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

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 = 60) and a published cohort (n = 81) in lung cancer and a melanoma cohort (n = 40) 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

Constitutive modeling of deformation behavior of high-entropy alloys with face-centered cubic crystal structure

A constitutive model based on the dislocation glide and deformation twinning is adapted to face-centered cubic high-entropy alloys (HEAs) as exemplified by the CrMnFeCoNi system. In this model, the total dislocation density is considered as the only internal variable, while the evolution equation describing its variation during plastic deformation is governed by the volume fraction of twinned material. The suitability of the model for describing the strain hardening behavior of HEAs was verified experimentally through compression tests on alloy CrMnFeCoNi and its microstructure characterization by electron backscatter diffraction and X-ray diffraction using synchrotron radiation. ? 2017 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.1111Ysciescopu

Loss of superhydrophobicity of hydrophobic micro/nano structures during condensation

Condensed liquid behavior on hydrophobic micro/nano-structured surfaces is a subject with multiple practical applications, but remains poorly understood. In particular, the loss of superhydrophobicity of hydrophobic micro/nanostructures during condensation, even when the same surface shows water-repellant characteristics when exposed to air, requires intensive investigation to improve and apply our understanding of the fundamental physics of condensation. Here, we postulate the criterion required for condensation to form from inside the surface structures by examining the grand potentials of a condensation system, including the properties of the condensed liquid and the conditions required for condensation. The results imply that the same hydrophobic micro/nano-structured surface could exhibit different liquid droplet behavior depending on the conditions. Our findings are supported by the observed phenomena: the initiation of a condensed droplet from inside a hydrophobic cavity, the apparent wetted state changes, and the presence of sticky condensed droplets on the hydrophobic micro/nano-structured surface. © 2015, Macmillan Publishers Limited. All rights reserved.open111616Nsciescopu

Time and Amplitude of Afterpulse Measured with a Large Size Photomultiplier Tube

We have studied the afterpulse of a hemispherical photomultiplier tube for an upcoming reactor neutrino experiment. The timing, the amplitude, and the rate of the afterpulse for a 10 inch photomultiplier tube were measured with a 400 MHz FADC up to 16 \ms time window after the initial signal generated by an LED light pulse. The time and amplitude correlation of the afterpulse shows several distinctive groups. We describe the dependencies of the afterpulse on the applied high voltage and the amplitude of the main light pulse. The present data could shed light upon the general mechanism of the afterpulse.Comment: 11 figure

Bi-modal structure of copper via room temperature partial recrystallization after cryogenic dynamic compression

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Neutrino oscillation parameters from MINOS, ICARUS and OPERA combined

We perform a detailed analysis of the capabilities of the MINOS, ICARUS and OPERA experiments to measure neutrino oscillation parameters at the atmospheric scale with their data taken separately and in combination. MINOS will determine $\Delta m^2_{32}$ and $\sin^2 2\theta_{23}$ to within 10% at the 99% C.L. with 10 kton-years of data. While no one experiment will determine $\sin^2 2\theta_{13}$ with much precision, if its value lies in the combined sensitivity region of the three experiments, it will be possible to place a lower bound of O(0.01) at the 95% C.L. on this parameter by combining the data from the three experiments. The same bound can be placed with a combination of MINOS and ICARUS data alone.Comment: Version to appear in PR

Measuring the Spectra of High Energy Neutrinos with a Kilometer-Scale Neutrino Telescope

We investigate the potential of a future kilometer-scale neutrino telescope such as the proposed IceCube detector in the South Pole, to measure and disentangle the yet unknown components of the cosmic neutrino flux, the prompt atmospheric neutrinos coming from the decay of charmed particles and the extra-galactic neutrinos, in the 10 TeV to 1 EeV energy range. Assuming a power law type spectra, $d\phi_\nu/dE_\nu \sim \alpha E_\nu^\beta$, we quantify the discriminating power of the IceCube detector and discuss how well we can determine magnitude ($\alpha$) as well as slope ($\beta$) of these two components of the high energy neutrino spectrum, taking into account the background coming from the conventional atmospheric neutrinos.Comment: 21 pages, 7 figure

Pseudogap formation of four-layer BaRuO3_3 and its electrodynamic response changes

We investiaged the optical properties of four-layer BaRuO$_{3}$, which shows a fermi-liquid-like behavior at low temperature. Its optical conductivity spectra clearly displayed the formation of a pseudogap and the development of a coherent peak with decreasing temperature. Temperature-dependences of the density $n$ and the scattering rate $1/\tau$ of the coherent component were also derived. As the temperature decreases, both $n$ and $1/\tau$ decrease for four-layer BaRuO$_{3}$. These electrodynamic responses were compared with those of nine-layer BaRuO$_{3}$, which also shows a pseudogap formation but has an insulator-like state at low temperature. It was found that the relative rates of change of both $n$ and $1/\tau$ determine either metallic or insulator-like responses in the ruthenates. The optical properties of the four-layer ruthenate were also compared with those of other pseudogap systems, such as high $T_{c}$ cuprates and heavy electron systems.Comment: 7 figures. submitted to Phys. Rev.

Performance of the CREAM calorimeter in accelerator beam test

The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results.The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results

Relative Abundances of Cosmic Ray Nuclei B-C-N-O in the Energy Region from 10 GeV/n to 300 GeV/n. Results from the Science Flight of the ATIC

The ATIC balloon-borne experiment measures the energy spectra of elements from H to Fe in primary cosmic rays from about 100 GeV to 100 TeV. ATIC is comprised of a fully active bismuth germanate calorimeter, a carbon target with embedded scintillator hodoscopes, and a silicon matrix that is used as a main charge detector. The silicon matrix produces good charge resolution for the protons and helium but only a partial resolution for heavier nuclei. In the present paper a charge resolution of ATIC device was essentially improved and backgrounds were reduced in the region from Be to Si by means of the upper layer of the scintillator hodoscope that was used as an additional charge detector together with the silicon matrix. The flux ratios of nuclei B/C, O/C, N/C in the energy region from about 10 GeV/nucleon to 300 GeV/nucleon that were obtained from new high-resolution and high-quality charge spectra of nuclei are presented. The results are compared with existing theoretical predictions