Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block ...the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers.
A low-carbon energy transition is permeating many industrialized countries due to the overuse of fossil fuels and the climate change. Some countries stress the hydrogen energy in optimizing their ...energy structures. This article examines both the markets and the policies of the hydrogen industry in the World's Top 4 largest economies. To make the comparative analysis more logical, a novel conceptual model for energy transition -- the institution-economics-technology-behavior framework -- has been adopted to make a multi-dimensional discussion. The results show that: (1) From the perspective of strategic intention, developing hydrogen energy is conductive to the energy transition. (2) From the horizontal comparison, each country has its own advantages, however, the main driving factors are different. (3) From the vertical comparison, the hydrogen energy development in each country is still in the stage of quantitative change, and the inflection point of qualitative change has not been reached yet.
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•A novel conceptual model -- IETB framework -- is adopted.•Hydrogen energy serves three functions in the energy transition.•The World's Top 4 largest economies are used for comparative analysis.•Each country has different advantages of developing its own hydrogen energy.•Qualitative inflection point of hydrogen energy development has not yet reached.
Immunotherapies that harness the immune system to kill cancer cells have showed significant therapeutic efficacy in many human malignancies. A growing number of studies have highlighted the relevance ...of neoantigens in recognizing cancer cells by intrinsic T cells. Cancer neoantigens are a direct consequence of somatic mutations presenting on the surface of individual cancer cells. Neoantigens are fully cancer-specific and exempt from central tolerance. In addition, neoantigens are important targets for checkpoint blockade therapy. Recently, technological innovations have made neoantigen discovery possible in a variety of malignancies, thus providing an impetus to develop novel immunotherapies that selectively enhance T cell reactivity for the destruction of cancer cells while leaving normal tissues unharmed. In this review, we aim to introduce the methods of the identification of neoantigens, the mutational patterns of human cancers, related clinical trials, neoantigen burden and sensitivity to immune checkpoint blockade. Moreover, we focus on relevant challenges of targeting neoantigens for cancer treatment.
The development of efficient catalysts to break down and convert woody biomass will be a paradigm shift in delivering the global target of sustainable economy and environment
via
the use of cheap, ...highly abundant, and renewable carbon resources. However, such development is extremely challenging due to the complexity of lignocellulose, and today most biomass is treated simply as waste. The solution lies in the design of multifunctional catalysts that can place effective control on substrate activation and product selectivity. This is, however, severely hindered by the lack of fundamental understanding of (i) the precise role of active sites, and (ii) the catalyst-substrate chemistry that underpins the catalytic activity. Moreover, active sites alone often cannot deliver the desired selectivity of products, and full understanding of the microenvironment of the active sites is urgently needed. Here, we review key recent advances in the study of reaction mechanisms of biomass conversion over emerging heterogeneous catalysts. These insights will inform the design of future catalytic systems showing improved activity and selectivity.
This review analyses the reaction mechanisms for the conversion of biomass and derivatives studied by inelastic neutron scattering, synchrotron X-ray diffraction, X-ray absorption spectroscopy, NMR, isotope-labelling and computational techniques.
Porous nanosheet-structured electrode materials are very attractive for the high efficiency storage of electrochemical energy. Herein, a porous cobalt sulfide nanosheet array on Ni foam (Co
S
...-NSA/NF) is successfully fabricated by a facile method, which involves the uniform growth of 2D Co-based leaf-like zeolitic imidazole frameworks (Co-ZIF-L) on Ni foam followed by subsequent sulfurization with thioacetamide (TAA). Benefiting from the unique porous nanosheet array architecture and conductive substrate, the Co
S
-NSA/NF exhibits excellent electrochemical performance with a high capacitance (1098.8 F g
at 0.5 A g
), good rate capacity (54.6% retention at 10 A g
) and long-term stability (87.4% retention over 1000 cycles), when acted as a binder-free electrode for supercapacitors. Furthermore, an assembled asymmetric supercapacitor device using the as-fabricated Co
S
-NSA as the positive electrode and activated carbon (AC) as the negative electrode also exhibits a high energy density of 20.0 W h kg
at a high power density of 828.5 W kg
. The method developed here can be extended to the construction of other structured metal (mono or mixed) sulfide electrode materials for more efficient energy storage.
To dynamically adjust the edge preservation and smoothness of low-light images, this paper proposed a fractional order gradient descent with momentum radial basis function neural network (FOGDMRBF) ...to optimizing Retinex.Its convergence is proved. In order to speed up the convergence process, an adaptive learning rate is used to adjust the training process reasonably. The results verify the theoretical results of the proposed algorithm such as its monotonicity and convergence. The descending curve of error values by FOGDM is more smoother than gradient descent and gradient descent with momentum method. The influence of regularization parameter is analyzed and compared. Compared with Dark Channel Prior, Histogram Equalization, Homomorphic Filtering and Multiple Exposure Fusion, the halo and noise generated are significantly reduced with higher Peak Signal-to-Noise Ratio and Structural Similarity Index.
To deal with the uncertain system models with less computational cost, expertise knowledge and parameter tuning, a linear matrix inequalities (LMI)‐based adaptive time‐delayed sliding mode control ...algorithm is proposed. It is used for ships berthing or sailing near the bank or the pier of a bridge considering ship–bank interaction effect and shallow water effect. The closed‐loop system is proved to be uniform ultimate bounded based on the Lyapunov–Razumikhin function in terms of LMI. The switching function is designed to make the system robust to uncertainties and external disturbances and avoid chattering. The trajectory of the system space is contractive and asymptotically tends to the desired position and attitude. The influence of different control parameters on the control effect are compared and analyzed. The results show that when the control coefficients are small, the overshoot of the system is small. The adjustment time of the system is long. When the control coefficients are large, the overshoot of the system is obvious. The adjustment time of the system is shortened. Influence analysis of different input time delays show that when the input delay is long, it takes longer time for the system to reach its desired position with higher overshoot. When the input delay is short, it takes shorter time for the system to reach its desired position with lower overshoot.
Ethylenediamine tetraacetate-intercalated Fe-Mn layered double hydroxides (MnFe-EDTA-LDHs) were prepared by coprecipitation. The influence of different factors on Cl− adsorption by MnFe-EDTA-LDHs was ...investigated. Additionally, MnFe-EDTA-LDHs were incorporated into the concrete to study the Cl− erosion properties. The result showed that the Cl− adsorption on MnFe-EDTA-LDHs was affected by the initial pH, dosage, and coexisting anions. The Cl− adsorption process by MnFe-EDTA-LDHs accorded with the pseudo-second-order model and the Redlich–Peterson model. The maximum adsorption capacity of Cl− on MnFe-EDTA-LDHs reached 129.50 mg/g. The adsorption mechanism involved the complexation of O-containing groups, ion exchange, and electrostatic interaction. Moderate additions of MnFe-EDTA-LDHs improved the resistance of the concrete to Cl− erosion, while excessive additions reduced the Cl− erosion resistance. This work indicated that MnFe-EDTA-LDHs effectively retarded the Cl− erosion on concrete.
This paper proposes a data-driven risk assessment model for ship overtaking based on the particle swarm optimization (PSO) improved kernel density estimation (KDE). By minimizing the mean square ...error between the real probability distribution of the ship overtaking point and the kernel density estimation probability distribution calculated by the current kernel density bandwidth, the longitude and latitude of the ship overtaking point are displayed by the color corresponding to the probability as the cost objective function of the search bandwidth of the algorithm. This can better show the distribution of the overtaking points of channel propagation traffic flow. A probability-based ship-overtaking risk evaluation model is developed through the bandwidth and density analysis optimized by an intelligent algorithm. In order to speed up searching the optimal variable width of the kernel density estimator for ship encountering positions, an improved adaptive variable-width kernel density estimator is proposed. The latter reduces the risk of too smooth probability density estimation phenomenon. Its convergence is proved. Finally, the model can efficiently evaluate the risk status of ship overtaking and provide navigational auxiliary decision support for pilots.
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