The integrated low-level trigger and data acquisition (TDAQ) system of the NA62 experiment at CERN is described. The requirements of a large and fast data reduction in a high-rate environment for a ...medium-scale, distributed ensemble of many different sub-detectors led to the concept of a fully digital integrated system with good scaling capabilities. The NA62 TDAQ system is rather unique in allowing full flexibility on this scale, allowing in principle any information available from the detector to be used for triggering. The design concept, implementation and performances from the first years of running are illustrated.
Despite the fundamental pathophysiological importance of β-catenin in tumor progression, the mechanism underlying its final transcriptional output has been partially elucidated. Here, we report that ...β-arrestin-1 (β-arr1) is an epigenetic regulator of endothelin (ET)-1-induced β-catenin signaling in epithelial ovarian cancer (EOC). In response to ET A receptor (ETAR) activation by ET-1, β-arr1 increases its nuclear translocation and direct binding to β-catenin. This in turn enhanced β-catenin nuclear accumulation and transcriptional activity, which was prevented by expressing a mutant β-arr1 incapable of nuclear distribution. β-arr1-β-catenin interaction controls β-catenin target gene expressions, such as ET-1, Axin 2, Matrix metalloproteinase 2, and Cyclin D1, by promoting histone deacetylase 1 (HDAC1) dissociation and the recruitment of p300 acetyltransferase on these promoter genes, resulting in enhanced H3 and H4 histone acetylation, and gene transcription, required for cell migration, invasion and epithelial-to-mesenchymal transition. These effects are abrogated by β-arr1 silencing or by mutant β-arr1, as well as by β-catenin or p300 silencing, confirming that nuclear β-arr1 forms a functional complex capable of regulating epigenetic changes in β-catenin-driven invasive behavior. In a murine orthotopic model of metastatic human EOC, silencing of β-arr1 or mutant β-arr1 expression, as well as ETAR blockade, inhibits metastasis. In human EOC tissues, β-arr1-β-catenin nuclear complexes are selectively enriched at β-catenin target gene promoters, correlating with tumor grade, confirming a direct in vivo β-arr1-β-catenin association at specific set of genes involved in EOC progression. Collectively, our study provides insights into how a β-arr1-mediated epigenetic mechanism controls β-catenin activity, unraveling new components required for its nuclear function in promoting metastasis.
ABSTRACT
STUDY QUESTION
What are the trends and developments in preimplantation genetic testing (PGT) in 2018 as compared to previous years?
SUMMARY ANSWER
The main trends observed in this 21st ...dataset on PGT are that the implementation of trophectoderm biopsy with comprehensive whole-genome testing is most often applied for PGT-A and concurrent PGT-M/SR/A, while for PGT-M and PGT-SR, single-cell testing with PCR and FISH still prevail.
WHAT IS KNOWN ALREADY
Since it was established in 1997, the ESHRE PGT Consortium has been collecting and analysing data from mainly European PGT centres. To date, 20 datasets and an overview of the first 10 years of data collections have been published.
STUDY DESIGN, SIZE, DURATION
The data for PGT analyses performed between 1 January 2018 and 31 December 2018 with a 2-year follow-up after analysis were provided by participating centres on a voluntary basis. Data were collected using an online platform, which is based on genetic analysis and has been in use since 2016.
PARTICIPANTS/MATERIALS, SETTING, METHODS
Data on biopsy method, diagnostic technology, and clinical outcome were submitted by 44 centres. Records with analyses for more than one PGT for monogenic disorders (PGT-M) and/or PGT for chromosomal structural rearrangements (PGT-SR), or with inconsistent data regarding the PGT modality, were excluded. All transfers performed within 2 years after the analysis were included, enabling the calculation of cumulative pregnancy rates. Data analysis, calculations, and preparation of figures and tables were carried out by expert co-authors.
MAIN RESULTS AND THE ROLE OF CHANCE
The current data collection from 2018 covers a total of 1388 analyses for PGT-M, 462 analyses for PGT-SR, 3003 analyses for PGT for aneuploidies (PGT-A), and 338 analyses for concurrent PGT-M/SR with PGT-A.
The application of blastocyst biopsy is gradually rising for PGT-M (from 19% in 2016–2017 to 33% in 2018), is status quo for PGT-SR (from 30% in 2016–2017 to 33% in 2018) and has become the most used biopsy stage for PGT-A (from 87% in 2016–2017 to 98% in 2018) and for concurrent PGT-M/SR with PGT-A (96%). The use of comprehensive, whole-genome amplification (WGA)-based diagnostic technology showed a small decrease for PGT-M (from 15% in 2016–2017 to 12% in 2018) and for PGT-SR (from 50% in 2016–2017 to 44% in 2018). Comprehensive testing was, however, the main technology for PGT-A (from 93% in 2016–2017 to 98% in 2018). WGA-based testing was also widely used for concurrent PGT-M/SR with PGT-A, as a standalone technique (74%) or in combination with PCR or FISH (24%). Trophectoderm biopsy and comprehensive testing strategies are linked with higher diagnostic efficiencies and improved clinical outcomes per embryo transfer.
