Figures of merit for a stochastic gravitational-wave background measurement by LISA: implications of LISA Pathfinder noise correlations

An important goal of the Laser Interferometer Space Antenna (LISA) is to observe a stochastic gravitational-wave background (SGWB). A study of possible correlated noise in LISA is relevant to establish limits for this future measurement. To test noise investigation methods under somewhat realistic conditions, we use the data of LISA Pathfinder (LPF). We calculate the coherence between the LPF differential acceleration of the two test-masses with magnetic fields, temperature, and micronewton cold gas thruster activity in the spacecraft. We apply our observed correlations to LISA, and estimate how the presence of such correlated noise would affect its search for a SGWB. In the context of a figure of merit, we estimate the effect of noise on the LISA SGWB search

Formalism for power spectral density estimation for non-identical and correlated noise using the null channel in Einstein Telescope

Several proposed gravitational wave interferometers have a triangular configuration, such as the Einstein Telescope and the Laser Interferometer Space Antenna. For such a configuration one can construct a unique null channel insensitive to gravitational waves from all directions. We expand on earlier work and describe how to use the null channel formalism to estimate the power spectral density for the Einstein Telescope interferometers with non-identical as well as correlated noise sources. The formalism is illustrated with two examples in the context of the Einstein Telescope, with increasing degrees of complexity and realism. By using known mixtures of noises we show the formalism is mathematically correct and internally consistent. Finally we highlight future research needed to use this formalism as an ingredient for a Bayesian estimation framework.Comment: The results have been updated (10/10/2022). Please refer to this new versio

How to Work Collaboratively Within the Health System: Workshop Summary and Facilitator Reflection

Effectiveness in health services research requires development of specific knowledge and skills for working in partnership with health system decision-makers. In an initial effort to frame capacity-building activities for researchers, we designed a workshop on working collaboratively within the health system. The workshop, based on recent research exploring health system experience and perspectives on research collaborations, was trialed at the annual Canadian Health Services and Policy Research (CAHSPR) conference in May 2019. Participants reported positive evaluations of the workshop. However, further efforts should target health services researchers that may not be as motivated to develop skills in collaborative research. Additional attention to equipping researchers with the skills needed to work in partnerships is recommended, including approaches and materials that avoid oversimplification of complex challenges

Fibulin-2: genetic mapping and exclusion as a candidate gene in Marfan syndrome type 2.

International audienceFibulin-2 (FBLN2) is a new extracellular matrix protein that has been considered a candidate gene for Marfan syndrome type 2 (locus MFS2) based on chromosomal colocation at 3p24.2-p25 and disease phenotype. In the absence of polymorphic markers reported for FBLN2, direct sequencing of the gene was performed and two intragenic polymorphisms were identified. Linkage was excluded between FBLN2 and the MFS2 gene. Furthermore, two-point lod scores were generated between these markers and anonymous markers arrayed on the genetic map of 3p and closely linked to MFS2. These analyses placed FBLN2 at marker D3S1585

Correlated 0.01Hz-40Hz seismic and Newtonian noise and its impact on future gravitational-wave detectors

We report correlations in underground seismic measurements with horizontal separations of several hundreds of meters to a few kilometers in the frequency range 0.01Hz to 40Hz. These seismic correlations could threaten science goals of planned interferometric gravitational-wave detectors such as the Einstein Telescope as well as atom interferometers such as MIGA and ELGAR. We use seismic measurements from four different sites, i.e. the former Homestake mine (USA) as well as two candidate sites for the Einstein Telescope, Sos Enattos (IT) and Euregio Maas-Rhein (NL-BE-DE) and the site housing the MIGA detector, LSBB (FR). At all sites, we observe significant coherence for at least 50% of the time in the majority of the frequency region of interest. Based on the observed correlations in the seismic fields, we predict levels of correlated Newtonian noise from body waves. We project the effect of correlated Newtonian noise from body waves on the capabilities of the triangular design of the Einstein Telescope's to observe an isotropic gravitational-wave background (GWB) and find that, even in case of the most quiet site, its sensitivity will be affected up to $\sim$20Hz. The resolvable amplitude of a GWB signal with a negatively sloped power-law behaviour would be reduced by several orders of magnitude. However, the resolvability of a power-law signal with a slope of e.g. $\alpha=0$ ($\alpha=2/3$) would be more moderately affected by a factor $\sim$ 6-9 ($\sim$3-4) in case of a low noise environment. Furthermore, we bolster confidence in our results by showing that transient noise features have a limited impact on the presented results

