Using Peer-to-Peer Technology for Knowledge Sharing in Communities of Practices

Communities of Practices (CoPs) are informal structures within organizations that bind people together through informal relationships and the sharing of expertise and experience. As such, they are effective tools for the creation and sharing of organizational knowledge, and, increasingly, organizations are adopting them as part of their knowledge management strategies. In this paper, we examine the knowledge sharing characteristics and roles of CoPs and develop a peer-to-peer knowledge sharing architecture that matches the behavioral characteristics of the members of the CoPs. We also propose a peer-to-peer knowledge sharing tool called KTella that enables members of CoPs to voluntarily share and retrieve knowledge more effectively

Development and validation of an in vitro–in vivo correlation (IVIVC) model for propranolol hydrochloride extended-release matrix formulations

AbstractThe objective of this study was to develop an in vitro–in vivo correlation (IVIVC) model for hydrophilic matrix extended-release (ER) propranolol dosage formulations. The in vitro release characteristics of the drug were determined using USP apparatus I at 100 rpm, in a medium of varying pH (from pH 1.2 to pH 6.8). In vivo plasma concentrations and pharmacokinetic parameters in male beagle dogs were obtained after administering oral, ER formulations and immediate-release (IR) commercial products. The similarity factor f2 was used to compare the dissolution data. The IVIVC model was developed using pooled fraction dissolved and fraction absorbed of propranolol ER formulations, ER-F and ER-S, with different release rates. An additional formulation ER-V, with a different release rate of propranolol, was prepared for evaluating the external predictability. The results showed that the percentage prediction error (%PE) values of Cmax and AUC0–∞ were 0.86% and 5.95%, respectively, for the external validation study. The observed low prediction errors for Cmax and AUC0–∞ demonstrated that the propranolol IVIVC model was valid

Pivot concept: achieving a good-quality capsulorrhexis through a 2.2 mm or less clear corneal incision by using standard capsulorhexis forceps

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Prognostic Implications of Epidermal Growth Factor Receptor and KRAS Gene Mutations and Epidermal Growth Factor Receptor Gene Copy Numbers in Patients with Surgically Resectable Non-small Cell Lung Cancer in Taiwan

IntroductionThe prognostic role of epidermal growth factor receptor (EGFR) mutations in patients with surgically resectable non-small cell lung cancer (NSCLC) without EGFR tyrosine kinase inhibitor treatment has not been well established, because the reports are still few.Materials and MethodsWe analyzed the survival data of 164 patients with surgically resectable (stages I to IIIA) NSCLC of two year groups (1996–1998 and 2002–2004), and compared with EGFR mutations, KRAS mutations, and EGFR gene copy numbers.ResultsComparing the survival of wild-type patients and patients having L858R mutations or exon 19 deletion, the median survival was much longer for patient with EGFR mutations (54.7 months) than wild type (34.9 months). The difference was not statistically significant by univariate analysis (p = 0.1981) but had borderline significance by multivariate analyses (p = 0.0506). In addition, the 3-year survival rates of patients with EGFR mutations were also significantly higher than wild type (p = 0.0232). After exclusion of 18 patients treated by EGFR-tyrosine kinase inhibitor for tumor recurrence, the trends were still the same. Patients with KRAS mutations had shorter median survival (21 months) than wild type (44.4 months). Patients with EGFR polysomy (≧copies) also had longer median survival (56.2 months) than wild type (53.4 months). But the survival differences of these two genetic markers were all not significant statistically.ConclusionIt is intriguing that patients with NSCLC with EGFR mutations had better survival than wild type. Such a tumor biology may confound the survival data in a study without the stratification by EGFR mutation

Genetic polymorphisms in glutathione S-transferase (GST) superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan

<p>Abstract</p> <p>Background</p> <p>Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC) is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers.</p> <p>Methods</p> <p>To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped.</p> <p>Results</p> <p>The GSTT1 null was marginally associated with increased urothelial carcinoma (UC) risk (HR, 1.91, 95% CI, 1.00-3.65), while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE) ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80). The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, <it>p </it>= 0.0151) and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22). The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20). Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183)A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74) when compared to the all-wildtype reference, respectively.</p> <p>Conclusions</p> <p>The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.</p

Discovery of selective inhibitors of Glutaminase-2, which inhibit mTORC1, activate autophagy and inhibit proliferation in cancer cells

Glutaminase, which converts glutamine to glutamate, is involved in Warburg effect in cancer cells. Two human glutaminase genes have been identified, GLS (GLS1) and GLS2. Two alternative transcripts arise from each glutaminase gene: first, the kidney isoform (KGA) and glutaminase C (GAC) for GLS; and, second, the liver isoform (LGA) and glutaminase B (GAB) for GLS2. While GLS1 is considered as a cancer therapeutic target, the potential role of GLS2 in cancer remains unclear. Here, we discovered a series of alkyl benzoquinones that preferentially inhibit glutaminase B isoform (GAB, GLS2) rather than the kidney isoform of glutaminase (KGA, GLS1). We identified amino acid residues in an allosteric binding pocket responsible for the selectivity. Treatment with the alkyl benzoquinones decreased intracellular glutaminase activity and glutamate levels. GLS2 inhibition by either alkyl benzoquinones or GLS2 siRNA reduced carcinoma cell proliferation and anchorage-independent colony formation, and induced autophagy via AMPK mediated mTORC1 inhibition. Our findings demonstrate amino acid sequences for selective inhibition of glutaminase isozymes and validate GLS2 as a potential anti-cancer target

