The relationship of examinees’ individual characteristics and perceived acceptability of smart device-based testing to test scores on the practice test of the Korea Emergency Medicine Technician Licensing Examination

Purpose Smart device-based testing (SBT) is being introduced into the Republic of Korea’s high-stakes examination system, starting with the Korean Emergency Medicine Technician Licensing Examination (KEMTLE) in December 2017. In order to minimize the effects of variation in examinees’ environment on test scores, this study aimed to identify any associations of variables related to examinees’ individual characteristics and their perceived acceptability of SBT with their SBT practice test scores. Methods Of the 569 candidate students who took the KEMTLE on September 12, 2015, 560 responded to a survey questionnaire on the acceptability of SBT after the examination. The questionnaire addressed 8 individual characteristics and contained 2 satisfaction, 9 convenience, and 9 preference items. A comparative analysis according to individual variables was performed. Furthermore, a generalized linear model (GLM) analysis was conducted to identify the effects of individual characteristics and perceived acceptability of SBT on test scores. Results Among those who preferred SBT over paper-and-pencil testing, test scores were higher for male participants (mean± standard deviation [SD], 4.36± 0.72) than for female participants (mean± SD, 4.21± 0.73). According to the GLM, no variables evaluated— including gender and experience with computer-based testing, SBT, or using a tablet PC—showed a statistically significant relationship with the total score, scores on multimedia items, or scores on text items. Conclusion Individual characteristics and perceived acceptability of SBT did not affect the SBT practice test scores of emergency medicine technician students in Korea. It should be possible to adopt SBT for the KEMTLE without interference from the variables examined in this study

Genetic Modifiers of Systemic Lupus Erythematosus in FcγRIIB−/− Mice

FcγRIIB is a potent lupus susceptibility gene as demonstrated by the observation that mice deficient in this molecule develop spontaneous antinuclear antibodies (ANA) and fatal glomerulonephritis when on the C57BL/6 background. To determine the mechanisms underlying the epistasis displayed by this gene we have constructed hybrids between FcγRIIB−/− and the systemic lupus erythematosus (SLE) modifiers yaa and lpr and the susceptibility locus Sle1. Sle1 and B6.RIIB−/− are both physically and functionally coupled; compound heterozygotes of Sle1 and B6.RIIB−/− develop significant disease, while single heterozygotes display no evidence of autoimmunity or disease, indicating that these genes lie on the same genetic pathway resulting in the loss of tolerance to nuclear antigens. However, the generation of ANA in itself is insufficient to account for the severity of autoimmune disease in this model, as demonstrated by analysis of yaa and lpr hybrids. Thus, B6.RIIB−/−/lpr mice are protected from disease progression, despite equivalent titers of ANA. In contrast, B6.RIIB−/−/yaa mice have significantly enhanced disease despite reduced ANA titers. Yaa modifies the specificity and thus the pathogenicity of the B6. RIIB−/− ANA, by converting them to antinucleolar antibodies. In addition to these known modifier pathways, we have discovered two novel, recessive loci contributed by the C57BL/6 genome that are required for the ANA phenotype, further indicating the epistatic properties of this SLE model

Effect of Ca Addition on the Corrosion Resistance of Gravity Cast AZ31 Magnesium Alloy

The effect of Ca addition on the corrosion resistance of AZ31 magnesium alloys was evaluated by observation of microstructure and measurement of corrosion potential and average corrosion rate. The main mechanism of corrosion of AZ31+xCa (x ¼ 0$5 mass%) alloys was galvanic-corrosion between -Mg and second phase. But the propagation behavior of corrosion was different with Ca content. In the alloy containing below 0.7 mass%Ca, a micro-galvanic cell formed between matrix -Mg and second phase formed semi-continuously at grain boundaries and the corrosion progressed in transgranular mode. The propagation of corrosion was retarded when the corrosion front met the second phase acted as corrosion barrier. But in the alloys containing above 1 mass%Ca, a micro-galvanic cell formed between eutectic -Mg and discontinuous second phase in the eutectic region and the corrosion rapidly progressed along eutectic -Mg formed continuously at grain boundaries because the discontinuous second phase could not prohibit the propagation of corrosion effectively

NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma.

