Supervised Collective Classification for Crowdsourcing

Crowdsourcing utilizes the wisdom of crowds for collective classification via information (e.g., labels of an item) provided by labelers. Current crowdsourcing algorithms are mainly unsupervised methods that are unaware of the quality of crowdsourced data. In this paper, we propose a supervised collective classification algorithm that aims to identify reliable labelers from the training data (e.g., items with known labels). The reliability (i.e., weighting factor) of each labeler is determined via a saddle point algorithm. The results on several crowdsourced data show that supervised methods can achieve better classification accuracy than unsupervised methods, and our proposed method outperforms other algorithms.Comment: to appear in IEEE Global Communications Conference (GLOBECOM) Workshop on Networking and Collaboration Issues for the Internet of Everythin

Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate.

Type IIA topoisomerases (Top2s) manipulate the handedness of DNA crossovers by introducing a transient and protein-linked double-strand break in one DNA duplex, termed the DNA-gate, whose opening allows another DNA segment to be transported through to change the DNA topology. Despite the central importance of this gate-opening event to Top2 function, the DNA-gate in all reported structures of Top2-DNA complexes is in the closed state. Here we present the crystal structure of a human Top2 DNA-gate in an open conformation, which not only reveals structural characteristics of its DNA-conducting path, but also uncovers unexpected yet functionally significant conformational changes associated with gate-opening. This structure further implicates Top2's preference for a left-handed DNA braid and allows the construction of a model representing the initial entry of another DNA duplex into the DNA-gate. Steered molecular dynamics calculations suggests the Top2-catalyzed DNA passage may be achieved by a rocker-switch-type movement of the DNA-gate

Activation of JNK Signaling Mediates Connective Tissue Growth Factor Expression and Scar Formation in Corneal Wound Healing

Connective Tissue Growth Factor (CTGF) and Transforming growth factor-β1 (TGF-β1) are key growth factors in regulating corneal scarring. Although CTGF was induced by TGF-β1 and mediated many of fibroproliferative effects of TGF-β1, the signaling pathway for CTGF production in corneal scarring remains to be clarified. In the present study, we firstly investigated the effects of c-Jun N-terminal kinase (JNK) on CTGF expression induce by TGF-β1 in Telomerase-immortalized human cornea stroma fibroblasts (THSF). Then, we created penetrating corneal wound model and determined the effect of JNK in the pathogenesis of corneal scarring. TGF-β1 activated MAPK pathways in THSF cells. JNK inhibitor significantly inhibited CTGF, fibronectin and collagen I expression induced by TGF-β1 in THSF. In corneal wound healing, the JNK inhibitor significantly inhibited CTGF expression, markedly improved the architecture of corneal stroma and reduced corneal scar formation, but did not have a measurable impact on corneal wound healing in vivo. Our results indicate that JNK mediates the expression of CTGF and corneal scarring in corneal wound healing, and might be considered as specific targets of drug therapy for corneal scarring

Associated clinical characteristics of patients with candidemia among different Candida species

BackgroundThe rising incidence of non-albicans Candida (NAC) infection has been associated with a potentially adverse outcome for patients with candidemia. However, categorizing various species causing candidemia into a single NAC group might lead to inappropriate conclusions due to heterogeneity in species. Thus we examined the associated factors among patients with candidemia caused by different species.MethodsThis retrospective study was conducted at a tertiary medical center in Taiwan from 2006 to 2009. Mortality rate, demographic and clinical characteristics, albumin levels, and severity scores of acute illness of patients at the onset of candidemia were analyzed.ResultsA total of 447 episodes among 418 patients were included for analysis. The overall 30-day crude mortality was 48.2%, with no significant difference between C. albicans and NAC candidemia, but apparently C. parapsilosis candidemia was associated with a lower mortality rate. Time to positivity for yeast was significantly different between species. Compared with infection involving C. albicans, more frequent use of total parenteral nutrition, lower Sequential Organ Failure Assessment score and higher albumin levels were observed for C. parapsilosis candidemia.ConclusionIdentifying associated factors for each species may be a more effective approach than single NAC grouping. Time to positivity may be a hint for treatment guidance in candidemia. More frequent use of total parenteral nutrition and less virulent nature were noted for C. parapsilosis candidemia

Critical Role of Klf5 in Regulating Gene Expression during Post-Eyelid Opening Maturation of Mouse Corneas

Background: Klf5 plays an important role in maturation and maintenance of the mouse ocular surface. Here, we quantify WT and Klf5-conditional null (Klf5CN) corneal gene expression, identify Klf5-target genes and compare them with the previously identified Klf4-target genes to understand the molecular basis for non-redundant functions of Klf4 and Klf5 in the cornea. Methodology/Principal Findings: Postnatal day-11 (PN11) and PN56 WT and Klf5CN corneal transcriptomes were quantified by microarrays to compare gene expression in maturing WT corneas, identify Klf5-target genes, and compare corneal Klf4- and Klf5-target genes. Whole-mount corneal immunofluorescent staining was employed to examine CD45+ cell influx and neovascularization. Effect of Klf5 on expression of desmosomal components was studied by immunofluorescent staining and transient co-transfection assays. Expression of 714 and 753 genes was increased, and 299 and 210 genes decreased in PN11 and PN56 Klf5CN corneas, respectively, with 366 concordant increases and 72 concordant decreases. PN56 Klf5CN corneas shared 241 increases and 98 decreases with those previously described in Klf4CN corneas. Xenobiotic metabolism related pathways were enriched among genes decreased in Klf5CN corneas. Expression of angiogenesis and immune response-related genes was elevated, consistent with neovascularization and CD45+ cell influx in Klf5CN corneas. Expression of 1574 genes was increased and 1915 genes decreased in WT PN56 compared with PN11 corneas. Expression of ECM-associated genes decreased, while that of solute carrier family members increased in WT PN56 compared with PN11 corneas. Dsg1a, Dsg1b and Dsp were down-regulated in Klf5CN corneas and their corresponding promoter activities were stimulated by Klf5 in transient co-transfection assays. Conclusions/Significance: Differences between PN11 and PN56 corneal Klf5-target genes reveal dynamic changes in functions of Klf5 during corneal maturation. Klf5 contributes to corneal epithelial homeostasis by regulating the expression of desmosomal components. Klf4- and Klf5-target genes are largely distinct, consistent with their non-redundant roles in the mouse cornea. © 2012 Kenchegowda et al

Synergistic anti-atherosclerotic effect of Yerba Maté (Illex Paraguariensis) polyphenols and Lox-1 silencing in foam cell model

Purpose: To elucidate the anti-atherosclerotic effect of Yerba Mate polyphenols (MP) as well as the anti-atherosclerotic effect of a combination of MP and silencing of lectin-like oxidized low-density lipoprotein receptor-1 interference group (LOX)-1.Methods: The anti-atherosclerotic effects of control group (CG), simvastatin group (SG), MP group (MP), LOX-1 interference group (LOX) and MP + LOX-1 interference group (MP-LOX) were determined using Oil Red O staining, enzyme-linked immunosorbent assay (ELISA) and Western blot assay.Results: The levels of foam cells, intracellular lipids, viz, total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE) and acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1); LOX-1, inflammation (TNF-alpha, IL-6 and pNF-κB/NF-κB); adhesion molecular status (ICAM-1 and VCAM-1), and monocyte chemotactic protein-1 in SG and in MP, LOX and MP-LOX groups were significantly decreased, when compared with CG (p < 0.01). The levels of these parameters were much lower in MPLOX group than in SG (p < 0.01). However, they were synergistically reduced in MP-LOX group, relative to MP group or LOX group (p < 0.01). Combination of LOX-1 gene silencing with MP produced synergistic anti-atherosclerotic effect which was reflected in decreases in foam cell formation, intracellular lipids, inflammatory status, adhesion molecular status, and MCP-1-mediated migration and infiltration of macrophages in foam cells.Conclusion: The synergistic anti-atherosclerotic effects of MP and LOX-1 gene silencing may be potential tools for development of anti-atherosclerotic agents

Metformin suppresses retinal angiogenesis and inflammation in vitro and in vivo

The oral anti-diabetic drug metformin has been found to reduce cardiovascular complications independent of glycemic control in diabetic patients. However, its role in diabetic retinal microvascular complications is not clear. This study is to investigate the effects of metformin on retinal vascular endothelium and its possible mechanisms, regarding two major pathogenic features of diabetic retinopathy: angiogenesis and inflammation. In human retinal vascular endothelial cell culture, metformin inhibited various steps of angiogenesis including endothelial cell proliferation, migration, and tube formation in a dose-dependent manner. Its anti-angiogenic activity was confirmed in vivo that metformin significantly reduced spontaneous intraretinal neovascularization in a very-low-density lipoprotein receptor knockout mutant mouse (p

The catalytic core of DEMETER guides active DNA demethylation in Arabidopsis.

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the maternal genome in the central cell prior to fertilization and is essential for seed viability. DME preferentially targets small transposons that flank coding genes, influencing their expression and initiating plant gene imprinting. DME also targets intergenic and heterochromatic regions, but how it is recruited to these differing chromatin landscapes is unknown. The C-terminal half of DME consists of 3 conserved regions required for catalysis in vitro. We show that this catalytic core guides active demethylation at endogenous targets, rescuing dme developmental and genomic hypermethylation phenotypes. However, without the N terminus, heterochromatin demethylation is significantly impeded, and abundant CG-methylated genic sequences are ectopically demethylated. Comparative analysis revealed that the conserved DME N-terminal domains are present only in flowering plants, whereas the domain architecture of DME-like proteins in nonvascular plants mainly resembles the catalytic core, suggesting that it might represent the ancestral form of the 5mC DNA glycosylase found in plant lineages. We propose a bipartite model for DME protein action and suggest that the DME N terminus was acquired late during land plant evolution to improve specificity and facilitate demethylation at heterochromatin targets

Urban energy consumption and CO2 emissions in Beijing: current and future

This paper calculates the energy consumption and CO2 emissions of Beijing over 2005–2011 in light of the Beijing’s energy balance table and the carbon emission coefficients of IPCC. Furthermore, based on a series of energy conservation planning program issued in Beijing, the Long-range Energy Alternatives Planning System (LEAP)-BJ model is developed to study the energy consumption and CO2 emissions of Beijing’s six end-use sectors and the energy conversion sector over 2012–2030 under the BAU scenario and POL scenario. Some results are found in this research: (1) During 2005–2011, the energy consumption kept increasing, while the total CO2 emissions fluctuated obviously in 2008 and 2011. The energy structure and the industrial structure have been optimized to a certain extent. (2) If the policies are completely implemented, the POL scenario is projected to save 21.36 and 35.37 % of the total energy consumption and CO2 emissions than the BAU scenario during 2012 and 2030. (3) The POL scenario presents a more optimized energy structure compared with the BAU scenario, with the decrease of coal consumption and the increase of natural gas consumption. (4) The commerce and service sector and the energy conversion sector will become the largest contributor to energy consumption and CO2 emissions, respectively. The transport sector and the industrial sector are the two most potential sectors in energy savings and carbon reduction. In terms of subscenarios, the energy conservation in transport (TEC) is the most effective one. (5) The macroparameters, such as the GDP growth rate and the industrial structure, have great influence on the urban energy consumption and carbon emissions