Influence of Thermal Cycling on Cryogenic Thermometers

The stringent requirements on temperature control of the superconducting magnets for the Large Hadron Collider (LHC), impose that the cryogenic temperature sensors meet compelling demands such as long-term stability, radiation hardness, readout accuracy better than 5 mK at 1.8 K and compatibility with industrial control equipment. This paper presents the results concerning long-term stability of resistance temperature sensors submitted to cryogenic thermal cycles. For this task a simple test facility has been designed, constructed and put into operation for cycling simultaneously 115 cryogenic thermometers between 300 K and 4.2 K. A thermal cycle is set to last 71/4 hours: 3 hours for either cooling down or warming up the sensors and 1 respectively 1/4 hour at steady temperature conditions at each end of the temperature cycle. A Programmable Logic Controller (PLC) drives automatically this operation by reading 2 thermometers and actuating on 3 valves and 1 heater. The first thermal cycle was accomplished in a temperature calibration facility and all the thermometers were recalibrated again after 10, 25 and 50 cycles. Care is taken in order not to expose the sensing elements to moisture that can reputedly affect the performance of some of the sensors under investigation. The temperature sensors included Allen-Bradley and TVO carbon resistors, Cernox, thin-film germanium, thin-film and wire-wound Rh-Fe sensors

New cryogenic facilities for testing superconducting equipments for the CERN Large Hadron Collider

CERN's major project, the Large Hadron Collider (LHC), has moved to an implementation phase with machine construction to be completed by 2005. To achieve the design proton-proton centre of mass energy of 14 TeV in the given 27 km circumference LEP tunnel, the LHC will make an extensive use of high-field superconducting magnets using Nb-Ti filament operated at 1.9 K. In order to test, on the one han d, the superconducting cables of the magnets and, on the other hand, the expected performance of several of these magnets assembled in a string representing the lattice period of the machine (107 m lo ng), CERN has installed new cryogenic test facilities. The paper briefly describes these new facilities with all their associated equipments

Cryogenics for CERN experiments: past, present and future

Use of cryogenics at CERN was originated (in the 1960s) by bubble chambers and the associated s.c. solenoids. Complex cryoplants were installed to provide cooling at LH2 and LHe temperatures. Continuity (in the 1970s) in He cryogenics for experiments was provided by spectrometer magnets for fixed target physics of the SPS accelerator. More recently (in the 1980s), large "particle-transparent" s.c. solenoids for collider experiments (LEP) have been built demanding new cryoplants. The LHC experiments (in the 2000s) will continue the tradition with s.c. dipoles (ALICE and LHCb), solenoids (CMS, ATLAS) and toroids (ATLAS) of unusual size. Cryogenics for experiments using noble liquids follows the same trend since the development (in the 1970s) of the first shower LAr detectors. A LKr calorimeter (about 10 m3) will be operated in 1996 and the ATLAS experiment foresees a set of three huge LAr calorimeters (almost 90 m3 total volume of liquid) to be installed underground

Large enhancement of deuteron polarization with frequency modulated microwaves

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar files in poltar.uu, which also brings cernart.sty and crna12.sty files neede

Delineation of phenotypes and genotypes related to cohesin structural protein RAD21

RAD21 encodes a key component of the cohesin complex, and variants in RAD21 have been associated with Cornelia de Lange Syndrome (CdLS). Limited information on phenotypes attributable to RAD21 variants and genotype–phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with RAD21 alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in NIPBL or SMC1A for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the RAD21 variant is uncertain. Variants were frequently familial, and genotype–phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of RAD21 variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a RAD21 variation.Spanish Ministry of Science, Innovation and Universities/State Research Agency RTC-2017-6494-1 and RTI2018-094434-B-I00 (MCIU/AEI/FEDER, UE) as well as funds from the European JPIAMR-VRI network “CONNECT” to PG-

De novo variants predicting haploinsufficiency for DIP2C are associated with expressive speech delay.

The disconnected (disco)-interacting protein 2 (DIP2) gene was first identified in D. melanogaster and contains a DNA methyltransferase-associated protein 1 (DMAP1) binding domain, Acyl-CoA synthetase domain and AMP-binding sites. DIP2 regulates axonal bifurcation of the mushroom body neurons in D. melanogaster and is required for axonal regeneration in the neurons of C. elegans. The DIP2 homologues in vertebrates, Disco-interacting protein 2 homolog A (DIP2A), Disco-interacting protein 2 homolog B (DIP2B), and Disco-interacting protein 2 homolog C (DIP2C), are highly conserved and expressed widely in the central nervous system. Although there is evidence that DIP2C plays a role in cognition, reports of pathogenic variants in these genes are rare and their significance is uncertain. We present 23 individuals with heterozygous DIP2C variants, all manifesting developmental delays that primarily affect expressive language and speech articulation. Eight patients had de novo variants predicting loss-of-function in the DIP2C gene, two patients had de novo missense variants, three had paternally inherited loss of function variants and six had maternally inherited loss-of-function variants, while inheritance was unknown for four variants. Four patients had cardiac defects (hypertrophic cardiomyopathy, atrial septal defects, and bicuspid aortic valve). Minor facial anomalies were inconsistent but included a high anterior hairline with a long forehead, broad nasal tip, and ear anomalies. Brainspan analysis showed elevated DIP2C expression in the human neocortex at 10-24 weeks after conception. With the cases presented herein, we provide phenotypic and genotypic data supporting the association between loss-of-function variants in DIP2C with a neurocognitive phenotype

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification. Methods and results A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis. There was no restriction made based on their clinical diagnosis. A total of 442 children {55.7% boys, 40.3% probands, median age: 8.0 [interquartile range (IQR) 9.5] years} from 350 families were included; 67.9% were asymptomatic at diagnosis. Four main phenotypes were identified: isolated progressive cardiac conduction disorders (25.6%), overlap phenotype (15.6%), isolated long QT syndrome type 3 (10.6%), and isolated Brugada syndrome type 1 (1.8%); 44.3% had a negative electrocardiogram phenotype. During a median follow-up of 5.9 (IQR 5.9) years, 272 cardiac events (CEs) occurred in 139 (31.5%) patients. Patients whose mutation localized in the C-terminus had a lower risk. Compound genotype, both gain- and loss-of-function SCN5A mutation, age ≤1 year at diagnosis in probands and age ≤1 year at diagnosis in non-probands were independent predictors of CE. Conclusion In this large paediatric cohort of SCN5A mutation-positive subjects, cardiac conduction disorders were the most prevalent phenotype; CEs occurred in about one-third of genotype-positive children, and several independent risk factors were identified, including age ≤1 year at diagnosis, compound mutation, and mutation with both gain- and loss-of-function

Measurement of the spin-dependent structure function g1(x) of the proton

Adams D, Adeva B, Arik E, et al. Measurement of the spin-dependent structure function g1(x) of the proton. Phys.Lett. B. 1994;329(2-3):399-406.We have measured the spin-dependent structure function $g_1~p$ of the proton in deep inelastic scattering of polarized muons off polarized protons, in the kinematic range $0.003<x<0.7$ and 1\,\mbox{GeV}~2. Its first moment, $\int_0~1 g_1~p(x) dx$, is found to be 0.136 \pm 0.011\,(\mbox{stat.})\pm 0.011\,(\mbox{syst.}) at Q~2=10\,\mbox{GeV}~2. This value is smaller than the prediction of the Ellis--Jaffe sum rule by two standard deviations, and is consistent with previous measurements. A combined analysis of all available proton, deuteron and neutron data confirms the Bjorken sum rule to within $10\%$ of the theoretical value

Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders.

Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders