Biliary epithelial cells (BECs) form bile ducts in the liver and are facultative liver stem cells that establish a ductular reaction (DR) to support liver regeneration following injury. Liver damage induces periportal LGR5+ putative liver stem cells that can form BEClike organoids, suggesting that RSPO-LGR4/5-mediated WNT/b-catenin activity is important for a DR. We addressed the roles of this and other signaling pathways in a DR by performing a focused CRISPRbased loss-of-function screen in BEC-like organoids, followed by in vivo validation and single-cell RNA sequencing. We found that BECs lack and do not require LGR4/5-mediated WNT/b-catenin signaling during a DR, whereas YAP and mTORC1 signaling are required for this process. Upregulation of AXIN2 and LGR5 is required in hepatocytes to enable their regenerative capacity in response to injury. Together, these data highlight heterogeneity within the BEC pool, delineate signaling pathways involved in a DR, and clarify the identity and roles of injury-induced periportal LGR5+ cells.

An inversion-based algorithm for computing the time-frequency analysis of reflection seismograms using constrained least-squares spectral analysis is formulated and applied to modeled seismic waveforms and real seismic data. The Fourier series coefficients are computed as a function of time directly by inverting a basis of truncated sinusoidal kernels for a moving time window. The method resulted in spectra that have reduced window smearing for a given window length relative to the discrete Fourier transform irrespective of window shape, and a time-frequency analysis with a combination of time and frequency resolution that is superior to the short time Fourier transform and the continuous wavelet transform. The reduction in spectral smoothing enables better determination of the spectral characteristics of interfering reflections within a short window. The degree of resolution improvement relative to the short time Fourier transform increases as window length decreases. As compared with the continuous wavelet transform, the method has greatly improved temporal resolution, particularly at low frequencies.

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In this abstract, we explore the viability of discriminating fizz water (low saturated gas sandstones) from commercial gas reservoirs based on the frequency shift (FS) caused by attenuation. Data from one well were used to build a simple geological model. Forward modeling of CDP gathers and normal incidence sections were carried out and their amplitude spectra were evaluated. For this study, we analyzed the FS in two different domains: 1. We tested the attenuation effect on the peak amplitude versus offset for the same seismic interface. 2. The peak frequency decay due to the presence of a high attenuating thin layer on normal incidence data.