Precipitation is the core data input to hydrological forecasting. The uncertainty in precipitation forecast data can lead to poor performance of predictive hydrological models. Radar-based precipitation measurement offers advantages over ground-based measurement in the quantitative estimation of temporal and spatial aspects of precipitation, but errors inherent in this method will still act to reduce the performance. Using data from White Lotus River of Hubei Province, China, five methods were used to assimilate radar rainfall data transformed from the classifiedZ-Rrelationship, and the postassimilation data were compared with precipitation measured by rain gauges. The five sets of assimilated rainfall data were then used as input to the Xinanjiang model. The effect of precipitation data input error on runoff simulation was analyzed quantitatively by disturbing the input data using the Breeding of Growing Modes method. The results of practical application demonstrated that the statistical weight integration and variational assimilation methods were superior. The corresponding performance in flood hydrograph prediction was also better using the statistical weight integration and variational methods compared to the others. It was found that the errors of radar rainfall data disturbed by the Breeding of Growing Modes had a tendency to accumulate through the hydrological model.
Aberrant self-renewal of leukemia initiation cells (LICs) drives aggressive acute myeloid leukemia (AML). Here, we report that UHRF1, an epigenetic regulator that recruits DNMT1 to methylate DNA, is highly expressed in AML and predicts poor prognosis. UHRF1 is required for myeloid leukemogenesis by maintaining self-renewal of LICs. Mechanistically, UHRF1 directly interacts with Sin3A-associated protein 30 (SAP30) through two critical amino acids, G572 and F573 in its SRA domain, to repress gene expression. Depletion of UHRF1 or SAP30 derepresses an important target gene, MXD4, which encodes a MYC antagonist, and leads to suppression of leukemogenesis. Further knockdown of MXD4 can rescue the leukemogenesis by activating the MYC pathway. Lastly, we identified a UHRF1 inhibitor, UF146, and demonstrated its significant therapeutic efficacy in the myeloid leukemia PDX model. Taken together, our study reveals the mechanisms for altered epigenetic programs in AML and provides a promising targeted therapeutic strategy against AML.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.