476 research outputs found
AGN Emission Line Diagnostics and the Mass-Metallicity Relation up to Redshift z~2: the Impact of Selection Effects and Evolution
Emission line diagnostic diagrams probing the ionization sources in galaxies,
such as the Baldwin-Phillips-Terlevich (BPT) diagram, have been used
extensively to distinguish AGN from purely star-forming galaxies. Yet, they
remain poorly understood at higher redshifts. We shed light on this issue with
an empirical approach based on a z~0 reference sample built from ~300,000 SDSS
galaxies, from which we mimic selection effects due to typical emission line
detection limits at higher redshift. We combine this low-redshift reference
sample with a simple prescription for luminosity evolution of the global galaxy
population to predict the loci of high-redshift galaxies on the BPT and
Mass-Excitation (MEx) diagnostic diagrams. The predicted bivariate
distributions agree remarkably well with direct observations of galaxies out to
z~1.5, including the observed stellar mass-metallicity (MZ) relation evolution.
As a result, we infer that high-redshift star-forming galaxies are consistent
with having "normal" ISM properties out to z~1.5, after accounting for
selection effects and line luminosity evolution. Namely, their optical line
ratios and gas-phase metallicities are comparable to that of low-redshift
galaxies with equivalent emission-line luminosities. In contrast, AGN
narrow-line regions may show a shift toward lower metallicities at higher
redshift. While a physical evolution of the ISM conditions is not ruled out for
purely star-forming galaxies, and may be more important starting at z>2, we
find that reliably quantifying this evolution is hindered by selections
effects. The recipes provided here may serve as a basis for future studies
toward this goal. Code to predict the loci of galaxies on the BPT and MEx
diagnostic diagrams, and the MZ relation as a function of emission line
luminosity limits, is made publicly available.Comment: Main article: 15 pages, 7 figures; Appendix: 13 pages, 11 figures.
Revisions: Paper now accepted for publication in the Astrophysical Journal
(same scientific content as previous arXiv version). IDL routines to make
empirical predictions on the BPT, MEx, and M-Z plane are now released at
https://sites.google.com/site/agndiagnostics/home/me
The XMM-LSS survey. Survey design and first results
We have designed a medium deep large area X-ray survey with XMM - the XMM
Large Scale Structure survey, XMM-LSS - with the scope of extending the
cosmological tests attempted using ROSAT cluster samples to two redshift bins
between 0<z<1 while maintaining the precision of earlier studies. Two main
goals have constrained the survey design: the evolutionary study of the
cluster-cluster correlation function and of the cluster number density. The
results are promising and, so far, in accordance with our predictions as to the
survey sensitivity and cluster number density. The feasibility of the programme
is demonstrated and further X-ray coverage is awaited in order to proceed with
a truly significant statistical analysis. (Abridged)Comment: Published in Journal of Cosmology and Astroparticle Physic
An Observed Link between Active Galactic Nuclei and Violent Disk Instabilities in High-Redshift Galaxies
We provide evidence for a correlation between the presence of giant clumps
and the occurrence of active galactic nuclei (AGN) in disk galaxies. Giant
clumps of 10^8-9 Msun arise from violent gravitational instability in gas-rich
galaxies, and it has been proposed that this instability could feed
supermassive black holes (BH). We use emission line diagnostics to compare a
sample of 14 clumpy (unstable) disks and a sample of 13 smoother (stable) disks
at redshift z~0.7. The majority of clumpy disks in our sample have a high
probability of containing AGN. Their [OIII] emission line is strongly excited,
inconsistent with low-metallicity star formation alone. [NeIII] excitation is
also higher. Stable disks rarely have such properties. Stacking ultra sensitive
Chandra observations (4 Ms) reveals an X-ray excess in clumpy galaxies, which
cannot be solely due to star formation and confirms the presence of AGN. The
clumpy galaxies in our intermediate-redshift sample have properties typical of
gas-rich disk galaxies rather than mergers, being in particular on the Main
Sequence of star formation. This suggests that our findings apply to the
physically-similar and numerous gas-rich unstable disks at z>1. Using the
observed [OIII] and X-ray luminosities, we conservatively estimate that AGN
hosted by clumpy disks have typical bolometric luminosities of the order of a
few 10^43 erg/s, BH growth rates ~10^-2 Msun/yr, and that these AGN are
substantially obscured in X-rays. This moderate-luminosity mode could be
sufficient to provide a large fraction of today's BH mass over a couple of Gyr
given that our observations suggest a high duty cycle (>10%), accretion bursts
with higher luminosities being possible over shorter phases. The observed
evolution of disk instabilities with mass and redshift could explain the
