Mathematical models of non-sinusoidal power supply of a three-phase transverse field MHD inductor

The article presents an approach to the development of mathematical models of non-sinusoidal and dual-frequency power supply for a linear induction MHD machine for metallurgical purposes. The issues of construction and numerical modeling of the modes of a three-phase inductor for a liquid aluminum stirrer are considered. Reduction of losses is ensured by the use of a toothless design of the MHD inductor. The absence of steel teeth reduces saturation of the magnetic circuit and current distortion. It is proposed to use the parametric model of the inductor under the furnace in the ANSYS environment to clarify the modes of the complex. To take into account mutual induction, using controlled sources, a circuit model was built, and a numerical calculation of the modes was carried out. The characteristics of instantaneous currents and voltages are obtained when powered from a three-phase source with close frequencies, with pronounced beats. It is shown that the presence of mutual inductance redistributes currents in the delta windings, which must be taken into account when developing the design of linear induction machines. It is proposed to use sources with non-sinusoidal periodic currents in the modeling system. The analysis is carried out and the main types of modulated voltage characteristics in the power supply system of the induction MHD stirrer are shown.

Dual but not single PD-1 or TIM-3 blockade enhances oncolytic virotherapy in refractory lung cancer

BackgroundProgrammed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy fails in the majority of patients with cancer. Oncolytic viruses represent a new class of therapeutic agents, yet the therapeutic efficacy is still disappointing. Moreover, intratumoral injection of viruses is the main approach and preclinical studies mainly employ syngeneic or xenograft models.MethodsUse an endogenous mouse lung cancer model that faithfully recapitulates human lung cancer, and various in vivo, ex vivo and in vitro assays, to investigate the efficacy, mechanism of action and resistance of systemically administered oncolytic vaccinia virus (oVV), immunotherapy and their combination, to find an effective therapy for refractory lung cancer.ResultsResembling human lung cancers, the majority of which are largely resistant to PD-1/PD-L1 blockade and with decreased PD-L1 expression and T-cell activation by our analysis, urethane-induced endogenous lung tumors in mice show reduced PD-L1 expression, low tumor-infiltrating lymphocytes and innate resistance to PD-1/PD-L1 blockade. Intravenous administration of oVV has efficacy and synergizes with simultaneous but not single blockade of PD-1 and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) in this cancer model. Besides direct tumor cell killing, oVV induces T-cell lung recruitment, tumor infiltration, along with expression of PD-1 and TIM-3 on T cells and PD-1 and TIM-3 ligands on tumor cells and tumor-associated immune cells. Blockade of PD-1 or TIM-3 also causes their mutual induction on T cells.ConclusionsWhile systemic administration of oVV shows efficacy in lung cancer by killing tumor cells directly and recruiting and activating T cells for indirect tumor killing, its induction of PD-1 and TIM-3 on T cells and PD-1 and TIM-3 ligands on tumors and tumor-associated immune cells as well as mutual induction of PD-1 or TIM-3 on T cells by their blockade restricts the efficacy of oVV or its combination with single PD-1 or TIM-3 blockade. The triple combination therapy is more effective for refractory lung cancer, and possibly other cold cancers as well.