125 research outputs found
Identification of Networks of Co-Occurring, Tumor-Related DNA Copy Number Changes Using a Genome-Wide Scoring Approach
Tumorigenesis is a multi-step process in which normal cells transform into malignant tumors following the accumulation of genetic mutations that enable them to evade the growth control checkpoints that would normally suppress their growth or result in apoptosis. It is therefore important to identify those combinations of mutations that collaborate in cancer development and progression. DNA copy number alterations (CNAs) are one of the ways in which cancer genes are deregulated in tumor cells. We hypothesized that synergistic interactions between cancer genes might be identified by looking for regions of co-occurring gain and/or loss. To this end we developed a scoring framework to separate truly co-occurring aberrations from passenger mutations and dominant single signals present in the data. The resulting regions of high co-occurrence can be investigated for between-region functional interactions. Analysis of high-resolution DNA copy number data from a panel of 95 hematological tumor cell lines correctly identified co-occurring recombinations at the T-cell receptor and immunoglobulin loci in T- and B-cell malignancies, respectively, showing that we can recover truly co-occurring genomic alterations. In addition, our analysis revealed networks of co-occurring genomic losses and gains that are enriched for cancer genes. These networks are also highly enriched for functional relationships between genes. We further examine sub-networks of these networks, core networks, which contain many known cancer genes. The core network for co-occurring DNA losses we find seems to be independent of the canonical cancer genes within the network. Our findings suggest that large-scale, low-intensity copy number alterations may be an important feature of cancer development or maintenance by affecting gene dosage of a large interconnected network of functionally related genes
Asteroseismology and Interferometry
Asteroseismology provides us with a unique opportunity to improve our
understanding of stellar structure and evolution. Recent developments,
including the first systematic studies of solar-like pulsators, have boosted
the impact of this field of research within Astrophysics and have led to a
significant increase in the size of the research community. In the present
paper we start by reviewing the basic observational and theoretical properties
of classical and solar-like pulsators and present results from some of the most
recent and outstanding studies of these stars. We centre our review on those
classes of pulsators for which interferometric studies are expected to provide
a significant input. We discuss current limitations to asteroseismic studies,
including difficulties in mode identification and in the accurate determination
of global parameters of pulsating stars, and, after a brief review of those
aspects of interferometry that are most relevant in this context, anticipate
how interferometric observations may contribute to overcome these limitations.
Moreover, we present results of recent pilot studies of pulsating stars
involving both asteroseismic and interferometric constraints and look into the
future, summarizing ongoing efforts concerning the development of future
instruments and satellite missions which are expected to have an impact in this
field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume
14, Issue 3-4, pp. 217-36
Business Ethics: The Promise of Neuroscience
Recent advances in cognitive neuroscience research portend well for furthering understanding of many of the fundamental questions in the field of business ethics, both normative and empirical. This article provides an overview of neuroscience methodology and brain structures, and explores the areas in which neuroscience research has contributed findings of value to business ethics, as well as suggesting areas for future research. Neuroscience research is especially capable of providing insight into individual reactions to ethical issues, while also raising challenging normative questions about the nature of moral responsibility, autonomy, intent, and free will. This article also provides a brief summary of the papers included in this special issue, attesting to the richness of scholarly inquiry linking neuroscience and business ethics. We conclude that neuroscience offers considerable promise to the field of business ethics, but we caution against overpromise
Projected heat-related mortality under climate change in the metropolitan area of Skopje
Constraints on the gluon PDF from top quark pair production at hadron colliders
Using the recently derived NNLO cross sections \cite{Czakon:2013goa}, we
provide NNLO+NNLL theoretical predictions for top quark pair production based
on all the available NNLO PDF sets, and compare them with the most precise LHC
and Tevatron data. In this comparison we study in detail the PDF uncertainty
and the scale, and dependence of the theoretical predictions
for each PDF set. Next, we observe that top quark pair production provides a
powerful direct constraint on the gluon PDF at large , and include Tevatron
and LHC top pair data consistently into a global NNLO PDF fit. We then explore
the phenomenological consequences of the reduced gluon PDF uncertainties, by
showing how they can improve predictions for Beyond the Standard Model
processes at the LHC. Finally, we update to full NNLO+NNLL the theoretical
predictions for the ratio of top quark cross sections between different LHC
center of mass energies, as well as the cross sections for hypothetical heavy
fourth-generation quark production at the LHC.Comment: 29 pages, 13 figures, accepted for publication in JHE
Jdp2 downregulates Trp53 transcription to promote leukaemogenesis in the context of Trp53 heterozygosity
We performed a genetic screen in mice to identify candidate genes that are associated with leukaemogenesis in the context of Trp53 heterozygosity. To do this we generated Trp53 heterozygous mice carrying the T2/Onc transposon and SB11 transposase alleles to allow transposon-mediated insertional mutagenesis to occur. From the resulting leukaemias/lymphomas that developed in these mice, we identified nine loci that are potentially associated with tumour formation in the context of Trp53 heterozygosity, including AB041803 and the Jun dimerization protein 2 (Jdp2). We show that Jdp2 transcriptionally regulates the Trp53 promoter, via an atypical AP-1 site, and that Jdp2 expression negatively regulates Trp53 expression levels. This study is the first to identify a genetic mechanism for tumour formation in the context of Trp53 heterozygosity
Gaia Early Data Release 3: Summary of the contents and survey properties
ABSTRACT: Context. We present the early installment of the third Gaia data release, Gaia EDR3, consisting of astrometry and photometry for 1.8 billion sources brighter than magnitude 21, complemented with the list of radial velocities from Gaia DR2.
Aims. A summary of the contents of Gaia EDR3 is presented, accompanied by a discussion on the differences with respect to Gaia DR2 and an overview of the main limitations which are present in the survey. Recommendations are made on the responsible use of Gaia EDR3 results.
Methods. The raw data collected with the Gaia instruments during the first 34 months of the mission have been processed by the Gaia Data Processing and Analysis Consortium and turned into this early third data release, which represents a major advance with respect to Gaia DR2 in terms of astrometric and photometric precision, accuracy, and homogeneity.
Results. Gaia EDR3 contains celestial positions and the apparent brightness in G for approximately 1.8 billion sources. For 1.5 billion of those sources, parallaxes, proper motions, and the (GBP ? GRP) colour are also available. The passbands for G, GBP, and GRP are provided as part of the release. For ease of use, the 7 million radial velocities from Gaia DR2 are included in this release, after the removal of a small number of spurious values. New radial velocities will appear as part of Gaia DR3. Finally, Gaia EDR3 represents an updated materialisation of the celestial reference frame (CRF) in the optical, the Gaia-CRF3, which is based solely on extragalactic sources. The creation of the source list for Gaia EDR3 includes enhancements that make it more robust with respect to high proper motion stars, and the disturbing effects of spurious and partially resolved sources. The source list is largely the same as that for Gaia DR2, but it does feature new sources and there are some notable changes. The source list will not change for Gaia DR3. Conclusions. Gaia EDR3 represents a significant advance over Gaia DR2, with parallax precisions increased by 30 per cent, proper motion precisions increased by a factor of 2, and the systematic errors in the astrometry suppressed by 30-40% for the parallaxes and by a factor ~2.5 for the proper motions. The photometry also features increased precision, but above all much better homogeneity across colour, magnitude, and celestial position. A single passband for G, GBP, and GRP is valid over the entire magnitude and colour range, with no systematics above the 1% levelThe Gaia mission and data processing have financially been supported by ; the Spanish Ministry of Economy (MINECO/FEDER, UE) through grants ESP2016-80079-C2-1-R, ESP2016-80079-C2-2-R, RTI2018-095076-B-C21, RTI2018-095076-B-C22, BES-2016-078499, and BES-2017-083126 and the Juan de la Cierva formaciĂłn 2015 grant FJCI-2015-2671, the Spanish Ministry of Education, Culture, and Sports through grant FPU16/03827, the Spanish Ministry of Science and Innovation (MICINN) through grant
AYA2017-89841P for project âEstudio de las propiedades de los fĂłsiles estelares en el entorno del Grupo Localâ and through grant TIN2015-65316-P for project
âComputaciĂłn de Altas Prestaciones VII
Pulsations in main sequence OBAF-type stars
CONTEXT: The third Gaia data release provides photometric time series covering 34 months for about 10 million stars. For many of those stars, a characterisation in Fourier space and their variability classification are also provided. This paper focuses on intermediate- to high-mass (IHM) main sequence pulsators (Mââ„ââ1.3âMâ) of spectral types O, B, A, or F, known as ÎČ Cep, slowly pulsating B (SPB), ÎŽ Sct, and Îł Dor stars. These stars are often multi-periodic and display low amplitudes, making them challenging targets to analyse with sparse time series. AIMS: We investigate the extent to which the sparse Gaia DR3 data can be used to detect OBAF-type pulsators and discriminate them from other types of variables. We aim to probe the empirical instability strips and compare them with theoretical predictions. The most populated variability class is that of the ÎŽ Sct variables. For these stars, we aim to confirm their empirical period-luminosity (PL) relation, and verify the relation between their oscillation amplitude and rotation. METHODS: All datasets used in this analysis are part of the Gaia DR3 data release. The photometric time series were used to perform a Fourier analysis, while the global astrophysical parameters necessary for the empirical instability strips were taken from the Gaia DR3 gspphot tables, and the v sin i data were taken from the Gaia DR3 esphs tables. The ÎŽâSct PL relation was derived using the same photometric parallax method as the one recently used to establish the PL relation for classical Cepheids using Gaia data. RESULTS: We show that for nearby OBAF-type pulsators, the Gaia DR3 data are precise and accurate enough to pinpoint them in the Hertzsprung-Russell (HR) diagram. We find empirical instability strips covering broader regions than theoretically predicted. In particular, our study reveals the presence of fast rotating gravity-mode pulsators outside the strips, as well as the co-existence of rotationally modulated variables inside the strips as reported before in the literature. We derive an extensive periodâluminosity relation for ÎŽ Sct stars and provide evidence that the relation features different regimes depending on the oscillation period. We demonstrate how stellar rotation attenuates the amplitude of the dominant oscillation mode of ÎŽ Sct stars. CONCLUSIONS: The Gaia DR3 time-series photometry already allows for the detection of the dominant (non-)radial oscillation mode in about 100 000 intermediate- and high-mass dwarfs across the entire sky. This detection capability will increase as the time series becomes longer, allowing the additional delivery of frequencies and amplitudes of secondary pulsation modes
Gaia Data Release 3: Mapping the asymmetric disc of the Milky Way
With the most recent Gaia data release the number of sources with complete 6D
phase space information (position and velocity) has increased to well over 33
million stars, while stellar astrophysical parameters are provided for more
than 470 million sources, in addition to the identification of over 11 million
variable stars. Using the astrophysical parameters and variability
classifications provided in Gaia DR3, we select various stellar populations to
explore and identify non-axisymmetric features in the disc of the Milky Way in
both configuration and velocity space. Using more about 580 thousand sources
identified as hot OB stars, together with 988 known open clusters younger than
100 million years, we map the spiral structure associated with star formation
4-5 kpc from the Sun. We select over 2800 Classical Cepheids younger than 200
million years, which show spiral features extending as far as 10 kpc from the
Sun in the outer disc. We also identify more than 8.7 million sources on the
red giant branch (RGB), of which 5.7 million have line-of-sight velocities,
allowing the velocity field of the Milky Way to be mapped as far as 8 kpc from
the Sun, including the inner disc. The spiral structure revealed by the young
populations is consistent with recent results using Gaia EDR3 astrometry and
source lists based on near infrared photometry, showing the Local (Orion) arm
to be at least 8 kpc long, and an outer arm consistent with what is seen in HI
surveys, which seems to be a continuation of the Perseus arm into the third
quadrant. Meanwhile, the subset of RGB stars with velocities clearly reveals
the large scale kinematic signature of the bar in the inner disc, as well as
evidence of streaming motions in the outer disc that might be associated with
spiral arms or bar resonances. (abridged
Insertional mutagenesis identifies multiple networks of cooperating genes driving intestinal tumorigenesis
The evolution of colorectal cancer suggests the involvement of many genes. We performed insertional mutagenesis with the Sleeping Beauty (SB) transposon system in mice carrying germline or somatic Apc mutation. Analysis of common insertion sites (CISs) isolated from 446 tumors revealed many hundreds of candidate cancer drivers. Comparison to human datasets suggested that 234 CIS genes are also deregulated in human colorectal cancers. 183 CIS genes are candidate Wnt targets, and 20 are shown to be novel modifiers of canonical Wnt signaling. We also identified gene mutations associated with a subset of tumors containing an expanded number of Paneth cells, a hallmark of deregulated Wnt signaling, and genes associated with more severe dysplasia included members of the FGF signaling cascade. Some 70 genes showed pairwise co-occurrence clustering into 38 sub-networks that may regulate tumor development
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