The clinical success of cancer immune checkpoint blockade(ICB)has refocused attention on tumor-infiltrating lymphocytes(TILs)across cancer types.The outcome of immune checkpoint inhibitor therapy in cancer patients ha...The clinical success of cancer immune checkpoint blockade(ICB)has refocused attention on tumor-infiltrating lymphocytes(TILs)across cancer types.The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell,NK cell,and more recently,B cell responses within the tumor microenvironment.State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion.Many of these states are conserved across tumor types,in line with the broad responses observed clinically.Despite this homology,not all cancer types with similar TIL landscapes respond similarly to immunotherapy,highlighting the complexity of the underlying tumor-immune interactions.This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy.Thus,while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging,the search for response and prognostic biomarkers is just beginning.Within this review,we discuss recent advances in the understanding of TIL biology,their prognostic benefit,and their predictive value for therapy.展开更多
With the rapid developments of the high-speed railway in China, a great number of long-span bridges have been constructed in order to cross rivers and gorges. At present, the longest main span of a constructed high-sp...With the rapid developments of the high-speed railway in China, a great number of long-span bridges have been constructed in order to cross rivers and gorges. At present, the longest main span of a constructed high-speed railway bridge is only 630 m. The main span of Hutong Yangtze River Bridge and of Wufengshan Yangtze River Bridge, which are under construction, will be much longer, at 1092 m each. In order to overcome the technical issues that originate from the extremely large dead loading and the relatively small structural stiffness of long-span high-speed railway bridges, many new technologies in bridge construction, design, materials, and so forth have been developed. This paper carefully reviews progress in the construction technologies of multi-function combined bridges in China, including com- bined highway and railway bridges and multi-track railway bridges. Innovations and practices regarding new types of bridge and composite bridge structures, such as bridges with three cable planes and three main trusses, inclined main trusses, slab-truss composite sections, and steel-concrete composite sections, are introduced. In addition, investigations into high-performance materials and integral fabrication and erection techniques for long-span railway bridges are summarized. At the end of the paper, prospects for the future development of long-span high-speed railwav bridges are provided.展开更多
For understanding the possible deep-seated processes and geodynamic constrains on gold mineralization, comprehensive physicochemical and geochemical studies of gold mineralization have been undertaken within the paleo...For understanding the possible deep-seated processes and geodynamic constrains on gold mineralization, comprehensive physicochemical and geochemical studies of gold mineralization have been undertaken within the paleo-lithosphere framework during the metailogenic epoch from the northwestern part of the Jiaodong Peninsula in this paper. A general image of the paleo-crust has been remained although it has been superimposed and reformed by post-metailogenic tectonic movements. The gold ore deposits occur usually in local uplifts and gradient belts featuring a turn from steep to gentle in granite-metamorphic contact zones, relative uplifts of gradient zones of the Curier isothermal interfaces, depressions of the Moho discontinuity and areas where depth contours are cut by isotherms perpendicularly. Gold mineralization and lithogenesis are characterized by high temperature, low pressure and high strength of thermal flux. The depth of mineralization ranges from 0.8 to 4.5 km. The depth of the top interface of the granitic complex in the metallogenic epoch is about 3 km. There is a low-velocity layer （LVL） at the bottom of the upper crust with a depth close to 19.5 km, which may be a detachment belt in the crust. The appearance of the LVL indicates the existence of paleo-hyperthermal fluid or relics of molten magma chambers, which reflects partial melting within the crust during the diagenetic and metallogenic epochs and the superposition effects of strike-slip shearing of the Taulu fault zone. The subsidence of the Moho is probably attributed to the coupling process of the NW-SE continental collision between North China and the Yangtze Block and the strike-slip movement of the Tanlu fault accompanied with underplating of mantle magma in the northwestern part of the Jiaodong Peninsula. The underplating of mantle magma may result in partial melting and make granite magma transfer upwards. This is favorable for the migration of metallogenic materials from deep to shallow to be enriched to form deposits. Coupling inter展开更多
The hydrodynamics of turbulent flow through submerged flexible vegetation is investigated in a flume using acoustic Doppler velocimetery(ADV)measurements.The flow characteristics such as the energetics and momentum tr...The hydrodynamics of turbulent flow through submerged flexible vegetation is investigated in a flume using acoustic Doppler velocimetery(ADV)measurements.The flow characteristics such as the energetics and momentum transfer derived from convcntional spectral and quadrant analyses are considered as the flow encounters a finite vegetation patch.Consistent with numerous canopy flow experiments,a shear layer and coherent vortex structures near the canopy top emerge caused by Kelvin-Helmholtz instabilities after the flow equilibrates with the vegetated layer.These in stabilities are commonly attributed to velocity differences between non-vegetated and vegetated canopy layers in agreement with numerous experiments and simulations conducted on dense rigid canopies.The power-spectral density function for vertical velocity turbulent fluctuations at different downstream positions starting from the edge of the vegetation layer are also computed.For a preset water depth,the dominant dimensionless frequency is found to be surprisingly invariant around 0.027 despite large differences in vegetation densities.The ejection and sweep events significantly contribute to the Reynolds stresses near the top of the vegetation.The momentum flux carried by ejections is larger than its counterpart carried by the sweeps above the canopy top.However,the momentum flux carried by sweeps is larger below the top of the canopy.展开更多
文摘The clinical success of cancer immune checkpoint blockade(ICB)has refocused attention on tumor-infiltrating lymphocytes(TILs)across cancer types.The outcome of immune checkpoint inhibitor therapy in cancer patients has been linked to the quality and magnitude of T cell,NK cell,and more recently,B cell responses within the tumor microenvironment.State-of-the-art single-cell analysis of TIL gene expression profiles and clonality has revealed a remarkable degree of cellular heterogeneity and distinct patterns of immune activation and exhaustion.Many of these states are conserved across tumor types,in line with the broad responses observed clinically.Despite this homology,not all cancer types with similar TIL landscapes respond similarly to immunotherapy,highlighting the complexity of the underlying tumor-immune interactions.This observation is further confounded by the strong prognostic benefit of TILs observed for tumor types that have so far respond poorly to immunotherapy.Thus,while a holistic view of lymphocyte infiltration and dysfunction on a single-cell level is emerging,the search for response and prognostic biomarkers is just beginning.Within this review,we discuss recent advances in the understanding of TIL biology,their prognostic benefit,and their predictive value for therapy.
文摘With the rapid developments of the high-speed railway in China, a great number of long-span bridges have been constructed in order to cross rivers and gorges. At present, the longest main span of a constructed high-speed railway bridge is only 630 m. The main span of Hutong Yangtze River Bridge and of Wufengshan Yangtze River Bridge, which are under construction, will be much longer, at 1092 m each. In order to overcome the technical issues that originate from the extremely large dead loading and the relatively small structural stiffness of long-span high-speed railway bridges, many new technologies in bridge construction, design, materials, and so forth have been developed. This paper carefully reviews progress in the construction technologies of multi-function combined bridges in China, including com- bined highway and railway bridges and multi-track railway bridges. Innovations and practices regarding new types of bridge and composite bridge structures, such as bridges with three cable planes and three main trusses, inclined main trusses, slab-truss composite sections, and steel-concrete composite sections, are introduced. In addition, investigations into high-performance materials and integral fabrication and erection techniques for long-span railway bridges are summarized. At the end of the paper, prospects for the future development of long-span high-speed railwav bridges are provided.
基金supported jointly by the Fostering Plan Fund for Trans-century Excellent Talents and the Key Project of Science and Technology Research of the Ministry of Education(No.03178)the National Natural Science Foundation of China(No.40572063 and No.40234051).
文摘For understanding the possible deep-seated processes and geodynamic constrains on gold mineralization, comprehensive physicochemical and geochemical studies of gold mineralization have been undertaken within the paleo-lithosphere framework during the metailogenic epoch from the northwestern part of the Jiaodong Peninsula in this paper. A general image of the paleo-crust has been remained although it has been superimposed and reformed by post-metailogenic tectonic movements. The gold ore deposits occur usually in local uplifts and gradient belts featuring a turn from steep to gentle in granite-metamorphic contact zones, relative uplifts of gradient zones of the Curier isothermal interfaces, depressions of the Moho discontinuity and areas where depth contours are cut by isotherms perpendicularly. Gold mineralization and lithogenesis are characterized by high temperature, low pressure and high strength of thermal flux. The depth of mineralization ranges from 0.8 to 4.5 km. The depth of the top interface of the granitic complex in the metallogenic epoch is about 3 km. There is a low-velocity layer （LVL） at the bottom of the upper crust with a depth close to 19.5 km, which may be a detachment belt in the crust. The appearance of the LVL indicates the existence of paleo-hyperthermal fluid or relics of molten magma chambers, which reflects partial melting within the crust during the diagenetic and metallogenic epochs and the superposition effects of strike-slip shearing of the Taulu fault zone. The subsidence of the Moho is probably attributed to the coupling process of the NW-SE continental collision between North China and the Yangtze Block and the strike-slip movement of the Tanlu fault accompanied with underplating of mantle magma in the northwestern part of the Jiaodong Peninsula. The underplating of mantle magma may result in partial melting and make granite magma transfer upwards. This is favorable for the migration of metallogenic materials from deep to shallow to be enriched to form deposits. Coupling inter
基金the National Natural Science Foundation of China(Grant Nos.51439007,11672213,11872285 and 51809286).
文摘The hydrodynamics of turbulent flow through submerged flexible vegetation is investigated in a flume using acoustic Doppler velocimetery(ADV)measurements.The flow characteristics such as the energetics and momentum transfer derived from convcntional spectral and quadrant analyses are considered as the flow encounters a finite vegetation patch.Consistent with numerous canopy flow experiments,a shear layer and coherent vortex structures near the canopy top emerge caused by Kelvin-Helmholtz instabilities after the flow equilibrates with the vegetated layer.These in stabilities are commonly attributed to velocity differences between non-vegetated and vegetated canopy layers in agreement with numerous experiments and simulations conducted on dense rigid canopies.The power-spectral density function for vertical velocity turbulent fluctuations at different downstream positions starting from the edge of the vegetation layer are also computed.For a preset water depth,the dominant dimensionless frequency is found to be surprisingly invariant around 0.027 despite large differences in vegetation densities.The ejection and sweep events significantly contribute to the Reynolds stresses near the top of the vegetation.The momentum flux carried by ejections is larger than its counterpart carried by the sweeps above the canopy top.However,the momentum flux carried by sweeps is larger below the top of the canopy.