simultaneous downsizing of star formation and of BH growth.Comment: ApJ in pres
Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images
Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images
of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL
maps are derived through computational staining using a convolutional neural network trained to
classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and
correlation with overall survival. TIL map structural patterns were grouped using standard
histopathological parameters. These patterns are enriched in particular T cell subpopulations
derived from molecular measures. TIL densities and spatial structure were differentially enriched
among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial
infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic
patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for
the TCGA image archives with insights into the tumor-immune microenvironment
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study
Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. Methods: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. Findings: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1â190·6), 10·1 million influenza-virus-associated ALRI cases (6·8â15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000â1 415 000), 15 300 in-hospital deaths (5800â43 800), and up to 34 800 (13 200â97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. Funding: WHO; Bill & Melinda Gates Foundation.Fil: Wang, Xin. University of Edinburgh; Reino UnidoFil: Li, You. University of Edinburgh; Reino UnidoFil: O'Brien, Katherine L.. University Johns Hopkins; Estados UnidosFil: Madhi, Shabir A.. University of the Witwatersrand; SudĂĄfricaFil: Widdowson, Marc Alain. Centers for Disease Control and Prevention; Estados UnidosFil: Byass, Peter. Umea University; SueciaFil: Omer, Saad B.. Yale School Of Public Health; Estados UnidosFil: Abbas, Qalab. Aga Khan University; PakistĂĄnFil: Ali, Asad. Aga Khan University; PakistĂĄnFil: Amu, Alberta. Dodowa Health Research Centre; GhanaFil: Azziz-Baumgartner, Eduardo. Centers for Disease Control and Prevention; Estados UnidosFil: Bassat, Quique. University Of Barcelona; EspañaFil: Abdullah Brooks, W.. University Johns Hopkins; Estados UnidosFil: Chaves, Sandra S.. Centers for Disease Control and Prevention; Estados UnidosFil: Chung, Alexandria. University of Edinburgh; Reino UnidoFil: Cohen, Cheryl. National Institute For Communicable Diseases; SudĂĄfricaFil: EchavarrĂa, Marcela Silvia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones MĂ©dicas e Investigaciones ClĂnicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Fasce, Rodrigo A.. Public Health Institute; ChileFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo GutiĂ©rrez"; ArgentinaFil: Gordon, Aubree. University of Michigan; Estados UnidosFil: Groome, Michelle. University of the Witwatersrand; SudĂĄfricaFil: Heikkinen, Terho. University Of Turku; FinlandiaFil: Hirve, Siddhivinayak. Kem Hospital Research Centre; IndiaFil: Jara, Jorge H.. Universidad del Valle de Guatemala; GuatemalaFil: Katz, Mark A.. Clalit Research Institute; IsraelFil: Khuri Bulos, Najwa. University Of Jordan School Of Medicine; JordaniaFil: Krishnan, Anand. All India Institute Of Medical Sciences; IndiaFil: de Leon, Oscar. Universidad del Valle de Guatemala; GuatemalaFil: Lucero, Marilla G.. Research Institute For Tropical Medicine; FilipinasFil: McCracken, John P.. Universidad del Valle de Guatemala; GuatemalaFil: Mira-Iglesias, Ainara. FundaciĂłn Para El Fomento de la InvestigaciĂłn Sanitaria; EspañaFil: MoĂŻsi, Jennifer C.. Agence de MĂ©decine PrĂ©ventive; FranciaFil: Munywoki, Patrick K.. No especifĂca;Fil: OurohirĂ©, Millogo. No especifĂca;Fil: Polack, Fernando Pedro. FundaciĂłn para la InvestigaciĂłn en InfectologĂa Infantil; ArgentinaFil: Rahi, Manveer. University of Edinburgh; Reino UnidoFil: Rasmussen, Zeba A.. National Institutes Of Health; Estados UnidosFil: Rath, Barbara A.. Vienna Vaccine Safety Initiative; AlemaniaFil: Saha, Samir K.. Child Health Research Foundation; BangladeshFil: SimĂ”es, Eric A.F.. University of Colorado; Estados UnidosFil: Sotomayor, Viviana. Ministerio de Salud de Santiago de Chile; ChileFil: Thamthitiwat, Somsak. Thailand Ministry Of Public Health; TailandiaFil: Treurnicht, Florette K.. University of the Witwatersrand; SudĂĄfricaFil: Wamukoya, Marylene. African Population & Health Research Center; KeniaFil: Lay-Myint, Yoshida. Nagasaki University; JapĂłnFil: Zar, Heather J.. University of Cape Town; SudĂĄfricaFil: Campbell, Harry. University of Edinburgh; Reino UnidoFil: Nair, Harish. University of Edinburgh; Reino Unid
Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types
Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies
Search for dark matter produced in association with bottom or top quarks in âs = 13 TeV pp collisions with the ATLAS detector
A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fbâ1 of protonâproton collision data recorded by the ATLAS experiment at âs = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements
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