First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea

It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam National University Hospital because of a 7-day history of chest pain and dyspnea. The patient was at another clinic and had been medicated with oseltamivir (75 mg twice daily) beginning 7 days before admission. Empirical antibiotics were started on the first day of hospitalization. Reverse-transcriptase polymerase chain reaction for 2009 pandemic influenza A (H1N1) was reported to be positive, and a double dose of oseltamivir (150 mg twice per day) was started on day four of hospitalization. However, the pneumonia worsened and the patient died, despite 3 days of high-dose antiviral therapy and 6 days of antibacterial therapy. An H275Y mutation was detected in the neuraminidase gene sequence. This case shows that oseltamivir resistance after short-term drug exposure is possible and can be fatal, emphasizing that early use of zanamivir should be considered in suspicious cases

The Effect of Competitive Advantage and Human Advantage on Industrial Competitive Strategy (Case Study: Smis in Gorontalo Province)

Small and Medium Industries (SMIs) have a strategic role in the Indonesian economy, as they earn 61.9 percent of the foreign exchange which goes to make up the nation\u27s Gross Domestic Product, and nationally they are able to absorb 97 percent of the workforce. The Global Competitiveness Report also notes that SMIs serve as the business units that affect every nation\u27s competitiveness. Considering this strategic role, the selection of a competitive strategy for these SMIs is absolutely necessary. Through an in-depth literature review, this study aims to explore what variables influence the competitive strategy of industries, particularly the SMIs. By using a Systematic Literature Review (SLR) with a total of 31 main literature (articles, papers and books), this study has found two dominant factors that influence industrial competitive strategy: Competitive advantage and human advantage, which are subsequently developed into six independent variables (construct variables), i.e. cost, delivery, product quality, product variety, know-how and innovativeness, with a total of 44 indicators. The results of measurements of the sample of SMIs in Gorontalo Province, using Structural Equation Modeling, found that both competitive advantage and human advantage jointly influence 40.2 percent of the industrial competitive strategies. These results indicate that competitive strategies, such as creating products with unique features, on-time delivery, flexibility in production, and employee involvement in the innovations, are indispensable to SMIs in order for them to produce quality products and be able to maintain their advantage

Substitution of Heavy Complementarity Determining Region 3 (CDR-H3) Residues Can Synergistically Enhance Functional Activity of Antibody and Its Binding Affinity to HER2 Antigen

To generate a biobetter that has improved therapeutic activity, we constructed scFv libraries via random mutagenesis of several residues of CDR-H3 and -L3 of hu4D5. The scFv clones were isolated from the phage display libraries by stringent panning, and their anti-proliferative activity against HER2-positive cancer cells was evaluated as a primary selection criterion. Consequently, we selected AH06 as a biobetter antibody that had a 7.2-fold increase in anti-proliferative activity (IC50: 0.81 nM) against the gastric cancer cell line NCI-N87 and a 7.4-fold increase in binding affinity (K-D : 60 pM) to HER2 compared to hu4D5. The binding energy calculation and molecular modeling suggest that the substitution of residues of CDR-H3 to W98, F100c, A101 and L102 could stabilize binding of the antibody to HER2 and there could be direct hydrophobic interactions between the aromatic ring of W98 and the aliphatic group of I613 within HER2 domain IV as well as the heavy and light chain hydrophobic interactions by residues F100c, A101 and L102 of CDR-H3. Therefore, we speculate that two such interactions were exerted by the residues W98 and F100c. A101 and L102 may have a synergistic effect on the increase in the binding affinity to HER2. AH06 specifically binds to domain IV of HER2, and it decreased the phosphorylation level of HER2 and AKT. Above all, it highly increased the overall level of p27 compared to hu4D5 in the gastric cancer cell line NCI-N82, suggesting that AH06 could potentially be a more efficient therapeutic agent than hu4D5.OAIID:RECH_ACHV_DSTSH_NO:T201620640RECH_ACHV_FG:RR00200001ADJUST_YN:EMP_ID:A002901CITE_RATE:2.67DEPT_NM:화학생물공학부EMAIL:[email protected]_YN:YCONFIRM: