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The X-ray Integral Field Unit (X-IFU) of the Advanced Telescope for High-ENergy Astrophysics (Athena) large-scale mission of ESA will provide spatially resolved high-resolution X-ray spectroscopy from 0.2 to 12 keV, with 5 ″  pixels over a field of view of 5 arc minute equivalent diameter and a spectral resolution of 2.5 eV (FWHM) up to 7 keV. The core scientific objectives of Athena drive the main performance parameters of the X-IFU. We present the current reference configuration of the X-IFU, and the key issues driving the design of the instrument.

CNES (French Space Agency) is in charge of the development of the X-ray Integral Field Unit (X-IFU) instrument for Athena, the high resolution X-ray spectrometer of the ESA Athena X-ray Observatory. X-IFU will deliver spectra from 0.2 to 12 keV with a spectral resolution in the range of 2.5 eV up to 7 keV on a 5′′ pixels, with a field of view > 4′ equivalent diameter. The main sensor array detection chain is a key part of the instrument, being by far the main contributor to its performance. It involves major partners: NASA GFSC, NIST, SRON, VTT, APC, and IRAP. The cryo-harness interconnecting the Focal Plane Assembly cold interface to the Warm Front End Electronics is under CNES responsibility. The different technical solutions are the loom technology and the shielded twisted pair technology. Characterizations have been performed on breadboards to assess the crosstalk performances for each solution. The results of these analysis are a driver to perform the trade-off between the available cryo-harness technologies.

The X-ray Integral Field Unit(X-IFU) of the Athena observatory, scheduled for launch in the mid2030's, will provide X-ray spectroscopy data with unprecedented spectral and spatial resolution. This will be achieved with a 2kilo-pixel array of transition-edge sensor (TES) microcalorimeters. The complete detection chain is under development by a large international collaboration. In order to perform an end-to-end demonstration of the X-IFU readout chain, a 50 mK test bench is being developed at IRAP in collaboration with CNES. The test bench uses a two-stage ADR cryostat from Entropy GmbH, a 1024-pixelarray, and will initially be operated using a warm electronics chain from NIST and NASA Goddard Space Flight Center. We describe the complete system being installed in the cryostat and the current results obtained with these electronics. We also review the status of the integration of the digital readout electronics (DRE)prototype into the demonstration chain and the plan for integrating and testing the complete X-IFU readout chain.

X-ray Astronomy provides a unique window on a wide variety of astrophysical phenomena. The currently operating X-ray space observatories perform X-ray spectral imaging with the use of CCDs. When available, cryogenic X-ray microcalorimeter arrays will far outperform CCDs in terms of spectral resolution, energy bandwidth and count rate. Experience has been gained with Infra-Red bolometer arrays at CEA-LETI (Grenoble) in collaboration with the CEA-SAp (Saclay); taking advantage of this background, we are now developing an X-ray spectro-imaging camera for the next generation space astronomy missions, using silicon technology (implanted and high temperature diffused thermistors). Each pixel of this array detector is made of a tantalum absorber bound, by indium bump hybridization, to a silicon thermistor. The absorber array is bound to the thermistor array in a single automatic step. The thermo-mechanical link, provided by hybridization, is being improved in terms of thermal capacitance. Finally, our main effort is in developing arrays of silicon thermistors with negligible excess 1/ f noise. The thermistor has been simulated with the 2D simulator ATHENA (SILVACO International). We studied the effects of the implants and their thermal treatment on both vertical and lateral dopant distributions at the edges of the thermistor. Prototypes have been created following the procedure optimized by the ATHENA simulation. We present the status of the development and results of measurements performed on these four main building blocks required to create a detector array up to 32×32 pixels in size.

A new 1–5 μm high‐resolution camera dedicated to the ESO adaptive optics system ADONIS has been developed as a collaborative project of Observatoire de Paris‐Meudon and Observatoire de Grenoble, under ESO contract. Since this camera has been designed to correctly sample the diffraction, two focal plate scales are available: 36 mas pixel−1for the 1–2.5 μm range and 100 mas pixel−1for the 3–5 μm range, yielding fields of view of \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $4\\farcs 5\\times 4\\farcs 5$ \\end{document} and \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $12\\farcs 8\\times 12\\farcs 8$ \\end{document} , respectively. Several broadband and narrowband filters are available as well as two circular variable filters, allowing low spectral resolution ( \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $R\\sim 60$ \\end{document} –120) imagery between 1.2 and 4.8 μm. This camera is equipped with a \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $128\\times 128$ \\end{document} HgCdTe/CCD array detector built by the CEA‐LETI‐LIR (Grenoble, France). Among its main characteristics, this detector offers a remarkably high storage capacity (more than 106electrons) with a total system readout noise of ≈1000 electrons rms, making it particularly well suited for long integration time imagery in the 3–5 μm range of the near‐infrared domain. The measured dark current is 2000 electrons s−1pixel−1at the regular operating temperature of 77 K, allowing long exposure times at short wavelengths ( \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $\\lambda < 3$ \\end{document} μm), where the performances are readout‐noise limited. At longer wavelengths ( \\documentclass{aastex} \\usepackage{amsbsy} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{bm} \\usepackage{mathrsfs} \\usepackage{pifont} \\usepackage{stmaryrd} \\usepackage{textcomp} \\usepackage{portland,xspace} \\usepackage{amsmath,amsxtra} \\usepackage[OT2,OT1]{fontenc} \\newcommand\\cyr{ \\renewcommand\\rmdefault{wncyr} \\renewcommand\\sfdefault{wncyss} \\renewcommand\\encodingdefault{OT2} \\normalfont \\selectfont} \\DeclareTextFontCommand{\\textcyr}{\\cyr} \\pagestyle{empty} \\DeclareMathSizes{10}{9}{7}{6} \\begin{document} \\landscape $\\lambda > 3$ \\end{document} μm), the performances are background‐noise limited. We have estimated the ADONIS + COMIC imaging performances using a method specially dedicated to high angular resolution cameras.

