In this paper, a 90-nm 128-Mcell non-volatile memory based on phase-change Ge 2 -Sb 2 -TeB alloy is presented. Memory cells are bipolar selected, and are based on a /xtrench architecture. ...Experimental investigation on multi-level cell (MLC) storage is addressed exploiting the chip MLC capability. To this end, a programming algorithm suitable for 2 bit/cell storage achieving tightly placed inner states (in terms of cell current or resistance) is proposed. Measurements showed the possibility of placing the required distinct cell current distributions, thus demonstrating the feasibility of the MLC phase-change memory (PCM) storage concept. Endurance tests were also carried out. Cumulative distribu tions after 2-bit/cell programming before cycling and after 100 k program cycles followed by 1 h/150 degC bake are presented. Experimental results on MLC endurance are also provided from a 180-nm 8-Mb PCM demonstrator with the same mutrench cell structure.
During the COVID-19 outbreak, the European Reference Network on Rare Bone Diseases (ERN BOND) coordination team and Italian rare bone diseases healthcare professionals created the "COVID-19 Helpline ...for Rare Bone Diseases" in an attempt to provide high-quality information and expertise on rare bone diseases remotely to patients and healthcare professionals. The present position statement describes the key characteristics of the Helpline initiative, along with the main aspects and topics that recurrently emerged as central for rare bone diseases patients and professionals. The main topics highlighted are general recommendations, pulmonary complications, drug treatment, trauma, pregnancy, children and elderly people, and patient associations role. The successful experience of the "COVID-19 Helpline for Rare Bone Diseases" launched in Italy could serve as a primer of gold-standard remote care for rare bone diseases for the other European countries and globally. Furthermore, similar COVID-19 helplines could be considered and applied for other rare diseases in order to implement remote patients' care.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. ...However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in 50% of BWS and 29% of SRS patients as a maternal hypomethylation syndrome. By next-generation sequencing, we searched for putative MLID-causative mutations in genes involved in methylation establishment/maintenance and found two novel missense mutations possibly causative of MLID: one in NLRP2, affecting ADP binding and protein activity, and one in ZFP42, likely leading to loss of DNA binding specificity. Both variants were paternally inherited. In silico protein modelling allowed to define the functional effect of these mutations. We found that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test could be important for a comprehensive clinical assessment. Finally, we highlighted the possible involvement of ZFP42 variants in MLID development and confirmed NLRP2 as causative locus in BWS-MLID.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
The genetic basis of Rubinstein–Taybi syndrome (RSTS), a rare, sporadic, clinically heterogeneous disorder characterized by cognitive impairment and a wide spectrum of multiple congenital anomalies, ...is primarily due to private mutations in CREBBP (approximately 55% of cases) or EP300 (approximately 8% of cases). Herein, we report the clinical and the genetic data taken from a cohort of 46 RSTS patients, all carriers of CREBBP point mutations. Molecular analysis revealed 45 different gene alterations including 31 inactivating (21 frameshift and 10 nonsense), 10 missense and 4 splicing mutations. Bioinformatic tools and transcript analyses were used to predict the functional effects of missense and splicing alterations. Of the 45 mutations, 42 are unreported and 3 were described previously. Recurrent mutations maybe a key tool in addressing genotype–phenotype correlations in patients sharing the same defects (at the genomic or transcript level) and specific clinical signs, demonstrated here in two cases. The clinical data of our cohort evidenced frequent signs such as arched eyebrows, epicanthus, synophrys and/or frontal hypertrichosis and broad phalanges that, previously overlooked in RSTS diagnosis, now could be considered. Some suggested correlations between organ‐specific anomalies and affected CREB‐binding protein domains broaden the RSTS clinical spectrum and perhaps will enhance patient follow‐up and clinical care.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
We provide data on fetal growth pattern on the molecular subtypes of Beckwith–Wiedemann syndrome (BWS): IC1 gain of methylation (IC1‐GoM), IC2 loss of methylation (IC2‐LoM), 11p15.5 paternal ...uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age‐corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1‐GoM (n = 21), UPD (n = 87), IC2‐LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1‐GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1‐GoM patients, lowest in IC2‐LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2‐LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1‐GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2‐LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2‐LoM, but manifest a body mass disproportion rather similar to that seen in IC1‐GoM cases.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
IDEA (Innovative Detector for Electron–positron Accelerators) is a detector concept designed for a future leptonic collider operating as a Higgs factory. It is based on innovative detector ...technologies developed over years of R&D. In September 2018, prototypes of the proposed sub-detectors have been tested for the first time on a beam line at CERN. The preliminary results from this test of a full slice of the IDEA detector and standalone measurements of dual read-out calorimeter prototypes are presented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Muon g-2 Experiment at Fermilab (E989) will measure the muon magnetic anomaly with unprecedented precision (0.14 ppm), which yields a factor of 4 improvement with respect to the previous ...measurements at Brookhaven National Laboratory (BNL) (E821). To achieve this goal, the relative response of each calorimeter channel must be calibrated and monitored at a level better than <inline-formula> <tex-math notation="LaTeX">10^{-3} </tex-math></inline-formula> in the time window of the muon fill. The calibration system uses a laser source and photodetectors. The data acquisition (DAQ) of the system is designed around two field-programmable gate array (FPGA)-based boards and a custom crate bus. The front-end board manages the photodetector operation and signal processing and performs a first-level data concentration task. Up to 12 FPGA boards can be housed in a 6U crate. A readout master controls the boards, implements event-building functionalities, manages the monitoring interface, and facilitates calibration and debugging tasks. A gigabit-ethernet interface is used to transfer data to the on-line farm for storage and further processing. Presently, the system is working at Fermi National Accelerator Laboratory (FNAL). In this article, we present the DAQ system design, run control user interface, and system evaluation.
The Muon g−2 experiment, E989, is currently taking data at Fermilab with the aim of reducing the experimental error on the muon anomaly by a factor of four and possibly clarifying the current ...discrepancy with the theoretical prediction. A central component of this four-fold improvement in precision is the laser calibration system of the calorimeters, which has to monitor the gain variations of the photo-sensors with a 0.04% precision on the short-term (∼1ms). This is about one order of magnitude better than what has ever been achieved for the calibration of a particle physics calorimeter. The system is designed to monitor also long-term gain variations, mostly due to temperature effects, with a precision below the per mille level. This article reviews the design, the implementation and the performance of the Muon g−2 laser calibration system, showing how the experimental requirements have been met.
Background
Beckwith–Wiedemann syndrome (BWS) is an overgrowth disorder caused by defects at the 11p15.5 imprinted region. Many cases of female monozygotic (MZ) twins discordant for BWS have been ...reported, but no definitive conclusions have been drawn regarding the link between epigenetic defects, twinning process, and gender. Here, we report a comprehensive characterization and follow‐up of female MZ twins discordant for BWS.
Methods
Methylation pattern at 11p15.5 and multilocus methylation disturbance (MLID) profiling were performed by pyrosequencing and MassARRAY in placental/umbilical cord samples and postnatal tissues. Whole‐exome sequencing was carried out to identify MLID causative mutations. X‐chromosome inactivation (XCI) was determined by HUMARA test.
Results
Both twins share KCNQ1OT1:TSS‐DMR loss of methylation (LOM) and MLID in blood and the epigenetic defect remained stable in the healthy twin over time. KCNQ1OT1:TSS‐DMRLOM was nonhomogeneously distributed in placental samples and the twins showed the same severely skewed XCI pattern. No MLID‐causative mutations were identified.
Conclusion
This is the first report on BWS‐discordant twins with methylation analyses extended to extraembryonic tissues. The results suggest that caution is required when attempting prenatal diagnosis in similar cases. Although the causative mechanism underlying LOM remains undiscovered, the XCI pattern and mosaic LOM suggest that both twinning and LOM/MLID occurred after XCI commitment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The electromagnetic performance of the RD52 fiber calorimeter Akchurin, N.; Bedeschi, F.; Cardini, A. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
2014, Volume:
735
Journal Article
Peer reviewed
Open access
The RD52 calorimeter is an instrument intended to detect both electromagnetic and hadronic showers, as well as muons, using the dual-readout principle. Scintillation and Cherenkov light provide the ...two signals which, in combination, allow for superior hadronic performance. In this paper, we report on the electromagnetic performance of this instrument, and compare this performance with that of other calorimeters that were constructed with similar goals in mind.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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