Targeting the immune checkpoint pathway has demonstrated antitumor cytotoxicity in treatment-refractory head and neck squamous cell carcinoma (HNSC). To understand the molecular mechanisms ...underpinning its antitumor response, we characterized the immune landscape of HNSC by their tumor and stromal compartments to identify novel immune molecular subgroups.
A training cohort of 522 HNSC samples from the Cancer Genome Atlas profiled by RNA sequencing was analyzed. We separated gene expression patterns from tumor, stromal, and immune cell gene using a non-negative matrix factorization algorithm. We correlated the expression patterns with a set of immune-related gene signatures, potential immune biomarkers, and clinicopathological features. Six independent datasets containing 838 HNSC samples were used for validation.
Approximately 40% of HNSCs in the cohort (211/522) were identified to show enriched inflammatory response, enhanced cytolytic activity, and active interferon-γ signaling (all, P < 0.001). We named this new molecular class of tumors the Immune Class. Then we found it contained two distinct microenvironment-based subtypes, characterized by markers of active or exhausted immune response. The Exhausted Immune Class was characterized by enrichment of activated stroma and anti-inflammatory M2 macrophage signatures, WNT/transforming growth factor-β signaling pathway activation and poor survival (all, P < 0.05). An enriched proinflammatory M1 macrophage signature, enhanced cytolytic activity, abundant tumor-infiltrating lymphocytes, high human papillomavirus (HPV) infection, and favorable prognosis were associated with Active Immune Class (all, P < 0.05). The robustness of these immune molecular subgroups was verified in the validation cohorts, and Active Immune Class showed potential response to programmed cell death-1 blockade (P = 0.01).
This study revealed a novel Immune Class in HNSC; two subclasses characterized by active or exhausted immune responses were also identified. These findings provide new insights into tailoring immunotherapeutic strategies for different HNSC subgroups.
Secondary organic aerosol (SOA) affects the earth's radiation balance and global climate. High-elevation areas are sensitive to global climate change. However, at present, SOA origins and seasonal ...variations are understudied in remote high-elevation areas. In this study, particulate samples were collected from July 2012 to July 2013 at the remote Nam Co (NC) site, Central Tibetan Plateau and analyzed for SOA tracers from biogenic (isoprene, monoterpenes and beta -caryophyllene) and anthropogenic (aromatics) precursors. Among these compounds, isoprene SOA (SOAI) tracers represented the majority (26.6 plus or minus 44.2 ng m-3), followed by monoterpene SOA (SOAM) tracers (0.97 plus or minus 0.57 ng m-3), aromatic SOA (SOAA) tracer (2,3-dihydroxy-4-oxopentanoic acid, DHOPA, 0.25 plus or minus 0.18 ng m-3) and beta -caryophyllene SOA tracer ( beta -caryophyllenic acid, 0.09 plus or minus 0.10 ng m-3). SOAI tracers exhibited high concentrations in the summer and low levels in the winter. The similar temperature dependence of SOAI tracers and isoprene emission suggested that the seasonal variation of SOAI tracers at the NC site was mainly influenced by the isoprene emission. The ratio of high-NOx to low-NOx products of SOAI (2-methylglyceric acid to 2-methyltetrols) was highest in the winter and lowest in the summer, due to the influence of temperature and relative humidity. The seasonal variation of SOAM tracers was impacted by monoterpenes emission and gas-particle partitioning. During the summer to the fall, temperature effect on partitioning was the dominant process influencing SOAM tracers' variation; while the temperature effect on emission was the dominant process influencing SOAM tracers' variation during the winter to the spring. SOAM tracer levels did not elevate with increased temperature in the summer, probably resulting from the counteraction of temperature effects on emission and partitioning. The concentrations of DHOPA were 1-2 orders of magnitude lower than those reported in the urban regions of the world. Due to the transport of air pollutants from the adjacent Bangladesh and northeastern India, DHOPA presented relatively higher levels in the summer. In the winter when air masses mainly came from northwestern India, mass fractions of DHOPA in total tracers increased, although its concentrations declined. The SOA-tracer method was applied to estimate secondary organic carbon (SOC) from these four precursors. The annual average of SOC was 0.22 plus or minus 0.29 mu gC m-3, with the biogenic SOC (sum of isoprene, monoterpenes and beta -caryophyllene) accounting for 75 %. In the summer, isoprene was the major precursor with its SOC contributions of 81 %. In the winter when the emission of biogenic precursors largely dropped, the contributions of aromatic SOC increased. Our study implies that anthropogenic pollutants emitted in the Indian subcontinent could be transported to the TP and have an impact on SOC over the remote NC.
Motivated by the recent development of phase field methods for modeling and simulating the fracture of brittle and quasi-brittle materials, a general approach is proposed to decompose the ...infinitesimal strain tensor (or Cauchy stress tensor) into a positive part and a negative part which are orthogonal in the sense of an inner product where the elastic stiffness (or compliance) tensor acts as a metric. This approach is based on a strain (or stress) transformation preserving the elastic energy, and gives rise to a generalized Pythagorean theorem. It is valid not only for the isotropic elastic case but also for all the anisotropic ones. Decompositions of the strain (or stress) tensor are given in a coordinate-free way. The main results obtained are illustrated and detailed for the elastic isotropic case in an analytical explicit manner.
•Coordinate-free decomposition of the strain tensor into positive and negative parts.•The elastic tensor acting as a metric for defining the orthogonality.•The strain orthogonal decomposition valid for all elastic symmetry classes.
Using Venn diagrams, we classify the different types of two-mode Gaussian continuous variable quantum correlation including directional entanglement and Einstein-Podolsky-Rosen (EPR) steering. We ...establish unified signatures for one- and two-way quantum steering, entanglement, and discord beyond entanglement in terms of an EPR-type variance. By focusing on Gaussian states, we link an optimized condition for entanglement based on an EPR variance to the Simon-Peres condition. This allows us to quantify the asymmetry of the Gaussian entanglement, and to relate the asymmetry to a directional quantum teleportation protocol where Alice and Bob possess asymmetrically noisy channels. Our analysis enables a determination of the type and direction of quantum correlation in a way that is easily measured in experiment. We also find that for symmetric states, when discord exceeds a certain threshold, the states are necessarily steerable.
We show that parity-time (PT) symmetry can be spontaneously broken in the recently reported energy level attraction of magnons and cavity photons. In the PT-broken phase, the magnon and photon form a ...high-fidelity Bell state with maximum entanglement. This entanglement is steady and robust against the perturbation of the environment, which is in contrast to the general wisdom that expects instability of the hybridized state when the symmetry is broken. This anomaly is further understood by the compete of non-Hermitian evolution and particle number conservation of the hybrid system. As a comparison, neither PT-symmetry breaking nor steady magnon-photon entanglement is observed inside the normal level repulsion case. Our results may open an exciting window to utilize magnon-photon entanglement as a resource for quantum information science.
The development of high-performance ultraelastic metals with superb strength, a large elastic strain limit and temperature-insensitive elastic modulus (Elinvar effect) are important for various ...industrial applications, from actuators and medical devices to high-precision instruments
. The elastic strain limit of bulk crystalline metals is usually less than 1 per cent, owing to dislocation easy gliding. Shape memory alloys
-including gum metals
and strain glass alloys
-may attain an elastic strain limit up to several per cent, although this is the result of pseudo-elasticity and is accompanied by large energy dissipation
. Recently, chemically complex alloys, such as 'high-entropy' alloys
, have attracted tremendous research interest owing to their promising properties
. In this work we report on a chemically complex alloy with a large atomic size misfit usually unaffordable in conventional alloys. The alloy exhibits a high elastic strain limit (approximately 2 per cent) and a very low internal friction (less than 2 × 10
) at room temperature. More interestingly, this alloy exhibits an extraordinary Elinvar effect, maintaining near-constant elastic modulus between room temperature and 627 degrees Celsius (900 kelvin), which is, to our knowledge, unmatched by the existing alloys hitherto reported.
The theory of elastodynamic homogenization initiated by J.R. Willis is revisited for periodically inhomogeneous media through a careful scrutiny of the main aspects of that theory in the 3D continuum ...context and by applying it to the thorough treatment of a simple 1D discrete periodic system. The Bloch theorem appears to be central to appropriately defining and interpreting effective fields. Based on some physical arguments, three necessary conditions are derived for the transition from the microscopic description to the macroscopic description of periodic media. The parameters involved in the Willis effective constitutive relation are expressed in terms of two localization tensors and specified with the help of the corresponding Green function in the spirit of micromechanics. These results are illustrated and discussed for the 1D discrete periodic system considered. In particular, inspired by Brillouin's study, the dependency of the effective constitutive parameters on the frequency is physically interpreted in terms of oscillation modes of the underlying microstructure.
We investigate the dependence of friction forces on normal load in incommensurate micrometer-size contacts between atomically smooth single-crystal graphite surfaces under ambient conditions. Our ...experimental results show that these contacts exhibit superlubricity (superlow friction), which is robust against the application of normal load. The measured friction coefficients are essentially zero and independent of the external normal load up to the maximum pressure of our experiment, 1.67 MPa. The observation of load-independent superlubricity in microscale contacts is a promising result for numerous practical applications.
Plastic film mulching has played an important role in Chinese agriculture due to its soil warming and moisture conservation effects. With the help of plastic film mulch technology, grain and cash ...crop yields have increased by 20-35% and 20-60%, respectively. The area of plastic film coverage in China reached approximately 20 million hectares, and the amount of plastic film used reached 1.25 million tons in 2011. While producing huge benefits, plastic film mulch technology has also brought on a series of pollution hazards. Large amounts of residual plastic film have detrimental effects on soil structure, water and nutrient transport and crop growth, thereby disrupting the agricultural environment and reducing crop production. To control pollution, the Chinese government urgently needs to elevate plastic film standards. Meanwhile, research and development of biodegradable mulch film and multi-functional mulch recovery machinery will help promote effective control and management of residual mulch pollution.
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