648 research outputs found

    DNA methylation loss promotes immune evasion of tumours with high mutation and copy number load

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    Mitotic cell division increases tumour mutation burden and copy number load, predictive markers of the clinical benefit of immunotherapy. Cell division correlates also with genomic demethylation involving methylation loss in late-replicating partial methylation domains. Here we find that immunomodulatory pathway genes are concentrated in these domains and transcriptionally repressed in demethylated tumours with CpG island promoter hypermethylation. Global methylation loss correlated with immune evasion signatures independently of mutation burden and aneuploidy. Methylome data of our cohort (n‚ÄČ=‚ÄČ60) and a published cohort (n‚ÄČ=‚ÄČ81) in lung cancer and a melanoma cohort (n‚ÄČ=‚ÄČ40) consistently demonstrated that genomic methylation alterations counteract the contribution of high mutation burden and increase immunotherapeutic resistance. Higher predictive power was observed for methylation loss than mutation burden. We also found that genomic hypomethylation correlates with the immune escape signatures of aneuploid tumours. Hence, DNA methylation alterations implicate epigenetic modulation in precision immunotherapy

    Effect of flow-field structure on discharging and charging behavior of hydrogen/bromine redox flow batteries

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    Designing and optimizing the flow-field structure for the liquid phase Br2/HBr electrolyte solution of H2/Br2 redox flow batteries (RFBs) is important for improving cell performance. In this study, two electrolyte flow modes, i.e. the flow-by and flow-through modes, are simulated by using a three-dimensional H2/Br2 RFB model. The model is first applied to real-scale H2/Br2 cell geometries and then validated against the experimental polarization curves acquired using the two different flow modes. The model predictions compare well with the experimental data and further highlight the advantages of using the flow-through mode relative to the flow-by mode. Detailed multi-dimensional contours of the electrolyte flow velocity and key species distributions reveal that more uniform diffusion and stronger convective transport are achieved by using the flow-through mode, which alleviates the ohmic loss associated with charge transport in the Br2 electrode

    Hepatic and Pancreatic Tumors Combined Hepatectomy and Radiofrequency Ablation for Multifocal Hepatocellular Carcinomas: Long-term Follow-up Results and Prognostic Factors

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    Background: For multifocal hepatocellular carcinomas (HCCs) that are untreatable with resection only, locoregional therapies added to hepatectomy have been introduced. However, some preliminary reports have documented average survival results and relatively high complication rates. We evaluated the long-term survival results and safety of combined hepatectomy and radiofrequency ablation (RFA) in patients with HCCs and assessed the prognostic factors affecting their survival. Methods: A total of 53 patients who had 148 HCCs in their livers underwent hepatectomy combined with ultrasound-guided intraoperative RFA. The mean diameter of the 82 resected tumors was 4.8 cm (range 1.3-21.0 cm) and that of 66 ablated tumors was 1.5 cm (range 0.8-3.5 cm). We evaluated the primary effectiveness rates, survival rates, and complications. In addition, we assessed the prognostic factors associated with the survival rates using Cox proportional hazard models. Results: The primary effectiveness rate of RFA was 98% (65 of 66). Local tumor progression was observed in two (3%) ablation zones of 65 tumors with complete primary effectiveness. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 87, 83, 80, 68, and 55%, respectively. Patients with smaller resected tumors (£5 cm) demonstrated better survival results (P = 0.004). No procedure-related deaths occurred. We observed hepatectomy-related complications in 4 patients (8%, 4 of 53) and an RFA-related complication in 1 patient (2%, 1 of 53). Conclusions: Combined hepatectomy and RFA is an effective and safe treatment modality for multifocal HCCs. Resected tumor size was a significant prognostic predictor of long-term survival

    Differential cross section measurements for the production of a W boson in association with jets in proton‚Äďproton collisions at ‚ąös = 7 TeV

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    Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript ‚ąí1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an