155 research outputs found
Dissecting the role of TP53 alterations in del(11q) chronic lymphocytic leukemia
[EN]Background
Several genetic alterations have been identified as driver events in chronic lymphocytic leukemia (CLL) pathogenesis and oncogenic evolution. Concurrent driver alterations usually coexist within the same tumoral clone, but how the cooperation of multiple genomic abnormalities contributes to disease progression remains poorly understood. Specifically, the biological and clinical consequences of concurrent high-risk alterations such as del(11q)/ATM-mutations and del(17p)/TP53-mutations have not been established.
Methods
We integrated next-generation sequencing (NGS) and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 techniques to characterize the in vitro and in vivo effects of concurrent monoallelic or biallelic ATM and/or TP53 alterations in CLL prognosis, clonal evolution, and therapy response.
Results
Targeted sequencing analysis of the co-occurrence of high-risk alterations in 271 CLLs revealed that biallelic inactivation of both ATM and TP53 was mutually exclusive, whereas monoallelic del(11q) and TP53 alterations significantly co-occurred in a subset of CLL patients with a highly adverse clinical outcome. We determined the biological effects of combined del(11q), ATM and/or TP53 mutations in CRISPR/Cas9-edited CLL cell lines. Our results showed that the combination of monoallelic del(11q) and TP53 mutations in CLL cells led to a clonal advantage in vitro and in in vivo clonal competition experiments, whereas CLL cells harboring biallelic ATM and TP53 loss failed to compete in in vivo xenotransplants. Furthermore, we demonstrated that CLL cell lines harboring del(11q) and TP53 mutations show only partial responses to B cell receptor signaling inhibitors, but may potentially benefit from ATR inhibition.
Conclusions
Our work highlights that combined monoallelic del(11q) and TP53 alterations coordinately contribute to clonal advantage and shorter overall survival in CLL
The SuperFGD Prototype charged particle beam tests
A novel scintillator detector, the SuperFGD, has been selected as the main neutrino target for an upgrade of the T2K experiment ND280 near detector. The detector design will allow nearly 4Ï coverage for neutrino interactions at the near detector and will provide lower energy thresholds, significantly reducing systematic errors for the experiment. The SuperFGD is made of optically-isolated scintillator cubes of size 10Ă10Ă10 mm3, providing the required spatial and energy resolution to reduce systematic uncertainties for future T2K runs. The SuperFGD for T2K will have close to two million cubes in a 1920 Ă 560 Ă 1840 mm3 volume. A prototype made of 24 Ă 8 Ă 48 cubes was tested at a charged particle beamline at the CERN PS facility. The SuperFGD Prototype was instrumented with readout electronics similar to the future implementation for T2K . Results on electronics and detector response are reported in this paper, along with a discussion of the 3D reconstruction capabilities of this type of detector. Several physics analyses with the prototype data are also discussed, including a study of stopping protons
Analysis of test beam data taken with a prototype of TPC with resistive Micromegas for the T2K Near Detector upgrade
In this paper we describe the performance of a prototype of the High Angle
Time Projection Chambers (HA-TPCs) that are being produced for the Near
Detector (ND280) upgrade of the T2K experiment. The two HA-TPCs of ND280 will
be instrumented with eight Encapsulated Resistive Anode Micromegas (ERAM) on
each endplate, thus constituting in total 32 ERAMs. This innovative technique
allows the detection of the charge emitted by ionization electrons over several
pads, improving the determination of the track position. The TPC prototype has
been equipped with the first ERAM module produced for T2K and with the HA-TPC
readout electronics chain and it has been exposed to the DESY Test Beam in
order to measure spatial and dE/dx resolution. In this paper we characterize
the performances of the ERAM and, for the first time, we compare them with a
newly developed simulation of the detector response. Spatial resolution better
than 800 and dE/dx resolution better than 10% are observed for
all the incident angles and for all the drift distances of interest. All the
main features of the data are correctly reproduced by the simulation and these
performances fully fulfill the requirements for the HA-TPCs of T2K
Database of spatial distribution of non indigenous species in Spanish marine waters
Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, managerâs and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend
Measurement of neutrino and antineutrino neutral-current quasielasticlike interactions on oxygen by detecting nuclear deexcitation Îł rays
Neutrino- and antineutrino-oxygen neutral-current quasielastic-like
interactions are measured at Super-Kamiokande using nuclear de-excitation
-rays to identify signal-like interactions in data from a $14.94 \
(16.35)\times 10^{20}\langle \sigma_{\nu {\rm -NCQE}} \rangle = 1.70 \pm 0.17 ({\rm stat.}) ^{+
{\rm 0.51}}_{- {\rm 0.38}} ({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}\langle \sigma_{\bar{\nu} {\rm
-NCQE}} \rangle = 0.98 \pm 0.16 ({\rm stat.}) ^{+ {\rm 0.26}}_{- {\rm 0.19}}
({\rm syst.}) \times 10^{-38} \ {\rm cm^2/oxygen}$ with a flux-averaged energy
of 0.68 GeV, for neutrinos and antineutrinos, respectively. These results are
the most precise to date, and the antineutrino result is the first cross
section measurement of this channel. They are compared with various theoretical
predictions. The impact on evaluation of backgrounds to searches for supernova
relic neutrinos at present and future water Cherenkov detectors is also
discussed
Measurements of the and -induced Coherent Charged Pion Production Cross Sections on by the T2K experiment
We report an updated measurement of the -induced, and the first
measurement of the -induced coherent charged pion production
cross section on nuclei in the T2K experiment. This is measured in a
restricted region of the final-state phase space for which
GeV, and , and at a mean
(anti)neutrino energy of 0.85 GeV using the T2K near detector. The measured
CC coherent pion production flux-averaged cross section on
is . The new measurement
of the -induced cross section on is . The results are compatible with both the NEUT
5.4.0 Berger-Sehgal (2009) and GENIE 2.8.0 Rein-Sehgal (2007) model
predictions
Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment
The Deep Underground Neutrino Experiment (DUNE) will produce world-leading
neutrino oscillation measurements over the lifetime of the experiment. In this
work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in
the neutrino sector, and to resolve the mass ordering, for exposures of up to
100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed
uncertainties on the flux prediction, the neutrino interaction model, and
detector effects. We demonstrate that DUNE will be able to unambiguously
resolve the neutrino mass ordering at a 3 (5) level, with a 66
(100) kt-MW-yr far detector exposure, and has the ability to make strong
statements at significantly shorter exposures depending on the true value of
other oscillation parameters. We also show that DUNE has the potential to make
a robust measurement of CPV at a 3 level with a 100 kt-MW-yr exposure
for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2.
Additionally, the dependence of DUNE's sensitivity on the exposure taken in
neutrino-enhanced and antineutrino-enhanced running is discussed. An equal
fraction of exposure taken in each beam mode is found to be close to optimal
when considered over the entire space of interest
Snowmass Neutrino Frontier: DUNE Physics Summary
The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of ÎŽCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter
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