1,019 research outputs found

    Toward better intelligent learning (iLearning) performance:what makes iLearning work for students in a university setting?

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    We explored the critical factors associated with iLearning that impact students’ learning performance and identified the factors with a notable influence to help managers in higher education institutions increase the effectiveness of iLearning for students. We initially synthesised 4 main dimensions (including 26 criteria): performance expectancy, lecturers’ influence, quality of service, and personal innovativeness. Subsequently, we conducted surveys in two stages. First, by studying a group of students with experience using iLearning at Taiwanese universities, we extracted 5 critical dimensions (including 18 criteria) through a factor analysis. Second, by studying a group of senior educators and practitioners in Taiwan, we prioritised the dimensions and criteria through the analytic hierarchy process (AHP). We found that performance expectancy is the top critical dimension, and the top five critical criteria pertain to enhancing the learning performance, increasing the learning participation, altering learning habits, ensuring access at all times, and enabling prompt use of learning resources. Moreover, we recommend several suggestions for the relevant managers to enhance the students’ iLearning performance

    γ\gamma-SUP: A clustering algorithm for cryo-electron microscopy images of asymmetric particles

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    Cryo-electron microscopy (cryo-EM) has recently emerged as a powerful tool for obtaining three-dimensional (3D) structures of biological macromolecules in native states. A minimum cryo-EM image data set for deriving a meaningful reconstruction is comprised of thousands of randomly orientated projections of identical particles photographed with a small number of electrons. The computation of 3D structure from 2D projections requires clustering, which aims to enhance the signal to noise ratio in each view by grouping similarly oriented images. Nevertheless, the prevailing clustering techniques are often compromised by three characteristics of cryo-EM data: high noise content, high dimensionality and large number of clusters. Moreover, since clustering requires registering images of similar orientation into the same pixel coordinates by 2D alignment, it is desired that the clustering algorithm can label misaligned images as outliers. Herein, we introduce a clustering algorithm γ\gamma-SUP to model the data with a qq-Gaussian mixture and adopt the minimum γ\gamma-divergence for estimation, and then use a self-updating procedure to obtain the numerical solution. We apply γ\gamma-SUP to the cryo-EM images of two benchmark macromolecules, RNA polymerase II and ribosome. In the former case, simulated images were chosen to decouple clustering from alignment to demonstrate γ\gamma-SUP is more robust to misalignment outliers than the existing clustering methods used in the cryo-EM community. In the latter case, the clustering of real cryo-EM data by our γ\gamma-SUP method eliminates noise in many views to reveal true structure features of ribosome at the projection level.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS680 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Ser-634 and Ser-636 of Kaposi’s Sarcoma-Associated Herpesvirus RTA are Involved in Transactivation and are Potential Cdk9 Phosphorylation Sites

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    The replication and transcription activator (RTA) of Kaposi’s sarcoma-associated herpesvirus (KSHV), K-RTA, is a lytic switch protein that moderates the reactivation process of KSHV latency. By mass spectrometric analysis of affinity purified K-RTA, we showed that Thr-513 or Thr-514 was the primary in vivo phosphorylation site. Thr-513 and Thr-514 are proximal to the nuclear localization signal (527KKRK530) and were previously hypothesized to be target sites of Ser/Thr kinase hKFC. However, substitutions of Thr with Ala at 513 and 514 had no effect on K-RTA subcellular localization or transactivation activity. By contrast, replacement of Ser with Ala at Ser-634 and Ser-636 located in a Ser/Pro-rich region of K-RTA, designated as S634A/S636A, produced a polypeptide with ∼10 kDa shorter in molecular weight and reduced transactivation in a luciferase reporter assay relative to the wild type. In contrast to prediction, the decrease in molecular weight was not due to lack of phosphorylation because the overall Ser and Thr phosphorylation state in K-RTA and S634A/S636A were similar, excluding that Ser-634 or Ser-636 motif served as docking sites for consecutive phosphorylation. Interestingly, S634A/S636A lost ∼30% immuno-reactivity to MPM2, an antibody specific to pSer/pThr-Pro motif, indicating that 634SPSP637 motif was in vivo phosphorylated. By in vitro kinase assay, we showed that K-RTA is a substrate of CDK9, a Pro-directed Ser/Thr kinase central to transcriptional regulation. Importantly, the capability of K-RTA in associating with endogenous CDK9 was reduced in S634A/S636A, which suggested that Ser-634 and Ser-636 may be involved in CDK9 recruitment. In agreement, S634A/S636A mutant exhibited ∼25% reduction in KSHV lytic cycle reactivation relative to that by the wild type K-RTA. Taken together, our data propose that Ser-634 and Ser-636 of K-RTA are phosphorylated by host transcriptional kinase CDK9 and such a process contributes to a full transcriptional potency of K-RTA

    Distinct Gene Expression Profiles in Immortalized Human Urothelial Cells Exposed to Inorganic Arsenite and Its Methylated Trivalent Metabolites

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    Inorganic arsenic is an environmental carcinogen. The generation of toxic trivalent methylated metabolites complicates the study of arsenic-mediated carcinogenesis. This study systematically evaluated the effect of chronic treatment with sodium arsenite (iAs(III)), monomethylarsonous acid (MMA(III)), and dimethylarsinous acid (DMA(III)) on immortalized human uroepithelial cells (SV-HUC-1 cells) using cDNA microarray. After exposure for 25 passages to iAs(III) (0.5 μM), MMA(III) (0.05, 0.1, or 0.2 μM), or DMA(III) (0.2 or 0.5 μM), significant compound-specific morphologic changes were observed. A set of 114 genes (5.7% of the examined genes) was differentially expressed in one or more sets of arsenical-treated cells compared with untreated controls. Expression analysis showed that exposure of cells to DMA(III) resulted in a gene profile different from that in cells exposed to iAs(III) or MMA(III), and that the iAs(III)-induced gene profile was closest to that in the tumorigenic HUC-1–derived 3-methylcholanthrene–induced tumorigenic cell line MC-SV-HUC T2, which was derived from SV-HUC-1 cells by methylcholanthrene treatment. Of the genes affected by all three arsenicals, only one, that coding for interleukin-1 receptor, type II, showed enhanced expression, a finding confirmed by the reduced increase in NF-κB (nuclear factor kappa B) activity seen in response to interleukin-1β in iAs(III)-exposed cells. The expression of 11 genes was suppressed by all three arsenicals. 5-Aza-deoxycytidine partially restored the transcription of several suppressed genes, showing that epigenetic DNA methylation was probably involved in arsenical-induced gene repression. Our data demonstrate that chronic exposure to iAs(III), MMA(III), or DMA(III) has different epigenetic effects on urothelial cells and represses NF-κB activity

    Dioscorea Phytocompounds Enhance Murine Splenocyte Proliferation Ex Vivo and Improve Regeneration of Bone Marrow Cells In Vivo

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    Specific cytokines have been tested clinically for immunotherapy of cancers; however, cytotoxicity has often impaired their usefulness. Consequently, alternative approaches are increasingly desirable. Dioscorea spp. tuber is a widely used traditional Chinese medicinal herb claimed to confer immunostimulatory activity. In this study, we evaluated Dioscorea as an adjuvant therapy for use alongside chemotherapy for cancer. Phytocompounds from Dioscorea tubers were ethanol fractioned and used for ex vivo splenocyte proliferation assay or in vivo force-feeding of mice pre-treated with the chemotherapy agent 5-fluorouracil. Co-treatment with a 50–75% ethanol-partitioned fraction of the tuber extract of D. batatas (DsCE-II) and interleukin (IL)-2 resulted in a significantly higher rate of murine splenocyte cell proliferation ex vivo than treatment with DsCE-II or IL-2 alone. This DsCE-II fraction, which contains a polysaccharide with a high proportion of β-1,4-linkage mannose (≥64%), also promoted the regeneration of specific progenitor cell populations in damaged bone marrow tissues of 5-fluorouracil-treated mice. Colony-forming unit (CFU) analyses demonstrated that the population of CFU-GM cells, but not CFU-GEMM or BFU-E cells, preferentially recovered to ~67% in the bone marrow of immune-suppressed mice fed with DsCE-II. DsCE-II efficacy level was ~85% of that obtained by subcutaneous administration of recombinant G-CSF proteins (5 μg kg−1) in mice tested in parallel. This study suggests that the DsCE-II fraction of D. batatas extract may be considered for further development as a dietary supplement for use alongside chemotherapy during cancer treatment
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