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Browsing by Author "Li, Fang"

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    The Community Land Model Version 5: Description of New Features, Benchmarking, and Impact of Forcing Uncertainty
    Lawrence, David M.; Fisher, Rosie A.; Koven, Charles D.; Oleson, Keith W.; Swenson, Sean C.; Bonan, Gordon B.; Collier, Nathan; Ghimire, Bardan; van Kampenhout, Leo; Kennedy, Daniel; Kluzek, Erik; Lawrence, Peter J.; Li, Fang; Li, Hongyi; Lombardozzi, Danica L.; Riley, William J.; Sacks, William J.; Shi, Mingjie; Vertenstein, Mariana; Wieder, William R.; Xu, Chonggang; Ali, Ashehad A.; Badger, Andrew M.; Bisht, Gautam; van den Broeke, Michiel; Brunke, Michael A.; Burns, Sean P.; Buzan, Jonathan; Clark, Martyn; Craig, Anthony; Dahlin, Kyla; Drewniak, Beth; Fisher, Joshua B.; Flanner, Mark; Fox, Andrew M.; Gentine, Pierre; Hoffman, Forrest; Keppel-Aleks, Gretchen; Knox, Ryan; Kumar, Sanjiv; Lenaerts, Jan; Leung, L. Ruby; Lipscomb, William H.; Lu, Yaqiong; Pandey, Ashutosh; Pelletier, Jon D.; Perket, Justin; Randerson, James T.; Ricciuto, Daniel M.; Sanderson, Benjamin M.; Slater, Andrew; Subin, Zachary M.; Tang, Jinyun; Thomas, R. Quinn; Martin, Maria Val; Zeng, Xubin (American Geophysical Union, 2019-10-19)
    The Community Land Model (CLM) is the land component of the Community Earth System Model (CESM) and is used in several global and regional modeling systems. In this paper, we introduce model developments included in CLM version 5 (CLM5), which is the default land component for CESM2. We assess an ensemble of simulations, including prescribed and prognostic vegetation state, multiple forcing data sets, and CLM4, CLM4.5, and CLM5, against a range of metrics including from the International Land Model Benchmarking (ILAMBv2) package. CLM5 includes new and updated processes and parameterizations: (1) dynamic land units, (2) updated parameterizations and structure for hydrology and snow (spatially explicit soil depth, dry surface layer, revised groundwater scheme, revised canopy interception and canopy snow processes, updated fresh snow density, simple firn model, and Model for Scale Adaptive River Transport), (3) plant hydraulics and hydraulic redistribution, (4) revised nitrogen cycling (flexible leaf stoichiometry, leaf N optimization for photosynthesis, and carbon costs for plant nitrogen uptake), (5) global crop model with six crop types and time-evolving irrigated areas and fertilization rates, (6) updated urban building energy, (7) carbon isotopes, and (8) updated stomatal physiology. New optional features include demographically structured dynamic vegetation model (Functionally Assembled Terrestrial Ecosystem Simulator), ozone damage to plants, and fire trace gas emissions coupling to the atmosphere. Conclusive establishment of improvement or degradation of individual variables or metrics is challenged by forcing uncertainty, parametric uncertainty, and model structural complexity, but the multivariate metrics presented here suggest a general broad improvement from CLM4 to CLM5.
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    Comprehensive off-target analysis of dCas9-SAM-mediated HIV reactivation via long noncoding RNA and mRNA profiling
    Zhang, Yonggang; Arango-Argoty, Gustavo; Li, Fang; Xiao, Xiao; Putatunda, Raj; Yu, Jun; Yang, Xiao-Feng; Wang, Hong; Watson, Layne T.; Zhang, Liqing; Hu, Wenhui (2018-09-10)
    Background CRISPR/CAS9 (epi)genome editing revolutionized the field of gene and cell therapy. Our previous study demonstrated that a rapid and robust reactivation of the HIV latent reservoir by a catalytically-deficient Cas9 (dCas9)-synergistic activation mediator (SAM) via HIV long terminal repeat (LTR)-specific MS2-mediated single guide RNAs (msgRNAs) directly induces cellular suicide without additional immunotherapy. However, potential off-target effect remains a concern for any clinical application of Cas9 genome editing and dCas9 epigenome editing. After dCas9 treatment, potential off-target responses have been analyzed through different strategies such as mRNA sequence analysis, and functional screening. In this study, a comprehensive analysis of the host transcriptome including mRNA, lncRNA, and alternative splicing was performed using human cell lines expressing dCas9-SAM and HIV-targeting msgRNAs. Results The control scrambled msgRNA (LTR_Zero), and two LTR-specific msgRNAs (LTR_L and LTR_O) groups show very similar expression profiles of the whole transcriptome. Among 839 identified lncRNAs, none exhibited significantly different expression in LTR_L vs. LTR_Zero group. In LTR_O group, only TERC and scaRNA2 lncRNAs were significantly decreased. Among 142,791 mRNAs, four genes were differentially expressed in LTR_L vs. LTR_Zero group. There were 21 genes significantly downregulated in LTR_O vs. either LTR_Zero or LTR_L group and one third of them are histone related. The distributions of different types of alternative splicing were very similar either within or between groups. There were no apparent changes in all the lncRNA and mRNA transcripts between the LTR_L and LTR_Zero groups. Conclusion This is an extremely comprehensive study demonstrating the rare off-target effects of the HIV-specific dCas9-SAM system in human cells. This finding is encouraging for the safe application of dCas9-SAM technology to induce target-specific reactivation of latent HIV for an effective “shock-and-kill” strategy.