170 research outputs found

    Dynamic EMCUD for knowledge acquisition

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    [[abstract]]Due to the knowledge explosion, the new objects will be evolved in a dynamic environment. Hence, the knowledge can be classified into static knowledge and dynamic knowledge. Although many knowledge acquisition methodologies, based upon the Repertory Grid technique, have been proposed to systematically elicit useful rules from static grid from domain experts, they lack the ability of grid evolution to incrementally acquire the dynamic knowledge of new evolved objects. In this paper, we propose dynamic EMCUD, a new Repertory Grid-based knowledge acquisition methodology to elicit the embedded meanings of knowledge (embedded rules bearing on m objects and k object attributes), to enhance the ability of original EMCUD to iteratively integrate new evolved objects and new added attributes into the original Acquisition Table (AT) and original Attribute Ordering Table (AOT). The AOT records the relative importance of each attribute to each object in EMCUD to capture the embedded meanings with acceptable certainty factor value by relaxing or ignoring some minor attributes. In order to discover the new evolved objects, a collaborative framework including local knowledge based systems (KBSs) and a collaborative KBS is proposed to analyze the correlations of inference behaviors of embedded rules between multiple KBSs in a dynamic environment. Each KBS monitors the frequent inference behaviors of interesting embedded rules to construct a small AT increment to facilitate the acquisition of dynamic knowledge after experts confirming the new evolved objects. Moreover, the significance of knowledge may change after a period of time, a trend of all attributes to each evolved object is used to construct a new AOT increment to help experts automatically adjust the relative importance of each attribute to each object using time series analysis approach. Besides, three cases are considered to assist experts in adjusting the certainty factor values of the dynamic knowledge of the new evolved objects from the collection of inference logs in the collaborative KBS. To evaluate the performance of dynamic EMCUD in incrementally integrating new knowledge into the knowledge base, a worm detection prototype system is implemented. (c) 2006 Elsevier Ltd. All rights reserved

    Attributing variance in supportive care needs during cancer: Culture-service, and individual differences, before clinical factors

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    Background Studies using the Supportive Care Needs Survey (SCNS) report high levels of unmet supportive care needs (SCNs) in psychological and less-so physical & daily living domains, interpreted as reflecting disease/treatment-coping deficits. However, service and culture differences may account for unmet SCNs variability. We explored if service and culture differences better account for observed SCNs patterns. Methods Hong Kong (n = 180), Taiwanese (n = 263) and Japanese (n = 109) CRC patients’ top 10 ranked SCNS-34 items were contrasted. Mean SCNS-34 domain scores were compared by sample and treatment status, then adjusted for sample composition, disease stage and treatment status using multivariate hierarchical regression. Results All samples were assessed at comparable time-points. SCNs were most prevalent among Japanese and least among Taiwanese patients. Japanese patients emphasized Psychological (domain mean = 40.73) and Health systems and information (HSI) (38.61) SCN domains, whereas Taiwanese and Hong Kong patients emphasized HSI (27.41; 32.92) and Patient care & support (PCS) (19.70; 18.38) SCN domains. Mean Psychological domain scores differed: Hong Kong = 9.72, Taiwan = 17.84 and Japan = 40.73 (p<0.03–0.001, Bonferroni). Other SCN domains differed only between Chinese and Japanese samples (all p<0.001). Treatment status differentiated Taiwanese more starkly than Hong Kong patients. After adjustment, sample origin accounted for most variance in SCN domain scores (p<0.001), followed by age (p = 0.01–0.001) and employment status (p = 0.01–0.001). Treatment status and Disease stage, though retained, accounted for least variance. Overall accounted variance remained low. Conclusions Health service and/or cultural influences, age and occupation differences, and less so clinical factors, differentially account for significant variation in published studies of SCNs.published_or_final_versio

    Microbe-Specific C3b Deposition in the Horseshoe Crab Complement System in a C2/Factor B-Dependent or -Independent Manner

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    Complement C3 plays an essential role in the opsonization of pathogens in the mammalian complement system, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. To understand the molecular mechanism of C3b deposition on microbes, we characterized two types of C2/factor B homologs (designated TtC2/Bf-1 and TtC2/Bf-2) identified from the horseshoe crab Tachypleus tridentatus. Although the domain architectures of TtC2/Bf-1 and TtC2/Bf-2 were identical to those of mammalian homologs, they contained five-repeated and seven-repeated complement control protein domains at their N-terminal regions, respectively. TtC2/Bf-1 and TtC2/Bf-2 were synthesized and glycosylated in hemocytes and secreted to hemolymph plasma, which existed in a complex with C3 (TtC3), and their activation by microbes was absolutely Mg2+-dependent. Flow cytometric analysis revealed that TtC3b deposition was Mg2+-dependent on Gram-positive bacteria or fungi, but not on Gram-negative bacteria. Moreover, this analysis demonstrated that Ca2+-dependent lectins (C-reactive protein-1 and tachylectin-5A) were required for TtC3b deposition on Gram-positive bacteria, and that a Ca2+-independent lectin (Tachypleus plasma lectin-1) was definitely indispensable for TtC3b deposition on fungi. In contrast, a horseshoe crab lipopolysaccharide-sensitive protease factor C was necessary and sufficient to deposit TtC3b on Gram-negative bacteria. We conclude that plasma lectins and factor C play key roles in microbe-specific TtC3b deposition in a C2/factor B-dependent or -independent manner

    Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care

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    Background: It is not known whether or not delivering acupuncture triggers mechanisms cited as placebo and if acupuncture or sham reduces radiotherapy-induced emesis more than standard care. Methodology/Principal Findings: Cancer patients receiving radiotherapy over abdominal/pelvic regions were randomized to verum (penetrating) acupuncture (n = 109; 99 provided data) in the alleged antiemetic acupuncture point PC6 or sham acupuncture (n = 106; 101 provided data) performed with a telescopic non-penetrating needle at a sham point 2-3 times/week during the whole radiotherapy period. The acupuncture cohort was compared to a reference cohort receiving standard care (n = 62; 62 provided data). The occurrence of emesis in each group was compared after a mean dose of 27 Gray. Nausea and vomiting were experienced during the preceding week by 37 and 8% in the verum acupuncture group, 38 and 7% in the sham acupuncture group and 63 and 15% in the standard care group, respectively. The lower occurrence of nausea in the acupuncture cohort (verum and sham) compared to patients receiving standard care (37% versus 63%, relative risk (RR) 0.6, 95 % confidence interval (CI) 0.5-0.8) was also true after adjustment for potential confounding factors for nausea (RR 0.8, CI 0.6 to 0.9). Nausea intensity was lower in the acupuncture cohort (78% no nausea, 13% a little, 8% moderate, 1% much) compared to the standard care cohort (52% no nausea, 32% a little, 15% moderate, 2% much) (p = 0.002). The acupuncture cohort expected antiemetic effects from their treatment (95%). Patients who expected nausea had increased risk for nausea compared to patients who expected low risk for nausea (RR 1.6; Cl 1.2-2.4). Conclusions/Significance: Patients treated with verum or sham acupuncture experienced less nausea and vomiting compared to patients receiving standard care, possibly through a general care effect or due to the high level of patient expectancy.Original Publication:Anna Enblom, Mats Lekander, Mats Hammar, Anna Johnsson, Erik Onelov, Martin Ingvar, Gunnar Steineck and Sussanne Börjeson, Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care, 2011, PLOS ONE, (6), 3, .http://dx.doi.org/10.1371/journal.pone.0014766Licensee: Public Library of Science (PLoS)http://www.plos.org

    Antimetastatic Effects of Norcantharidin on Hepatocellular Carcinoma by Transcriptional Inhibition of MMP-9 through Modulation of NF-kB Activity

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    The rate of morbidity and mortality of hepatocellular carcinoma (HCC) in Taiwan has not lessened because of difficulty in treating tumor metastasis. Norcantharidin (NCTD) is currently used as an anticancer drug for hepatoma, breast cancer, and colorectal adenocarcinoma. NCTD possesses various biological anticancer activities, including apoptosis. However, detailed effects and molecular mechanisms of NCTD on metastasis are unclear. Thus, HCC cells were subjected to treatment with NCTD and then analyzed to determine the effects of NCTD on cell metastasis.Modified Boyden chamber assays revealed that NCTD treatment inhibited cell migration and invasion capacities of HCC cells substantially. Results of zymography and western blotting showed that activities and protein levels of matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (u-PA) were inhibited by NCTD. Western blot analysis showed that NCTD inhibits phosphorylation of ERK1/2. Testing of mRNA level, quantitative real-time PCR, and promoter assays evaluated the inhibitory effects of NCTD on MMP-9 and u-PA expression in HCC cells. The chromatin immunoprecipitation (ChIP) assay for analyzing the genomic DNA sequences bound to these proteins was reactive to the transcription protein nuclear factor (NF)-kappaB, which was inhibited by NCTD. The expression of NF-kappa B was measured by western blot analysis, which revealed decreased nuclear-factor DNA-binding activity after NCTD treatment.NCTD inhibited MMP-9 and u-PA expression through the phosphorylation of ERK1/2 and NF-kappaB signaling pathway which serves as a powerful chemopreventive agent in HCC cell metastasis

    MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells

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    <p>Abstract</p> <p>Background</p> <p>Mesenchymal stem cell (MSC) found in bone marrow (BM-MSCs) and the Wharton's jelly matrix of human umbilical cord (WJ-MSCs) are able to transdifferentiate into neuronal lineage cells both <it>in vitro </it>and <it>in vivo </it>and therefore hold the potential to treat neural disorders such as stroke or Parkinson's disease. In bone marrow MSCs, miR-130a and miR-206 have been show to regulate the synthesis of neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. However, how neuronal differentiation is controlled in WJ-MSC remains unclear.</p> <p>Methods</p> <p>WJ-MSCs were isolated from human umbilical cords. We subjected WJ-MSCs into neurogenesis by a published protocol, and the miRNome patterns of WJ-MSCs and their neuronal progenitors (day 9 after differentiation) were analyzed by the Agilent microRNA microarray.</p> <p>Results</p> <p>Five miRNAs were enriched in WJ-MSCs, including miR-345, miR-106a, miR-17-5p, miR-20a and miR-20b. Another 11 miRNAs (miR-206, miR-34a, miR-374, miR-424, miR-100, miR-101, miR-323, miR-368, miR-137, miR-138 and miR-377) were abundantly expressed in transdifferentiated neuronal progenitors. Among these miRNAs, miR-34a and miR-206 were the only 2 miRNAs been linked to BM-MSC neurogenesis. Overexpressing miR-34a in cells suppressed the expression of 136 neuronal progenitor genes, which all possess putative miR-34a binding sites. Gene enrichment analysis according to the Gene Ontology database showed that those 136 genes were associated with cell motility, energy production (including those with oxidative phosphorylation, electron transport and ATP synthesis) and actin cytoskeleton organization, indicating that miR-34a plays a critical role in precursor cell migration. Knocking down endogenous miR-34a expression in WJ-MSCs resulted in the augment of WJ-MSC motility.</p> <p>Conclusions</p> <p>Our data suggest a critical role of miRNAs in MSC neuronal differentiation, and miR-34a contributes in neuronal precursor motility, which may be crucial for stem cells to home to the target sites they should be.</p
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