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by gene amplification or translocation alone. We demonstrate the utility of the NDMT gene signature to predict a unique subtype of HCC, which is associated with a poor prognosis in three independent cohorts encompassing diverse etiologies, demographics, and viral status. The application of gene signatures, such as the NDMT signature, offers patients access to personalized risk assessments, which may be utilized to direct future care

Mechanistic Insights into Validoxylamine A 7\u27-Phosphate Synthesis by VldE Using the Structure of the Entire Product Complex

The pseudo-glycosyltransferase VldE catalyzes non-glycosidic C-N coupling between an unsaturated cyclitol and a saturated aminocyclitol with the conservation of the stereochemical configuration of the substrates to form validoxylamine A 7′-phosphate, the biosynthetic precursor of the antibiotic validamycin A. To study the molecular basis of its mechanism, the three-dimensional structures of VldE from Streptomyces hygroscopicus subsp. limoneus was determined in apo form, in complex with GDP, in complex with GDP and validoxylamine A 7′-phosphate, and in complex with GDP and trehalose. The structure of VldE with the catalytic site in both an open and closed conformation is also described. With these structures, the preferred binding of the guanine moiety by VldE, rather than the uracil moiety as seen in OtsA could be explained. The elucidation of the VldE structure in complex with the entirety of its products provides insight into the internal return mechanism by which catalysis occurs with a net retention of the stereochemical configuration of the donated cyclitol. © 2012 Cavalier et al

Investigating combinatorial approaches in virtual screening on human inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3): A case study for small molecule kinases

Efforts toward improving the predictiveness in tier-based approaches to virtual screening (VS) have mainly focused on protein kinases. Despite their significance as drug targets, small molecule kinases have been rarely tested with these approaches. In this paper, we investigate the efficacy of a pharmacophore screening-combined structure-based docking approach on the human inducible 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase, an emerging target for cancer chemotherapy. Six out of a total 1364 compounds from NCI\u27s Diversity Set II were selected as true actives via throughput screening. Using a database constructed from these compounds, five programs were tested for structure-based docking (SBD) performance, the MOE of which showed the highest enrichments and second highest screening rates. Separately, using the same database, pharmacophore screening was performed, reducing 1364 compounds to 287 with no loss in true actives, yielding an enrichment of 4.75. When SBD was retested with the pharmacophore filtered database, 4 of the 5 SBD programs showed significant improvements to enrichment rates at only 2.5% of the database, with a 7-fold decrease in an average VS time. Our results altogether suggest that combinatorial approaches of VS technologies are easily applicable to small molecule kinases and, moreover, that such methods can decrease the variability associated with single-method SBD approaches. © 2011 Elsevier Inc. All rights reserved

Endothelin A Receptor Blockade Influences Apoptosis and Cellular Proliferation in the Developing Rat Kidney

Endothelin systems are believed to play important roles in the emergence and maintenance of functions of various organs during perinatal development, including the kidney. The present study was designed to investigate the roles of endothelin systems on physiologic renal growth and development. Newborn rat pups were treated with either Bristol-Myers Squibb-182874 (30 mg/kg/day), a selective endothelin A receptor (ETAR) antagonist, or vehicle for 7 days. To identify cellular changes, kidneys were examined for apoptotic cells by terminal deoxynucleotide transferase-mediated nick-end labeling stain and proliferating cell nuclear antigen (PCNA) by immunohistochemical (IHC) stain. To clarify the molecular control of these processes, immunoblots and reverse transcriptase-polymerase chain reaction for Clusterin, Bcl-2, Bcl-XL, Bax, and p53 were performed. ETAR antagonist treatment resulted in reduced kidney weights, decreased PCNA-positive proliferating cells, and increased apoptotic cells. The protein expressions of renal Bcl-XL and Bax in the ETAR antagonist-treated group were significantly decreased, whereas the mRNA expressions of these genes were not changed. There were no significant differences in the expressions of Clusterin, Bcl-2, and p53. In conclusion, inhibition of endogenous endothelins impairs renal growth, in which decreased cellular proliferation, increased apoptosis and decreased expressions of renal Bcl-XL and Bax are possibly implicated