Hepatic resection is the most curative treatment option for early-stage hepatocellular carcinoma, but is associated with a high recurrence rate, which exceeds 50% at 5 years after surgery. Understanding the genetic basis of hepatocellular carcinoma at surgically curable stages may enable the identification of new molecular biomarkers that accurately identify patients in need of additional early therapeutic interventions. Whole exome sequencing and copy number analysis was performed on 231 hepatocellular carcinomas (72% with hepatitis B viral infection) that were classified as early-stage hepatocellular carcinomas, candidates for surgical resection. Recurrent mutations were validated by Sanger sequencing. Unsupervised genomic analyses identified an association between specific genetic aberrations and postoperative clinical outcomes. Recurrent somatic mutations were identified in nine genes, including TP53, CTNNB1, AXIN1, RPS6KA3, and RB1. Recurrent homozygous deletions in FAM123A, RB1, and CDKN2A, and high-copy amplifications in MYC, RSPO2, CCND1, and FGF19 were detected. Pathway analyses of these genes revealed aberrations in the p53, Wnt, PIK3/Ras, cell cycle, and chromatin remodeling pathways. RB1 mutations were significantly associated with cancer-specific and recurrence-free survival after resection (multivariate P 5 0.038 and P 5 0.012, respectively). FGF19 amplifications, known to activate Wnt signaling, were mutually exclusive with CTNNB1 and AXIN1 mutations, and significantly associated with cirrhosis (P 5 0.017). Conclusion: RB1 mutations can be used as a prognostic molecular biomarker for resectable hepatocellular carcinoma. Further study is required to investigate the potential role of FGF19 amplification in driving hepatocarcinogenesis in patients with liver cirrhosis and to investigate the potential of anti-FGF19 treatment in these patients. (HEPATOLOGY 2014;60:1972-1982 See Editorial on Page 1812 H epatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and exhibits the third highest mortality rate. Recent
DNA barcode (mitochondrial COI) sequences are provided for species identification of aphids from the Korean Peninsula. Most (98%) of the 154 species had distinct COI sequences (average 0.05% intraspecific pairwise divergence) relative to the degree of sequence divergence among species (average value 5.84%). For species in common with other regions, barcodes for Korean samples fell near or within known levels of variation. Based on these results, we conclude that DNA barcodes can provide an effective tool for identifying aphid species in such applications as pest management, monitoring and plant quarantine.
Flexural strength evaluation models for steel fiber reinforced ultra high strength concrete were suggested and evaluated with test results. Suggested flexural strength models were composed of compression stress blocks and tension stress blocks. Rectangular stress block, triangular stress block, and real distribution shape of stress were used on compression side. Under tension, rectangular stress block distributed to whole area of tension side and partial area of tension side was used. The last model for tension side is realistic stress distribution. All these models were verified with test result which was carried out in this study. Test was conducted by four-point loading with 2,000 kN actuator for slender beam specimen. Additional verifications were carried out with previous researches on flexural strength of steel fiber reinforced concrete or ultra high strength concrete. Total of 21 test specimens were evaluated. As a result of comparison for flexural strength of section, neutral axis depth at ultimate state, models with triangular compression stress block, and strain-softening type tension stress block can be used as exact solution for ultra high performance concrete. For the conservative and convenient design of section, modified rectangular stress block model can be used with strain softening type tension stress block.
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