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Advanced hepatic fibrosis, driven by the activation of hepatic stellate cells (HSCs), affects millions worldwide and is the strongest predictor of mortality in nonalcoholic steatohepatitis (NASH); however, there are no approved antifibrotic therapies. To identify antifibrotic drug targets, we integrated progressive transcriptomic and morphological responses that accompany HSC activation in advanced disease using single-nucleus RNA sequencing and tissue clearing in a robust murine NASH model. In advanced fibrosis, we found that an autocrine HSC signaling circuit emerged that was composed of 68 receptor-ligand interactions conserved between murine and human NASH. These predicted interactions were supported by the parallel appearance of markedly increased direct stellate cell-cell contacts in murine NASH. As proof of principle, pharmacological inhibition of one such autocrine interaction, neurotrophic receptor tyrosine kinase 3–neurotrophin 3, inhibited human HSC activation in culture and reversed advanced murine NASH fibrosis. In summary, we uncovered a repertoire of antifibrotic drug targets underlying advanced fibrosis in vivo. The findings suggest a therapeutic paradigm in which stage-specific therapies could yield enhanced antifibrotic efficacy in patients with advanced hepatic fibrosis. This is all of the human data samples and analysis for the paperAn autocrine signaling circuit in hepatic stellate cells underlies advanced fibrosis in nonalcoholic steatohepatitis. GEO data here: GSE212837 The folderliver_data_cellranger_all.zipcontains the raw and filtered cellranger output for every sample. This allows reprocessing of all cells including the use of methods that use empty droplets to calculate ambient RNA. The folderAutocrine_liver_paper_jupyter_notebooks.zipcontains all of the notebooks used for analysis: Autocrine_signaling_liver_data_merge_all_select_celltype_subsets.ipynb is the initial noteboook for processing all datasets and merging. It also contains in the first cell instructions for creating a conda environment that will allow all of the tools to run. There are 5 notebooks for qc and cleaning of each celltype: Autocrine_signaling_liver_data_Stellate_cell_recluster.ipynb,Autocrine_signaling_liver_data_Hepatocyte_cell_recluster.ipynb, Autocrine_signaling_liver_data_Endo_cell_recluster.ipynb,Autocrine_signaling_liver_data_Cholangiocyte_cell_recluster.ipynb, and Autocrine_signaling_liver_data_NKTcell_cell_recluster.ipynb There is a final notebook for re-merging the cleaned celltype objects and final clustering, DE and analysis:Autocrine_signaling_liver_data_recluster_all_cleaned_celltypes_analysis.ipynb The fileraw_all_cellranger.h5ad.gzis all cells passing cellranger filter annotated with celltype and ambient RNA and doublet scoring, but otherwise no cells or genes have been removed. The foldercelltype_subsets_v1.zipcontains the roughly filtered celltypes for each of the celltypes. The foldercleaned_celltype_subsets_for_merge.zipcontains the final qc'd and filtered celltypes that are merged for final analysis. It also contains the final merged and batch normalized object. The python scriptcellphone_db_liver_all_cells_clean.pycontains a script for running cellphoneDB on final data.

The Cadmium Zinc Telluride Imager (CZTI) onboard AstroSat, an open detector above $\sim$100 keV, is a promising tool for the investigation of hard X-ray characteristics of $\gamma$-ray pulsars. A custom algorithm has been developed to detect pulsars from long integration ($\sim$years) of archival data, as reported by us earlier. Here we extend this method to include in the analysis an additional $\sim$20% of the CZTI pixels that were earlier ignored due to their lower gain values. Recent efforts have provided better and more secure calibration of these pixels, demonstrating their higher thresholds and extended energy range up to $\sim$1 MeV. Here we use the additional information provided by these pixels, enabling the construction of pulse profiles over a larger energy range. We compare the profiles of the Crab pulsar at different sub-bands and show that the behaviour is consistent with the extended energy coverage. As detailed spectroscopy over this full band remains difficult due to the limited count rate, we construct hardness ratios which, together with AstroSat Mass Model simulations, are able to constrain the power-law index of the radiation spectrum. We present our results for the phase-resolved spectrum of PSR J0534+2200 and for the total pulsed emission of PSR J1513-5908. The recovered photon indices are found to be accurate to within $\sim 20$%., Comment: Accepted for publication in the Journal of Astrophysics and Astronomy, 11 pages, 5 figures, 7 tables

We present a 140ks observation of NGC 4593 with XMM-Newton providing simultaneous and continuous PN X-ray and OM UV (UVW1 2910\AA) lightcurves which sample short-timescale variations better than previous observations. These observations were simultaneous with 22d of Swift X-ray and UV/optical monitoring, reported previously, and 4d of AstroSat X-ray (SXT), far (FUV 1541\AA), and near (NUV 2632\AA) UV allowing lag measurements between them and the highly-sampled XMM. From the XMM we find that UVW1 lags behind the X-rays by 29.5$\pm$1.3ks, $\sim$half the lag previously determined from the Swift monitoring. Re-examination of the \textit{Swift} data reveals a bimodal lag distribution, with evidence for both the long and short lags. However if we detrend the Swift lightcurves by LOWESS filtering with a 5d width, only the shorter lag (23.8$\pm$21.2ks) remains. The NUV observations, compared to PN and SXT, confirm the $\sim$30ks lag found by XMM and, after 4d filtering is applied to remove the long-timescale component, the FUV shows a lag of $\sim$23ks. The resultant new UVW1, FUV, and NUV lag spectrum extends to the X-ray band without requiring additional X-ray to UV lag offset, which if the UV arises from reprocessing of X-rays, implies direct illumination of the reprocessor. By referencing previous Swift and HST lag measurements, we obtain an X-ray to optical lag spectrum which agrees with a model using the KYNreverb disc-reprocessing code, assuming the accepted mass of $7.63\times10^{6}M_{\odot}$ and a spin approaching maximum. Previously noted lag contribution from the BLR in the Balmer and Paschen continua are still prominent., Comment: 13 pages, 23 figures

In order to deliver the full science potential of the Square Kilometer Array (SKA) telescope, several SKA Regional Centres (SRCs) will be required to be constructed in different SKA member countries around the world. These SRCs will provide high performance compute and storage for the generation of advanced science data products from the basic data streams generated by the SKA Science Data Handling and Processing system, critically necessary to the success of the key science projects to be carried out by the SKA user community. They will also provide support to astronomers to enable them to carry out analysis on very large SKA datasets. Construction of such large data centres is a technical challenge for all SKA member nations. In such a situation, each country plans to construct a smaller SRC over the next few years (2022 onwards), known as a proto-SRC. In India, we propose to construct a proto-SRC which will be used for the analysis of data from SKA pathfinders and precursors with strong Indian involvement such as uGMRT, Meerkat and MWA. We describe our thinking on some aspects of the the storage, compute and network of the proto-SRC and how it will be used for data analysis as well as for carrying out various simulations related to SKA key science projects led by Indian astronomers. We also present our thoughts on how the proto-SRC plans to evaluate emerging hardware and software technologies and to also begin software development in areas of relevance to SKA data processing and analysis such as algorithm implementation, pipeline development and data visualisation software., 7 pages, 2 figures, accepted for publication for the special issue on "Indian participation in the SKA" in the Journal of Astrophysics and Astronomy (JoAA)

We present a new Monte-Carlo radiative transfer code, which we have used to model the cyclotron line features in the environment of a variable magnetic field and plasma density. The code accepts an input continuum and performs only the line transfer by including the three cyclotron resonant processes (cyclotron absorption, cyclotron emission, cyclotron scattering). Subsequently, the effects of gravitational red-shift and light bending on the emergent spectra are computed. We have applied our code to predict the observable spectra from three different emission geometries; 1) an optically thin slab near the stellar surface, 2) an accretion mound formed by the accumulation of the accreted matter, 3) an accretion column representing the zone of a settling flow onto the star. Our results show that the locally emergent spectra from the emission volume are significantly anisotropic. However, in the presence of strong light bending the anisotropy reduces considerably. This averaging also drastically reduces the strength of harmonics higher than second in the observable cyclotron spectra. We find that uniform field slabs produce line features that are too narrow, and mounds with large magnetic distortions produce features that are too wide compared to the average widths of the spectral features observed from various sources. The column with a gently varying (dipole) field produces widths in the intermediate range, similar to those observed., 15 pages, 15 figures, Accepted for publication in MNRAS

Portal hypertension (PH) is associated with complications such as ascites and esophageal varices and is typically diagnosed through invasive hepatic venous pressure gradient (HVPG) measurement, which is not widely available. In this study, we aim to assess the diagnostic performance of 2D/3D MR elastography (MRE) and shear wave elastography (SWE) measures of liver and spleen stiffness (LS and SS) and spleen volume, to noninvasively diagnose clinically significant portal hypertension (CSPH) using HVPG measurement as the reference.In this prospective study, patients with liver disease underwent 2D/3D MRE and SWE of the liver and spleen, as well as HVPG measurement. The correlation between MRE/SWE measures of LS/SS and spleen volume with HVPG was assessed. ROC analysis was used to determine the utility of MRE, SWE, and spleen volume for diagnosing CSPH.Thirty-six patients (M/F 22/14, mean age 55 ± 14 years) were included. Of the evaluated parameters, 3D MRE SS had the strongest correlation with HVPG (r = 0.686, p0.001), followed by 2D MRE SS (r = 0.476, p = 0.004). 3D MRE SS displayed the best performance for diagnosis of CSPH (AUC = 0.911) followed by 2D MRE SS (AUC = 0.845) and 3D MRE LS (AUC = 0.804). SWE SS showed poor performance for diagnosis of CSPH (AUC = 0.583) while spleen volume was a fair predictor (AUC = 0.738). 3D MRE SS was significantly superior to SWE LS/SS (p ≤ 0.021) for the diagnosis of CSPH.SS measured with 3D MRE outperforms SWE for the diagnosis of CSPH. SS appears to be a useful biomarker for assessing PH severity. These results need further validation.• Spleen stiffness measured with 2D and 3D MR elastography correlates significantly with hepatic venous pressure gradient measurement. • Spleen stiffness measured with 3D MR elastography demonstrates excellent performance for the diagnosis of clinically significant portal hypertension (AUC 0.911). • Spleen stiffness measured with 3D MR elastography outperforms liver and spleen stiffness measured with shear wave elastography for diagnosis of clinically significant portal hypertension.

We present the results of timing and spectral analysis of the HMXB pulsar, Cen X-3, with the help of observations carried out using the Large Area X-ray Proportional Counter (LAXPC) on board $\textit{AstroSat}$. As part of our analysis, we sampled the source properties during 4 different observation epochs covering two widely different intensity states. We obtain a timing solution and report precise measurements of the spin and orbital parameters corresponding to these observational epochs. The pulse profiles during the two intensity states reveal dramatically varying shapes within a time span of one month. We report the detection of one of the lowest measured frequencies of quasi-periodic oscillations (QPO) at 0.026$\pm$0.001 Hz for Cen X-3 during its low-intensity state. We also find correlated periodic and aperiodic noise components in the power density spectra. We further carried out a phase averaged and a pulse phase resolved spectral study, where we find that the best fit continuum spectrum is well described by an absorbed comptonization model along with a blackbody. Cen X-3 exhibited the presence of the $\sim$28 keV CRSF absorption line and a $\sim$6.6 keV Fe emission line in both the intensity states. Significant variations in the line forming regions and mode of accretion for Cen X-3 within time spans of a month make Cen X-3 a highly dynamic persistent binary., Comment: 14 pages, 8 figures, 2 tables

The Cadmium Zinc Telluride Imager (CZTI) onboard AstroSat consists of an array of a large number of pixellated CZT detectors capable of measuring the polarization of incident hard X-rays. The polarization measurement capability of CZTI for on-axis sources was experimentally confirmed before the launch. CZTI has yielded tantalizing results on the X-ray polarization of the Crab nebula and pulsar in the energy range of 100 - 380 keV. CZTI has also contributed to the measurement of prompt emission polarization for several Gamma-Ray Bursts (GRBs). However, polarization measurements of off-axis sources like GRBs are challenging. It is vital to experimentally calibrate the CZTI sensitivity to off-axis sources to enhance the credence of the measurements. In this context, we report the verification of the off-axis polarimetric capability of pixellated CZT detectors through the controlled experiments carried out with a CZT detector similar to that used in CZTI and extensive Geant4 simulations of the experimental set-up. Our current results show that the CZT detectors can be used to measure the polarization of bright GRBs up to off-axis angles of ~60 degrees. However, at incidence angles between 45-60 degrees, there might be some systematic effects which needs to be taken into account while interpreting the measured polarisation fraction., Comment: Accepted for publication in JATIS

The CZTI (Cadmium Zinc Telluride Imager) onboard AstroSat is a high energy coded mask imager and spectrometer in the energy range of 20 - 100 keV. Above 100 keV, the dominance of Compton scattering cross-section in CZTI results in a significant number of 2-pixel Compton events and these have been successfully utilized for polarization analysis of Crab pulsar and nebula (and transients like Gamma-ray bursts) in 100 - 380 keV. These 2-pixel Compton events can also be used to extend the spectroscopic energy range of CZTI up to 380 keV for bright sources. However, unlike the spectroscopy in primary energy range, where simultaneous background measurement is available from masked pixels, Compton spectroscopy requires blank sky observation for background measurement. Background subtraction, in this case, is non-trivial because of the presence of both short-term and long-term temporal variations in the data, which depend on multiple factors like earth rotation and the effect of South Atlantic Anomaly (SAA) regions etc. We have developed a methodology of background selection and subtraction that takes into account for these effects. Here, we describe these background selection and subtraction techniques and validate them using spectroscopy of Crab in the extended energy range of 30 - 380 keV region, and compare the obtained spectral parameters with the INTEGRAL results. This new capability allows for the extension of the energy range of AstroSat spectroscopy and will also enable the simultaneous spectro-polarimetric study of other bright sources like Cygnus X-1., Comment: 11 pages, 15 figures, Accepted for publication in MNRAS Journal

The Cadmium Zinc Telluride Imager (CZTI) on board AstroSat has been regularly detecting gamma-ray bursts (GRBs) since its launch in 2015. Its sensitivity to polarization measurements at energies above 100 keV allows CZTI to attempt spectropolarimetric studies of GRBs. Here, we present the first catalog of GRB polarization measurements made by CZTI during its first five years of operation. This includes the time-integrated polarization measurements of the prompt emission of 20 GRBs in the energy range 100–600 keV. The sample includes the bright GRBs that were detected within an angle range of 0°–60° and 120°–180° where the instrument has useful polarization sensitivity and is less prone to systematics. We implement a few new modifications in the analysis to enhance the polarimetric sensitivity of the instrument. The majority of the GRBs in the sample are found to possess less/null polarization across the total bursts’ duration in contrast to a small fraction of five GRBs that exhibit high polarization. The low polarization across the bursts might be due either to the burst being intrinsically weakly polarized or to a varying polarization angle within the burst even when it is highly polarized. In comparison to POLAR measurements, CZTI has detected a larger number of cases with high polarization. This may be a consequence of the higher energy window of CZTI observations, which results in the sampling of a shorter duration of burst emissions than POLAR, thereby probing emissions with less temporal variation in polarization properties.