MAT2A Mutations Predispose Individuals to Thoracic Aortic Aneurysms

Up to 20% of individuals who have thoracic aortic aneurysms or acute aortic dissections but who do not have syndromic features have a family history of thoracic aortic disease. Significant genetic heterogeneity is established for this familial condition. Whole-genome linkage analysis and exome sequencing of distant relatives from a large family with autosomal-dominant inheritance of thoracic aortic aneurysms variably associated with the bicuspid aortic valve was used for identification of additional genes predisposing individuals to this condition. A rare variant, c.1031A>C (p.Glu344Ala), was identified in MAT2A, which encodes methionine adenosyltransferase II alpha (MAT IIα). This variant segregated with disease in the family, and Sanger sequencing of DNA from affected probands from unrelated families with thoracic aortic disease identified another MAT2A rare variant, c.1067G>A (p.Arg356His). Evidence that these variants predispose individuals to thoracic aortic aneurysms and dissections includes the following: there is a paucity of rare variants in MAT2A in the population; amino acids Glu344 and Arg356 are conserved from humans to zebrafish; and substitutions of these amino acids in MAT Iα are found in individuals with hypermethioninemia. Structural analysis suggested that p.Glu344Ala and p.Arg356His disrupt MAT IIα enzyme function. Knockdown of mat2aa in zebrafish via morpholino oligomers disrupted cardiovascular development. Co-transfected wild-type human MAT2A mRNA rescued defects of zebrafish cardiovascular development at significantly higher levels than mRNA edited to express either the Glu344 or Arg356 mutants, providing further evidence that the p.Glu344Ala and p.Arg356His substitutions impair MAT IIα function. The data presented here support the conclusion that rare genetic variants in MAT2A predispose individuals to thoracic aortic disease

Pathogenic variants in THSD4, encoding the ADAMTS-like 6 protein, predispose to inherited thoracic aortic aneurysm

Purpose Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening disease with often unrecognized inherited forms. We sought to identify novel pathogenic variants associated with autosomal dominant inheritance of TAAD. Methods We analyzed exome sequencing data from 35 French TAAD families and performed next-generation sequencing capture panel of genes in 1114 unrelated TAAD patients. Functional effects of pathogenic variants identified were validated in cell, tissue, and mouse models. Results We identified five functional variants inTHSD4of which two heterozygous variants lead to a premature termination codon.THSD4encodes ADAMTSL6 (member of the ADAMTS/L superfamily), a microfibril-associated protein that promotes fibrillin-1 matrix assembly. TheTHSD4variants studied lead to haploinsufficiency or impaired assembly of fibrillin-1 microfibrils.Thsd4(+/-)mice showed progressive dilation of the thoracic aorta. Histologic examination of aortic samples from a patient carrying aTHSD4variant and fromThsd4(+/-)mice, revealed typical medial degeneration and diffuse disruption of extracellular matrix. Conclusion These findings highlight the role of ADAMTSL6 in aortic physiology and TAAD pathogenesis. They will improve TAAD management and help develop new targeted therapies

Mutations in STAT3 and IL12RB1 impair the development of human IL-17–producing T cells

The cytokines controlling the development of human interleukin (IL) 17–producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17–producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) β, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17–producing T cells. These data suggest that IL-12Rβ1– and STAT-3–dependent signals play a key role in the differentiation and/or expansion of human IL-17–producing T cell populations in vivo

Science with the Einstein Telescope: a comparison of different designs

The Einstein Telescope (ET), the European project for a third-generation gravitational-wave detector, has a reference configuration based on a triangular shape consisting of three nested detectors with 10 km arms, where in each arm there is a `xylophone' configuration made of an interferometer tuned toward high frequencies, and an interferometer tuned toward low frequencies and working at cryogenic temperature. Here, we examine the scientific perspectives under possible variations of this reference design. We perform a detailed evaluation of the science case for a single triangular geometry observatory, and we compare it with the results obtained for a network of two L-shaped detectors (either parallel or misaligned) located in Europe, considering different choices of arm-length for both the triangle and the 2L geometries. We also study how the science output changes in the absence of the low-frequency instrument, both for the triangle and the 2L configurations. We examine a broad class of simple `metrics' that quantify the science output, related to compact binary coalescences, multi-messenger astronomy and stochastic backgrounds, and we then examine the impact of different detector designs on a more specific set of scientific objectives.Comment: 197 pages, 72 figure