The RNA polymerase II complex (pol II) is responsible for transcription of all ∼21,000 human protein-encoding genes. Here, we describe sixteen individuals harboring de novo heterozygous variants in ...POLR2A, encoding RPB1, the largest subunit of pol II. An iterative approach combining structural evaluation and mass spectrometry analyses, the use of S. cerevisiae as a model system, and the assessment of cell viability in HeLa cells allowed us to classify eleven variants as probably disease-causing and four variants as possibly disease-causing. The significance of one variant remains unresolved. By quantification of phenotypic severity, we could distinguish mild and severe phenotypic consequences of the disease-causing variants. Missense variants expected to exert only mild structural effects led to a malfunctioning pol II enzyme, thereby inducing a dominant-negative effect on gene transcription. Intriguingly, individuals carrying these variants presented with a severe phenotype dominated by profound infantile-onset hypotonia and developmental delay. Conversely, individuals carrying variants expected to result in complete loss of function, thus reduced levels of functional pol II from the normal allele, exhibited the mildest phenotypes. We conclude that subtle variants that are central in functionally important domains of POLR2A cause a neurodevelopmental syndrome characterized by profound infantile-onset hypotonia and developmental delay through a dominant-negative effect on pol-II-mediated transcription of DNA.
In this paper we present new results on upper limits for the search of Heavy Neutral Leptons (HNL) with data collected by NA48/2 (2003-2004), NA62-RK (2007) and NA62 (2015) CERN experiments. The data ...collected with different trigger configuration allow to search for both long and short living heavy neutrinos in the mass range below the kaon mass. In addition the status of the search for
K
+
→ π
+
v
v
with the NA62 detector will be briefly presented.
Performance of the NA62 trigger system Cortina Gil, E.; Kleimenova, A.; Minucci, E. ...
The journal of high energy physics,
03/2023, Letnik:
2023, Številka:
3
Journal Article
Recenzirano
Odprti dostop
A
bstract
The NA62 experiment at CERN targets the measurement of the ultra-rare
K
+
→
π
+
ν
ν
¯
decay, and carries out a broad physics programme that includes probes for symmetry violations and ...searches for exotic particles. Data were collected in 2016–2018 using a multi-level trigger system, which is described highlighting performance studies based on 2018 data.
A
bstract
Measurement of the ultra-rare
K
+
→
π
+
ν
ν
¯
decay at the NA62 experiment at CERN requires high-performance particle identification to distinguish muons from pions. Calorimetric ...identification currently in use, based on a boosted decision tree algorithm, achieves a muon misidentification probability of 1
.
2 × 10
−
5
for a pion identification efficiency of 75% in the momentum range of 15–40 GeV/
c
. In this work, calorimetric identification performance is improved by developing an algorithm based on a convolutional neural network classifier augmented by a filter. Muon misidentification probability is reduced by a factor of six with respect to the current value for a fixed pion-identification efficiency of 75%. Alternatively, pion identification efficiency is improved from 72% to 91% for a fixed muon misidentification probability of 10
−
5
.
The NA62 experiment at the CERN SPS reports the first search for K+ → π+ν ν ¯ using the decay-in-flight technique, based on a sample of 1.21 x 1011 K+ decays collected in 2016.
Design, construction and tests of the ICARUS T600 detector Amerio, S.; Amoruso, S.; Antonello, M. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
07/2004, Letnik:
527, Številka:
3
Journal Article
Recenzirano
We have constructed and operated the ICARUS T600 liquid argon (LAr) time projection chamber (TPC). The ICARUS T600 detector is the largest LAr TPC ever built, with a size of about
500
tons
of fully ...imaging mass. The design and assembly of the detector relied on industrial support and represents the applications of concepts matured in laboratory tests to the kton scale.
The ICARUS T600 was commissioned for a technical run that lasted about 3 months. During this period all the detector features were extensively tested with an exposure to cosmic-rays at surface with a resulting data collection of about 30
000 events.
The detector was developed as the first element of a modular design. Thanks to the concept of modularity, it will be possible to realize a detector with several ktons active mass, to act as an observatory for astroparticle and neutrino physics at the Gran Sasso Underground Laboratory and a second-generation nucleon decay experiment.
In this paper a description of the ICARUS T600 is given, detailing its design specifications, assembly procedures and acceptance tests. Commissioning procedures and results of the technical run are also reported, as well as results from the off-line event reconstruction.
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