Browsing by Author "Sun, Furong"

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    Some Advances in Local Approximate Gaussian Processes
    Sun, Furong (Virginia Tech, 2019-10-03)
    Nowadays, Gaussian Process (GP) has been recognized as an indispensable statistical tool in computer experiments. Due to its computational complexity and storage demand, its application in real-world problems, especially in "big data" settings, is quite limited. Among many strategies to tailor GP to such settings, Gramacy and Apley (2015) proposed local approximate GP (laGP), which constructs approximate predictive equations by constructing small local designs around the predictive location under certain criterion. In this dissertation, several methodological extensions based upon laGP are proposed. One methodological contribution is the multilevel global/local modeling, which deploys global hyper-parameter estimates to perform local prediction. The second contribution comes from extending the laGP notion of "locale" to a set of predictive locations, along paths in the input space. These two contributions have been applied in the satellite drag emulation, which is illustrated in Chapter 3. Furthermore, the multilevel GP modeling strategy has also been applied to synthesize field data and computer model outputs of solar irradiance across the continental United States, combined with inverse-variance weighting, which is detailed in Chapter 4. Last but not least, in Chapter 5, laGP's performance has been tested on emulating daytime land surface temperatures estimated via satellites, in the settings of irregular grid locations.
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    Structural basis for interactions of the Phytophthora sojae RxLR effector Avh5 with phosphatidylinositol 3-phosphate and for host cell entry
    Sun, Furong (Virginia Tech, 2012-04-09)
    Oomycetes, such as Phytophthora sojae, are plant pathogens that employ protein effectors that enter host cells to facilitate infection. Plants may overcome infection by recognizing pathogen effectors via intracellular receptors (R proteins) that form part of their defense system. Entry of some effector proteins into plant cells is mediated by conserved RxLR motifs in the effectors and phosphoinositides (PIPs) resident in the host plasma membrane such as phosphatidylinositol 3-phosphate (PtdIns(3)P). Recent reports differ regarding the regions on RxLR effector proteins involved in PIP recognition. To clarify these differences, I have structurally and functionally characterized the P. sojae effector, avirulence homolog-5 (Avh5). Using NMR spectroscopy, I demonstrate that Avh5 is helical in nature with a long N-terminal disordered region. Heteronuclear single quantum coherence titrations of Avh5 with the PtdIns(3)P head group, inositol 1,3-bisphosphate (Ins(1,3)P2), allowed us to identify a C-terminal lysine-rich helical region (helix 2) as the principal lipid-binding site in the protein, with the N-terminal RxLR (RFLR) motif playing a more minor role. Furthermore, mutations in the RFLR motif slightly affected PtdIns(3)P binding, while mutations in the basic helix almost abolished it. Avh5 exhibited moderate affinity for PtdIns(3)P, which increased the thermal stability of the protein. Mutations in the RFLR motif or in the basic region of Avh5 both significantly reduced protein entry into plant and human cells. Both regions independently mediated cell entry via a PtdIns(3)P-dependent mechanism. My findings support a model in which Avh5 transiently interacts with PtdIns(3)P by electrostatic interactions mainly through its positively charged helix 2 region, providing stability to the protein during RFLR-mediated host entry.