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.
Recent works on video salient object detection have demonstrated that directly transferring the generalization ability of image-based models to video data without modeling spatial-temporal ...information remains nontrivial and challenging. Considering both intraframe accuracy and interframe consistency of saliency detection, this article presents a novel cross-attention based encoder-decoder model under the Siamese framework (CASNet) for video salient object detection. A baseline encoder-decoder model trained with Lovász softmax loss function is adopted as a backbone network to guarantee the accuracy of intraframe salient object detection. Self- and cross-attention modules are incorporated into our model in order to preserve the saliency correlation and improve intraframe salient detection consistency. Extensive experimental results obtained by ablation analysis and cross-data set validation demonstrate the effectiveness of our proposed method. Quantitative results indicate that our CASNet model outperforms 19 state-of-the-art image- and video-based methods on six benchmark data sets.
There has been a long-standing debate about the mechanism of the unusual superconductivity in alkali-intercalated fullerides. In this Letter, using high-resolution angle-resolved photoemission ...spectroscopy, we systematically investigate the electronic structures of superconducting K_{3}C_{60} thin films. We observe a dispersive energy band crossing the Fermi level with the occupied bandwidth of about 130 meV. The measured band structure shows prominent quasiparticle kinks and a replica band involving the Jahn-Teller active phonon modes, which reflects strong electron-phonon coupling in the system. The electron-phonon coupling constant is estimated to be about 1.2, which dominates the quasiparticle mass renormalization. Moreover, we observe an isotropic nodeless superconducting gap beyond the mean-field estimation (2Δ/k_{B}T_{c}≈5). Both the large electron-phonon coupling constant and large reduced superconducting gap suggest a strong-coupling superconductivity in K_{3}C_{60}, while the electronic correlation effect is suggested by the observation of a waterfall-like band dispersion and the small bandwidth compared with the effective Coulomb interaction. Our results not only directly visualize the crucial band structure but also provide important insights into the mechanism of the unusual superconductivity of fulleride compounds.
It has so far remained a major challenge to quantitatively predict the boson peak, a THz vibrational anomaly universal for glasses, from features in the amorphous structure. Using molecular dynamics ...simulations of a model Cu_{50}Zr_{50} glass, we decompose the boson peak to contributions from atoms residing in different types of Voronoi polyhedra. We then introduce a microscopic structural parameter to depict the "orientational order," using the vector pointing from the center atom to the farthest vertex of its Voronoi coordination polyhedron. This order parameter represents the most probable direction of transverse vibration at low frequencies. Its magnitude scales linearly with the boson peak intensity, and its spatial distribution accounts for the quasilocalized modes. This correlation is shown to be universal for different types of glasses.
This paper explores the influence of the confining stress on rock fragmentation under the cutter of tunnel boring machine (TBM) by indentation test. Acoustic emission (AE) system was employed for ...real-time monitoring the rock fragmentation process during the indentation test. Granite and marble samples were used in the indentation test. The rock fragmentation processes with the different confining stress levels was studied based on the characteristics of force–penetration depth curve and the AE parameters, including AE energy rate, hit counts, amplitude and location of AE events. After the indentation test, the rock samples were cut along the centerline of rock samples and subsequently the crack distribution and the size of crushed zone were measured. The test results showed that the force for crack initiation and crushed zone size increased with increasing confining stress. The cracks tend to propagate to the free surface as the confining stress increases. But for the marble samples, there exists a critical confining stress condition, such that if the confining stress is more than the critical value, the force for crack initiation and crushed zone size decrease dramatically. Moreover, it was found that rock slabbing induced by confining stress had occurred before TBM cutter indentation. Such confining stress condition promotes rock fragmentation.
•Influence of confining stress on rock fragmentation by a TBM cutter is studied by indentation test.•AE technique is used for real-time monitoring rock fragmentation during indentation test.•The damage zone and crack distribution are observed by the cross-section of the failed samples.
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