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Open Access Publications from the University of California

Scholarly Works (20 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2006)

Although much work has been done on duplicate document detection (DDD) and its applications, we observe the absence of a systematic study of the performance and scalability of large-scale DDD. It is still unclear how various parameters of DDD, such as similarity threshold, precision/recall requirement, sampling ratio, document size, correlate mutually. In this paper, correlations among several most important parameters of DDD are studied and the impact of sampling ratio is of most interest since it heavily affects the accuracy and scalability of DDD algorithms. An empirical analysis is conducted on a million documents from the TREC .GOV collection. Experimental results show that even using the same sampling ratio, the precision of DDD varies greatly on documents with different size. Based on this observation, an adaptive sampling strategy for DDD is proposed, which minimizes the sampling ratio within the constraint of a given precision threshold. We believe the insights from our analysis are helpful for guiding the future large scale DDD work.

    Cover page: A systematic study of parameter correlations in large scale duplicate document detection
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2008)

    Although much work has been done on duplicate document detection (DDD) and its applications, we observe the absence of a systematic study on the performance and scalability of large-scale DDD algorithms. It is still unclear how various parameters in DDD correlate mutually, such as similarity threshold, precision/recall requirement, sampling ratio, and document size. This paper explores the correlations among several most important parameters in DDD and the impact of sampling ratio is of most interest since it heavily affects the accuracy and scalability of DDD algorithms. An empirical analysis is conducted on a million HTML documents from the TREC .GOV collection. Experimental results show that even when using the same sampling ratio, the precision of DDD varies greatly on documents with different sizes. Based on this observation, we propose an adaptive sampling strategy for DDD, which minimizes the sampling ratio with the constraint of a given precision requirement. We believe that the insights from our analysis are helpful for guiding the future large-scale DDD work.

