5 research outputs found
The Rapidly Flaring Afterglow of the Very Bright and Energetic GRB 070125
We report on multi-wavelength observations, ranging from the X-ray to radio
wave bands, of the IPN-localized gamma-ray burst GRB 070125. Spectroscopic
observations reveal the presence of absorption lines due to O I, Si II, and C
IV, implying a likely redshift of z = 1.547. The well-sampled light curves, in
particular from 0.5 to 4 days after the burst, suggest a jet break at 3.7 days,
corresponding to a jet opening angle of ~7.0 degrees, and implying an intrinsic
GRB energy in the 1 - 10,000 keV band of around E = (6.3 - 6.9)x 10^(51) erg
(based on the fluences measured by the gamma-ray detectors of the IPN network).
GRB 070125 is among the brightest afterglows observed to date. The spectral
energy distribution implies a host extinction of Av < 0.9 mag. Two
rebrightening episodes are observed, one with excellent time coverage, showing
an increase in flux of 56% in ~8000 seconds. The evolution of the afterglow
light curve is achromatic at all times. Late-time observations of the afterglow
do not show evidence for emission from an underlying host galaxy or supernova.
Any host galaxy would be subluminous, consistent with current GRB host-galaxy
samples. Evidence for strong Mg II absorption features is not found, which is
perhaps surprising in view of the relatively high redshift of this burst and
the high likelihood for such features along GRB-selected lines of sight.Comment: 50 pages, 9 figures, 5 tables Accepted to the Astrophysical Journa
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Proteogenomic characterization of pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor patient survival. Toward understanding the underlying molecular alterations that drive PDAC oncogenesis, we conducted comprehensive proteogenomic analysis of 140 pancreatic cancers, 67 normal adjacent tissues, and 9 normal pancreatic ductal tissues. Proteomic, phosphoproteomic, and glycoproteomic analyses were used to characterize proteins and their modifications. In addition, whole-genome sequencing, whole-exome sequencing, methylation, RNA sequencing (RNA-seq), and microRNA sequencing (miRNA-seq) were performed on the same tissues to facilitate an integrated proteogenomic analysis and determine the impact of genomic alterations on protein expression, signaling pathways, and post-translational modifications. To ensure robust downstream analyses, tumor neoplastic cellularity was assessed via multiple orthogonal strategies using molecular features and verified via pathological estimation of tumor cellularity based on histological review. This integrated proteogenomic characterization of PDAC will serve as a valuable resource for the community, paving the way for early detection and identification of novel therapeutic targets.
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•Proteogenomic characterization reveals the functional impact of genomic alterations•Phosphoproteomics uncovers putative therapeutic targets downstream of KRAS•Multiomics links endothelial cell remodeling and glycolysis to immune exclusion•Proteomics and glycoproteomics reveal candidates for early detection or intervention
Comparative multiomic analyses of pancreatic ductal adenocarcinoma tumors with normal adjacent and pancreatic ductal tissues provide insight into genomic, proteomic, and immune dysregulation in driving disease
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Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma
We present a proteogenomic study of 108 human papilloma virus (HPV)-negative head and neck squamous cell carcinomas (HNSCCs). Proteomic analysis systematically catalogs HNSCC-associated proteins and phosphosites, prioritizes copy number drivers, and highlights an oncogenic role for RNA processing genes. Proteomic investigation of mutual exclusivity between FAT1 truncating mutations and 11q13.3 amplifications reveals dysregulated actin dynamics as a common functional consequence. Phosphoproteomics characterizes two modes of EGFR activation, suggesting a new strategy to stratify HNSCCs based on EGFR ligand abundance for effective treatment with inhibitory EGFR monoclonal antibodies. Widespread deletion of immune modulatory genes accounts for low immune infiltration in immune-cold tumors, whereas concordant upregulation of multiple immune checkpoint proteins may underlie resistance to anti-programmed cell death protein 1 monotherapy in immune-hot tumors. Multi-omic analysis identifies three molecular subtypes with high potential for treatment with CDK inhibitors, anti-EGFR antibody therapy, and immunotherapy, respectively. Altogether, proteogenomics provides a systematic framework to inform HNSCC biology and treatment.[Display omitted]•A systematic inventory of HNSCC-associated proteins, phosphosites, and pathways•Three multi-omic subtypes linked to targeted treatment approaches and immunotherapy•Widespread deletion of immune modulatory genes accounts for loss of immunogenicity•Two modes of EGFR activation inform response to anti-EGFR monoclonal antibodiesHuang et al. report a proteogenomic study on 108 HPV-negative head and neck squamous cell carcinomas (HNSCCs). In addition to creating a comprehensive resource for pathogenic insights, multi-omic analysis identifies therapeutic hypotheses that may inform more precise approaches to treatment