LIMITATIONS, REASONS FOR CAUTION
The findings apply to the data submitted by 44 participating centres and do not represent worldwide trends in PGT. Details on the health of babies born were not provided in this manuscript.
WIDER IMPLICATIONS OF THE FINDINGS
The Consortium datasets provide a valuable resource for following trends in PGT practice.
STUDY FUNDING/COMPETING INTEREST(S)
The study has no external funding, and all costs are covered by ESHRE. There are no competing interests declared.
TRIAL REGISTRATION NUMBER
N/A.
The Mu2e experiment at Fermilab searches for the charged-lepton flavor violating (CLFV) conversion of a negative muon into an electron in the field of an aluminum nucleus, with a distinctive ...signature of a monoenergetic electron of energy slightly below the muon rest mass (104.967 MeV). The Mu2e goal is to improve by four orders of magnitude the search sensitivity with respect to the previous experiments. Any observation of a CLFV signal will be a clear indication of new physics. The Mu2e detector is composed of a tracker, an electromagnetic calorimeter, and an external veto for cosmic rays surrounding the solenoid. The calorimeter plays an important role in providing particle identification capabilities, a fast online trigger filter, a seed for track reconstruction while working in vacuum, in the presence of 1-T axial magnetic field and in a harsh radiation environment. The calorimeter requirements are to provide a large acceptance for 100-MeV electrons and reach at these energies: 1) a time resolution better than 0.5 ns; 2) an energy resolution <10%; and 3) a position resolution of 1 cm. The calorimeter design consists of two disks, each one made of 674-undoped cesium iodine crystals read by two large area arrays of UV-extended silicon photomultipliers (SiPMs). We report here the construction and the test of the Module-0 prototype. The Module-0 has been exposed to an electron beam in the energy range around 100 MeV at the Beam Test Facility in Frascati. Preliminary results of timing and energy resolution at normal incidence are shown. A discussion of the technical aspects of the calorimeter engineering is also reported in this paper.
The large-scale polarization explorer (LSPE) is a cosmology program for the measurement of large-scale curl-like features (B-modes) in the polarization of the cosmic microwave background. Its goal is ...to constrain the background of inflationary gravity waves traveling through the universe at the time of matter-radiation decoupling. The two instruments of LSPE are meant to synergically operate by covering a large portion of the northern microwave sky. LSPE/STRIP is a coherent array of receivers planned to be operated from the Teide Observatory in Tenerife, for the control and characterization of the low-frequency polarized signals of galactic origin; LSPE/SWIPE is a balloon-borne bolometric polarimeter based on 330 large throughput multi-moded detectors, designed to measure the CMB polarization at 150 GHz and to monitor the polarized emission by galactic dust above 200 GHz. The combined performance and the expected level of systematics mitigation will allow LSPE to constrain primordial B-modes down to a tensor/scalar ratio of
10
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2
. We here report the status of the STRIP pre-commissioning phase and the progress in the characterization of the key subsystems of the SWIPE payload (namely the cryogenic polarization modulation unit and the multi-moded TES pixels) prior to receiver integration.
The Mu2e experiment at the Fermilab Muon Campus will search for the coherent neutrinoless conversion of a muon into an electron in the field of an aluminum nucleus with a sensitivity improvement by a ...factor of 10 000 over existing limits. Such a charged lepton flavor-violating reaction probes new physics at a scale unavailable with direct searches at either present or planned high-energy colliders. The Mu2e Trigger and Data Acquisition (TDAQ) system exploits otsdaq as its online Data Acquisition System (DAQ) solution. Developed at Fermilab, otsdaq integrates both the artdaq DAQ and the art analysis frameworks for event transfer, filtering, and processing. otsdaq is an online DAQ software suite with a focus on flexibility and scalability and provides a multi-user, web-based, interface accessible through a web browser. The read out controllers (ROCs) stream out zero-suppressed data continuously from the detector subsystems to the data transfer controllers (DTCs). The data stream is then read over the peripheral component interconnect express (PCIe) bus to a software filter algorithm that selects events which are combined with the data flux coming from a cosmic-ray veto (CRV) system. The detector control system (DCS) has been developed using the experimental physics and industrial control system (EPICS) open source platform for monitoring, controlling, alarming, and archiving. The DCS has been integrated into otsdaq . A prototype of the TDAQ system and the DCS has been built at Fermilab's Feynman Computing Center. In this article, we report on the progress of the integration of this prototype in the online otsdaq software.
The Mu2e experiment is constructing a calorimeter consisting of 1348 undoped cesium iodide (CsI) crystals in two disks. Each crystal has a dimension of 34 × 34 × 200 mm3 and is readout by a ...large-area silicon photomultipliers array. A series of technical specifications on mechanical and optical parameters was defined according to the calorimeter physics requirements. Preproduction CsI crystals were procured from three firms: Amcrys, Saint-Gobain, and Shanghai Institute of Ceramics. We report the quality assurance on crystal's scintillation properties and their radiation hardness against ionization dose and neutrons. With a fast decay time of about 30 ns and a light output of more than 100 p.e./MeV measured by a bialkali photomultiplier tube, undoped CsI crystals provide a cost-effective solution for Mu2e.
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