Search

Abstract Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and systemic fibrosis. Research on SSc has been hindered largely by lack of relevant models to study the progressive nature of the disease and to recapitulate the cell plasticity that is observed in this disease context. Generation of models for fibrotic disease using pluripotent stem cells is important for recapitulating the heterogeneity of the fibrotic tissue and are a potential platform for screening anti-fibrotic drugs. We previously reported a novel in-vitro model for fibrosis using induced pluripotent stem cell-derived mesenchymal cells (iSCAR). Here we report the generation of a “scar-like phenotype” when iPSC derived mesenchymal cells are cultured on hydrogel that mimicks a wound healing/scarring response (iSCAR). First, we performed RNA sequencing (RNA-seq) based transcriptome profiling of iSCAR culture at 48 h and 13 days to characterize early and latestage scarring phenotypes. The next generation RNA-seq of these iSCAR culture at different timepoints detected expression 92% of early “scar associated” genes and 85% late “scar associated” genes, respectively. Comparative transcriptomic analysis of a gene level SSc compendium matrix to the iSCAR wound associated model revealed genes common in both data sets. Early scar formation genes showed biological processes of hypoxia (27.5%), vascular development (13.7%) and glycolysis (27.5), while late scar formation showed genes associated with senescence (22.6%). Next we show the effects of two different antifibrotic compounds to validate the utility of the model as a screening tool to study early and late-stagelate-stage fibrosis. An autotaxin inhibitor was used to validate the iSCAR late stage fibrotic model (iSCAR-T) and an antifibrotic tool screening compound of unknown mechanism (EX00015097) was used to study and validate both early (iSCAR-P) and late-stage (iSCAR-T) fibrosis in the iSCAR model.

Abstract The evolution of charge structure involved in lightning discharge of a thunderstorm over the central Tibetan Plateau is investigated for the first time, based on the data from very high frequency interferometer, radar and sounding. During the developing‐mature stage, the TP thunderstorm exhibited a tripolar charge structure evolved from an initial inverted dipole. At the mature stage, a bottom‐heavy tripole charge structure is clearly presented, with a strong lower positive charge center (LPCC) at temperatures above −10°C, a middle negative charge region between −30°C and −15°C, and an upper positive charge region at T

The Lightning Mapping Imager (LMI) onboard the Fengyun-4A (FY-4A) satellite is the first independently developed satellite-borne lightning imager in China. It enables continuous lightning detection in China and surrounding areas, regardless of weather conditions. The FY-4A LMI uses a Charge-Coupled Device (CCD) array for lightning detection, and the accuracy of lightning positioning is influenced by cloud top height (CTH). In this study, we proposed an ellipsoid CTH parallax correction (ECPC) model for lightning positioning applicable to FY-4A LMI. The model utilizes CTH data from the Advanced Geosynchronous Radiation Imager (AGRI) on FY-4A to correct the lightning positioning data. According to the model, when the CTH is 12 km, the maximum deviation in lightning positioning caused by CTH in Beijing is approximately 0.1177° in the east–west direction and 0.0530° in the north–south direction, corresponding to a horizontal deviation of 13.1558 km, which exceeds the size of a single ground detection unit of the geostationary satellite lightning imager. Therefore, it is necessary to be corrected. A comparison with data from the Beijing Broadband Lightning Network (BLNET) and radar data shows that the corrected LMI data exhibit spatial distribution that is closer to the simultaneous BLNET lightning positioning data. The coordinate differences between the two datasets are significantly reduced, indicating higher consistency with radar data. The correction algorithm decreases the LMI lightning location deviation caused by CTH, thereby improving the accuracy and reliability of satellite lightning positioning data. The proposed ECPC model can be used for the real-time correction of lightning data when CTH is obtained at the same time, and it can be also used for the post-correction of space-based lightning detection with other cloud top height data.

Very-high-frequency (VHF) electromagnetic signals have been well used to image lightning channels with high temporal and spatial resolution due to their capability to penetrate clouds. A lightning broadband VHF interferometer with three VHF antennas configured in a scalene-triangle shape has been installed in Lhasa since 2019, to detect the lightning VHF signals. Using the signals from the VHF interferometer, a new hybrid algorithm, called the TDOA-EMTR technique, combining the time difference of arrival (TDOA) and the electromagnetic time reversal (EMTR) technique is introduced to image the two-dimensional lightning channels. The TDOA technique is firstly applied to calculate the initial solutions for the whole lightning flash. According to the results by the TDOA method, the domain used for the EMTR technique is predetermined, and then the EMTR technique is operated to obtain the final positioning result. Unlike the original EMTR technique, the low-power frequency points for each time window are removed based on the FFT spectrum. Metrics used to filter noise events are adjusted. Detailed imaging results of a negative cloud-to-ground (CG) lightning flash and an intra-cloud (IC) lightning flash by the TDOA method and the TDOA-EMTR are presented. Compared with the original EMTR method, the positioning efficiency can be improved by more than a factor of 3 to 4, depending on the scope of the pre-determined domain. Results show that the new algorithm can obtain much weaker radiation sources and simultaneously occurring sources, compared with the TDOA method.