49 research outputs found
Nuclear recoil energy scale in liquid xenon with application to the direct detection of dark matter
We show for the first time that the quenching of electronic excitation from
nuclear recoils in liquid xenon is well-described by Lindhard theory, if the
nuclear recoil energy is reconstructed using the combined (scintillation and
ionization) energy scale proposed by Shutt {\it et al.}. We argue for the
adoption of this perspective in favor of the existing preference for
reconstructing nuclear recoil energy solely from primary scintillation. We show
that signal partitioning into scintillation and ionization is well-described by
the Thomas-Imel box model. We discuss the implications for liquid xenon
detectors aimed at the direct detection of dark matter
Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders
Background Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions.
Objective We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs.
Methods Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping.
Results A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays.
Conclusion This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes