Besides cytokine release syndromes (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated HLH-like syndrome (IEC-HS) is increasingly recognized across CAR-T recipients. This emergent and fatal syndrome is difficult to separate from other disorders during the early phase, and urgently requires more integrated diagnostic and therapeutic frameworks.
Paint coated corrosion detection and evaluation is a big challenge for steel performance and structure health. Eddy current pulsed thermography (ECPT) technique is investigated because it can reflect the corrosion physical properties through paint coating by the infrared signal. This paper proposes skewness method, which presents the feature of temperature curve’s shape automatically, and compares it with principal component analysis (PCA), phase analysis, and kurtosis feature extraction methods for paint coated corrosion characterization and evaluation. The averaged skewness shows the best sensitivity for 0–6 months corrosion. The normalized second principal component (PC) presents good sensitivity and the best measurement scale for corroded time. Furthermore, the temperature curve analysis proves that the electrical conductivity dominates the induced heating and heat distribution. The corrosion height is utilized to explain why ECPT technique is valid within 10 months corroded time. ECPT technique is proved as a smart sensor system for paint coated corrosion detection and characterization.
Deep reinforcement learning (RL) has been widely applied to motion planning problems of autonomous vehicles in urban traffic. However, traditional deep RL algorithms cannot ensure safe trajectories throughout training and deployment. We propose a provably safe RL algorithm for urban autonomous driving to address this. We add a novel safety layer to the RL process to verify the safety of high-level actions before they are performed. Our safety layer is based on invariably safe braking sets to constrain actions for safe lane changing and safe intersection crossing. We introduce a generalized discrete high-level action space, which can represent all high-level intersection driving maneuvers and various desired accelerations. Finally, we conducted extensive experiments on the inD dataset containing urban driving scenarios. Our analysis demonstrates that the safe agent never causes a collision and that the safety layer's lane changing verification can even improve the goal-reaching performance compared to the unsafe baseline agent.
Potato Fusarium Wilt is a soil-borne fungal disease that can seriously harm potatoes throughout their growth period and occurs at different degrees in major potato-producing areas in China. To reduce the use of chemical agents and improve the effect of biocontrol agents, the inhibitory effects of the fermentation broth of Bacillus subtilis ZWZ-19 (B) and Trichoderma asperellum PT-29 (T) on Fusarium oxysporum were compared under single-culture and co-culture conditions. Furthermore, metabolomic analysis of the fermentation broths was conducted. The results showed that the inhibitory effect of the co-culture fermentation broth with an inoculation ratio of 1:1 (B1T1) was better than that of the separately cultured fermentation broths and had the best control effect in a potted experiment. Using LC-MS analysis, 134 metabolites were determined and classified into different types of amino acids. Furthermore, 10 metabolic pathways had the most significant variations, and 12 were related to amino acid metabolism in the KEGG analysis. A correlation analysis of the 79 differential metabolites generated through the comprehensive comparison between B, T, and B1T1 was conducted, and the results showed that highly abundant amino acids in B1T1 were correlated with amino acids in B, but not in T.
Abstract Background T cell receptor (TCR)-T cells possess similar effector function, but milder and more durable signal activation compared with chimeric antigen receptor-T cells. TCR-T cell therapy is another active field of cellular immunotherapy for cancer. Methods We previously developed a human anti-CD19 antibody (ET190L1) and generated novel CD19-specific γ/δ TCR-T cells, ET019003, by fusing the Fab fragment of ET190L1 with γ/δ TCR constant chain plus adding an ET190L1-scFv/CD28 co-stimulatory molecule. ET019003 cells were tested in preclinical studies followed by a phase 1 clinical trial. Results ET019003 cells produced less cytokines but retained comparable antitumor potency than ET190L1-CAR-T cells in vivo and in vitro. In the first-in-human trial, eight patients with relapsed or refractory DLBCL were treated. CRS of grade 1 was observed in three (37.5%) patients; ICANS of grade 3 was noted in one (12.5%) patient. Elevation of serum cytokines after ET019003 infusion was almost modest. With a median follow-up of 34 (range 6–38) months, seven (87.5%) patients attained clinical responses and six (75%) achieved complete responses (CR). OS, PFS and DOR at 3 years were 75.0%, 62.5%, and 71.4%, respectively. Notably, patient 1 with primary CNS lymphoma did not experience CRS or ICANS and got an ongoing CR for over 3 years after infusion, with detectable ET019003 cells in CSF. ET019003 showed striking in vivo expansion and persisted in 50% of patients at 12 months. Three patients received a second infusion, one for consolidation therapy after CR and two for salvage therapy after disease progression, but no response was observed. ET019003 expansion was striking in the first infusion, but poor in the second infusion. Conclusions CD19-specific γ/δ TCR-T cells, ET019003, had a good safety profile and could induce rapid responses and durable CR in patients with relapsed or refractory DLBCL, even primary CNS lymphoma, presenting a novel and potent therapeutic option for these patients. Trial registration : NCT04014894.
A new organic‐inorganic phase transition material (CH 3 NH 3 ) 4 [InCl 6 ]Cl ( 1 ), has been successfully synthesized and characterized. The compound undergoes a reversible first‐order phase transition at Curie temperature Tc=284 K, accompanied with a wide hysteresis of 12 K, which investigated by differential scanning calorimetry (DSC). The temperature dependence of the dielectric permittivity discloses an obvious step‐like dielectric anomaly. Single crystal X‐ray diffraction reveals that the order‐disorder transition of the [InCl 6 ] 3– anion and the methylammonium cation were the main factor drove the phase transition from high temperature phase with the space group P 2/ m to low temperature phase with the space group P 2/ n . This finding indicates that In‐based organic–inorganic hybrids compounds can be used to build phase transition materials, which broaden the way for exploring dielectric switching materials.
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