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.
An interatomic potential for the Al-Tb alloy around the composition of Al
90
Tb
10
is developed using the deep neural network (DNN) learning method. The atomic configurations and the corresponding ...total potential energies and forces on each atom obtained from
ab initio
molecular dynamics (AIMD) simulations are collected to train a DNN model to construct the interatomic potential for the Al-Tb alloy. We show that the obtained DNN model can well reproduce the energies and forces calculated by AIMD simulations. Molecular dynamics (MD) simulations using the DNN interatomic potential also accurately describe the structural properties of the Al
90
Tb
10
liquid, such as partial pair correlation functions (PPCFs) and bond angle distributions, in comparison with the results from AIMD simulations. Furthermore, the developed DNN interatomic potential predicts the formation energies of the crystalline phases of the Al-Tb system with an accuracy comparable to
ab initio
calculations. The structure factors of the Al
90
Tb
10
metallic liquid and glass obtained by MD simulations using the developed DNN interatomic potential are also in good agreement with the experimental X-ray diffraction data. The development of short-range order (SRO) in the Al
90
Tb
10
liquid and the undercooled liquid is also analyzed and three dominant SROs,
i.e.
, Al-centered distorted icosahedron (DISICO) and Tb-centered '3661' and '15551' clusters, respectively, are identified.
The developed deep neural network (DNN) potential can describe the structural properties of the Al
90
Tb
10
liquid and the formation energies of Al-Tb crystals with the accuracy of
ab initio
calculations.
In this Letter, we develop a new car-following model with the consideration of the driver's forecast effect (DFE). The analytical and numerical results show that the stability of traffic flow will ...gradually be enhanced with the increase of the forecast effect coefficient and the forecast time.
In this paper, we propose an extended car-following model and an electricity consumption model to study the effects of the road’s slope on the electric vehicle’s electricity consumption. The ...numerical results show that each electric vehicle’s electricity consumption increases with the uphill’s tilt angle and decreases with the downhill’s tilt angle. In addition, each electric vehicle’s electricity consumption increases with the uphill’s (downhill’s) length under a certain tilt angle.
•An extended car-following model is proposed.•An electricity consumption model is proposed.•The electric vehicle’s electricity consumption is explored on uphill.•The electric vehicle’s electricity consumption is studied on downhill.
•A car-following model with real-time road condition has been developed.•We study the effects of real-time road condition on uniform flow.•Real-time road condition produces oscillating ...phenomena.•Real-time road condition enhances the vehicle’s fuel consumption and emissions.
In this paper, we use empirical data to calibrate the speed-headway function and propose a car-following model to investigate the effects of real-time road condition on each vehicle’s speed, acceleration, headway, fuel consumption, CO, HC and NOX under uniform flow. Numerical results illustrate that real-time road condition produces oscillating phenomena and enhance each vehicle’s fuel consumption and exhaust emissions. These results can help researchers understand the effects of real-time road condition on the driving behavior and help traffic engineers construct the theory of homogeneous roads in order to reduce the vehicle’s fuel consumption and exhaust emissions.
Molecular dynamics simulations were performed to study the effects of Si solute on the glass formation and crystallization of Pd liquid. Pure Pd samples prepared by a quenching process with a cooling ...rate of 1013 K s−1 can be in an amorphous state but the structural analysis indicates there is nearly no glass-forming motif in the sample. However, doping a small amount of Si (Si concentration ~4%) the sample can be vitrified at a cooling rate of 1012 K s−1. The glass-forming motifs such as Pd-centered Z13, Si-centered Z9-like and mixed-ICO-cube clusters with five-fold local symmetry are found to be the dominant short-range orders in the glassy samples. With the increasing of the Si-doping concentration, these glass-forming motifs tend to aggregate and connect with each other forming a network structure. Our calculated results revealed that Si solutes in liquid Pd can significantly enhance the glass-forming ability.
We retrospectively report our experience of managing 30 patients with a primary malignant tumour of the distal tibia; 25 were treated by limb salvage surgery and five by amputation. We compared the ...clinical outcomes of following the use of different methods of reconstruction.
There were 19 male and 11 female patients. The mean age of the patients was 19 years (6 to 59) and the mean follow-up was 5.1 years (1.25 to 12.58). Massive allograft was used in 11 patients, and autograft was used in 14 patients. The time to union, the survival time of the reconstruction, complication rate, and functional outcomes following the different surgical techniques were compared. The overall patient survival was also recorded.
Out of 14 patients treated with an autograft, 12 (86%) achieved union at both the proximal and distal junctions. The time to union at both junctions of the autograft was significantly shorter than in those treated with an allograft (11.1 vs 17.2 months, p = 0.02; 9.5 vs 16.2 months, p = 0.04). The complication rate of allograft reconstruction was 55%. The five patients treated with an amputation did not have a complication. Out of the 25 patients who were treated with limb salvage, three (12%) developed local recurrence and underwent amputation. The mean functional Musculoskeletal Tumor Society (MSTS) score after autograft reconstruction was higher than after allograft reconstruction (81% vs 67%; p = 0.06), and similar to that after amputation (81% vs 82%; p = 0.82). The two- and five-year overall rates of survival were 83% and 70%, respectively.
This consecutive case series supports the safety of limb salvage and the effectiveness of biological reconstruction after the resection of a primary tumour of the distal tibia. Autograft might be a preferable option. In some circumstances, below-knee amputation remains a valid option.
► A car-following model with consideration of roadside memorial has been developed. ► We use it to explore the effects of the roadside memorial on traffic system. ► Results show that it can describe ...complex phenomena resulted by roadside memorial. ► Whatʼs more, considering roadside memorial can improve traffic safety. ► The results help us understand effects of roadside memorial on traffic flow.
In this Letter, a car-following model with consideration of roadside memorial is proposed. The numerical results show that the proposed model can qualitatively describe the impacts of roadside memorial on traffic flow and the traffic risk coefficient. It is also shown that roadside memorial can enhance the traffic safety.
In this paper, we propose a macro model with consideration of multi static bottlenecks to study the impacts of multi static bottlenecks on traffic flow. The numerical results show that the influences ...are related to the number of static bottlenecks, the distance between two adjacent static bottlenecks and the initial density.
•A macro model with consideration of multi static bottlenecks has been developed.•Impacts of the number of static bottlenecks have been explored.•Impacts of the distance between adjacent static bottlenecks have been explored.•These results can help us better understand and explain some traffic phenomena.
In this Letter, we present a new car-following model based on the driver's forecast effect (DFE). Applying the relationship between the micro and macro variables, we obtain a new macro model for ...traffic flow with the consideration of DFE. The analytical results show that our model can improve the stability of traffic flow if properly considering DFE and will reduce the stable region of traffic flow if over considering DFE. The numerical results show that our model can not only reproduce the evolution of shock, rarefaction wave and small perturbation, but also improve the stability of traffic flow.
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