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Background: While protein truncating variants in RAD51C have been shown to predispose to triple negative breast cancer (TNBC) and ovarian cancer, little is known about the pathogenicity of missense (MS) variants. Methods: The frequency of rare RAD51C MS variants were assessed in the BEACCON study of 5,734 familial breast cancer cases and 14,382 population controls, and integrated with tumour sequencing data from 21 cases carrying a candidate variant to assess bi-allelic inactivation. Results: Collectively, a significant enrichment of rare missense variants was detected in cases (MAF < 0.001, OR 1.57, 95%CI 1.00 - 2.44, p = 0.05), particularly for variants with a REVEL score > 0.5 (OR 3.95, 95%CI 1.40 - 12.01, p = 0.006). Despite the large sample size, the majority of variants detected were very rare, precluding definitive conclusions about pathogenicity based solely on the case-control data. Sequencing of 21 tumours from carriers of one of eight candidate MS variants, identified four cases with bi-allelic inactivation through loss of the wild-type allele, while six lost the variant allele and ten remained heterozygous. Loss of the wild-type alleles corresponded strongly with ER- and triple-negative breast tumours and a high homologous recombination deficiency score. Conclusions: Using this approach, the p.Gly264Ser variant, which was previously suspected to be pathogenic based on small case-control analyses and loss of activity in in vitro functional assays, was shown to be benign with similar prevalence in cases and controls, and eight out of nine tumours showing loss of the variant allele or retention of heterozygosity. Conversely, the combined case-control and tumour sequencing data identified p.Ile144Thr, p.Arg212His, p.Gln143Arg and p.Gly114Arg as variants warranting further investigation.

Current methods for dengue virus (DENV) genome amplification, amplify parts of the genome in at least 5 overlapping segments and then combine the output to characterize a full genome. This process is laborious, costly and requires at least 10 primers per serotype, thus increasing the likelihood of PCR bias. We introduce an assay to amplify near full-length dengue virus genomes as intact molecules, sequence these amplicons with third generation “nanopore” technology without fragmenting and use the sequence data to differentiate within-host viral variants with a bioinformatics tool (Nano-Q). The new assay successfully generated near full-length amplicons from DENV serotypes 1, 2 and 3 samples which were sequenced with nanopore technology. Consensus DENV sequences generated by nanopore sequencing had over 99.5% pairwise sequence similarity to Illumina generated counterparts provided the coverage was > 100 with both platforms. Maximum likelihood phylogenetic trees generated from nanopore consensus sequences were able to reproduce the exact trees made from Illumina sequencing with a conservative 99% bootstrapping threshold (after 1000 replicates and 10% burn-in). Pairwise genetic distances of within host variants identified from the Nano-Q tool were less than that of between host variants, thus enabling the phylogenetic segregation of variants from the same host.

This paper presents the design and dynamic response of a proposed non- Micro-Electro Mechanical Systems (MEMS) 1D torsional spring resonant scanner. The torsional spring was selected as the compliant structure of the device, and it was fabricated using aluminum with dimensions of 49 x 3.50 x 0.18 mm (L x W x T). An Analysis of Variance (ANOVA) test was performed to determine the difference in mean between the operating resonant frequency and the three types of materials, which are aluminum, stainless steel, and carbon steel. The device operates at a resonant frequency of 80.65 Hz, yielding a maximum scanning angle of 58.06 ˚. Hysteresis was observed from the frequency response chart of the system. By comparing the resonant frequency of the experimental results with the dynamic analysis of this device, the percentage error of the resonant frequency and optical scanning angle was found to be 6.67% and 16.84%, respectively.

The aim of the study was to evaluate the efficacy of liver fibrosis (LF) with acoustic radiation force impulse (ARFI) elastography for post-transplant (post-LT) HCV recurrence.We enrolled 89 adult recipients of living donor liver transplantation (LDLT) who had HCV, with or without post-LT HCV recurrence and treated or not treated. The post-LT HCV recurrence was diagnosed on the basis of RNA viral load present. ARFI examination was performed every 3 months for all patients, with shear wave velocity (SWV) obtained quantitatively in m/s and correlated with histopathologic fibrosis scoring of liver biopsy (LB).There were 50 (50 of 89) patients without HCV recurrence and 39 (39 of 89) with post-LT recurrence in the 89 patients studied. The recurrent group had significantly higher median SWVs (1.87 ± 0.52 vs 1.37 ± 0.52 m/s, P .0001), in which 18 (18 of 39) patients had antiviral drug treatment and obtained significant improvement with SWVs from 1.83 ± 0.49 to 1.68 ± 0.56 m/s, P = .043. The correlations of LF staging between ARFI elastography and Ishak histopathologic LF scores showed great significance, P = .045. The HCV RNA titer after antiviral treatment decreased from 3,831,750 to 0, P .0001, but the RNA titer of nontreated patients remained high and the median SWV increased. The Ishak LF staging in the nontreated group progressed from stage 1 to 2, P = .012 and SWV increased from 1.69 ± 0.54 to 1.91 ± 0.66 m/s, P = .085 at 1-year follow-up.ARFI elastography has efficient quantitative LF monitoring correlated with histopathologic staging for post-LT HCV recurrence. It could be an alternative, noninvasive method for frequent LB in the disease follow-up.

Difference in gene expressions is characteristic of the function of different cell types and those genes with low expression variance can be used as standards for quantitative gene expression studies. Microarray technology is used to study global gene expression within a cell; hence, represents a suitable source of data to mine for genes with low expression variance. The coefficient of variation (COV) of each gene was determined and a threshold of less than 0.1 COV was used to select stably expressed genes in each data set. Our results showed that microtubule affinity-regulating kinase 3 (MARK3) has the lowest COV in eight microarray datasets. In addition, the gene expression of housekeeping genes, which is very likely to be stably expressed, tends to fluctuate highly under different conditions, marking them as being less reliable for use as reference genes.