Browsing by Author "Li, Y"
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Item Open Access A stochastic version of Stein Variational Gradient Descent for efficient samplingLi, L; Li, Y; Liu, JG; Liu, Z; Lu, JWe propose in this work RBM-SVGD, a stochastic version of Stein Variational Gradient Descent (SVGD) method for efficiently sampling from a given probability measure and thus useful for Bayesian inference. The method is to apply the Random Batch Method (RBM) for interacting particle systems proposed by Jin et al to the interacting particle systems in SVGD. While keeping the behaviors of SVGD, it reduces the computational cost, especially when the interacting kernel has long range. Numerical examples verify the efficiency of this new version of SVGD.Item Open Access Butterfly-Net: Optimal Function Representation Based on Convolutional Neural NetworksLi, Y; Cheng, X; Lu, JDeep networks, especially Convolutional Neural Networks (CNNs), have been successfully applied in various areas of machine learning as well as to challenging problems in other scientific and engineering fields. This paper introduces Butterfly-Net, a low-complexity CNN with structured hard-coded weights and sparse across-channel connections, which aims at an optimal hierarchical function representation of the input signal. Theoretical analysis of the approximation power of Butterfly-Net to the Fourier representation of input data shows that the error decays exponentially as the depth increases. Due to the ability of Butterfly-Net to approximate Fourier and local Fourier transforms, the result can be used for approximation upper bound for CNNs in a large class of problems. The analysis results are validated in numerical experiments on the approximation of a 1D Fourier kernel and of solving a 2D Poisson's equation.Item Open Access Chinese residential electricity consumption: Estimation and forecast using micro-data(Resource and Energy Economics, 2017-11) Cao, J; Ho, MS; Li, Y; Newell, RG; Pizer, WA© 2017 Elsevier B.V. Based on econometric estimation using data from the Chinese Urban Household Survey, we develop a preferred forecast range of 85-143 percent growth in residential per capita electricity demand over 2009-2025. Our analysis suggests that per capita income growth drives a 43% increase, with the remainder due to an unexplained time trend. Roughly one-third of the income-driven demand comes from increases in the stock of specific major appliances, particularly AC units. The other two-thirds comes from non-specific sources of income-driven growth and is based on an estimated income elasticity that falls from 0.28 to 0.11 as income rises. While the stock of refrigerators is not projected to increase, we find that they contribute nearly 20 percent of household electricity demand. Alternative plausible time trend assumptions are responsible for the wide range of 85-143 percent. Meanwhile we estimate a price elasticity of demand of -0.7. These estimates point to carbon pricing and appliance efficiency policies that could substantially reduce demand.Item Open Access Comprehensive gene expression profiling and immunohistochemical studies support application of immunophenotypic algorithm for molecular subtype classification in diffuse large B-cell lymphoma: a report from the International DLBCL Rituximab-CHOP Consortium Program Study.(Leukemia, 2012-09) Visco, C; Li, Y; Xu-Monette, ZY; Miranda, RN; Green, TM; Li, Y; Tzankov, A; Wen, W; Liu, W-M; Kahl, BS; d'Amore, ESG; Montes-Moreno, S; Dybkær, K; Chiu, A; Tam, W; Orazi, A; Zu, Y; Bhagat, G; Winter, JN; Wang, H-Y; O'Neill, S; Dunphy, CH; Hsi, ED; Zhao, XF; Go, RS; Choi, WWL; Zhou, F; Czader, M; Tong, J; Zhao, X; van Krieken, JH; Huang, Q; Ai, W; Etzell, J; Ponzoni, M; Ferreri, AJM; Piris, MA; Møller, MB; Bueso-Ramos, CE; Medeiros, LJ; Wu, L; Young, KHGene expression profiling (GEP) has stratified diffuse large B-cell lymphoma (DLBCL) into molecular subgroups that correspond to different stages of lymphocyte development-namely germinal center B-cell like and activated B-cell like. This classification has prognostic significance, but GEP is expensive and not readily applicable into daily practice, which has lead to immunohistochemical algorithms proposed as a surrogate for GEP analysis. We assembled tissue microarrays from 475 de novo DLBCL patients who were treated with rituximab-CHOP chemotherapy. All cases were successfully profiled by GEP on formalin-fixed, paraffin-embedded tissue samples. Sections