From a shareholder to stakeholder orientation:Evidence from the analyses of CEO dismissal in large U.S. firms

Not applicableOthersSocial Sciences and Humanities Research Council of Canada, Grant/Award Number: 435-2013-1409Published24 month

Scale-up study for ex-vivo expansion of allogeneic natural killer cells in stirred-tank bioreactor

Natural killer (NK) cells are a type of lymphocyte in the blood that are responsible for innate and adaptive immune response, and they mature in the liver and bone marrow. Being a key role in host defense system with direct and indirect killing of virus-infected cells or cancer cells, NK cell has been considered an attractive candidate for cancer therapy. Peripheral blood shows the low frequency of NK cells, so ex vivo expansion method is important to obtain sufficient NK cells for therapeutic use. Currently, we successfully developed bioreactor process for NK cell expansion on lab-scale. Stirred-tank bioreactor could be considered as optimal alternative system for large-scale NK cell expansion compared with other ones because it is automated, less labor intensive, scalable, well-controlled and cost-effective. In bioreactor process, agitation is one of important parameters for NK cell expansion because it is necessary to provide homogenous culture conditions. So we defined effects of agitation in bioreactor and figured out an optimum condition. After that scale-up studies were carried out with manufacturing-scale bioreactor based on these results. The results in terms of growth rate, viability cytotoxicity and purity, were comparable with lab-scale

Observation of warping effects in the band and angular momentum structures of topological insulator Bi2Te3

We performed angle resolved photoemission (ARPES) experiments on Bi2Te3 with circularly polarized light. ARPES data show very strong circular dichroism, indicating existence of orbital angular momentum (OAM). Moreover, the alignment of OAM is found to have a strong binding energy dependence. Such energy dependence comes from a relatively strong band warping effect in Bi2Te3 compared to Bi2Se3. OAM close to Dirac point has an ideal chiral structure (sin ?) without out-of-plane component. Warping effect comes in as the binding energy decreases and circular dichroism along a constant energy contour can no longer be explained by a simple sin? function but requires a sin3? term. When the warping effect becomes even stronger near the Fermi energy, circular dichroism gains an additional sin6? term. Such behavior is found to be compatible with the theoretically predicted OAM structure

Generation of Functional Insulin-Producing Cells from Neonatal Porcine Liver-Derived Cells by PDX1/VP16, BETA2/NeuroD and MafA

Abstract Surrogate b-cells derived from stem cells are needed to cure type 1 diabetes, and neonatal liver cells may be an attractive alternative to stem cells for the generation of b-cells. In this study, we attempted to generate insulin-producing cells from neonatal porcine liver-derived cells using adenoviruses carrying three genes: pancreatic and duodenal homeobox factor1 (PDX1)/VP16, BETA2/NeuroD and v-maf musculo aponeurotic fibrosarcoma oncogene homolog A (MafA), which are all known to play critical roles in pancreatic development. Isolated neonatal porcine liver-derived cells were sequentially transduced with triple adenoviruses and grown in induction medium containing a high concentration of glucose, epidermal growth factors, nicotinamide and a low concentration of serum following the induction of aggregation for further maturation. We noted that the cells displayed a number of molecular characteristics of pancreatic b-cells, including expressing several transcription factors necessary for b-cell development and function. In addition, these cells synthesized and physiologically secreted insulin. Transplanting these differentiated cells into streptozotocin-induced immunodeficient diabetic mice led to the reversal of hyperglycemia, and more than 18% of the cells in the grafts expressed insulin at 6 weeks after transplantation. These data suggested that neonatal porcine liver-derived cells can be differentiated into functional insulin-producing cells under the culture conditions presented in this report and indicated that neonatal porcine liverderived cells (NPLCs) might be useful as a potential source of cells for b-cell replacement therapy in efforts to cure type I diabetes

Comparison of Rapid Diagnostic Tests for the Detection of Plasmodium vivax Malaria in South Korea

South Korea is one of many countries with endemic Plasmodium vivax malaria. Here we report the evaluation of four rapid diagnostic tests (RDTs) for diagnosis of this disease. A total of 253 subjects were enrolled in the study. The sensitivities, specificities and agreement frequencies were estimated by comparing the four RDTs against the standard of nested-PCR and microscopic examination. The CareStartTM and SD Bioline had higher test sensitivities (99.4 and 98.8%, respectively) compared with the NanoSign and Asan Easy tests (93.0 and 94.7%, respectively). The CareStartTM and SD Bioline tests could detect P. vivax in samples with parasite densities <150/μl, which was a slightly better performance than the other two RDTs. The quantitative accuracy of the four RDTs was also estimated by comparing results with P. vivax counts from blood samples. Lower test price would result in increased use of these RDTs in the field. The results of this study contribute valuable information that will aid in the selection of a diagnostic method for the detection of malaria

The efficacy and safety of Montelukast sodium in the prevention of bronchopulmonary dysplasia

PurposeThe purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD).MethodsThe Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study.ResultsThe incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414).ConclusionMontelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants

Determinants of penetrance and variable expressivity in monogenic metabolic conditions across 77,184 exomes

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants