3,348 research outputs found
Defects of splicing in antithrombin deficiency
Background: There is increasing evidence supporting the relevance of aberrant splicing in multiple disorders. In antithrombin deficiency only 22 intronic mutations affecting splicing sites (7% of SERPINC1 mutations) are considered as splicing mutations.
Methods: SERPINC1 was analyzed by Sanger sequencing and MLPA in 141 unrelated
cases with antithrombin deficiency. Plasma antithrombin was studied by functional
and western blot assays, purified by FPLC and characterized by proteomic analysis. In
silico predictions on splicing was done with the Human Splicing Finder software.
Results: We detected 89 different SERPINC1 defects, 13 with potential effect on splicing. Ten cases presented 9 mutations disturbing splicing sites, 5 new. Three gross or
small gene defects also disturbed a correct splicing. Interestingly, the first duplication
of a single exon ever described (c.1154-13_1218+115dup), caused mild deficiency
(75%). A deeper intronic mutation (c.1154-14G>A), identified in three unrelated patients with traces of disulphide dimers of antithrombin in plasma, created a cryptic
splicing site that might generate a variant with 4 additional in frame residues according
to in silico predictions. This aberrant splicing was confirmed by proteomic analysis of
the dimer purified from plasma.
Conclusions: A high proportion of cases with antithrombin deficiency (up to 13%) may be
explained by an aberrant splicing. Up to 15% of mutations in SERPINC1: splicing site variations, gross gene defects and deep intronic mutations, may affect a correct splicing with
three potential consequences type I, type II, and even moderate antithrombin deficiency
Encouraging natural ventilation to improve indoor environmental conditions at schools. Case studies in the north of Spain before and during COVID
The COVID pandemic has strongly affected daily life both in Spanish schools and worldwide. Providing
the best environmental conditions for children allowing face-to-face learning with healthy and safe
indoor spaces is a challenge. In the present study, empirical research about how these environmental
conditions change with COVID is presented comparing the situation from March 2020 to January 2021.
The methodology combines surveys conducted in nine schools with a case study in a selected school
where a detailed monitoring of the building was developed during both heating seasons. This data ana-
lyzes the impact of the new COVID prevention protocols on indoor environmental conditions (especially
those related to natural ventilation). Results show a mean CO2 reduction of 1,400 ppm, having in the sec-
ond term values around 1,000 ppm, although temperatures diminished nearly 2 °C to mean values of
18 °C. Evolution of temperature and CO2 concentration throughout the day was also analyzed, being these
indoor conditions especially important for the children with poorer health. Mechanical ventilation with
heating recovery should complement natural ventilation, at least during the coldest months or hours of
the day, although systems have to be carefully designed and installed to work effectively
IKZF1/3 and CRL4-CRBN E3 ubiquitin ligase mutations and IMiD resistance in multiple myeloma
The work was supported by the Deutsche Forschungsgemeinschaft (KFO216), the IZKF, the
BTHA and the CDW Stiftung (KMK). UM was supported by a grant of the German Excellence
Initiative to the Graduate School of Life Sciences, University of Würzburg.S
NectarCAM : a camera for the medium size telescopes of the Cherenkov Telescope Array
NectarCAM is a camera proposed for the medium-sized telescopes of the
Cherenkov Telescope Array (CTA) covering the central energy range of ~100 GeV
to ~30 TeV. It has a modular design and is based on the NECTAr chip, at the
heart of which is a GHz sampling Switched Capacitor Array and a 12-bit Analog
to Digital converter. The camera will be equipped with 265 7-photomultiplier
modules, covering a field of view of 8 degrees. Each module includes the
photomultiplier bases, high voltage supply, pre-amplifier, trigger, readout and
Ethernet transceiver. The recorded events last between a few nanoseconds and
tens of nanoseconds. The camera trigger will be flexible so as to minimize the
read-out dead-time of the NECTAr chips. NectarCAM is designed to sustain a data
rate of more than 4 kHz with less than 5\% dead time. The camera concept, the
design and tests of the various subcomponents and results of thermal and
electrical prototypes are presented. The design includes the mechanical
structure, cooling of the electronics, read-out, clock distribution, slow
control, data-acquisition, triggering, monitoring and services.Comment: In Proceedings of the 34th International Cosmic Ray Conference
(ICRC2015), The Hague, The Netherlands. All CTA contributions at
arXiv:1508.0589
Dark Matter and Fundamental Physics with the Cherenkov Telescope Array
The Cherenkov Telescope Array (CTA) is a project for a next-generation
observatory for very high energy (GeV-TeV) ground-based gamma-ray astronomy,
currently in its design phase, and foreseen to be operative a few years from
now. Several tens of telescopes of 2-3 different sizes, distributed over a
large area, will allow for a sensitivity about a factor 10 better than current
instruments such as H.E.S.S, MAGIC and VERITAS, an energy coverage from a few
tens of GeV to several tens of TeV, and a field of view of up to 10 deg. In the
following study, we investigate the prospects for CTA to study several science
questions that influence our current knowledge of fundamental physics. Based on
conservative assumptions for the performance of the different CTA telescope
configurations, we employ a Monte Carlo based approach to evaluate the
prospects for detection. First, we discuss CTA prospects for cold dark matter
searches, following different observational strategies: in dwarf satellite
galaxies of the Milky Way, in the region close to the Galactic Centre, and in
clusters of galaxies. The possible search for spatial signatures, facilitated
by the larger field of view of CTA, is also discussed. Next we consider
searches for axion-like particles which, besides being possible candidates for
dark matter may also explain the unexpectedly low absorption by extragalactic
background light of gamma rays from very distant blazars. Simulated
light-curves of flaring sources are also used to determine the sensitivity to
violations of Lorentz Invariance by detection of the possible delay between the
arrival times of photons at different energies. Finally, we mention searches
for other exotic physics with CTA.Comment: (31 pages, Accepted for publication in Astroparticle Physics
Phenotypic, transcriptomic, and genomic features of clonal plasma cells in light-chain amyloidosis
Immunoglobulin light-chain amyloidosis (AL) and multiple myeloma (MM) are 2 distinct monoclonal gammopathies that involve the same cellular compartment: clonal plasma cells (PCs). Despite the fact that knowledge about MM PC biology has significantly increased in the last decade, the same does not apply for AL. Here, we used an integrative phenotypic, molecular, and genomic approach to study clonal PCs from 24 newly diagnosed patients with AL. Through principal-component-analysis, we demonstrated highly overlapping phenotypic profiles between AL and both monoclonal gammopathy of undetermined significance and MM PCs. However, in contrast to MM, highly purified fluorescence-activated cell-sorted clonal PCs from AL (n = 9) showed almost normal transcriptome, with only 38 deregulated genes vs normal PCs; these included a few tumor-suppressor (CDH1, RCAN) and proapoptotic (GLIPR1, FAS) genes. Notwithstanding, clonal PCs in AL (n=11) were genomically unstable, with a median of 9 copy number alterations (CNAs) per case, many of such CNAs being similar to those found in MM. Whole-exome sequencing (WES) performed in 5 AL patients revealed a median of 15 nonrecurrent mutations per case. Altogether, our results show that in the absence of a unifying mutation by WES, clonal PCs in AL display phenotypic and CNA profiles similar to MM, but their transcriptome is remarkably similar to that of normal PCs
First bounds on the very high energy gamma-ray emission from Arp 220
Using the Major Atmospheric Gamma Imaging Cherenkov Telescope (MAGIC), we
have observed the nearest ultra-luminous infrared galaxy Arp 220 for about 15
hours. No significant signal was detected within the dedicated amount of
observation time. The first upper limits to the very high energy -ray
flux of Arp 220 are herein reported and compared with theoretical expectations.Comment: Accepted for publication in Ap
The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in
the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent
a series of upgrades, involving the exchange of the MAGIC-I camera and its
trigger system, as well as the upgrade of the readout system of both
telescopes. We use observations of the Crab Nebula taken at low and medium
zenith angles to assess the key performance parameters of the MAGIC stereo
system. For low zenith angle observations, the standard trigger threshold of
the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources
with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula
flux in 50 h of observations. The angular resolution, defined as the sigma of a
2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while
the energy resolution is 16%. We also re-evaluate the effect of the systematic
uncertainty on the data taken with the MAGIC telescopes after the upgrade. We
estimate that the systematic uncertainties can be divided in the following
components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for
the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle
Physic
Probing the very-high-energy gamma-ray spectral curvature in the blazar PG 1553+113 with the MAGIC telescopes
PG 1553+113 is a very-high-energy (VHE, ) -ray
emitter classified as a BL Lac object. Its redshift is constrained by
intergalactic absorption lines in the range . The MAGIC telescopes
have monitored the source's activity since 2005. In early 2012, PG 1553+113 was
found in a high-state, and later, in April of the same year, the source reached
its highest VHE flux state detected so far. Simultaneous observations carried
out in X-rays during 2012 April show similar flaring behaviour. In contrast,
the -ray flux at observed by Fermi-LAT is
compatible with steady emission. In this paper, a detailed study of the flaring
state is presented. The VHE spectrum shows clear curvature, being well fitted
either by a power law with an exponential cut-off or by a log-parabola. A
simple power-law fit hypothesis for the observed shape of the PG 1553+113 VHE
-ray spectrum is rejected with a high significance (fit probability
P=2.6 ). The observed curvature is compatible with the
extragalactic background light (EBL) imprint predicted by current generation
EBL models assuming a redshift . New constraints on the redshift are
derived from the VHE spectrum. These constraints are compatible with previous
limits and suggest that the source is most likely located around the optical
lower limit, , based on the detection of Ly absorption. Finally,
we find that the synchrotron self-Compton (SSC) model gives a satisfactory
description of the observed multi-wavelength spectral energy distribution
during the flare.Comment: 13 pages, 7 figures, accepted for publication in MNRA
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