Browsing by Author "Jiang, S"
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Item Open Access Heavy-Tailed Density Estimation(Journal of the American Statistical Association, 2022-01-01) Tokdar, ST; Jiang, S; Cunningham, ELA novel statistical method is proposed and investigated for estimating a heavy tailed density under mild smoothness assumptions. Statistical analyses of heavy-tailed distributions are susceptible to the problem of sparse information in the tail of the distribution getting washed away by unrelated features of a hefty bulk. The proposed Bayesian method avoids this problem by incorporating smoothness and tail regularization through a carefully specified semiparametric prior distribution, and is able to consistently estimate both the density function and its tail index at near minimax optimal rates of contraction. A joint, likelihood driven estimation of the bulk and the tail is shown to help improve uncertainty assessment in estimating the tail index parameter and offer more accurate and reliable estimates of the high tail quantiles compared to thresholding methods. Supplementary materials for this article are available online.Item Open Access Potent and broad neutralizing activity of a single chain antibody fragment against cell-free and cell-associated HIV-1.(MAbs, 2010-05) Zhang, MY; Borges, AR; Ptak, RG; Wang, Y; Dimitrov, AS; Alam, SM; Wieczorek, L; Bouma, P; Fouts, T; Jiang, S; Polonis, VR; Haynes, BF; Quinnan, GV; Montefiori, DC; Dimitrov, DSSeveral human monoclonal antibodies (hmAbs) exhibit relatively potent and broad neutralizing activity against HIV-1, but there has not been much success in using them as potential therapeutics. We have previously hypothesized and demonstrated that small engineered antibodies can target highly conserved epitopes that are not accessible by full-size antibodies. However, their potency has not been comparatively evaluated with known HIV-1-neutralizing hmAbs against large panels of primary isolates. We report here the inhibitory activity of an engineered single chain antibody fragment (scFv), m9, against several panels of primary HIV-1 isolates from group M (clades A-G) using cell-free and cell-associated virus in cell line-based assays. M9 was much more potent than scFv 17b, and more potent than or comparable to the best-characterized broadly neutralizing hmAbs IgG(1) b12, 2G12, 2F5 and 4E10. It also inhibited cell-to-cell transmission of HIV-1 with higher potency than enfuvirtide (T-20, Fuzeon). M9 competed with a sulfated CCR5 N-terminal peptide for binding to gp120-CD4 complex, suggesting an overlapping epitope with the coreceptor binding site. M9 did not react with phosphatidylserine (PS) and cardiolipin (CL), nor did it react with a panel of autoantigens in an antinuclear autoantibody (ANA) assay. We further found that escape mutants resistant to m9 did not emerge in an immune selection assay. These results suggest that m9 is a novel anti-HIV-1 candidate with potential therapeutic or prophylactic properties, and its epitope is a new target for drug or vaccine development.