Host factors do not influence the colonization or infection by fluconazole resistant Candida species in hospitalized patients

Nosocomial yeast infections have significantly increased during the past two decades in industrialized countries, including Taiwan. This has been associated with the emergence of resistance to fluconazole and other antifungal drugs. The medical records of 88 patients, colonized or infected with Candida species, from nine of the 22 hospitals that provided clinical isolates to the Taiwan Surveillance of Antimicrobial Resistance of Yeasts (TSARY) program in 1999 were reviewed. A total of 35 patients contributed fluconazole resistant strains [minimum inhibitory concentrations (MICs) ≧ 64 mg/l], while the remaining 53 patients contributed susceptible ones (MICs ≦ 8 mg/l). Fluconazole resistance was more frequent among isolates of Candida tropicalis (46.5%) than either C. albicans (36.8%) or C. glabrata (30.8%). There was no significant difference in demographic characteristics or underlying diseases among patients contributing strains different in drug susceptibility

A Sliced Inverse Regression (SIR) Decoding the Forelimb Movement from Neuronal Spikes in the Rat Motor Cortex

Several neural decoding algorithms have successfully converted brain signals into commands to control a computer cursor and prosthetic devices. A majority of decoding methods, such as population vector algorithms (PVA), optimal linear estimators (OLE), and neural networks (NN), are effective in predicting movement kinematics, including movement direction, speed and trajectory but usually require a large number of neurons to achieve desirable performance. This study proposed a novel decoding algorithm even with signals obtained from a smaller numbers of neurons. We adopted sliced inverse regression (SIR) to predict forelimb movement from single-unit activities recorded in the rat primary motor (M1) cortex in a water-reward lever-pressing task. SIR performed weighted principal component analysis (PCA) to achieve effective dimension reduction for nonlinear regression. To demonstrate the decoding performance, SIR was compared to PVA, OLE, and NN. Furthermore, PCA and sequential feature selection (SFS) which are popular feature selection techniques were implemented for comparison of feature selection effectiveness. Among SIR, PVA, OLE, PCA, SFS, and NN decoding methods, the trajectories predicted by SIR (with a root mean square error, RMSE, of 8.47 ± 1.32 mm) was closer to the actual trajectories compared with those predicted by PVA (30.41 ± 11.73 mm), OLE (20.17 ± 6.43 mm), PCA (19.13 ± 0.75 mm), SFS (22.75 ± 2.01 mm), and NN (16.75 ± 2.02 mm). The superiority of SIR was most obvious when the sample size of neurons was small. We concluded that SIR sorted the input data to obtain the effective transform matrices for movement prediction, making it a robust decoding method for conditions with sparse neuronal information

Functional characterization of cellulases identified from the cow rumen fungus Neocallimastix patriciarum W5 by transcriptomic and secretomic analyses

<p>Abstract</p> <p>Background</p> <p><it>Neocallimastix patriciarum</it> is one of the common anaerobic fungi in the digestive tracts of ruminants that can actively digest cellulosic materials, and its cellulases have great potential for hydrolyzing cellulosic feedstocks. Due to the difficulty in culture and lack of a genome database, it is not easy to gain a global understanding of the glycosyl hydrolases (<it>GHs</it>) produced by this anaerobic fungus.</p> <p>Results</p> <p>We have developed an efficient platform that uses a combination of transcriptomic and proteomic approaches to <it>N. patriciarum </it>to accelerate gene identification, enzyme classification and application in rice straw degradation. By conducting complementary studies of transcriptome (Roche 454 GS and Illumina GA IIx) and secretome (ESI-Trap LC-MS/MS), we identified 219 putative <it>GH </it>contigs and classified them into 25 <it>GH</it> families. The secretome analysis identified four major enzymes involved in rice straw degradation: β-glucosidase, endo-1,4-β-xylanase, xylanase B and Cel48A exoglucanase. From the sequences of assembled contigs, we cloned 19 putative cellulase genes, including the <it>GH1</it>, <it>GH3</it>, <it>GH5</it>, <it>GH6</it>, <it>GH9</it>, <it>GH18</it>, <it>GH43 </it>and <it>GH48 </it>gene families, which were highly expressed in <it>N. patriciarum </it>cultures grown on different feedstocks.</p> <p>Conclusions</p> <p>These <it>GH </it>genes were expressed in Pichia pastoris and/or Saccharomyces cerevisiae for functional characterization. At least five novel cellulases displayed cellulytic activity for glucose production. One β-glucosidase (W5-16143) and one exocellulase (W5-CAT26) showed strong activities and could potentially be developed into commercial enzymes.</p

Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20( S )-Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents

Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate