and 0.525 (0.37, 0.66) for left eye]. The standard errors of measurement were very low (0.08, 0.05, 0.08 for binocular VA, right eyes VA and left eyes VA, respectively). There was no difference between two tests for right eye ( P =0.126), left eye ( P =0.098) and binocular acuity ( P =0.085). Non inferiority was proved for all binocular [-0.06 (-0.09, -0.03)], right eye [-0.04 (-0.07, -0.01)] and left eye [-0.06 (-0.09, -0.02)] VA. The sensitivity and specificity, which correspond to the ability for our app to detect amblyopia, were 92% and 80% respectively., Conclusion: Our touchpad application represents an efficient and valid test of VA in children with a high specificity to detect visual impairment., (International Journal of Ophthalmology Press.)

A poorly understood feature of the tauopathies is their very different clinical presentations. The frontotemporal lobar degeneration (FTLD) spectrum is dominated by motor and emotional/psychiatric abnormalities, whereas cognitive and memory deficits are prominent in the early stages of Alzheimer's disease (AD). We report two novel mouse models overexpressing different human tau protein constructs. One is a full-length tau carrying a double mutation [P301S/G335D; line 66 (L66)] and the second is a truncated 3-repeat tau fragment which constitutes the bulk of the PHF core in AD corresponding to residues 296-390 fused with a signal sequence targeting it to the endoplasmic reticulum membrane (line 1; L1). L66 has abundant tau pathology widely distributed throughout the brain, with particularly high counts of affected neurons in hippocampus and entorhinal cortex. The pathology is neuroanatomically static and declines with age. Behaviourally, the model is devoid of a higher cognitive phenotype but presents with sensorimotor impairments and motor learning phenotypes. L1 displays a much weaker histopathological phenotype, but shows evidence of neuroanatomical spread and amplification with age that resembles the Braak staging of AD. Behaviourally, the model has minimal motor deficits but shows severe cognitive impairments affecting particularly the rodent equivalent of episodic memory which progresses with advancing age. In both models, tau aggregation can be dissociated from abnormal phosphorylation. The two models make possible the demonstration of two distinct but nevertheless convergent pathways of tau molecular pathogenesis. L1 appears to be useful for modelling the cognitive impairment of AD, whereas L66 appears to be more useful for modelling the motor features of the FTLD spectrum. Differences in clinical presentation of AD-like and FTLD syndromes are therefore likely to be inherent to the respective underlying tauopathy, and are not dependent on presence or absence of concomitant APP pathology.