Increasing availability of therapeutic options for COPD may drive new treatment pathways. This study describes COPD treatment in France, focusing on identifying initial treatment modifications in patients with COPD who either initiated long-acting bronchodilator (LABD)-based therapy or escalated to triple therapy (long-acting muscarinic antagonist [LAMA] + long-acting β -agonist [LABA] + inhaled corticosteroid [ICS]). This retrospective analysis of patients with COPD in a large general practitioner database (IQVIA Longitudinal Patient Database) in France included two cohorts: Cohort 1 - new initiators of LABD-based therapy (LAMA, LABA, LAMA + LABA, LAMA + ICS, LABA + ICS or LAMA + LABA + ICS); Cohort 2 - patients escalating to triple therapy from mono- or dual-bronchodilator-based maintenance treatment. Both cohorts were indexed on the date of initiation/escalation (January 2008-December 2013), and the first treatment modification (at class level) within the 18-month post-index observational period was described. Five mutually exclusive outcomes were defined: continuous use (no modification), discontinuation (permanent [≥91 days with no restart] or temporary [≥91 days with subsequent restart]), switch, and augmentation (Cohort 1 only). Exploratory analysis of Cohort 1 explored potential drivers of treatment initiation. Overall, 5,065 patients initiated LABD-based therapy (Cohort 1), and 501 escalated to triple therapy (Cohort 2). In Cohort 1, 7.0% of patients were continuous users, 46.5% discontinued permanently, 28.5% discontinued temporarily, 2.8% augmented (added LAMA and/or LABA and/or ICS), and 15.2% switched therapy. In Cohort 2, 18.2% of patients were continuous users, 7.2% discontinued permanently, 27.9% discontinued temporarily, and 46.7% switched therapy. Exploratory analyses showed that time since COPD diagnosis was first recorded, pre-index exacerbation events, and concomitant medical conditions were potential drivers of initial maintenance treatment choices. Discontinuation among new initiators of LABD-based therapy was high in France, whereas few switched or augmented treatment. In comparison, permanent discontinuation within 18 months was low in patients escalating to triple therapy.

Rhabdomyosarcoma (RMS) is the most frequent form of pediatric soft-tissue sarcoma. It is divided into two main subtypes: ERMS (embryonal) and ARMS (alveolar). Current treatments are based on chemotherapy, surgery, and radiotherapy. The 5-year survival rate has plateaued at 70% since 2000, despite several clinical trials. RMS cells are thought to derive from the muscle lineage. During development, myogenesis includes the expansion of muscle precursors, the elimination of those in excess by cell death and the differentiation of the remaining ones into myofibers. The notion that these processes may be hijacked by tumor cells to sustain their oncogenic transformation has emerged, with RMS being considered as the dark side of myogenesis. Thus, dissecting myogenic developmental programs could improve our understanding of RMS molecular etiology. We focused herein on ANT1, which is involved in myogenesis and is responsible for genetic disorders associated with muscle degeneration. ANT1 is a mitochondrial protein, which has a dual functionality, as it is involved both in metabolism via the regulation of ATP/ADP release from mitochondria and in regulated cell death as part of the mitochondrial permeability transition pore. Bioinformatics analyses of transcriptomic datasets revealed that ANT1 is expressed at low levels in RMS. Using the CRISPR-Cas9 technology, we showed that reduced ANT1 expression confers selective advantages to RMS cells in terms of proliferation and resistance to stress-induced death. These effects arise notably from an abnormal metabolic switch induced by ANT1 downregulation. Restoration of ANT1 expression using a Tet-On system is sufficient to prime tumor cells to death and to increase their sensitivity to chemotherapy. Based on our results, modulation of ANT1 expression and/or activity appears as an appealing therapeutic approach in RMS management.

Political responses to the COVID-19 pandemic led to changes in city soundscapes around the globe. From March to October 2020, a consortium of 261 contributors from 35 countries brought together by the Silent Cities project built a unique soundscape recordings collection to report on local acoustic changes in urban areas. We present this collection here, along with metadata including observational descriptions of the local areas from the contributors, open-source environmental data, open-source confinement levels and calculation of acoustic descriptors. We performed a technical validation of the dataset using statistical models run on a subset of manually annotated soundscapes. Results confirmed the large-scale usability of ecoacoustic indices and automatic sound event recognition in the Silent Cities soundscape collection. We expect this dataset to be useful for research in the multidisciplinary field of environmental sciences.

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O 6 -alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age ∼13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m −2 /150 mg m −2  day −1 , 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1–7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin–temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m −2 cisplatin and 150 mg m −2 × 5 temozolomide in heavily treated, and 200 mg m −2 × 5 temozolomide in less-heavily pretreated children.

CAGIRE is the near infrared camera of the Colibrí robotic telescope, designed for the follow-up of SVOM alerts. It is based on the ALFA 2k x 2k detector, from the LYNRED French Company, operating in \"Up the Ramp\" mode. An observation consists in a series of short (1-2 minutes) exposures during which the pixels are read out every 1.3 second, while continuously accumulating charges proportionally to the received flux. We discuss here the preprocessing of CAGIRE data and a method that can be used to recover the flux received by each pixel from the slope of the ramp.