      Cover page: A systematic study on parameter correlations in large-scale duplicate document detection
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (1999)
      The assembly of signaling molecules surrounding the integrin family of adhesion receptors remains poorly understood. Recently, the membrane protein caveolin was found in complexes with beta1 integrins. Caveolin binds cholesterol and several signaling molecules potentially linked to integrin function, e.g., Src family kinases, although caveolin has not been directly implicated in integrin-dependent adhesion. Here we report that depletion of caveolin by antisense methodology in kidney 293 cells disrupts the association of Src kinases with beta1 integrins resulting in loss of focal adhesion sites, ligand-induced focal adhesion kinase (FAK) phosphorylation, and adhesion. The nonintegrin urokinase receptor (uPAR) associates with and stabilizes beta1 integrin/caveolin complexes. Depletion of caveolin in uPAR-expressing 293 cells also disrupts uPAR/integrin complexes and uPAR-dependent adhesion. Further, beta1 integrin/caveolin complexes could be disassociated by uPAR-binding peptides in both uPAR-transfected 293 cells and human vascular smooth muscle cells. Disruption of complexes by peptides in intact smooth muscle cells blocks the association of Src family kinases with beta1 integrins and markedly impairs their migration on fibronectin. We conclude that ligand-induced signaling necessary for normal beta1 integrin function requires caveolin and is regulated by uPAR. Caveolin and uPAR may operate within adhesion sites to organize kinase-rich lipid domains in proximity to integrins, promoting efficient signal transduction.
        Cover page: A Role for Caveolin and the Urokinase Receptor in Integrin-mediated Adhesion and Signaling
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2018)
        In this paper, we develop procedures to construct simultaneous confidence bands for p ˜ potentially infinite-dimensional parameters after model selection for general moment condition models where p ˜ is potentially much larger than the sample size of available data, n. This allows us to cover settings with functional response data where each of the p ˜ parameters is a function. The procedure is based on the construction of score functions that satisfy Neyman orthogonality condition approximately. The proposed simultaneous confidence bands rely on uniform central limit theorems for high-dimensional vectors (and not on Donsker arguments as we allow for p ˜ ≫ n ). To construct the bands, we employ a multiplier bootstrap procedure which is computationally efficient as it only involves resampling the estimated score functions (and does not require resolving the high-dimensional optimization problems). We formally apply the general theory to inference on regression coefficient process in the distribution regression model with a logistic link, where two implementations are analyzed in detail. Simulations and an application to real data are provided to help illustrate the applicability of the results.
          Cover page: Uniformly valid post-regularization confidence regions for many functional parameters in z-estimation framework
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2013)
          The cytoskeleton of Trypanosoma brucei, a unicellular eukaryote and a parasitic protozoan, is defined by the subpellicular microtubule corset that is arranged underneath the plasma membrane. We recently identified two orphan kinesins, TbKIN-C and TbKIN-D, that cooperate to regulate the organization of the subpellicular microtubule corset and thereby maintain cell morphology in the procyclic form of T. brucei. In this report, we characterize the function of TbKIN-C and TbKIN-D in the bloodstream form of T. brucei and investigate their functional cooperation in both the bloodstream and procyclic forms. TbKIN-C and TbKIN-D form a tight complex in vivo in the bloodstream form. TbKIN-C is strongly enriched at the posterior tip of the cell, whereas TbKIN-D is distributed throughout the cell body at all cell cycle stages. RNAi of TbKIN-C or TbKIN-D in the bloodstream form inhibits cell proliferation and leads to cell death, due to cytokinesis defects. RNAi of TbKIN-C and TbKIN-D also results in defects in basal body segregation, but does not affect the synthesis and segregation of the flagellum and the flagellum attachment zone (FAZ) filament. Knockdown of TbKIN-C and TbKIN-D does not disrupt the organization of the subpellicular microtubule corset, but produces multinucleated cells with an enlarged flagellar pocket and misplaced flagella. Interestingly, depletion of TbKIN-C results in rapid degradation of TbKIN-D and, similarly, knockdown of TbKIN-C destabilizes TbKIN-D, suggesting that formation of TbKIN-C/TbKIN-D complex stabilizes both kinesins and is required for the two kinesins to execute their essential cellular functions. Altogether, our results demonstrate the essential role of the two kinesins in cell morphogenesis and cytokinesis in the bloodstream form and the requirement of heteromeric complex formation for maintaining the stability of the two kinesins.
            Cover page: The Cooperative Roles of Two Kinetoplastid-Specific Kinesins in Cytokinesis and in Maintaining Cell Morphology in Bloodstream TrypanosomesCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2003)
            The integrin alpha3beta1 mediates cellular adhesion to the matrix ligand laminin-5. A second integrin ligand, the urokinase receptor (uPAR), associates with alpha3beta1 via a surface loop within the alpha3 beta-propeller (residues 242-246) but outside the laminin binding region, suggesting that uPAR-integrin interactions could signal differently from matrix engagement. To explore this, alpha3-/- epithelial cells were reconstituted with wild-type (wt) alpha3 or alpha3 with Ala mutations within the uPAR-interacting loop (H245A or R244A). Wt or mutant-bearing cells showed comparable expression and adhesion to laminin-5. Cells expressing wt alpha3 and uPAR dissociated in culture, with increased Src activity, up-regulation of SLUG, and down-regulation of E-cadherin and gamma-catenin. Src kinase inhibition or expression of Src 1-251 restored the epithelial phenotype. The H245A and R244A mutants were unaffected by coexpression of uPAR. We conclude that alpha3beta1 regulates both cell-cell contact and matrix adhesion, but through distinct protein interaction sites within its beta-propeller. These studies reveal an integrin- and Src-dependent pathway for SLUG expression and mesenchymal transition.
              Cover page: Distinct ligand binding sites in integrin α3β1 regulate matrix adhesion and cell–cell contact
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2014)
              A high-throughput small-molecule screen was conducted to identify inhibitors of epithelial-mesenchymal transition (EMT) that could be used as tool compounds to test the importance of EMT signaling in vivo during fibrogenesis. Transforming growth factor (TGF)-β1-induced fibronectin expression and E-cadherin repression in A549 cells were used as 48-hour endpoints in a cell-based imaging screen. Compounds that directly blocked Smad2/3 phosphorylation were excluded. From 2,100 bioactive compounds, methacycline was identified as an inhibitor of A549 EMT with the half maximal inhibitory concentration (IC50) of roughly 5 μM. In vitro, methacycline inhibited TGF-β1-induced α-smooth muscle actin, Snail1, and collagen I of primary alveolar epithelial cells . Methacycline inhibited TGF-β1-induced non-Smad pathways, including c-Jun N-terminal kinase, p38, and Akt activation, but not Smad or β-catenin transcriptional activity. Methacycline had no effect on baseline c-Jun N-terminal kinase, p38, or Akt activities or lung fibroblast responses to TGF-β1. In vivo, 100 mg/kg intraperitoneal methacycline delivered daily beginning 10 days after intratracheal bleomycin improved survival at Day 17 (P < 0.01). Bleomycin-induced canonical EMT markers, Snail1, Twist1, collagen I, as well as fibronectin protein and mRNA, were attenuated by methacycline (Day 17). Methacycline did not attenuate inflammatory cell accumulation or alter TGF-β1-responsive genes in alveolar macrophages. These studies identify a novel inhibitor of EMT as a potent suppressor of fibrogenesis, further supporting the concept that EMT signaling is important to lung fibrosis. The findings also provide support for testing the impact of methacycline or doxycycline, an active analog, on progression of human pulmonary fibrosis.
                Cover page: Inhibition of Epithelial-to-Mesenchymal Transition and Pulmonary Fibrosis by Methacycline
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2009)
                Injury-initiated epithelial to mesenchymal transition (EMT) depends on contextual signals from the extracellular matrix, suggesting a role for integrin signaling. Primary epithelial cells deficient in their prominent laminin receptor, alpha3beta1, were found to have a markedly blunted EMT response to TGF-beta1. A mechanism for this defect was explored in alpha3-null cells reconstituted with wild-type (wt) alpha3 or point mutants unable to engage laminin 5 (G163A) or epithelial cadherin (E-cadherin; H245A). After TGF-beta1 stimulation, wt epithelial cells but not cells expressing the H245A mutant internalize complexes of E-cadherin and TGF-beta1 receptors, generate phospho-Smad2 (p-Smad2)-pY654-beta-catenin complexes, and up-regulate mesenchymal target genes. Although Smad2 phosphorylation is normal, p-Smad2-pY654-beta-catenin complexes do not form in the absence of alpha3 or when alpha3beta1 is mainly engaged on laminin 5 or E-cadherin in adherens junctions, leading to attenuated EMT. These findings demonstrate that alpha3beta1 coordinates cross talk between beta-catenin and Smad signaling pathways as a function of extracellular contact cues and thereby regulates responses to TGF-beta1 activation.
                  Cover page: Integrin α3β1–dependent β-catenin phosphorylation links epithelial Smad signaling to cell contacts
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2008)
                  Neutropenia associated with race/ethnicity has essentially been unexplained and, although thought to be benign, may affect therapy for cancer or other illnesses. A recent study linked a single nucleotide polymorphism (SNP) (rs2814778) in the Duffy antigen/receptor chemokine gene (DARC) with white blood cell count. We therefore analysed the association of the rs2814778 CC, TC and TT genotypes with absolute neutrophil count (ANC) among asymptomatic women from the Caribbean, Europe and the United States. Among 261 study participants, 33/47 women from Barbados/Trinidad-Tobago, 34/49 from Haiti, 26/37 from Jamaica, and 29/38 US-born black women, but only 4/50 from the Dominican Republic and 0/40 US- or European-born whites (P = 0.0001) had the CC genotype. In a linear regression model that included percentage African ancestry, national origin, cytokines, socio-economic factors and the ELA2 rs57834246 SNP, only the DARC rs2814778 genotype and C-reactive protein were associated with ANC (P < 0.0001). Women with the CC genotype had lower ANC than other women. Further research is needed on the associations of rs2814778 genotype with neutropenia and treatment delay in the setting of cancer. A better understanding of these associations may help to improve cancer outcomes among individuals of African ancestry.
                    Cover page: Duffy (Fy), DARC, and neutropenia among women from the United States, Europe and the Caribbean
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2011)
                    Pseudogenes have been shown to acquire unique regulatory roles from more and more organisms. We report the observation of a cluster of siRNAs derived from pseudogenes of African Trypanosoma brucei using high through-put analysis. We show that these pseudogene-derived siRNAs suppress gene expression through RNA interference. The discovery that siRNAs may originate from pseudogenes and regulate gene expression in a unicellular eukaryote provides insights into the functional roles of pseudogenes and into the origin of noncoding small RNAs.
                    • 1 supplemental PDF
                    Cover page: Pseudogene-derived small interference RNAs regulate gene expression in African Trypanosoma bruceiCreative Commons 'BY' version 4.0 license
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