Service scenarios - A socio-technical approach to business service modeling

Massively Multiplayer Online Game (MMOG) is a unique categorization of electronic game which allows thousands of players to play simultaneously through the Internet in the same virtual environment. A number of researchers have started to introduce the use of MMOG as a new generation of educational platform, allowing players to interact and to learn together through collaborative game-play. However, the answers for the occurrence of collaborative learning behaviour and the motivational drivers for learning collaboratively in a MMOG are still underresearched. Motivated by such concerns, this study tests a theoretical model to explain individual’s intention to learn by peer motivations. The model employs motivational theories to propose two external motivational factors, namely peer intrinsic motivation and peer extrinsic motivation, and investigates effects of the two new constructs on MMOG players’ intention to learn individually and intention to learn collaboratively by building on the cognitive learning theory. Based on a study with 94 valid current MMOG player responses, PLS analysis shows that peer intrinsic motivation to play has a significant positive influence on the intention to learn collaboratively, while peer extrinsic motivation to play has a significant positive influence on the intention to learn individually. The results of our findings indicate potential implications to researchers, educators and game developers

Understanding and promoting oral health of Indonesian domestic helpers in Hong Kong

Includes bibliographical references (p. 44).published_or_final_versio

A single residue substitution in the receptor-binding domain of H5N1 hemagglutinin is critical for packaging into pseudotyped lentiviral particles

© 2012 Tang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Serological studies for influenza infection and vaccine response often involve microneutralization and hemagglutination inhibition assays to evaluate neutralizing antibodies against human and avian influenza viruses, including H5N1. We have previously characterized lentiviral particles pseudotyped with H5-HA (H5pp) and validated an H5pp-based assay as a safe alternative for high-throughput serological studies in BSL-2 facilities. Here we show that H5-HAs from different clades do not always give rise to efficient production of H5pp and the underlying mechanisms are addressed. Methodology/Findings: We have carried out mutational analysis to delineate the molecular determinants responsible for efficient packaging of HA from A/Cambodia/40808/2005 (H5Cam) and A/Anhui/1/2005 (H5Anh) into H5pp. Our results demonstrate that a single A134V mutation in the 130-loop of the receptor binding domain is sufficient to render H5Anh the ability to generate H5Anh-pp efficiently, whereas the reverse V134A mutation greatly hampers production of H5Cam-pp. Although protein expression in total cell lysates is similar for H5Anh and H5Cam, cell surface expression of H5Cam is detected at a significantly higher level than that of H5Anh. We further demonstrate by several independent lines of evidence that the behaviour of H5Anh can be explained by a stronger binding to sialic acid receptors implicating residue 134. Conclusions: We have identified a single A134V mutation as the molecular determinant in H5-HA for efficient incorporation into H5pp envelope and delineated the underlying mechanism. The reduced binding to sialic acid receptors as a result of the A134V mutation not only exerts a critical influence in pseudotyping efficiency of H5-HA, but has also an impact at the whole virus level. Because A134V substitution has been reported as a naturally occurring mutation in human host, our results may have implications for the understanding of human host adaptation of avian influenza H5N1 virusesThis work was supported by grants from the Research Fund for the Control of Infectious Diseases of Hong Kong (RFCID#08070972), the Area of Excellence Scheme of the University Grants Committee (grant AoE/M-12/-06 of the Hong Kong Special Administrative Region, China), the French Ministry of Health, and the RESPARI project of the Institut Pasteur International Network

Evolutionary and Transmission Dynamics of Reassortant H5N1 Influenza Virus in Indonesia

H5N1 highly pathogenic avian influenza (HPAI) viruses have seriously affected the Asian poultry industry since their recurrence in 2003. The viruses pose a threat of emergence of a global pandemic influenza through point mutation or reassortment leading to a strain that can effectively transmit among humans. In this study, we present phylogenetic evidences for the interlineage reassortment among H5N1 HPAI viruses isolated from humans, cats, and birds in Indonesia, and identify the potential genetic parents of the reassorted genome segments. Parsimony analyses of viral phylogeography suggest that the reassortant viruses may have originated from greater Jakarta and surroundings, and subsequently spread to other regions in the West Java province. In addition, Bayesian methods were used to elucidate the genetic diversity dynamics of the reassortant strain and one of its genetic parents, which revealed a more rapid initial growth of genetic diversity in the reassortant viruses relative to their genetic parent. These results demonstrate that interlineage exchange of genetic information may play a pivotal role in determining viral genetic diversity in a focal population. Moreover, our study also revealed significantly stronger diversifying selection on the M1 and PB2 genes in the lineages preceding and subsequent to the emergence of the reassortant viruses, respectively. We discuss how the corresponding mutations might drive the adaptation and onward transmission of the newly formed reassortant viruses

Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells

Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer

Predictors and Outcomes Associated with Household Hunger in Lusaka, Zambia: Secondary Analysis of a Citywide Survey

Background: Food insecurity has important social and health consequences for affected individuals and households. We sought to measure one aspect of food insecurity—household hunger—and evaluated its possible association with household morbidity and mortality. Methods: We analyzed data from the final two rounds of a repeat cross-sectional, population-based survey conducted in Lusaka Zambia (May and August 2011). Using the Household Hunger Scale, we categorized participating households into three groups using established convention in the public health literature: little to no hunger, moderate hunger, and severe hunger. We used multilevel logistic regression to investigate associations between household hunger and the following morbidities, adjusting for individual, household, and cluster characteristics: malaria, persistent cough, tuberculosis, diarrhea, hospitalization, and death. Results: Overall, 90.0%, (95%CI: 88.1–91.7%) participating households were considered to have little to no household hunger; 9.8% (95%CI: 8.2–11.6%) reported moderate household hunger; and 0.2% (95%CI: 0.1–0.4%) reported severe household hunger. Marital status, functional status, education, employment, household member requiring nursing care, and household wealth index were associated with all levels of hunger. Adjusted for individual and household characteristics and sampling cluster, hunger was associated with malaria (OR:1.29, 95%CI:1.03–1.63 [mild] and OR:3.68, 95% CI:1.76 –13.74 [severe]), persistent cough (OR:1.64, 95%CI:1.13–2.38 [mild]), tuberculosis (OR:2.24, 95%CI:1.45–3.46 [mild], OR:6.06; 95%CI:1.56–23.57 [severe]), and hospitalization (OR:1.95; 95%CI:1.38–2.76 [mild]; OR:5.52; 95%CI:1.78-17.16 [severe]).Household hunger was not associated with death (p>0.05). Conclusions: Household hunger was associated with a number of adverse health outcomes. Although further studies are needed, our findings suggest that programs to alleviate household hunger—an important aspect of food insecurity—could lead to measurable public health impacts

Arsenic trioxide exerts synergistic effects with cisplatin on non-small cell lung cancer cells via apoptosis induction

<p>Abstract</p> <p>Background</p> <p>Despite multidisciplinary treatment, lung cancer remains a highly lethal disease due to poor response to chemotherapy. The identification of therapeutic agents with synergistic effects with traditional drugs is an alternative for lung cancer therapy. In this study, the synergistic effects of arsenic trioxide (As₂O₃) with cisplatin (DDP) on A549 and H460 non-small cell lung cancer (NSCLC) cells were explored.</p> <p>Methods</p> <p>A549 and H460 human lung cancer cells were treated with As₂O₃and/or DDP. Cell growth curves, cell proliferation, cell cycle, and apoptosis of human cancer cell lines were determined by the 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method, clonogenic assay, and flow cytometry (FCM). Apoptosis was further assessed by TUNEL staining. Cell cycle and apoptosis related protein p21, cyclin D1, Bcl-2, bax, clusterin, and caspase-3 were detected by western blot.</p> <p>Results</p> <p>MTT and clonogenic assay showed As₂O₃within 10^-2μM to 10 μM exerted inhibition on the proliferation of NSCLC cells, and 2.5 μM As₂O₃exerted synergistic inhibition on proliferation with 3 μg/ml DDP. The combination indices (CI) for A549 and H460 were 0.5 and 0.6, respectively, as confirmed by the synergism of As₂O₃with DDP. FCM showed As₂O₃did not affect the cell cycle. The G0/G1 fraction ranged from 57% to 62% for controlled A549 cells and cells treated with As₂O₃and/or DDP. The G0/G1 fraction ranged from 37% to 42% for controlled H460 cells and cells treated with As₂O₃and/or DDP. FCM and TUNEL staining illustrated that the combination of As₂O₃and DDP provoked synergistic effects on apoptosis induction based on the analysis of the apoptosis index. Western blotting revealed that the expression of cell cycle related protein p21 and cyclin D1 were not affected by the treatments, whereas apoptosis related protein bax, Bcl-2, and clusterin were significantly regulated by As₂O₃and/or DDP treatments compared with controls. The expression of caspase-3 in cells treated with the combination of As₂O₃and DDP did not differ from that in cells treated with a single agent.</p> <p>Conclusion</p> <p>As₂O₃exerted synergistic effects with DDP on NSCLC cells, and the synergistic effects were partly due to the induction of caspase-independent apoptosis.</p

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)

Multiparticle azimuthal correlations for extracting event-by-event elliptic and triangular flow in Au + Au collisions at sNN =200 GeV

We present measurements of elliptic and triangular azimuthal anisotropy of charged particles detected at forward rapidity 1&lt;|η|&lt;3 in Au + Au collisions at sNN=200 GeV, as a function of centrality. The multiparticle cumulant technique is used to obtain the elliptic flow coefficients v2{2},v2{4},v2{6}, and v2{8}, and triangular flow coefficients v3{2} and v3{4}. Using the small-variance limit, we estimate the mean and variance of the event-by-event v2 distribution from v2{2} and v2{4}. In a complementary analysis, we also use a folding procedure to study the distributions of v2 and v3 directly, extracting both the mean and variance. Implications for initial geometrical fluctuations and their translation into the final-state momentum distributions are discussed