5,255 research outputs found
The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer
RNA-binding proteins (RBPs) are increasingly identified as post-transcriptional drivers of cancer progression. The RBP LARP1 is an mRNA stability regulator, and elevated expression of the protein in hepatocellular and lung cancers is correlated with adverse prognosis. LARP1 associates with an mRNA interactome that is enriched for oncogenic transcripts. Here we explore the role of LARP1 in epithelial ovarian cancer, a disease characterized by the rapid acquisition of resistance to chemotherapy through the induction of pro-survival signalling. We show, using ovarian cell lines and xenografts, that LARP1 is required for cancer cell survival and chemotherapy resistance. LARP1 promotes tumour formation in vivo and maintains cancer stem cell-like populations. Using transcriptomic analysis following LARP1 knockdown, cross-referenced against the LARP1 interactome, we identify BCL2 and BIK as LARP1 mRNA targets. We demonstrate that, through an interaction with the 3 untranslated regions (3 UTRs) of BCL2 and BIK, LARP1 stabilizes BCL2 but destabilizes BIK with the net effect of resisting apoptosis. Together, our data indicate that by differentially regulating the stability of a selection of mRNAs, LARP1 promotes ovarian cancer progression and chemotherapy resistance
Mesoscale theory of grains and cells: crystal plasticity and coarsening
Solids with spatial variations in the crystalline axes naturally evolve into
cells or grains separated by sharp walls. Such variations are mathematically
described using the Nye dislocation density tensor. At high temperatures,
polycrystalline grains form from the melt and coarsen with time: the
dislocations can both climb and glide. At low temperatures under shear the
dislocations (which allow only glide) form into cell structures. While both the
microscopic laws of dislocation motion and the macroscopic laws of coarsening
and plastic deformation are well studied, we hitherto have had no simple,
continuum explanation for the evolution of dislocations into sharp walls. We
present here a mesoscale theory of dislocation motion. It provides a
quantitative description of deformation and rotation, grounded in a microscopic
order parameter field exhibiting the topologically conserved quantities. The
topological current of the Nye dislocation density tensor is derived from a
microscopic theory of glide driven by Peach-Koehler forces between dislocations
using a simple closure approximation. The resulting theory is shown to form
sharp dislocation walls in finite time, both with and without dislocation
climb.Comment: 5 pages, 3 figure
Blazar Flaring Patterns (B-FlaP): Classifying Blazar Candidates of Uncertain type in the third Fermi-LAT catalog by Artificial Neural Networks
The Fermi Large Area Telescope (LAT) is currently the most important facility
for investigating the GeV -ray sky. With Fermi LAT more than three
thousand -ray sources have been discovered so far. 1144 () of
the sources are active galaxies of the blazar class, and 573 () are
listed as Blazar Candidate of Uncertain type (BCU), or sources without a
conclusive classification. We use the Empirical Cumulative Distribution
Functions (ECDF) and the Artificial Neural Networks (ANN) for a fast method of
screening and classification for BCUs based on data collected at -ray
energies only, when rigorous multiwavelength analysis is not available. Based
on our method, we classify 342 BCUs as BL Lacs and 154 as FSRQs, while 77
objects remain uncertain. Moreover, radio analysis and direct observations in
ground-based optical observatories are used as counterparts to the statistical
classifications to validate the method. This approach is of interest because of
the increasing number of unclassified sources in Fermi catalogs and because
blazars and in particular their subclass High Synchrotron Peak (HSP) objects
are the main targets of atmospheric Cherenkov telescopes.Comment: 18 pages, 17 figures, accepted for publication on MNRA
From carbon dependence to renewables: The European oil majors' strategies to face climate change
International oil companies play a central role in the transition towards a low-carbon economy. These companies have the leadership and influence to advance technological alternatives or sustain the current dependence on fossil fuels. This article aims to analyse the decarbonisation strategies that European oil companies are performing in the wake of climate change. A document analysis was integrated with carbon emission data from 10 European international oil companies and uncovered the four main strategies adopted by companies: sustained carbon dependence, carbon emissions compensation, carbon emissions mitigation and carbon independence. The results indicate that companies have adopted variable levels of action, despite their overlapping discourse on climate mitigation, with only one of the analysed firms performing a transition away from fossil fuels
Optical counterparts of undetermined type -ray Active Galactic Nuclei with blazar-like Spectral Energy Distributions
During its first four years of scientific observations, the Fermi Large Area
Telescope (Fermi-LAT) detected 3033 -ray sources above a 4
significance level. Although most of the extra-Galactic sources are active
galactic nuclei (AGN) of the blazar class, other families of AGNs are observed
too, while a still high fraction of detections () remains with
uncertain association or classification. According to the currently accepted
interpretation, the AGN -ray emission arises from inverse Compton (IC)
scattering of low energy photons by relativistic particles confined in a jet
that, in the case of blazars, is oriented very close to our line of sight.
Taking advantage of data from radio and X-ray wavelengths, which we expect to
be produced together with -rays, providing a much better source
localization potential, we focused our attention on a sample of -ray
Blazar Candidates of Undetermined Type (BCUs), starting a campaign of optical
spectroscopic observations. The main aims of our investigation include a census
of the AGN families that contribute to -ray emission and a study of
their redshift distribution, with the subsequent implications on the intrinsic
source power. We furthermore analyze which -ray properties can better
constrain the nature of the source, thus helping in the study of objects not
yet associated with a reliable low frequency counterpart. In this communication
we report on the instruments and techniques used to identify the optical
counterparts of -ray sources, we give an overview on the status of our
work, and we discuss the implications of a large scale study of -ray
emitting AGNs.Comment: 9 pages, 2 figures, proceedings of the 10th Serbian Conference on
Spectral Line Shapes in Astrophysics. JOAA, accepte
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