Transcriptome dynamics of CD4(+) T cells during malaria maps gradual transit from effector to memory
NATURE IMMUNOLOGY
Authors: Soon, Megan S. F.; Lee, Hyun Jae; Engel, Jessica A.; Straube, Jasmin; Thomas, Bryce S.; Pernold, Clara P. S.; Clarke, Lachlan S.; Laohamonthonkul, Pawat; Haldar, Rohit N.; Williams, Cameron G.; Lansink, Lianne I. M.; Moreira, Marcela L.; Bramhall, Michael; Koufariotis, Lambros T.; Wood, Scott; Chen, Xi; James, Kylie R.; Lonnberg, Tapio; Lane, Steven W.; Belz, Gabrielle T.; Engwerda, Christian R.; Khoury, David S.; Davenport, Miles P.; Svensson, Valentine; Teichmann, Sarah A.; Haque, Ashraful
Abstract
The dynamics of CD4(+) T cell memory development remain to be examined at genome scale. In malaria-endemic regions, anti-malarial chemoprevention protects long after its cessation and associates with effects on CD4(+) T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T(H)1) and follicular helper T (T-FH) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T(H)1 and T-FH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T-FH and central memory were revealed, with antimalarials modulating these responses and boosting T(H)1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4(+) T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations (http://haquelab.mdhs.unimelb.edu.au/cd4_memory/).
A fast hybrid PLL with an adaptive all-pass filter under abnormal grid conditions
ELECTRIC POWER SYSTEMS RESEARCH
Authors: Sevilmis, Fehmi; Karaca, Hulusi
Abstract
Recently, various phase locked loop (PLL) methods have been improved for a reliable and robust synchronization under non-ideal grid conditions. One of the PLLs is a hybrid PLL (HPLL) which is an improved structure of the quasi-type-1 PLL (QT1-PLL) method. In this paper, an enhanced HPLL that offers both fast transient response and increased disturbance rejection capability for dominant harmonics is proposed. The proposed PLL includes adaptive all-pass-filters (APFs) in pre-filtering stage to eliminate fundamental frequency negative sequence (FFNS) component. Thus, window-width of the moving average filter (MAF) is reduced by three times compared with the HPLL by means of removing the FFNS component. So, the proposed PLL, which is called fast-hybrid PLL (FH-PLL), considerably ensures a fast transient response. Also, in case of grid faults (for example, type-B, type-C, type-D, and etc.), at the same time frequency change occurs, the FH-PLL completely blocks the FFNS component by means of using adaptive DAPF. In this study, it is experimentally implemented HPLL, QT1-PLL, and the proposed FH-PLL methods. The effectiveness of the FH-PLL is verified owing to experimental results and comparison with the QT1-PLL and HPLL.