The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033

The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase

The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer, studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory, a versatile observatory designed to address the Hot and Energetic Universe science theme, selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), it aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR, browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters. Finally we briefly discuss on the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, and touch on communication and outreach activities, the consortium organisation, and finally on the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental Astronomy with minor editin

VLSI Laser Spot Sensors for 3D Digitization

This paper presents activities on VLSI laser spot sensors for digital 3-D imaging developed for industrial and scientific applications. All the sensors have been fabricated using standard CMOS technology that allows the monolithic integration of photo-sensors, together with readout circuits and digital signal processors. Preliminary results are presented

Smart Sensors for 3D Digitization

This paper presents our activities on smart VLSI opto-sensors for 3D vision. A description of the integrated devices jointly developed for industrial and scientific applications will be given. All the sensors presented here have been fabricated using standard CMOS technology that allows the monolithic integration of photo-sensors, together with readout circuits, and digital signal processor

Optimized Position Sensors for Flying-Spot Active Triangulation Systems

A description of the integrated sensors developed for flying-spot active triangulation will be given. All the sensors have been fabricated using standard CMOS technology that allows the monolithic integration of photo-sensors, together with readout circuits, and digital signal processors. Position sensors are categorized into two classes that allow a better understanding of the pros and cons of each one. A description of the proposed position sensor that is optimized for accurate and fast 3D acquisition is given alongside some experimental result

Tha natural history of Hashimoto's thyroiditis

The study shows the natural history of Hashimoto's thyroiditi

Long-term outcome of chronic myeloid leukemia patients treated frontline with imatinib

For almost 10 years imatinib has been the therapeutic standard of chronic myeloid leukemia. The introduction of other tyrosine kinase inhibitors (TKIs) raised a debate on treatment optimization. The debate is still heated: some studies have protocol restrictions or limited follow-up; in other studies, some relevant data are missing. The aim of this report is to provide a comprehensive, long-term, intention-to-treat, analysis of 559 newly diagnosed, chronic-phase, patients treated frontline with imatinib. With a minimum follow-up of 66 months, 65% of patients were still on imatinib, 19% were on alternative treatment, 12% died and 4% were lost to follow-up. The prognostic value of BCR-ABL1 ratio at 3 months (≤10% in 81% of patients) was confirmed. The prognostic value of complete cytogenetic response and major molecular response at 1 year was confirmed. The 6-year overall survival was 89%, but as 50% of deaths occurred in remission, the 6-year cumulative incidence of leukemia-related death was 5%. The long-term outcome of first-line imatinib was excellent, also because of second-line treatment with other TKIs, but all responses and outcomes were inferior in high-risk patients, suggesting that to optimize treatment results, a specific risk-adapted treatment is needed for such patients

Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis.

Direct-acting oral anticoagulants (DOACs) are used in patients with splanchnic vein thrombosis (SVT) and cirrhosis, but evidence for safety and efficacy in this setting is limited. Our aim was to identify indications and reasons for starting or switching to DOACs and to report adverse effects, complications and short-term outcome. Data collection including demographic information, laboratory values, treatment and complications through the Vascular Liver Disease Interest Group Consortium. Forty-five centres (90%) of the consortium completed the initial eCRF. We report here a series of 94 patients from 17 centres. Thirty-six patients (38%) had cirrhosis. Child-Pugh score was 6 (range 5-8), and MELD score 10.2 (range 6-19). Indications for anticoagulation were splanchnic vein thrombosis (75%), deep vein thrombosis (5%), atrial fibrillation (14%) and others (6%). DOACs used were rivaroxaban (83%), dabigatran (11%) and apixaban (6%). Patients were followed up for a median duration of 15 months (cirrhotic) and 26.5 months (non-cirrhotic). Adverse events occurred in 17% of patients and included one case of recurrent portal vein thrombosis and five cases of bleeding. Treatment with DOACs was stopped in three cases. The major reasons for choosing DOACs were no need for monitoring or inadequacy of INR to guide anticoagulation in cirrhotic patients. Renal and liver function did not change during treatment. A consistent number of patients with SVT and/or cirrhosis are currently treated with DOACs, which seem to be effective and safe. These data provide a basis for performing randomized clinical trials of DOACs vs. low molecular weight heparin or vitamin K antagonists

Bcr-Abl stabilizes β-catenin in chronic myeloid leukemia through its tyrosine phosphorylation

Self-renewal of Bcr-Abl(+) chronic myeloid leukemia (CML) cells is sustained by a nuclear activated serine/threonine-(S/T) unphosphorylated β-catenin. Although β-catenin can be tyrosine (Y)-phosphorylated, the occurrence and biological relevance of this covalent modification in Bcr-Abl-associated leukemogenesis is unknown. Here we show that Bcr-Abl levels control the degree of β-catenin protein stabilization by affecting its Y/S/T-phospho content in CML cells. Bcr-Abl physically interacts with β-catenin, and its oncogenic tyrosine kinase activity is required to phosphorylate β-catenin at Y86 and Y654 residues. This Y-phospho β-catenin binds to the TCF4 transcription factor, thus representing a transcriptionally active pool. Imatinib, a Bcr-Abl antagonist, impairs the β-catenin/TCF-related transcription causing a rapid cytosolic retention of Y-unphosphorylated β-catenin, which presents an increased binding affinity for the Axin/GSK3β complex. Although Bcr-Abl does not affect GSK3β autophosphorylation, it prevents, through its effect on β-catenin Y phosphorylation, Axin/GSK3β binding to β-catenin and its subsequent S/T phosphorylation. Silencing of β-catenin by small interfering RNA inhibited proliferation and clonogenicity of Bcr-Abl(+) CML cells, in synergism with Imatinib. These findings indicate the Bcr-Abl triggered Y phosphorylation of β-catenin as a new mechanism responsible for its protein stabilization and nuclear signalling activation in CML