111 research outputs found

    Planning Technologies for Interactive Storytelling

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    Since AI planning was first proposed for the task of narrative generation in interactive storytelling (IS), it has emerged as the dominant approach in this field. This chapter traces the use of planning technologies in this area, considers the core issues involved in the application of planning technologies in IS, and identifies some of the remaining challenges

    Causative agent distribution and antibiotic therapy assessment among adult patients with community acquired pneumonia in Chinese urban population

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    <p>Abstract</p> <p>Background</p> <p>Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003–2004 among CAP of adult Chinese urban populations.</p> <p>Methods</p> <p>Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed.</p> <p>Results</p> <p>Non-viral pathogens were found in 324/610 (53.1%) patients among whom <it>M. pneumoniae </it>was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of <it>S. pneumoniae </it>to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with β-lactam antibiotics alone and with combination of a β-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed <it>M. pneumoniae </it>and/or <it>C. pneumoniae </it>infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a β-lactam plus a macrolide, or a fluoroquinolone) than with β-lactam alone (75.8% vs. 42.9%, <it>p </it>= 0.045).</p> <p>Conclusion</p> <p>In Chinese adult CAP patients, <it>M. pneumoniae </it>was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With <it>S. pneumoniae</it>, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.</p

    Total syntheses of shizukaols A and E

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    Shizukaols possess a common heptacyclic framework containing more than ten contiguousstereocenters and potential biological activities. Here we report that the total syntheses ofshizukaols A (1)and E(2), two lindenane-type dimers from the Chloranthaceae family, areachieved via a modified biomimetic Diels–Alder reaction. The common crucial biomimetic diene23and ethylene species (6,17) are obtained through either a highlyZ-selective olefination ofα-siloxy ketone with ynolate anions or an intramolecular Horner–Wadsworth–Emmons olefinationfrom commercially available Wieland–Miescher ketone (7). This synthetic approach here opensup practical avenues for the total syntheses of the intriguing Chloranthaceae family members, aswell as the understanding of their relevant biological action in natur

    A genetic network model of cellular responses to lithium treatment and cocaine abuse in bipolar disorder

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    <p>Abstract</p> <p>Background</p> <p>Lithium is an effective treatment for Bipolar Disorder (BD) and significantly reduces suicide risk, though the molecular basis of lithium's effectiveness is not well understood. We seek to improve our understanding of this effectiveness by posing hypotheses based on new experimental data as well as published data, testing these hypotheses in silico, and posing new hypotheses for validation in future studies. We initially hypothesized a gene-by-environment interaction where lithium, acting as an environmental influence, impacts signal transduction pathways leading to differential expression of genes important in the etiology of BD mania.</p> <p>Results</p> <p>Using microarray and rt-QPCR assays, we identified candidate genes that are differentially expressed with lithium treatment. We used a systems biology approach to identify interactions among these candidate genes and develop a network of genes that interact with the differentially expressed candidates. Notably, we also identified cocaine as having a potential influence on the network, consistent with the observed high rate of comorbidity for BD and cocaine abuse. The resulting network represents a novel hypothesis on how multiple genetic influences on bipolar disorder are impacted by both lithium treatment and cocaine use. Testing this network for association with BD and related phenotypes, we find that it is significantly over-represented for genes that participate in signal transduction, consistent with our hypothesized-gene-by environment interaction. In addition, it models related pharmacogenomic, psychiatric, and chemical dependence phenotypes.</p> <p>Conclusions</p> <p>We offer a network model of gene-by-environment interaction associated with lithium's effectiveness in treating BD mania, as well as the observed high rate of comorbidity of BD and cocaine abuse. We identified drug targets within this network that represent immediate candidates for therapeutic drug testing. Posing novel hypotheses for validation in future work, we prioritized SNPs near genes in the network based on functional annotation. We also developed a "concept signature" for the genes in the network and identified additional candidate genes that may influence the system because they are significantly associated with the signature.</p

    The endothelial glycocalyx: composition, functions, and visualization

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    This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging

    Elevation of the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline: a blood pressure-independent beneficial effect of angiotensin I-converting enzyme inhibitors

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    Blockade of the renin-angiotensin system (RAS) is well recognized as an essential therapy in hypertensive, heart, and kidney diseases. There are several classes of drugs that block the RAS; these drugs are known to exhibit antifibrotic action. An analysis of the molecular mechanisms of action for these drugs can reveal potential differences in their antifibrotic roles. In this review, we discuss the antifibrotic action of RAS blockade with an emphasis on the potential importance of angiotensin I-converting enzyme (ACE) inhibition associated with the antifibrotic peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP)
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