Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although the MYC oncogene has been implicated in cancer, a systematic assessment of alterations of MYC, related transcription factors, and co-regulatory proteins, forming the proximal MYC network (PMN), across human cancers is lacking. Using computational approaches, we define genomic and proteomic features associated with MYC and the PMN across the 33 cancers of The Cancer Genome Atlas. Pan-cancer, 28% of all samples had at least one of the MYC paralogs amplified. In contrast, the MYC antagonists MGA and MNT were the most frequently mutated or deleted members, proposing a role as tumor suppressors. MYC alterations were mutually exclusive with PIK3CA, PTEN, APC, or BRAF alterations, suggesting that MYC is a distinct oncogenic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such as immune response and growth factor signaling; chromatin, translation, and DNA replication/repair were conserved pan-cancer. This analysis reveals insights into MYC biology and is a reference for biomarkers and therapeutics for cancers with alterations of MYC or the PMN. We present a computational study determining the frequency and extent of alterations of the MYC network across the 33 human cancers of TCGA. These data, together with MYC, positively correlated pathways as well as mutually exclusive cancer genes, will be a resource for understanding MYC-driven cancers and designing of therapeutics

Extreme value statistical analysis to determine the endurance limit of a 1045 induction hardened steel alloy

AbstractSurface hardened components are used in fatigue critical applications such as axles and gears. Inclusions are critical microstructural features where fatigue cracks have been observed to nucleate in these parts. In this investigation, the effect of inclusion populations on fatigue performance of induction hardened 1045 steel was examined. The steel was heat treated to have a tempered martensite starting microstructure and was induction hardened to two different case depths. Utilizing extreme value statistical analysis, the largest inclusion as well as the largest inclusion in each of five categories, MnS, MnCaS, MnAlS, Al2O3, and Al2O3-MgO, was estimated for a critically stressed area in a fully reversed cantilever bending fatigue sample. The inclusion size estimates were used to predict the endurance limit of the sample with a fracture mechanics-based model. This methodology has been traditionally used for homogeneous materials but has been modified here for bending fatigue and inhomogeneous case hardened material. The predicted endurance limits are closely correlated to experimentally measured endurance limits

Decomposition of regional metropolitan and nonmetropolitan income inequality

This paper examines the inequality characteristics for regional per capita personal income in metropolitan and nonmetropolian areas. Total inequality is disaggregated into between and within portions. The findings show no statistically significant differences between metro and nonmetro. For both metro and nonmetro during the early 1970s decade, there was a general trend toward equality whereby the nonmetro areas’ income approached the metro areas’ income but showed significant divergences thereafter. *** DIRECT SUPPORT *** A00DH021 0000

Measurement of the tt¯ charge asymmetry in events with highly Lorentz-boosted top quarks in pp collisions at s=13 TeV

The measurement of the charge asymmetry in top quark pair events with highly Lorentz-boosted top quarks decaying to a single lepton and jets is presented. The analysis is performed using proton-proton collisions at s=13TeV with the CMS detector at the LHC and corresponding to an integrated luminosity of 138 fb−1. The selection is optimized for top quarks produced with large Lorentz boosts, resulting in nonisolated leptons and overlapping jets. The top quark charge asymmetry is measured for events with a tt¯ invariant mass larger than 750 GeV and corrected for detector and acceptance effects using a binned maximum likelihood fit. The measured top quark charge asymmetry of (0.42−0.69+0.64)% is in good agreement with the standard model prediction at next-to-next-to-leading order in quantum chromodynamic perturbation theory with next-to-leading-order electroweak corrections. The result is also presented for two invariant mass ranges, 750–900 and >900GeV

Portable Acceleration of CMS Computing Workflows with Coprocessors as a Service

Computing demands for large scientific experiments, such as the CMS experiment at the CERN LHC, will increase dramatically in the next decades. To complement the future performance increases of software running on central processing units (CPUs), explorations of coprocessor usage in data processing hold great potential and interest. Coprocessors are a class of computer processors that supplement CPUs, often improving the execution of certain functions due to architectural design choices. We explore the approach of Services for Optimized Network Inference on Coprocessors (SONIC) and study the deployment of this as-a-service approach in large-scale data processing. In the studies, we take a data processing workflow of the CMS experiment and run the main workflow on CPUs, while offloading several machine learning (ML) inference tasks onto either remote or local coprocessors, specifically graphics processing units (GPUs). With experiments performed at Google Cloud, the Purdue Tier-2 computing center, and combinations of the two, we demonstrate the acceleration of these ML algorithms individually on coprocessors and the corresponding throughput improvement for the entire workflow. This approach can be easily generalized to different types of coprocessors and deployed on local CPUs without decreasing the throughput performance. We emphasize that the SONIC approach enables high coprocessor usage and enables the portability to run workflows on different types of coprocessors

Search for new heavy resonances decaying to WW, WZ, ZZ, WH, or ZH boson pairs in the all-jets final state in proton-proton collisions at s=13TeV

A search for new heavy resonances decaying to WW, WZ, ZZ, WH, or ZH boson pairs in the all-jets final state is presented. The analysis is based on proton-proton collision data recorded by the CMS detector in 2016–2018 at a centre-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 138fb−1. The search is sensitive to resonances with masses between 1.3 and 6TeV, decaying to bosons that are highly Lorentz-boosted such that each of the bosons forms a single large-radius jet. Machine learning techniques are employed to identify such jets. No significant excess over the estimated standard model background is observed. A maximum local significance of 3.6 standard deviations, corresponding to a global significance of 2.3 standard deviations, is observed at masses of 2.1 and 2.9 TeV. In a heavy vector triplet model, spin-1 Z′ and W′ resonances with masses below 4.8TeV are excluded at the 95% confidence level (CL). These limits are the most stringent to date. In a bulk graviton model, spin-2 gravitons and spin-0 radions with masses below 1.4 and 2.7TeV, respectively, are excluded at 95% CL. Production of heavy resonances through vector boson fusion is constrained with upper cross section limits at 95% CL as low as 0.1fb

Study of azimuthal anisotropy of ϒ(1S) mesons in pPb collisions at sNN = 8.16 TeV

The azimuthal anisotropy of Image 1 mesons in high-multiplicity proton-lead collisions is studied using data collected by the CMS experiment at a nucleon-nucleon center-of-mass energy of 8.16TeV. The Image 1 mesons are reconstructed using their dimuon decay channel. The anisotropy is characterized by the second Fourier harmonic coefficients, found using a two-particle correlation technique, in which the Image 1 mesons are correlated with charged hadrons. A large pseudorapidity gap is used to suppress short-range correlations. Nonflow contamination from the dijet background is removed using a low-multiplicity subtraction method, and the results are presented as a function of Image 1 transverse momentum. The azimuthal anisotropies are smaller than those found for charmonia in proton-lead collisions at the same collision energy, but are consistent with values found for Image 1 mesons in lead-lead interactions at a nucleon-nucleon center-of-mass energy of 5.02 TeV