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A novel recombinant SIRPα-Fc fusion protein, IMM01, was constructed and produced using an in-house developed CHO-K1 cell expression system, and the anti-tumor mechanism of IMM01 targeting the CD47-SIRPα pathway was explored. The phagocytosis and in vitro anti-tumor activity of IMM01 were evaluated by antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC) assays. In vivo mouse tumor model studies were used to explore therapeutic efficacy as well as the mechanism of action. An in vitro binding assay revealed that IMM01 has a strong binding affinity to CD47 with an EC50 of 0.4967 nM. IMM01 can induce strong ADCP and moderate ADCC, but not CDC. IMM01-induced strong phagocytosis against tumor cells was attributed to dual activities of blocking the "don't eat me" signal and activating the "eat me" signal, and IMM01 exhibits strong and robust in vivo anti-tumor activities either as monotherapy on hematological malignancies, or in combination therapy with PD-L1 monoclonal antibody (mAb), PD-1 mAb, and HER-2 mAb on solid tumors. Finally, IMM01 demonstrated a favorable safety profile with no human RBC binding activity or hemagglutination induction. IMM01 inhibits the growth of tumor cells by the following three possible mechanisms: (1) directly activating macrophages to phagocytize tumor cells; (2) activated macrophages degrade phagocytized tumor cells and present tumor antigens to T cells through MHC molecules to activate T cells; (3) activated macrophages can convert "cold tumors" into "hot tumors" and increase the infiltration of immune cells through chemotaxis by secreting some cytokines and chemokines. [ABSTRACT FROM AUTHOR]

Background: Targeting the CD47/SIRPα signaling pathway represents a novel approach to enhance anti-tumor immunity. However, the crystal structure of the CD47/SIRPα has not been fully studied. This study aims to analyze the structure interface of the complex of CD47 and IMM01, a novel recombinant SIRPα-Fc fusion protein. Methods: IMM01-Fab/CD47 complex was crystalized, and diffraction images were collected. The complex structure was determined by molecular replacement using the program PHASER with the CD47-SIRPαv2 structure (PDB code 2JJT) as a search model. The model was manually built using the COOT program and refined using TLS parameters in REFMAC from the CCP4 program suite. Results: Crystallization and structure determination analysis of the interface of IMM01/CD47 structure demonstrated CD47 surface buried by IMM01. Comparison with the literature structure (PDB ID 2JJT) showed that the interactions of IMM01/CD47 structure are the same. All the hydrogen bonds that appear in the literature structure are also present in the IMM01/CD47 structure. These common hydrogen bonds are stable under different crystal packing styles, suggesting that these hydrogen bonds are important for protein binding. In the structure of human CD47 in complex with human SIRPα, except SER66, the amino acids that form hydrogen bonds are all conserved. Furthermore, comparing with the structure of PDB ID 2JJT, the salt bridge interaction from IMM01/CD47 structure are very similar, except the salt bridge bond between LYS53 in IMM01 and GLU106 in CD47, which only occurs between the B and D chains. However, as the side chain conformation of LYS53 in chain A is slightly different, the salt bridge bond is absent between the A and C chains. At this site between chain A and chain C, there are a salt bridge bond between LYS53 (A) and GLU104 (C) and a salt bridge bond between HIS56 (A) and GLU106 (C) instead. According to the sequence alignment results of SIRPα, SIRPβ and SIRPγ in the literature of PDB ID 2JJT, except ASP100, the amino acids that form common salt bridge bonds are all conserved. Conclusion: Our data demonstrated crystal structure of the IMM01/CD47 complex and provides a structural basis for the structural binding interface and future clinical applications. [ABSTRACT FROM AUTHOR]

A minimal three-dimensional hurricane model formulated on an $$f$$ -plane is used to investigate the asymmetries that develop when a model storm is subjected to ambient vertical wind shear. The asymmetries that form in the moist version of the model have a different structure to those that form in a dry version. In the moist case, there are two competing factors that influence the inner-core asymmetries: vertical wind shear and frictional convergence in the boundary layer. We show that the relative importance of these factors is different in the different stages of vortex evolution and different also in the core region compared with the outer region of the vortex. In the developing stage, the patterns of vertical velocity and temperature deviation above the boundary layer are primarily determined by the shear. When saturation occurs in the core region, the vortex rapidly intensifies and the upper and lower portions of the vortex become strongly coupled so that there is little tilt of the core region. In the mature stage, ascent associated with frictional convergence in the core tends to dominate the vertical motion field induced by the shear, but there are individual times when the patterns of ascent at the top of the boundary layer and at the upper level differ significantly. These times coincide mostly with fluctuations in the vortex track, which, in turn, must be influenced by asymmetries in the horizontal flow in the vortex. Even though the inner core of the vortex becomes upright with the onset of deep moist convection, the outer regions continue to have a significant tilt. Outside the core region, the asymmetries in the pattern of vertical motion above the boundary layer are associated primarily with the tilt of the outer vortex. [ABSTRACT FROM AUTHOR]

The main challenge to solve the transient stability constrained optimal power flow (TSC‐OPF) problem is its huge dimension due to numerous discretised transient variables and constraints. This problem becomes more serious when large power systems are considered. This study presents a fast approach to realise a global TSC‐OPF based on dynamic reduction method, which decomposes the power system into several coherent areas and represents the original system by a reduced equivalent system. In this approach, the single transient stability constraint is obtained by simulating the reduced system instead of the full system. The new approach reduces the simulation execution time and thus increases the efficiency of the TSC‐OPF. Two case studies indicate that the proposed approach can remarkably reduce the CPU time of the TSC‐OPF procedure, compared with the TSC‐OPF based on the full‐system simulation. The new approach is very practical in solving the TSC‐OPF problem in large power systems where numerous machines are coherent. [ABSTRACT FROM AUTHOR]

Transient stability constrained optimal power flow (TSC‐OPF) is originally a non‐linear optimisation problem with variables and constraints in time domain, which is not easy to deal with directly because of its huge dimension. This study presents an efficient approach to realise TSC‐OPF by introducing an independent dynamics simulation algorithm into the optimisation procedure. In the new approach, the simulation algorithm is used to realise the dynamics constraints and to deduce the transient stability constraint, whereas the optimisation algorithm verifies the steady state and the transient stability constraints together. The new TSC‐OPF has just one more constraint than that of a conventional OPF and can be solved by a conventional OPF algorithm with small modification. Moreover, the new approach makes it easy to improve the accuracy and efficiency of TSC‐OPF, because of its flexibility in choosing machine models and simulation methods, which is important for large power systems. In the study, the proposed approach is tested with two small power systems, where the two‐axis machine model and a mixed time step simulation method are used to assess system transient stability with a 1‐ms time resolution. [ABSTRACT FROM AUTHOR]

The rheological behavior of poly(m-phenyleneisophthalamide) (PMIA) in 1-n-butyl-3-methylimidazolium chloride ([Bmim]Cl, ionic liquid) has been investigated. The polymer in the concentration range investigated exhibits very different behavior between [Bmim]Cl and DMAc/LiCl solvent. Unlike in DMAc/LiCl solvent, PMIA/[Bmim]Cl solution exhibits maxima in apparent viscosity-concentration plots in the range studied. The complex viscosity-frequency behavior of the PMIA/[Bmim]Cl solutions is similar to that steady-state rheological behavior. The different rheological behavior shows the interaction between macromolecule and IL which leading the supermolecular aggregates in PMIA/[Bmim]Cl solution. [ABSTRACT FROM AUTHOR]

By using meteorology and pollution observation data from Zhejiang province, and data from the National Centers for Environmental Prediction's Global Data Assimilation System from 1 June 2013, to 31 May 2016, we analyzed air quality characteristics in Ningbo and applied the HYSPLIT model to do backward trajectory clustering statistics for pollution cases of moderate, heavy and severe (henceforth referred to as moderate-and-above) levels. The results indicated that the percentage of moderate-and-above pollution was approximately 6%, which mostly occurred from November to February, with the primary pollutant being particulate matter with a diameter of ≤2.5 μm; Moderate-and-above pollution was mainly caused by pollutants from three types of trajectories (type mx, type 1, and type 2), with type 2 differing significantly from types 1 and mx. Type 2 occurred in stable boundary layers, whereas types mx and 1 occurred in unstable and conditionally unstable layers respectively. These three trajectory types were all related to cold air, but type 2 was weaker than the other two. Analysis of typical cases of various pollution types revealed that a heavy pollution outbreak was due to continuous superposition of pollutants. The input particles most likely originated from the northwest. The upstream situation was the focus of investigation to assist in local pollution forecasting. [ABSTRACT FROM AUTHOR]

A correction to the article "The comparative effects of frictional convergence and vertical wind shear on the interior asymmetries of a tropical cyclone" that was published in a 2014 issue is presented.