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Background: Immunogenicity derived from the murine scFv, a major molecular design of CAR, may limit the persistence of CAR-T cells, resulting in high relapase rate in cured relapsed/refractory acute lymphoblastic leukemia (r/r ALL) patients after successful treatment. In this study, we aimed to develop a humanized anti-CD19 scFv CAR-T (hCAR-T) and treated patients with r/r ALL. Methods: In this one-arm, open-labelled phaseⅠ/Ⅱ study, we infused the T cells modified with hCAR-T to patients with r/r ALL. Long term followup for response and safety to treatment were evaluated. Findings: Eleven patients with r/r ALL were recruited in this study. Nine patients were response-evaluable and all achieved CR at three months; Seven patients remain CR till now and five have been in CR for over 12 months without further treatment. Long persistence of hCAR-T cells was observed in the most of patients. Among these patients, three of them with high and rapidly progressive tumour burden (median 90%) experienced grade 3-4 of CRS. These severe CRS were successfully controlled by earlier use of tocilizumab, glucocorticoid and plasma exchange (PE). Interpretation: T cells expressing the humanized anti-CD19 scFv CAR exhibited the sustained therapeutic efficacy in treatment of r/r ALL. Low replase rate was assocated with long persistence of CAR-T cells. The severe CRS could be controlled by tocilizumab, glucocorticoid and plasma exchange (PE). Clinical Trial Number: The study was registered at Clinicaltrials.gov (NCT02349698).Funding Statement: This work was supported by National Key Research and Development Program (2016YFC1303405), National Natural Science Foundation of China 81520108025), Clinical Research Project of the Southwest Hospital (SWH2016ZDCX1005, SWH2016LCZD-02), Chongqing Precision Biotech Co., Ltd. Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This study was approved by the Ethics Committee of the Southwest Hospital of Third Military Medical University (Chongqing, China). It was performed according to the principles of the Declaration of Helsinki. All patients or their guardians provided written informed consent before they were recruited in this study.
Modular multilevel converter (MMC) is a promising circuit topology in the field of high-voltage direct current transmission (HVDC) systems. To enhance the reliability of the MMC in this field, the popular method is the addition of redundant submodules (SMs). However, the MMC will become unbalanced when some SMs fails and the performance will be deteriorated, especially when the number of the failed SMs is high. This paper analyzes the impact of the SM fault on the performance of the MMC. Theoretical analyses show that fundamental frequency component appears in the dc side current when some SMs fails. Furthermore, the approximate expression of the fundamental frequency component is derived. Based on the analyses, the number of the redundant SM design criterion is proposed. In addition, a rebalancing method is proposed to eliminate the harmonic component in the dc side and arm currents under SM faults scenario. Simulation results verified the theoretical analyses and the proposed rebalancing method.
From 1-D to 3-D zinc coordination polymers based on multifunctional flexible 4-(1,2,4-triazole-methylene)-benzonitrile (tzbt), {[Zn(tzbt)2(bdc)]·2H2O}n (1), [Zn(tzbc)2]n (2), and [Zn(bpdc)(H2O)]n (3) (bdc = 1,4-benzenedicarboxylic acid, tzbc = 4-(1,2,4-triazole-methylene)-benzoic acid, bpdc = 4,4′-biphenyldicarboxylic acid), were synthesized under hydrothermal conditions. The tzbt was synthesized by N-alkylation and hydrolyzed in situ to produce tzbc (in 2). Single-crystal X-ray diffraction analysis reveals that 1 displays 1-D wave-like chains based on [Zn(bdc)]n. 2 is a chiral twofold interpenetrating 2-D architecture constructed with “V”-shaped tzbc. 3 is a 3-D chiral compound constructed from achiral H2bpdc with right-handed helical chains. 1–3 display stable blue-emitting luminescence with emission maxima ranging from 383 to 410 nm, depending on ligand-centered π*→π transitions. The effects of different polarity solvents and temperature on luminescence are discussed. TGA and VT-XPRD reveal that 2 has thermal stability to 360 °C.
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