The immunotherapeutic treatment of various cancers with an increasing number of immune checkpoint inhibitors (ICIs) has profoundly improved the clinical management of advanced diseases. However, just ...a fraction of patients clinically responds to and benefits from the mentioned therapies; a large proportion of patients do not respond or quickly become resistant, and hyper- and pseudoprogression occur in certain patient populations. Furthermore, no effective predictive factors have been clearly screened or defined. In this review, we discuss factors underlying the elucidation of potential immunotherapeutic resistance mechanisms and the identification of predictive factors for immunotherapeutic responses. Considering the heterogeneity of tumours and the complex immune microenvironment (composition of various immune cell subtypes, disease processes, and lines of treatment), checkpoint expression levels may not be the only factors underlying immunotherapy difficulty and resistance. Researchers should consider the tumour microenvironment (TME) landscape in greater depth from the aspect of not only immune cells but also the tumour histology, molecular subtype, clonal heterogeneity and evolution as well as micro-changes in the fine structural features of the tumour area, such as myeloid cell polarization, fibroblast clusters and tertiary lymphoid structure formation. A comprehensive analysis of the immune and molecular profiles of tumour lesions is needed to determine the potential predictive value of the immune landscape on immunotherapeutic responses, and precision medicine has become more important.
Atomically dispersed iron sites on nitrogen-doped carbon (Fe-NC) are the most active Pt-group-metal-free catalysts for oxygen reduction reaction (ORR). However, due to oxidative corrosion and the ...Fenton reaction, Fe-NC catalysts are insufficiently active and stable. Herein, w e demonstrated that the axial Cl-modified Fe-NC (Cl-Fe-NC) electrocatalyst is active and stable for the ORR in acidic conditions with high H
O
tolerance. The Cl-Fe-NC exhibits excellent ORR activity, with a high half-wave potential (E
) of 0.82 V versus a reversible hydrogen electrode (RHE), comparable to Pt/C (E
= 0.85 V versus RHE) and better than Fe-NC (E
= 0.79 V versus RHE). X-ray absorption spectroscopy analysis confirms that chlorine is axially integrated into the FeN4. More interestingly, compared to Fe-NC, the Fenton reaction is markedly suppressed in Cl-Fe-NC. In situ electrochemical impedance spectroscopy reveals that Cl-Fe-NC provides efficient electron transfer and faster reaction kinetics than Fe-NC. Density functional theory calculations reveal that incorporating Cl into FeN4 can drive the electron density delocalization of the FeN4 site, leading to a moderate adsorption free energy of OH* (∆G
), d-band center, and a high onset potential, and promotes the direct four-electron-transfer ORR with weak H
O
binding ability compared to Cl-free FeN4, indicating superior intrinsic ORR activity.
•Proposed a new surrogate safety measure: time to collision with disturbance (TTCD).•Risk rate quantified by TTCD was better aligned with rear-end crash rate.•Introduced a procedure for processing ...connected vehicle data for safety application.•Successfully leveraged connected vehicle data for identifying high-risk locations.
Traditional methods for the identification of high-risk locations rely heavily on historical crash data. Rich information generated from connected vehicles could be used to obtain surrogate safety measures (SSMs) for risk identification. Conventional SSMs such as time to collision (TTC) neglect the potential risk of car-following scenarios in which the following vehicle’s speed is slightly less than or equal to the leading vehicle’s but the spacing between two vehicles is relatively small that a slight disturbance would yield collision risk. To address this limitation, this study proposes time to collision with disturbance (TTCD) for risk identification. By imposing a hypothetical disturbance, TTCD can capture rear-end conflict risks in various car following scenarios, even when the leading vehicle has a higher speed. Real-world connected vehicle pilot test data collected in Ann Arbor, Michigan is used in this study. A detailed procedure of cleaning and processing the connected vehicle data is presented. Results show that risk rate identified by TTCD can achieve a higher Pearson’s correlation coefficient with rear-end crash rate than other traditional SSMs. We show that high-risk locations identified by connected vehicle data from a relatively shorter time period are similar to the ones identified by using the historical crash data. The proposed method can substantially reduce the data collection time, compared with traditional safety analysis that generally requires more than three years to get sufficient crash data. The connected vehicle data has thus shown the potential to be used to develop proactive safety solutions and the risk factors can be eliminated in a timely manner.
Detecting anomalous traffic is a critical task for advanced Internet management. Many anomaly detection algorithms have been proposed recently. However, constrained by their matrix-based traffic data ...model, existing algorithms often suffer from low accuracy in anomaly detection. To fully utilize the multi-dimensional information hidden in the traffic data, this paper takes the initiative to investigate the potential and methodologies of performing tensor factorization for more accurate Internet anomaly detection. More specifically, we model the traffic data as a three-way tensor and formulate the anomaly detection problem as a robust tensor recovery problem with the constraints on the rank of the tensor and the cardinality of the anomaly set. These constraints, however, make the problem extremely hard to solve. Rather than resorting to the convex relaxation at the cost of low detection performance, we propose TensorDet to solve the problem directly and efficiently. To improve the anomaly detection accuracy and tensor factorization speed, TensorDet exploits the factorization structure with two novel techniques, sequential tensor truncation and two-phase anomaly detection. We have conducted extensive experiments using Internet traffic trace data Abilene and GÈANT. Compared with the state of art algorithms for tensor recovery and matrix-based anomaly detection, TensorDet can achieve significantly lower false positive rate and higher true positive rate. Particularly, benefiting from our well designed algorithm to reduce the computation cost of tensor factorization, the tensor factorization process in TensorDet is 5 (Abilene) and 13 (GÈANT) times faster than that of the traditional Tucker decomposition solution.
Taking reservoir rocks and fluids of the Daqing, Dagang and Changqing oilfields as research objects, the EOR mechanisms and technical approach of polymer flooding were discussed. By comparing the ...displacement performances of ordinary polymer, glycerol, polymer in “sheet-net” structure and heterogeneous weak gel at the same viscosity and concentration, the relationship between the viscosity of polymer displacement agents and displacement performance was demonstrated, and the method of improving polymer flooding effect was worked out. The main mechanism of polymer flooding to increase oil recovery is the swept volume expansion of water injection due to polymer retention in porous media. The viscosity of polymer agents has no positive correlation with polymer flooding effect. Although polymer of “sheet-net” structure has strong capacity in increasing viscosity, it has poor compatibility with pore throat structure of reservoir rock, low injectivity and low shear resistance. Heterogeneous weak gel system has higher adsorption and capture capacity in porous media, which is easy to retain in porous media, and can effectively establish seepage resistance in high permeability layers (zones). Compared with polymer solutions with the same viscosity or concentration, it has stronger ability to expand swept volume. Long term injection of polymer flooding agents will inevitably lead to fluid entry profile reversal, and thus worsening of polymer flooding effect. Alternate injection of high retention and low or non-retention displacement agents can further improve the displacement effect of polymer flooding agents.
A properly strained graphene monolayer or bilayer is expected to harbour periodic pseudo-magnetic fields with high symmetry, yet to date, a convincing demonstration of such pseudo-magnetic fields has ...been lacking, especially for bilayer graphene. Here, we report a definitive experimental proof for the existence of large-area, periodic pseudo-magnetic fields, as manifested by vortex lattices in commensurability with the moiré patterns of low-angle twisted bilayer graphene. The pseudo-magnetic fields are strong enough to confine the massive Dirac electrons into circularly localized pseudo-Landau levels, as observed by scanning tunneling microscopy/spectroscopy, and also corroborated by tight-binding calculations. We further demonstrate that the geometry, amplitude, and periodicity of the pseudo-magnetic fields can be fine-tuned by both the rotation angle and heterostrain. Collectively, the present study substantially enriches twisted bilayer graphene as a powerful enabling platform for exploration of new and exotic physical phenomena, including quantum valley Hall effects and quantum anomalous Hall effects.
Low availability of nitrogen (N) is often a major limiting factor to crop yield in most nutrient-poor soils. Arbuscular mycorrhizal (AM) fungi are beneficial symbionts of most land plants that ...enhance plant nutrient uptake, particularly of phosphate. A growing number of reports point to the substantially increased N accumulation in many mycorrhizal plants; however, the contribution of AM symbiosis to plant N nutrition and the mechanisms underlying the AM-mediated N acquisition are still in the early stages of being understood. Here, we report that inoculation with AM fungus Rhizophagus irregularis remarkably promoted rice (Oryza sativa) growth and N acquisition, and about 42% of the overall N acquired by rice roots could be delivered via the symbiotic route under N-NO₃⁻ supply condition. Mycorrhizal colonization strongly induced expression of the putative nitrate transporter gene OsNPF4.5 in rice roots, and its orthologs ZmNPF4.5 in Zea mays and SbNPF4.5 in Sorghum bicolor. OsNPF4.5 is exclusively expressed in the cells containing arbuscules and displayed a low-affinity NO₃⁻ transport activity when expressed in Xenopus laevis oocytes. Moreover, knockout of OsNPF4.5 resulted in a 45% decrease in symbiotic N uptake and a significant reduction in arbuscule incidence when NO₃⁻ was supplied as an N source. Based on our results, we propose that the NPF4.5 plays a key role in mycorrhizal NO₃⁻ acquisition, a symbiotic N uptake route that might be highly conserved in gramineous species.
Many people criticize the inequity of traditional taxi (TT) services and believe the entry of ride-hailing taxis (RT) can address the issue. However, this has been understudied in the literature. ...This paper aims to estimate the equity of TT and RT services during peak hours and to study how the entry of RT affects equity by analyzing trip data of TT and RT in New York City in 2010 and 2017 (before and after the entry of RT). First, we used the Lorenz curve and the Gini coefficient to estimate the equity of taxi services against population and employment. The results show that the equity of RT in 2017 is higher than that of TT and the equity of TT + RT in 2017 is higher than that of 2010. Mixed geographically weighted regression (MGWR) was applied to determine whether the relationships between taxi trips and population/employment would vary across different taxi zones. The coefficient of variation (CV) of local coefficients of population/employment is used as an indicator of equity. Results show that RT services were more equitable than TT services in 2017 and that the overall taxi service in 2017 was more equitable than that of 2010.
Aiming at the problem that traditional wireless sensor networks produce errors in the positioning and tracking of motorised targets due to noise interference, this paper proposes a motorised target ...tracking method with a convolutional bi-directional long and short-term memory neural network and extended Kalman filtering, which is trained by using the simulated RSSI value and the actual target value of motorised targets collected from the convolutional bi-directional neural network to the sensor anchor node, so as to obtain a more accurate initial value of the manoeuvre target, and at the same time, the extended Kalman filtering method is used to accurately locate and track the real-time target, so as to obtain the accurate positioning and tracking information of the real-time target. Through experimental simulation, it can be seen that the algorithm proposed in this paper has good tracking effect in both linear manoeuvre target tracking scenarios and non-linear manoeuvre target tracking scenarios.
Dielectric elastomer actuator (DEA) is considered as an ideal artificial muscle with soft and light in nature, widespread application in soft robotics and sensors. Dielectric elastomer (DE), the core ...component of DEA, with high output force and large actuation strain under relatively low driving electric field is critical for high‐performance DEA. However, the widely used VHB series (3M) DE suffered from very large pre‐strain and high driving voltage to get their high actuation performance, limiting their scope of application. In this work, the DEs with good mechanical and dielectric properties were prepared via UV curing method consisting of acrylic acid (AA) with strong polar groups as functional monomer, n‐butyl acrylate (BA) as soft monomer and urethane acrylate as cross‐linker (c‐p(BA‐AA)). The c‐p(BA‐AA) DE films obtained the simultaneous increasing of dielectric constant and breakdown strength with the increasing content of AA, which guaranteed the good actuation performance. The c‐p(BA‐AA) film exhibited excellent actuating performance (44.11% actuation strain at 45 kV/mm) without pre‐strain. Besides, a simple linear actuator based on the c‐p(BA‐AA) film could easily output weight that is tens of times of its own active weight (654.1 mN/g at 30 kV/mm).
Acrylate‐based dielectric elastomers with enhanced mechanical and dielectric properties were prepared by simple and fast UV curing method. The dielectric constant and breakdown strength of the DEs were decouplingly enhanced with the increasing of acrylic acid. The linear actuator based on the DE film can achieve an output force per unit mass of 654.1 mN/g at 30 kV/mm.
PDF
