193 research outputs found

    Beyond Scale-Free Networks: integrating Multilayer Social Networks With Molecular Clusters in the Local Spread of Covid-19

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    This study evaluates the scale-free network assumption commonly used in COVID-19 epidemiology, using empirical social network data from SARS-CoV-2 Delta variant molecular local clusters in Houston, Texas. We constructed genome-informed social networks from contact and co-residence data, tested them for scale-free power-law distributions that imply highly connected hubs, and compared them to alternative models (exponential, log-normal, power-law with exponential cutoff, and Weibull) that suggest more evenly distributed network connections. Although the power-law model failed the goodness of fit test, after incorporating social network ties, the power-law model was at least as good as, if not better than, the alternatives, implying the presence of both hub and non-hub mechanisms in local SARS-CoV-2 transmission. These findings enhance our understanding of the complex social interactions that drive SARS-CoV-2 transmission, thereby informing more effective public health interventions

    The ASTRO-H X-ray Observatory

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    The joint JAXA/NASA ASTRO-H mission is the sixth in a series of highly successful X-ray missions initiated by the Institute of Space and Astronautical Science (ISAS). ASTRO-H will investigate the physics of the high-energy universe via a suite of four instruments, covering a very wide energy range, from 0.3 keV to 600 keV. These instruments include a high-resolution, high-throughput spectrometer sensitive over 0.3-2 keV with high spectral resolution of Delta E < 7 eV, enabled by a micro-calorimeter array located in the focal plane of thin-foil X-ray optics; hard X-ray imaging spectrometers covering 5-80 keV, located in the focal plane of multilayer-coated, focusing hard X-ray mirrors; a wide-field imaging spectrometer sensitive over 0.4-12 keV, with an X-ray CCD camera in the focal plane of a soft X-ray telescope; and a non-focusing Compton-camera type soft gamma-ray detector, sensitive in the 40-600 keV band. The simultaneous broad bandpass, coupled with high spectral resolution, will enable the pursuit of a wide variety of important science themes.Comment: 22 pages, 17 figures, Proceedings of the SPIE Astronomical Instrumentation "Space Telescopes and Instrumentation 2012: Ultraviolet to Gamma Ray

    The Quiescent Intracluster Medium in the Core of the Perseus Cluster

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    Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

    The Relation Between the Surface Brightness and the Diameter for Galactic Supernova Remnants

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    In this work, we have constructed a relation between the surface brightness (Σ\Sigma) and diameter (D) of Galactic C- and S-type supernova remnants (SNRs). In order to calibrate the Σ\Sigma-D dependence, we have carefully examined some intrinsic (e.g. explosion energy) and extrinsic (e.g. density of the ambient medium) properties of the remnants and, taking into account also the distance values given in the literature, we have adopted distances for some of the SNRs which have relatively more reliable distance values. These calibrator SNRs are all C- and S-type SNRs, i.e. F-type SNRs (and S-type SNR Cas A which has an exceptionally high surface brightness) are excluded. The Sigma-D relation has 2 slopes with a turning point at D=36.5 pc: Σ\Sigma(at 1 GHz)=8.46.3+19.5^{+19.5}_{-6.3}×1012\times10^{-12} D5.990.33+0.38^{{-5.99}^{+0.38}_{-0.33}} Wm2^{-2}Hz1^{-1}ster1^{-1} (for Σ\Sigma3.7×1021\le3.7\times10^{-21} Wm2^{-2}Hz1^{-1}ster1^{-1} and D\ge36.5 pc) and Σ\Sigma(at 1 GHz)=2.71.4+2.1^{+2.1}_{-1.4}×\times 1017^{-17} D2.470.16+0.20^{{-2.47}^{+0.20}_{-0.16}} Wm2^{-2}Hz1^{-1}ster1^{-1} (for Σ\Sigma>3.7×1021>3.7\times10^{-21} Wm2^{-2}Hz1^{-1}ster1^{-1} and D<<36.5 pc). We discussed the theoretical basis for the Σ\Sigma-D dependence and particularly the reasons for the change in slope of the relation were stated. Added to this, we have shown the dependence between the radio luminosity and the diameter which seems to have a slope close to zero up to about D=36.5 pc. We have also adopted distance and diameter values for all of the observed Galactic SNRs by examining all the available distance values presented in the literature together with the distances found from our Σ\Sigma-D relation.Comment: 45 pages, 2 figures, accepted for publication in Astronomical and Astrophysical Transaction

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    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

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    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

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    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

    Feasibility and diagnostic power of transthoracic coronary Doppler for coronary flow velocity reserve in patients referred for myocardial perfusion imaging

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    <p>Abstract</p> <p>Background</p> <p>Myocardial perfusion imaging (MPI), using single photon emission computed tomography (SPECT) is a validated method for detecting coronary artery disease. Transthoracic Doppler echocardiography (TTDE) of flow at rest and during adenosine provocation has previously been evaluated in selected patient groups. We therefore wanted to compare the diagnostic ability of TTDE in the left anterior descending coronary artery (LAD) to that of MPI in an unselected population of patients with chest pain referred for MPI. Our hypothesis was that TTDE with high accuracy would identify healthy individuals and exclude them from the need for further studies, enabling invasive investigations to be reserved for patients with a high probability of disease.</p> <p>Methods</p> <p>Sixty-nine patients, 44 men and 25 women, age 61 ± 10 years (range 35–82), with a clinical suspicion of stress induced myocardial ischemia, were investigated. TTDE was performed at rest and during adenosine stress for myocardial scintigraphy.</p> <p>Results</p> <p>We found that coronary flow velocity reserve (CFVR) determined from diastolic measurements separated normal from abnormal MPI findings with statistical significance. TTDE identified coronary artery disease, defined from MPI, as reversible ischemia and/or permanent defect, with a sensitivity of 60% and a specificity of 79%. The positive predictive value was 43% and the negative predictive value was 88%. There was an overlap between groups which could be due to abnormal endothelial function in patients with normal myocardial perfusion having either hypertension or diabetes.</p> <p>Conclusion</p> <p>TTDE is an attractive non-invasive method to evaluate chest pain without the use of isotopes, but the diagnostic power is strongly dependent on the population investigated. Even in our heterogeneous clinical cardiac population, we found that CFVR>2 in the LAD excluded significant coronary artery disease detected by MPI.</p
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