The SPARC Toroidal Field Model Coil Program

The SPARC Toroidal Field Model Coil (TFMC) Program was a three-year effort between 2018 and 2021 that developed novel Rare Earth Yttrium Barium Copper Oxide (REBCO) superconductor technologies and then successfully utilized these technologies to design, build, and test a first-in-class, high-field (~20 T), representative-scale (~3 m) superconducting toroidal field coil. With the principal objective of demonstrating mature, large-scale, REBCO magnets, the project was executed jointly by the MIT Plasma Science and Fusion Center (PSFC) and Commonwealth Fusion Systems (CFS). The TFMC achieved its programmatic goal of experimentally demonstrating a large-scale high-field REBCO magnet, achieving 20.1 T peak field-on-conductor with 40.5 kA of terminal current, 815 kN/m of Lorentz loading on the REBCO stacks, and almost 1 GPa of mechanical stress accommodated by the structural case. Fifteen internal demountable pancake-to-pancake joints operated in the 0.5 to 2.0 nOhm range at 20 K and in magnetic fields up to 12 T. The DC and AC electromagnetic performance of the magnet, predicted by new advances in high-fidelity computational models, was confirmed in two test campaigns while the massively parallel, single-pass, pressure-vessel style coolant scheme capable of large heat removal was validated. The REBCO current lead and feeder system was experimentally qualified up to 50 kA, and the crycooler based cryogenic system provided 600 W of cooling power at 20 K with mass flow rates up to 70 g/s at a maximum design pressure of 20 bar-a for the test campaigns. Finally, the feasibility of using passive, self-protection against a quench in a fusion-scale NI TF coil was experimentally assessed with an intentional open-circuit quench at 31.5 kA terminal current.Comment: 17 pages 9 figures, overview paper and the first of a six-part series of papers covering the TFMC Progra

Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases

Biomarkers of disease activity have come into wide use in the study of mechanisms of human disease and in clinical medicine to both diagnose and predict disease course; as well as to monitor response to therapeutic intervention. Here we review biomarkers of the involvement of mast cells, basophils, and eosinophils in human allergic inflammation. Included are surface markers of cell activation as well as specific products of these inflammatory cells that implicate specific cell types in the inflammatory process and are of possible value in clinical research as well as within decisions made in the practice of allergy-immunology

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Twist exome capture allows for lower average sequence coverage in clinical exome sequencing

Background Exome and genome sequencing are the predominant techniques in the diagnosis and research of genetic disorders. Sufficient, uniform and reproducible/consistent sequence coverage is a main determinant for the sensitivity to detect single-nucleotide (SNVs) and copy number variants (CNVs). Here we compared the ability to obtain comprehensive exome coverage for recent exome capture kits and genome sequencing techniques. Results We compared three different widely used enrichment kits (Agilent SureSelect Human All Exon V5, Agilent SureSelect Human All Exon V7 and Twist Bioscience) as well as short-read and long-read WGS. We show that the Twist exome capture significantly improves complete coverage and coverage uniformity across coding regions compared to other exome capture kits. Twist performance is comparable to that of both short- and long-read whole genome sequencing. Additionally, we show that even at a reduced average coverage of 70× there is only minimal loss in sensitivity for SNV and CNV detection. Conclusion We conclude that exome sequencing with Twist represents a significant improvement and could be performed at lower sequence coverage compared to other exome capture techniques

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock