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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 transient model of a squirrel-cage induction machine, including air-gap flux saturation harmonics, is presented in this paper. The machine model is based on a flux model, where the winding magnetizing fluxes are directly calculated from the resultant air-gap magnetomotive force, avoiding the use of complicated inductance harmonics. The effects of the fundamental and third harmonic components of the air-gap flux are incorporated in the model by two saturation factors. Moreover, the saturation effects arc incorporated in the machine's torque equation, allowing the model to investigate the machine's performance under an, load condition. The machine parameters, including saturation data, are obtained via the conventional no-load and locked-rotor tests, with access to the stator neutral connection. The proposed model is validated h x experimental results for a squirrel-cage machine and can be used to predict machine transient states. Index Terms--Harmonic, induction machine, iron saturation, modeling.

The coagulation dynamics of acrylic polymer (PAN) with 1-butyl-3-methylimidazolium chloride [BMIM]Cl as solvent for PAN and [H.sub.2]O as nonsolvent was investigated in detail. On the basis of Fick's second law of diffusion, a mass-transfer model of [BMIM]Cl from concentrated PAN/[BMIM]Cl solution was established as verified with the experimental data. The established model has a good fit with the experimental data and the diffusion coefficient D of [BMIM]Cl was calculated according to the model. The diffusion coefficient D decreased a little when the concentration of solution increased. As increasing the coagulation bath concentration, the diffusion coefficient D initially increased and then decreased, reaching a maximum of 5 wt% in the coagulation bath. The diffusion coefficient D decreased with the coagulation bath temperature. From the diffusion coefficient and the structure of the coagulated filament, it can be concluded that the diffusion rate of [BMIM]Cl from PAN concentrate solutions is relatively slow, which is prospective to prepare uniform-structure fibers. POLYM. ENG. SCI., 48:184-190, 2008. © 2007 Society of Plastics Engineers, INTRODUCTION Acrylic fiber is a very versatile fiber, which has emerged not only as a major substitute for wool but also as the important precursor for carbon fiber. So far, [...]

In large synchronous generators, the stator windings are usually parallel-connected in order to increase the machine current capacity. In analysis and modeling, the parallel windings are usually lumped into one equivalent stator winding since equal currents flow in these windings. However, when an internal fault occurs in the windings, the symmetry between the parallel windings is broken and different currents will flow in the parallel windings since unsymmetrical magnetic linkage may exist between the stator windings. The aim of this paper is to present a simulation model to investigate the internal fault currents of large synchronous generators with parallel-connected windings. This model is based on a modified winding function theory that takes into account all space harmonics. Moreover, the calculation of the machine inductances is made easier by the use of the machine electrical parameters instead of the geometrical ones. The simulation results illustrate the existence of different currents in parallel windings in the case of internal faults. Results are given for an implementation of the internal fault model in a real-time simulator of large power networks. Index Terms--Internal faults, parallel-connected windings, real-time simulation, space harmonics, synchronous generators, winding function theory.

A synchronous machine internal faults model based on the actual winding arrangement is described in this paper. Based on the winding function approach, the machine inductances are calculated directly from the machine winding distribution, thereby the space harmonics produced by the machine windings are readily taken into account. Moreover, the calculation of the machine inductances is made easier by the use of the machine electrical parameters instead of the geometrical ones. Simulation results for internal faults on a laboratory generator are compared with experimental results to verify the accuracy of the proposed model. Index Terms--Internal faults, space harmonics, synchronous machines, winding function.

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]

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs)., Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems., Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38 + tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38 + /CD47 + tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice., Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo . As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile., Competing Interests: WT and SL hold ownership interest including patents in ImmuneOnco Biopharmaceuticals Shanghai Inc. Authors SoL, DC, YY, HG, DL, NS, XB, KW, TL, GL, CY, WZ, LZ, GZ, LP, SiL, XT, RZ, and WT were employed by the company ImmuneOnco Biopharmaceuticals Shanghai Inc. The authors declare that this study was funded in its entirety by Immuneonco Biopharmaceuticals (Shanghai) Inc. The funder had the following involvement in the study: study design, collection, analysis, interpretation of data, the writing of this article, and the decision to submit it for publication., (Copyright © 2024 Li, Chen, Yang, Guo, Liu, Sun, Bai, Wang, Li, Li, Yang, Zhang, Zhang, Zhao, Peng, Liu, Tu, Zhang and Tian.)

Background: A significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC., Methods: IMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys., Results: In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile., Conclusion: IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling., Competing Interests: All authors were employed by the company ImmuneOnco Biopharmaceuticals Shanghai Inc. WT, SL, DC, and HG are inventors of the patent application on IMM40H., (Copyright © 2023 Li, Chen, Guo, Liu, Yang, Zhang, Wang, Zhang, Bai, Yang, Sun, Zhang, Zhang, Zhao, Peng, Tu and Tian.)