Massive Open Online Course for Health Informatics Education

Chris Paton 대한의료정보학회 2014 Healthcare Informatics Research Vol.20 No.2

Objectives: This paper outlines a new method of teaching health informatics to large numbers of students from around the world through a Massive Open Online Course (MOOC). Methods: The Health Informatics Forum is one of examples of MOOCs through a social networking site for educating health informatics students and professionals. It is running a MOOC for students from around the world that uses creative commons licenced content funded by the US government and developed by five US universities. The content is delivered through narrated lectures with slides that can be viewed online with discussion threads on the forum for class interactions. Students can maintain a professional profile, upload photos and files, write their own blog posts and post discussion threads on the forum. Results: The Health Informatics Forum MOOC has been accessed by 11,316 unique users from 127 countries from August 2, 2012 to January 24, 2014. Most users accessed the MOOC via a desktop computer, followed by tablets and mobile devices and 55% of users were female. Over 400,000 unique users have now accessed the wider Health Informatics Forum since it was established in 2008. Conclusions: Advances in health informatics and educational technology have both created a demand for online learning material in health informatics and a solution for providing it. By using a MOOC delivered through a social networking platform it is hoped that high quality health informatics education will be able to be delivered to a large global audience of future health informaticians without cost.

‘When the Book Takes Over’: Creativity, the Writing Process and Flow in Australian Fiction Writing

Elizabeth Paton 대한사고개발학회 2012 The International Journal of Creativity & Problem Vol.22 No.1

This paper explores the concept of flow (Csikszentmihalyi 1988a; 1988b; 1997a; 1997b) in relation to creative practice as discussed by a sample of Australian fiction writers. Approximately 68% of these writers experienced what they felt was an altered state of consciousness or an unconscious process at work more generally. For example, more than a quarter of the writers interviewed (27%) discussed a sense of empathy with their characters to the degree where they felt the characters ‘come to life’ as separate entities. It can be seen that this experience of a flow-like state with regard to character in particular and content more generally substantially derives from an intense familiarity garnered through idea generation, research, development and the drafting process itself. This discussion of flow, looking at the specific example of character empathy, goes some way towards explaining the apparent dichotomy between writers’ descriptions of conscious, controlled writing and a subconscious or uncontrolled state.

The Culture of Fengshui in Korea: An Exploration of East Asian Geomancy. By Hong-Key Yoon. Lanham MD: Lexington Books, 2006. 352 pp., $75.00.

Michael Paton(서평자) The Academy of Korean Studies 2007 THE REVIEW OF KOREAN STUDIES Vol.10 No.4

Investigations on recyclisation and hydrolysis in avibactam mediated serine β-lactamase inhibition

Choi, Hwanho,Paton, Robert S.,Park, Hwangseo,Schofield, Christopher J. Royal Society of Chemistry 2016 Organic & biomolecular chemistry Vol.14 No.17

<▼1><P>In contrast to the β-lactams, which react irreversibly, avibactam reacts reversibly with serine β-lactamases.</P></▼1><▼2><P>β-Lactams inhibit penicillin-binding proteins (PBPs) and serine β-lactamases by acylation of a nucleophilic active site serine. Avibactam is approved for clinical use in combination with ceftazidime, and is a breakthrough non β-lactam β-lactamase inhibitor also reacting <I>via</I> serine acylation. Molecular dynamics (MD) and quantum chemical calculations on avibactam-mediated inhibition of a clinically relevant cephalosporinase reveal that recyclisation of the avibactam derived carbamoyl complex is favoured over hydrolysis. In contrast, we show that analogous recyclisation in β-lactam mediated inhibition is disfavoured. Avibactam recyclisation is promoted by a proton shuttle, a ‘structural’ water protonating the nucleophilic serine, and stabilization of the negative charge developed on aminocarbonyl oxygen. The results imply the potential of calculations for distinguishing between bifurcating pathways during inhibition and in generating hypotheses for predicting resistance. The inability of β-lactams to undergo recyclisation may be an Achilles heel, but one that can be addressed by suitably functionalized reversibly binding inhibitors.</P></▼2>

Determination of Chemical Availability of Nickel and Copper in Soil

Mary Allago,Paton. G.i.,Hedda. W.i. 한국토양비료학회 2014 한국토양비료학회 학술발표회 초록집 Vol.2014 No.6

Angiopoietin-Like Protein Responses to Pecan-Enriched Diets Versus a Nut-Excluded Diet

Liana L. Guarneiri,Chad M. Paton,Jamie A. Cooper 한국식품영양과학회 2022 Journal of medicinal food Vol.25 No.11

Daily pecan consumption improves fasting and postprandial triglycerides, but its effect on angiopoietin-like proteins (ANGPTLs) is unknown. The objective of this study was to investigate the impact of daily pecan consumption for 8 weeks on fasting and postprandial ANGPTL3, −8, and −4. This was an 8-week, randomized, controlled trial with three treatments: two pecan groups and a nut-free control group (n = 16). The ADD group (n = 15) consumed pecans (68 g) as part of a free-living diet, and the SUB group (n = 16) substituted the pecans (68 g) for isocaloric foods from their habitual diet. Fifty-six participants were randomized but nine subjects did not begin or finish the 8-week intervention and/or testing visits. At pre- and post-intervention, a high saturated fat meal was consumed with 3.5 h postprandial blood draws to determine changes in ANGPTL3, −8, and −4. There was a significant suppression in postprandial ANGPTL3 from pre- to post-intervention within ADD and SUB (P = .004 and P = .002, respectively) but not control (ns). There were no other changes within or between groups for fasting and postprandial outcomes. Daily pecan consumption improved postprandial ANGPTL3, which may mediate improvements in lipid metabolism.

Unraveling innate substrate control in site-selective palladium-catalyzed C–H heterocycle functionalization

Choi, Hwanho,Min, Minsik,Peng, Qian,Kang, Dahye,Paton, Robert S.,Hong, Sungwoo Royal Society of Chemistry 2016 Chemical Science Vol.7 No.6

<▼1><P>Pd(<SMALL>II</SMALL>)-catalyzed direct arylation of chromones and enaminones gives divergent site-selectivities. Computational and experimental studies reveal a switch in mechanism, from a C3-selective CMD mechanism to a C2-selective carbopalladation pathway. This model accounts for the opposite selectivities of enaminone and chromone, and also correctly predicts selectivities for the C–H functionalization of heteroaromatic substrates as a function of the coupling partner.</P></▼1><▼2><P>Understanding the regioselectivity of C–H activation in the absence of directing groups is an important step towards the design of site-selective C–H functionalizations. The Pd(<SMALL>II</SMALL>)-catalyzed direct arylation of chromones and enaminones provides an intriguing example where a simple substitution leads to a divergence in substrate-controlled site-selectivity. We describe computational and experimental studies which reveal this results from a switch in mechanism and therefore the selectivity-determining step. We present computational results and experimentally measured kinetic isotope effects and labelling studies consistent with this proposal. The C–H activation of these substrates proceeds <I>via</I> a CMD mechanism, which favors more electron rich positions and therefore displays a pronounced kinetic selectivity for the C3-position. However, C2-selective carbopalladation is also a competitive pathway for chromones so that the overall regiochemical outcome depends on which substrate undergoes activation first. Our studies provide insight into the site-selectivity based on the favorability of two competing CMD and carbopalladation processes of the substrates undergoing coupling. This model can be utilized to predict the regioselectivity of coumarins which are proficient substrates for carbopalladation. Furthermore, our model is able to account for the opposite selectivities observed for enaminone and chromone, and explains how a less reactive coupling partner leads to a switch in selectivity.</P></▼2>

Pneumolysin-induced autophagy contributes to inhibition of osteoblast differentiation through downregulation of Sp1 in human osteosarcoma cells

Kim, J.,Lee, H.W.,Rhee, D.K.,Paton, J.C.,Pyo, S. Elsevier/North-Holland 2017 Biochimica et biophysica acta, General subjects Vol.1861 No.11

Background information: The 53kDa protein pneumolysin (PLY) is the main virulence factor of Streptococcus pneumoniae, a leading cause of invasive pneumococcal diseases. PLY forms pores in cholesterol-containing membranes, thereby interfering with the function of cells. Bone destruction is a serious matter in chronic inflammatory diseases such as septic arthritis and osteomyelitis. S. pneumoniae is increasingly being recognized as a common cause of septic arthritis, but its pathogenesis is poorly defined. Method: We examined the effect of PLY on osteoblast differentiation and its mechanisms of action. The effect of PLY on osteoblast differentiation was evaluated by qRT-PCR, ALP activity assay, flow cytometric analysis, and Western blotting. We also examined the role of PLY-induced autophagy in osteoblast differentiation using RNA interference analysis. Results: PLY inhibited osteoblast differentiation by decreasing the expression of osteoblast marker genes such as Runx2 and OCN, along with ALP activity. ROS production was increased by PLY during osteoblast differentiation. PLY induced autophagy through ROS-mediated regulation of AMPK and mTOR, which downregulated the expression of Sp1 and subsequent inhibition of differentiation. Treatment with autophagy inhibitors or Atg5 siRNA alleviated the PLY-induced inhibition of differentiation. Conclusion: The results suggest that PLY inhibits osteoblast differentiation by downregulation of Sp1 accompanied by induction of autophagy through ROS-mediated regulation of the AMPK/mTOR pathway. General significance: This study proposes a molecular mechanism for inhibition of osteoblast differentiation in response to PLY.

Concise Substrate-Controlled Asymmetric Total Syntheses of Dioxabicyclic Marine Natural Products with 2,10-Dioxabicyclo-[7.3.0]dodecene and 2,9-Dioxabicyclo[6.3.0]undecene Skeletons

Kim, Mi Jung,Sohn, Te-ik,Kim, Deukjoon,Paton, Robert S. American Chemical Society 2012 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.134 No.49

<P>We report a completely substrate-controlled approach to the asymmetric total synthesis of representative dioxabicyclic bromoallene marine natural products with either a 2,10-dioxabicyclo[7.3.0]dodecene or 2,9-dioxabicyclo[6.3.0]undecene skeleton from commercially available glycidol as a common starting material. The former include (−)-isolaurallene (<B>1</B>), the enantiomeric form of natural (+)-neolaurallene (<B>2</B>), and (+)-itomanallene A (<B>3c</B>), and the latter are (+)-laurallene (<B>4</B>) and (+)-pannosallene (<B>5a</B>). In addition, our first syntheses of <B>3c</B> and <B>5a</B> established the structure and absolute stereochemistry of both natural products. Our general approach to establish the α,α′-relative stereochemistry of the medium-ring (oxonene or oxocene) and tetrahydrofuran, respectively, involved the judicious pairing of our protecting-group-dependent intermolecular amide enolate alkylation (either chemoselective chelation-controlled or dianion alkylation) with either our intramolecular amide enolate or nitrile anion alkylation. Remarkable selectivity was achieved through the use of the appropriate alkylation steps, and this approach offered us optional access to any of these dioxabicyclic bromoallene marine natural products. In addition, a computational analysis was performed to investigate conformational effects on the rate of oxonene formation via RCM, a key step in these approaches. The results suggested an alternative rationale for reactivity based on the avoidance of eclipsing torstional interactions in the <B>AS2</B>-type ring conformation.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2012/jacsat.2012.134.issue-49/ja310249u/production/images/medium/ja-2012-10249u_0014.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja310249u'>ACS Electronic Supporting Info</A></P>

Modulation of Adherence, Invasion, and Tumor Necrosis Factor Alpha Secretion during the Early Stages of Infection by Streptococcus pneumoniae ClpL

Tu, Le Nhat,Jeong, Hye-Yoon,Kwon, Hyog-Young,Ogunniyi, Abiodun D.,Paton, James C.,Pyo, Suhk-Neung,Rhee, Dong-Kwon American Society for Microbiology 2007 Infection and immunity Vol.75 No.6

<B>ABSTRACT</B><P>Heat shock proteins (HSPs) play a pivotal role as chaperones in the folding of native and denatured proteins and can help pathogens penetrate host defenses. However, the underlying mechanism(s) of modulation of virulence by HSPs has not been fully determined. In this study, the role of the chaperone ClpL in the pathogenicity of <I>Streptococcus pneumoniae</I> was assessed. A <I>clpL</I> mutant adhered to and invaded nasopharyngeal or lung cells much more efficiently than the wild type adhered to and invaded these cells in vitro, as well as in vivo, although it produced the same amount of capsular polysaccharide. However, the level of secretion of tumor necrosis factor alpha (TNF-α) from macrophages infected with the <I>clpL</I> mutant was significantly lower than the level of secretion elicited by the wild type during the early stages of infection. Interestingly, treatment of the human lung epithelial carcinoma A549 and murine macrophage RAW 264.7 cell lines with cytochalasin D, an inhibitor of actin polymerization, increased adherence of the mutant to the host cells. In contrast, cytochalasin D treatment of RAW 264.7 cells decreased TNF-α secretion after infection with either the wild type or the mutant. However, pretreatment of cell lines with the actin polymerization activator jasplakinolide reversed these phenotypes. These findings indicate, for the first time, that the ClpL chaperone represses adherence of <I>S. pneumoniae</I> to host cells and induces secretion of TNF-α via a mechanism dependent upon actin polymerization during the initial infection stage.</P>