1,285 research outputs found
FGC: an efficient constraint-based frequent set miner
Despite advances in algorithmic design, association rule mining remains problematic from a performance viewpoint when the size of the underlying transaction database is large. The well-known a priori approach, while reducing the computational effort involved still suffers from the problem of scalability due to its reliance on generating candidate itemsets. In this paper we present a novel approach that combines the power of preprocessing with the application of user-defined constraints to prune the itemset space prior to building a compact FP-tree. Experimentation shows that that our algorithm significantly outperforms the current state of the art algorithm, FP-bonsai
Protein Expression, Characterization and Activity Comparisons of Wild Type and Mutant DUSP5 Proteins
Background
The mitogen-activated protein kinases (MAPKs) pathway is critical for cellular signaling, and proteins such as phosphatases that regulate this pathway are important for normal tissue development. Based on our previous work on dual specificity phosphatase-5 (DUSP5), and its role in embryonic vascular development and disease, we hypothesized that mutations in DUSP5 will affect its function. Results
In this study, we tested this hypothesis by generating full-length glutathione-S-transferase-tagged DUSP5 and serine 147 proline mutant (S147P) proteins from bacteria. Light scattering analysis, circular dichroism, enzymatic assays and molecular modeling approaches have been performed to extensively characterize the protein form and function. We demonstrate that both proteins are active and, interestingly, the S147P protein is hypoactive as compared to the DUSP5 WT protein in two distinct biochemical substrate assays. Furthermore, due to the novel positioning of the S147P mutation, we utilize computational modeling to reconstruct full-length DUSP5 and S147P to predict a possible mechanism for the reduced activity of S147P. Conclusion
Taken together, this is the first evidence of the generation and characterization of an active, full-length, mutant DUSP5 protein which will facilitate future structure-function and drug development-based studies
Appropriately differentiated ARPE-19 cells regain phenotype and gene expression profiles similar to those of native RPE cells.
PurposeThe RPE cell line ARPE-19 provides a dependable and widely used alternative to native RPE. However, replication of the native RPE phenotype becomes more difficult because these cells lose their specialized phenotype after multiple passages. Compounding this problem is the widespread use of ARPE-19 cells in an undifferentiated state to attempt to model RPE functions. We wished to determine whether suitable culture conditions and differentiation could restore the RPE-appropriate expression of genes and proteins to ARPE-19, along with a functional and morphological phenotype resembling native RPE. We compared the transcriptome of ARPE-19 cells kept in long-term culture with those of primary and other human RPE cells to assess the former's inherent plasticity relative to the latter.MethodsARPE-19 cells at passages 9 to 12 grown in DMEM containing high glucose and pyruvate with 1% fetal bovine serum were differentiated for up to 4 months. Immunocytochemistry was performed on ARPE-19 cells grown on filters. Total RNA extracted from ARPE-19 cells cultured for either 4 days or 4 months was used for RNA sequencing (RNA-Seq) analysis using a 2 × 50 bp paired end protocol. The RNA-Seq data were analyzed to identify the affected pathways and recognize shared ontological classification among differentially expressed genes. RPE-specific mRNAs and miRNAs were assessed with quantitative real-time (RT)-PCR, and proteins with western blotting.ResultsARPE-19 cells grown for 4 months developed the classic native RPE phenotype with heavy pigmentation. RPE-expressed genes, including RPE65, RDH5, and RDH10, as well as miR-204/211, were greatly increased in the ARPE-19 cells maintained at confluence for 4 months. The RNA-Seq analysis provided a comprehensive view of the relative abundance and differential expression of the genes in the differentiated ARPE-19 cells. Of the 16,757 genes with detectable signals, nearly 1,681 genes were upregulated, and 1,629 genes were downregulated with a fold change of 2.5 or more differences between 4 months and 4 days of culture. Gene Ontology analysis showed that the upregulated genes were associated with visual cycle, phagocytosis, pigment synthesis, cell differentiation, and RPE-related transcription factors. The majority of the downregulated genes play a role in cell cycle and proliferation.ConclusionsThe ARPE-19 cells cultured for 4 months developed a phenotype characteristic of native RPE and expressed proteins, mRNAs, and miRNAs characteristic of the RPE. Comparison of the ARPE-19 RNA-Seq data set with that of primary human fetal RPE, embryonic stem cell-derived RPE, and native RPE revealed an important overall similar expression ratio among all the models and native tissue. However, none of the cultured models reached the absolute values in the native tissue. The results of this study demonstrate that low-passage ARPE-19 cells can express genes specific to native human RPE cells when appropriately cultured and differentiated
Current limiting and negative differential resistance in indium oxide based ceramics
Indium oxide based ceramics with bismuth oxide addition were sintered in air in the temperature range 800-1300 ºC. Current-voltage characteristics of In2O3-Bi2O3 ceramics sintered at different temperatures are weakly nonlinear. After an additional heat treatment in air at about 200 ºC samples sintered at a temperature within the narrow range of about 1050-1100 ºC exhibit a current-limiting effect accompanied by low-frequency current oscillations. It is shown that the observed electrical properties are controlled by the grain-boundary barriers and the heat treatment in air at 200 ºC leads to the decrease in the barrier height. Electrical measurements, scanning electron microscopy and X-ray photoelectron spectroscopy results suggest that the current-limiting effect observed in In2O3-Bi2O3 may be explained in terms of a modified barrier model; the observed current-limiting effect is the result of an increase of barrier height with increasing electric field, due to additional oxygen absorption. It is found that In2O3-Bi2O3-Co3O4-Cr2O3 ceramic exhibits current-voltage characteristics with negative differential resistance due to Joule micro heating.This study was performed in part in the frames of the project SEP-2003-C02-42821, CONACYT, México. Funding from the Royal Society, United Kingdom (2007R1/R26999) is gratefully acknowledged
Iron phosphate glasses: Bulk properties and atomic scale structure
Bulk properties such as glass transition temperature, density and thermal expansion of iron phosphate glass compositions, with replacement of Cs by Ba, are investigated as a surrogate for the transmutation of 137Cs to 137Ba, relevant to the immobilisation of Cs in glass. These studies are required to establish the appropriate incorporation rate of 137Cs in iron phosphate glass. Density and glass transition temperature increases with the addition of BaO indicating the shrinkage and reticulation of the iron phosphate glass network. The average thermal expansion coefficient reduces from 19.8 × 10−6 K−1 to 13.4 × 10−6 K−1, when 25 wt. % of Cs2O was replaced by 25 wt. % of BaO in caesium loaded iron phosphate glass. In addition to the above bulk properties, the role of Ba as a network modifier in the structure of iron phosphate glass is examined using various spectroscopic techniques. The FeII content and average coordination number of iron in the glass network was estimated using Mössbauer spectroscopy. The FeII content in the un-doped iron phosphate glass and barium doped iron phosphate glasses was 20, 21 and 22 ± 1% respectively and the average Fe coordination varied from 5.3 ± 0.2 to 5.7 ± 0.2 with increasing Ba content. The atomic scale structure was further probed by Fe K-edge X-ray absorption spectroscopy. The average coordination number provided by extended X-ray absorption fine structure spectroscopy and X-ray absorption near edge structure was in good agreement with that given by the Mössbauer data
Association between proton pump inhibitor therapy and clostridium difficile infection: a contemporary systematic review and meta-analysis.
Abstract
Introduction
Emerging epidemiological evidence suggests that proton pump inhibitor (PPI) acid-suppression therapy is associated with an increased risk of Clostridium difficile infection (CDI).
Methods
Ovid MEDLINE, EMBASE, ISI Web of Science, and Scopus were searched from 1990 to January 2012 for analytical studies that reported an adjusted effect estimate of the association between PPI use and CDI. We performed random-effect meta-analyses. We used the GRADE framework to interpret the findings.
Results
We identified 47 eligible citations (37 case-control and 14 cohort studies) with corresponding 51 effect estimates. The pooled OR was 1.65, 95% CI (1.47, 1.85), I2 = 89.9%, with evidence of publication bias suggested by a contour funnel plot. A novel regression based method was used to adjust for publication bias and resulted in an adjusted pooled OR of 1.51 (95% CI, 1.26–1.83). In a speculative analysis that assumes that this association is based on causality, and based on published baseline CDI incidence, the risk of CDI would be very low in the general population taking PPIs with an estimated NNH of 3925 at 1 year.
Conclusions
In this rigorously conducted systemic review and meta-analysis, we found very low quality evidence (GRADE class) for an association between PPI use and CDI that does not support a cause-effect relationship
Parameterized Complexity of Biclique Contraction and Balanced Biclique Contraction
In this work, we initiate the complexity study of Biclique Contraction andBalanced Biclique Contraction. In these problems, given as input a graph G andan integer k, the objective is to determine whether one can contract at most kedges in G to obtain a biclique and a balanced biclique, respectively. We firstprove that these problems are NP-complete even when the input graph isbipartite. Next, we study the parameterized complexity of these problems andshow that they admit single exponential-time FPT algorithms when parameterizedby the number k of edge contractions. Then, we show that Balanced BicliqueContraction admits a quadratic vertex kernel while Biclique Contraction doesnot admit any polynomial compression (or kernel) under standardcomplexity-theoretic assumptions.<br
Revisiting Path Contraction and Cycle Contraction
The Path Contraction and Cycle Contraction problems take as input an
undirected graph with vertices, edges and an integer and
determine whether one can obtain a path or a cycle, respectively, by performing
at most edge contractions in . We revisit these NP-complete problems and
prove the following results. Path Contraction admits an algorithm running in
time. This improves over the current algorithm known for
the problem [Algorithmica 2014]. Cycle Contraction admits an algorithm running
in time where is inversely proportional to .
Central to these results is an algorithm for a general variant of Path
Contraction, namely, Path Contraction With Constrained Ends. We also give an
-time algorithm to solve the optimization version of
Cycle Contraction.
Next, we turn our attention to restricted graph classes and show the
following results. Path Contraction on planar graphs admits a polynomial-time
algorithm. Path Contraction on chordal graphs does not admit an algorithm
running in time for any , unless the Orthogonal Vectors Conjecture fails. Here, is the
treewidth of the input graph. The second result complements the
-time, i.e., -time, algorithm known
for the problem [Discret. Appl. Math. 2014]
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