Planet Hunters: The First Two Planet Candidates Identified by the Public using the Kepler Public Archive Data

Planet Hunters is a new citizen science project, designed to engage the public in an exoplanet search using NASA Kepler public release data. In the first month after launch, users identified two new planet candidates which survived our checks for false- positives. The follow-up effort included analysis of Keck HIRES spectra of the host stars, analysis of pixel centroid offsets in the Kepler data and adaptive optics imaging at Keck using NIRC2. Spectral synthesis modeling coupled with stellar evolutionary models yields a stellar density distribution, which is used to model the transit orbit. The orbital periods of the planet candidates are 9.8844 \pm0.0087 days (KIC 10905746) and 49.7696 \pm0.00039 (KIC 6185331) days and the modeled planet radii are 2.65 and 8.05 R\oplus. The involvement of citizen scientists as part of Planet Hunters is therefore shown to be a valuable and reliable tool in exoplanet detection.Comment: Submitted to MNRAS, added 1 line to table

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

An AluYa5 Insertion in the 3'UTR of COL4A1 and Cerebral Small Vessel Disease

International audienceImportance: Cerebral small vessel diseases (CSVDs) account for one-fifth of stroke cases. Numerous familial cases remain unresolved after routine screening of known CSVD genes.Objective: To identify novel genes and mechanisms associated with familial CSVD.Design, setting, and participants: This 2-stage study involved linkage analysis and a case-control study; linkage analysis and whole exome and genome sequencing were used to identify candidate gene variants in 2 large families with CSVD (9 patients with CSVD). Then, a case-control analysis was conducted on 246 unrelated probands, including probands from these 2 families and 244 additional probands. All probands (clinical onset <age 55 years and ≥1 first-degree relative with CSVD) were referred to the French cerebrovascular referral center between 2013 and 2023. The large-scale gnomAD structural variant database and 467 healthy individuals of French ancestry were used as a control group.Main outcomes and measures: A pathogenic AluYa5 insertion was identified within the COL4A1 3'UTR in the 2 large families with CSVD. Reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), Western blot, and long-read RNA sequencing were used to investigate outcomes associated with the insertion using patient fibroblasts. Clinical and magnetic resonance imaging features of probands with variants and available relatives were assessed.Results: Among 246 probands (141 females [57.3%]; median [IQR] age at referral, 56 [49-64] years), 7 patients of French ancestry carried the insertion. This insertion was absent in 467 healthy French individuals in a control group (odds ratio, ∞; 95% CI, 2.78 to ∞; P = 5 × 10-4) and 10 847 individuals from the gnomAD structural variant database (odds ratio, ∞; 95% CI, 64.77 to ∞; P = 2.42 × 10-12). In these 7 patients' families, 19 family members with CSVD carried the insertion. RT-qPCR and Western blot showed an upregulation of COL4A1 mRNA (10.6-fold increase; 95% CI, 1.4-fold to 17.1-fold increase) and protein levels (2.8-fold increase; 95% CI, 2.1-fold to 3.5-fold increase) in patient vs control group fibroblasts. Long-read RNA sequencing data showed that the insertion was associated with perturbation in the use of canonical COL4A1 polyadenylation signals (approximately 87% of isoforms transcribed from the wild type allele vs 5% of isoforms transcribed from the allele with the insertion used the 2 distal canonical polyadenylation signals). The main clinical feature of individuals with CSVD was the recurrence of pontine ischemic lesions starting at an early age (17 of 19 patients [89.5%]).Conclusions and relevance: This study found a novel mechanism associated with COL4A1 upregulation and a highly penetrant adult-onset CSVD. These findings suggest that quantitative alterations of the cerebrovascular matrisome are associated with CSVD pathogenesis, with diagnostic and therapeutic implications

Status of the ITER Electron Cyclotron Heating and Current Drive System

The electron cyclotron (EC) heating and current drive (H&CD) system developed for the ITER is made of 12 sets of high-voltage power supplies feeding 24 gyrotrons connected through 24 transmission lines (TL), to five launchers, four located in upper ports and one at the equatorial level. Nearly all procurements are in-kind, following general ITER philosophy, and will come from Europe, India, Japan, Russia and the USA. The full system is designed to couple to the plasma 20 MW among the 24 MW generated power, at the frequency of 170 GHz, for various physics applications such as plasma start-up, central H&CD and magnetohydrodynamic (MHD) activity control. The design takes present day technology and extends toward high-power continuous operation, which represents a large step forward as compared to the present state of the art. The ITER EC system will be a stepping stone to future EC systems for DEMO and beyond. The development of the EC system is facing significant challenges, which includes not only an advanced microwave system but also compliance with stringent requirements associated with nuclear safety as ITER became the first fusion device licensed as basic nuclear installations as of 9 November 2012. Since the conceptual design of the EC system was established in 2007, the EC system has progressed to a preliminary design stage in 2012 and is now moving forward toward a final design

Progress in the ITER electron cyclotron heating and current drive system design

An electron cyclotron system is one of the four auxiliary plasma heating systems to be installed on the ITER tokamak. The ITER EC system consists of 24 gyrotrons with associated 12 high voltage power supplies, a set of evacuated transmission lines and two types of launchers. The whole system is designed to inject 20 MW of microwave power at 170 GHz into the plasma. The primary functions of the system include plasma start-up, central heating and current drive, and magneto-hydrodynamic instabilities control. The design takes present day technology and extends towards high power CW operation, which represents a large step forward as compared to the present state of the art. The ITER EC system will be a stepping stone to future EC systems for DEMO and beyond. The EC system is faced with significant challenges, which not only includes an advanced microwave system for plasma heating and current drive applications but also has to comply with stringent requirements associated with nuclear safety as ITER became the first fusion device licensed as basic nuclear installations as of 9 November 2012. Since conceptual design of the EC system established in 2007, the EC system has progressed to a preliminary design stage in 2012, and is now moving forward towards a final design. The majority of the subsystems have completed the detailed design and now advancing towards the final design completion. (C) 2014 Elsevier B.V. All rights reserved

Status of the ITER Electron Cyclotron Heating and Current Drive System

The electron cyclotron (EC) heating and current drive (H&CD) system developed for the ITER is made of 12 sets of high-voltage power supplies feeding 24 gyrotrons connected through 24 transmission lines (TL), to five launchers, four located in upper ports and one at the equatorial level. Nearly all procurements are in-kind, following general ITER philosophy, and will come from Europe, India, Japan, Russia and the USA. The full system is designed to couple to the plasma 20 MW among the 24 MW generated power, at the frequency of 170 GHz, for various physics applications such as plasma start-up, central H&CD and magnetohydrodynamic (MHD) activity control. The design takes present day technology and extends toward high-power continuous operation, which represents a large step forward as compared to the present state of the art. The ITER EC system will be a stepping stone to future EC systems for DEMO and beyond.The development of the EC system is facing significant challenges, which includes not only an advanced microwave system but also compliance with stringent requirements associated with nuclear safety as ITER became the first fusion device licensed as basic nuclear installations as of 9 November 2012.Since the conceptual design of the EC system was established in 2007, the EC system has progressed to a preliminary design stage in 2012 and is now moving forward toward a final design

Status of the ITER Ion Cyclotron H&CD

The ITER Ion Cyclotron Heating and Current Drive system (IC H&CD) is designed to deliver 20MW to a broad range of plasma scenarios between 40 and 55MHz, during very long pulses. It consists of two broadband equatorial port plug antennas, their pre-matching and matching systems, transmission lines, Radio Frequency (RF) Sources and High Voltage Power Supplies. The overall project schedule has been revised and agreed by ITER Council; it re-integrates the second antenna and its power supplies in construction baseline and sets the dates for progressive installation with DT phase planned in 2035. Recent progress on ICRF subsystems is reported, covering design evolution, qualification of test articles and specific R&D results in domestic agencies, suppliers, associated laboratories and IO

Status of the ITER Ion Cyclotron H&CD

The ITER Ion Cyclotron Heating and Current Drive system (IC H&CD) is designed to deliver 20MW to a broad range of plasma scenarios between 40 and 55MHz, during very long pulses. It consists of two broadband equatorial port plug antennas, their pre-matching and matching systems, transmission lines, Radio Frequency (RF) Sources and High Voltage Power Supplies. The overall project schedule has been revised and agreed by ITER Council; it re-integrates the second antenna and its power supplies in construction baseline and sets the dates for progressive installation with DT phase planned in 2035. Recent progress on ICRF subsystems is reported, covering design evolution, qualification of test articles and specific R&D results in domestic agencies, suppliers, associated laboratories and IO