were stained with antibodies reactive with CD10, GCET1, FOXP1, MUM1 and BCL6 and cases were classified following a rationale of sequential steps of differentiation of B cells. Cutoffs for each marker were obtained using receiver-operating characteristic curves, obviating the need for any arbitrary method. An algorithm based on the expression of CD10, FOXP1 and BCL6 was developed that had a simpler structure than other recently proposed algorithms and 92.6% concordance with GEP. In multivariate analysis, both the International Prognostic Index and our proposed algorithm were significant independent predictors of progression-free and overall survival. In conclusion, this algorithm effectively predicts prognosis of DLBCL patients matching GEP subgroups in the era of rituximab therapy.Item Open Access Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent.(PLoS One, 2012) Badea, CT; Athreya, KK; Espinosa, G; Clark, D; Ghafoori, AP; Li, Y; Kirsch, DG; Johnson, GA; Annapragada, A; Ghaghada, KBPURPOSE: To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer. METHODS: Primary lung cancers with mutations in K-ras alone (Kras(LA1)) or in combination with p53 (LSL-Kras(G12D);p53(FL/FL)) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules. RESULTS: A good correlation was seen between volume and diameter-based assessment of nodules (R(2)>0.8) for both lung cancer models. The LSL-Kras(G12D);p53(FL/FL) model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in Kras(LA1) mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-Kras(G12D);p53(FL/FL) mice compared to nodules in Kras(LA1) mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules. CONCLUSIONS: The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring.Item Open Access EphB2 receptor controls proliferation/migration dichotomy of glioblastoma by interacting with focal adhesion kinase.(Oncogene, 2012-12-13) Wang, SD; Rath, P; Lal, B; Richard, J-P; Li, Y; Goodwin, CR; Laterra, J; Xia, SGlioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumors in adults. Uncontrolled proliferation and abnormal cell migration are two prominent spatially and temporally disassociated characteristics of GBMs. In this study, we investigated the role of the receptor tyrosine kinase EphB2 in controlling the proliferation/migration dichotomy of GBM. We studied EphB2 gain of function and loss of function in glioblastoma-derived stem-like neurospheres, whose in vivo growth pattern closely replicates human GBM. EphB2 expression stimulated GBM neurosphere cell migration and invasion, and inhibited neurosphere cell proliferation in vitro. In parallel, EphB2 silencing increased tumor cell proliferation and decreased tumor cell migration. EphB2 was found to increase tumor cell invasion in vivo using an internally controlled dual-fluorescent xenograft model. Xenografts derived from EphB2-overexpressing GBM neurospheres also showed decreased cellular proliferation. The non-receptor tyrosine kinase focal adhesion kinase (FAK) was found to be co-associated with and highly activated by EphB2 expression, and FAK activation facilitated focal adhesion formation, cytoskeleton structure change and cell migration in EphB2-expressing GBM neurosphere cells. Taken together, our findings indicate that EphB2 has pro-invasive and anti-proliferative actions in GBM stem-like neurospheres mediated, in part, by interactions between EphB2 receptors and FAK. These novel findings suggest that tumor cell invasion can be therapeutically targeted by inhibiting EphB2 signaling, and that optimal antitumor responses to EphB2 targeting may require concurrent use of anti-proliferative agents.Item Open Access Experimental study of the A(e,e′π+) reaction on H1, H2, C12, Al27, Cu63, and Au197(Physical Review C - Nuclear Physics, 2010-05-25) Qian, X; Horn, T; Clasie, B; Arrington, J; Asaturyan, R; Benmokhtar, F; Boeglin, W; Bosted, P; Bruell, A; Christy, ME; Chudakov, E; Dalton, MM; Daniel, A; Day, D; Dutta, D; El Fassi, L; Ent, R; Fenker, HC; Ferrer, J; Fomin, N; Gao, H; Garrow, K; Gaskell, D; Gray, C; Huber, GM; Jones, MK; Kalantarians, N; Keppel, CE; Kramer, K; Li, Y; Liang, Y; Lung, AF; Malace, S; Markowitz, P; Matsumura, A; Meekins, DG; Mertens, T; Miyoshi, T; Mkrtchyan, H; Monson, R; Navasardyan, T; Niculescu, G; Niculescu, I; Okayasu, Y; Opper, AK; Perdrisat, C; Punjabi, V; Rauf, AW; Rodriquez, VM; Rohe, D; Seely, J; Segbefia, E; Smith, GR; Sumihama, M; Tadevosyan, V; Tang, L; Villano, A; Vulcan, WF; Wesselmann, FR; Wood, SA; Yuan, L; Zheng, XCross sections for the H1(e,e′π+)n process on H1, H2, C12, Al27, Cu63, and Au197 targets were measured at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) to extract nuclear transparencies. Data were taken from Q2=1.1-4.7 GeV2 for a fixed center-of-mass energy of W=2.14 GeV. The ratio of σL and σT was extracted from the measured cross sections for H1, H2, C12, and Cu63 targets at Q2=2.15 and 4.0 GeV2, allowing for additional studies of the reaction mechanism. In this article, we present the experimental setup and the analysis of the data in detail, including systematic uncertainty studies. Differential cross sections and nuclear transparencies as a function of the pion momentum at different values of Q2 are presented. Our results are consistent with the predicted early onset of color transparency in mesons. Global features of the data are discussed and the data are compared with model calculations for the H1(e,e′π+)n reaction from nuclear targets. © 2010 The American Physical Society.Item Open Access Game-Theoretic Question Selection for Tests(JOURNAL OF ARTIFICIAL INTELLIGENCE RESEARCH, 2017) Li, Y; Conitzer, VItem Open Access GxE interactions between FOXO genotypes and drinking tea are significantly associated with prevention of cognitive decline in advanced age in China.(J Gerontol A Biol Sci Med Sci, 2015-04) Zeng, Y; Chen, H; Ni, T; Ruan, R; Feng, L; Nie, C; Cheng, L; Li, Y; Tao, W; Gu, J; Land, KC; Yashin, A; Tan, Q; Yang, Z; Bolund, L; Yang, H; Hauser, E; Willcox, DC; Willcox, BJ; Tian, X; Vaupel, JWLogistic regression analysis based on data from 822 Han Chinese oldest old aged 92+ demonstrated that interactions between carrying FOXO1A-266 or FOXO3-310 or FOXO3-292 and tea drinking at around age 60 or at present time were significantly associated with lower risk of cognitive disability at advanced ages. Associations between tea drinking and reduced cognitive disability were much stronger among carriers of the genotypes of FOXO1A-266 or FOXO3-310 or FOXO3-292 compared with noncarriers, and it was reconfirmed by analysis of three-way interactions across FOXO genotypes, tea drinking at around age 60, and at present time. Based on prior findings from animal and human cell models, we postulate that intake of tea compounds may activate FOXO gene expression, which in turn may positively affect cognitive function in the oldest old population. Our empirical findings imply that the health benefits of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles.Item Open Access Impact of simian immunodeficiency virus infection on chimpanzee population dynamics.(PLoS Pathog, 2010-09-23) Rudicell, RS; Jones, JH; Wroblewski, EE; Learn, GH; Li, Y; Robertson, JD; Greengrass, E; Grossmann, F; Kamenya, S; Pintea, L; Mjungu, DC; Lonsdorf, EV; Mosser, A; Lehman, C; Collins, DA; Keele, BF; Goodall, J; Hahn, BH; Pusey, AE; Wilson, MLLike human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus of chimpanzees (SIVcpz) can cause CD4+ T cell loss and premature death. Here, we used molecular surveillance tools and mathematical modeling to estimate the impact of SIVcpz infection on chimpanzee population dynamics. Habituated (Mitumba and Kasekela) and non-habituated (Kalande) chimpanzees were studied in Gombe National Park, Tanzania. Ape population sizes were determined from demographic records (Mitumba and Kasekela) or individual sightings and genotyping (Kalande), while SIVcpz prevalence rates were monitored using non-invasive methods. Between 2002-2009, the Mitumba and Kasekela communities experienced mean annual growth rates of 1.9% and 2.4%, respectively, while Kalande chimpanzees suffered a significant decline, with a mean growth rate of -6.5% to -7.4%, depending on population estimates. A rapid decline in Kalande was first noted in the 1990s and originally attributed to poaching and reduced food sources. However, between 2002-2009, we found a mean SIVcpz prevalence in Kalande of 46.1%, which was almost four times higher than the prevalence in Mitumba (12.7%) and Kasekela (12.1%). To explore whether SIVcpz contributed to the Kalande decline, we used empirically determined SIVcpz transmission probabilities as well as chimpanzee mortality, mating and migration data to model the effect of viral pathogenicity on chimpanzee population growth. Deterministic calculations indicated that a prevalence of greater than 3.4% would result in negative growth and eventual population extinction, even using conservative mortality estimates. However, stochastic models revealed that in representative populations, SIVcpz, and not its host species, frequently went extinct. High SIVcpz transmission probability and excess mortality reduced population persistence, while intercommunity migration often rescued infected communities, even when immigrating females had a chance of being SIVcpz infected. Together, these results suggest that the decline of the Kalande community was caused, at least in part, by high levels of SIVcpz infection. However, population extinction is not an inevitable consequence of SIVcpz infection, but depends on additional variables, such as migration, that promote survival. These findings are consistent with the uneven distribution of SIVcpz throughout central Africa and explain how chimpanzees in Gombe and elsewhere can be at equipoise with this pathogen.Item Open Access Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4.(J Clin Invest, 2010-06) Jiang, D; Liang, J; Campanella, GS; Guo, R; Yu, S; Xie, T; Liu, N; Jung, Y; Homer, R; Meltzer, EB; Li, Y; Tager, AM; Goetinck, PF; Luster, AD; Noble, PWPulmonary fibrosis is a progressive, dysregulated response to injury culminating in compromised lung function due to excess extracellular matrix production. The heparan sulfate proteoglycan syndecan-4 is important in mediating fibroblast-matrix interactions, but its role in pulmonary fibrosis has not been explored. To investigate this issue, we used intratracheal instillation of bleomycin as a model of acute lung injury and fibrosis. We found that bleomycin treatment increased syndecan-4 expression. Moreover, we observed a marked decrease in neutrophil recruitment and an increase in both myofibroblast recruitment and interstitial fibrosis in bleomycin-treated syndecan-4-null (Sdc4-/-) mice. Subsequently, we identified a direct interaction between CXCL10, an antifibrotic chemokine, and syndecan-4 that inhibited primary lung fibroblast migration during fibrosis; mutation of the heparin-binding domain, but not the CXCR3 domain, of CXCL10 diminished this effect. Similarly, migration of fibroblasts from patients with pulmonary fibrosis was inhibited in the presence of CXCL10 protein defective in CXCR3 binding. Furthermore, administration of recombinant CXCL10 protein inhibited fibrosis in WT mice, but not in Sdc4-/- mice. Collectively, these data suggest that the direct interaction of syndecan-4 and CXCL10 in the lung interstitial compartment serves to inhibit fibroblast recruitment and subsequent fibrosis. Thus, administration of CXCL10 protein defective in CXCR3 binding may represent a novel therapy for pulmonary fibrosis.Item Open Access Interaction Between the FOXO1A-209 Genotype and Tea Drinking Is Significantly Associated with Reduced Mortality at Advanced Ages.(Rejuvenation Res, 2016-06) Zeng, Y; Chen, H; Ni, T; Ruan, R; Nie, C; Liu, X; Feng, L; Zhang, F; Lu, J; Li, J; Li, Y; Tao, W; Gregory, SG; Gottschalk, W; Lutz, MW; Land, KC; Yashin, A; Tan, Q; Yang, Z; Bolund, L; Ming, Q; Yang, H; Min, J; Willcox, DC; Willcox, BJ; Gu, J; Hauser, E; Tian, X; Vaupel, JWOn the basis of the genotypic/phenotypic data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) and Cox proportional hazard model, the present study demonstrates that interactions between carrying FOXO1A-209 genotypes and tea drinking are significantly associated with lower risk of mortality at advanced ages. Such a significant association is replicated in two independent Han Chinese CLHLS cohorts (p = 0.028-0.048 in the discovery and replication cohorts, and p = 0.003-0.016 in the combined dataset). We found the associations between tea drinking and reduced mortality are much stronger among carriers of the FOXO1A-209 genotype compared to non-carriers, and drinking tea is associated with a reversal of the negative effects of carrying FOXO1A-209 minor alleles, that is, from a substantially increased mortality risk to substantially reduced mortality risk at advanced ages. The impacts are considerably stronger among those who carry two copies of the FOXO1A minor allele than those who carry one copy. On the basis of previously reported experiments on human cell models concerning FOXO1A-by-tea-compounds interactions, we speculate that results in the present study indicate that tea drinking may inhibit FOXO1A-209 gene expression and its biological functions, which reduces the negative impacts of FOXO1A-209 gene on longevity (as reported in the literature) and offers protection against mortality risk at oldest-old ages. Our empirical findings imply that the health outcomes of particular nutritional interventions, including tea drinking, may, in part, depend upon individual genetic profiles, and the research on the effects of nutrigenomics interactions could potentially be useful for rejuvenation therapies in the clinic or associated healthy aging intervention programs.Item Open Access Interpolative Butterfly FactorizationLi, Y; Yang, HItem Open Access Loss of PRDM1/BLIMP-1 function contributes to poor prognosis of activated B-cell-like diffuse large B-cell lymphoma.(Leukemia, 2017-03) Xia, Y; Xu-Monette, ZY; Tzankov, A; Li, X; Manyam, GC; Murty, V; Bhagat, G; Zhang, S; Pasqualucci, L; Visco, C; Dybkaer, K; Chiu, A; Orazi, A; Zu, Y; Richards, KL; Hsi, ED; Choi, WWL; van Krieken, JH; Huh, J; Ponzoni, M; Ferreri, AJM; Møller, MB; Parsons, BM; Winter, JN; Piris, MA; Westin, J; Fowler, N; Miranda, RN; Ok, CY; Li, Y; Li, J; Medeiros, LJ; Young, KHPRDM1/BLIMP-1, a master regulator of plasma-cell differentiation, is frequently inactivated in activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) patients. Little is known about its genetic aberrations and relevant clinical implications. A large series of patients with de novo DLBCL was effectively evaluated for PRDM1/BLIMP-1 deletion, mutation, and protein expression. BLIMP-1 expression was frequently associated with the ABC phenotype and plasmablastic morphologic subtype of DLBCL, yet 63% of the ABC-DLBCL patients were negative for BLIMP-1 protein expression. In these patients, loss of BLIMP-1 was associated with Myc overexpression and decreased expression of p53 pathway molecules. In addition, homozygous PRDM1 deletions and PRDM1 mutations within exons 1 and 2, which encode for domains crucial for transcriptional repression, were found to show a poor prognostic impact in patients with ABC-DLBCL but not in those with germinal center B-cell-like DLBCL (GCB-DLBCL). Gene expression profiling revealed that loss of PRDM1/BLIMP-1 expression correlated with a decreased plasma-cell differentiation signature and upregulation of genes involved in B-cell receptor signaling and tumor-cell proliferation. In conclusion, these results provide novel clinical and biological insight into the tumor-suppressive role of PRDM1/BLIMP-1 in ABC-DLBCL patients and suggest that loss of PRDM1/BLIMP-1 function contributes to the overall poor prognosis of ABC-DLBCL patients.Item Open Access Mixtures of g-priors in Generalized Linear Models(2015) Li, Y; Clyde, MAMixtures of Zellner's g-priors have been studied extensively in linear models and have been shown to have numerous desirable properties for Bayesian variable selection and model averaging. Several extensions of g-priors to Generalized Linear Models (GLMs) have been proposed in the literature; however, the choice of prior distribution of g and resulting properties for inference have received considerably less attention. In this paper, we extend mixtures of g-priors to GLMs by assigning the truncated Compound Confluent Hypergeometric (tCCH) distribution to 1/(1+g) and illustrate how this prior distribution encompasses several special cases of mixtures of g-priors in the literature, such as the Hyper-g, truncated Gamma, Beta-prime, and the Robust prior. Under an integrated Laplace approximation to the likelihood, the posterior distribution of 1/(1+g) is in turn a tCCH distribution, and approximate marginal likelihoods are thus available analytically. We discuss the local geometric properties of the g-prior in GLMs and show that specific choices of the hyper-parameters satisfy the various desiderata for model selection proposed by Bayarri et al, such as asymptotic model selection consistency, information consistency, intrinsic consistency, and measurement invariance. We also illustrate inference using these priors and contrast them to others in the literature via simulation and real examples.Item Open Access Multidimensional Butterfly Factorization(Applied and Computational Harmonic Analysis) Li, Y; Yang, H; Ying, LItem Open Access Item Open Access The scale of population structure in Arabidopsis thaliana.(PLoS Genet, 2010-02-12) Platt, A; Horton, M; Huang, Y; Li, Y; Anastasio, A; Mulyati, W; Agren, J; Bossdorf, O; Byers, D; Donohue, K; Dunning, M; Holub, E; Hudson, A; Le Corre, V; Loudet, O; Rivero, L; Scholl, R; Nordborg, M; Bergelson, J; Borevitz, JOThe population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales.