GSA: an independent development algorithm for calling copy number and detecting homologous recombination deficiency (HRD) from target capture sequencing.

BACKGROUND: The gain or loss of large chromosomal regions or even whole chromosomes is termed as genomic scarring and can be observed as copy number variations resulting from the failure of DNA damage repair. RESULTS: In this study, a new algorithm called genomic scar analysis (GSA) has developed and validated to calculate homologous recombination deficiency (HRD) score. The two critical submodules were tree recursion (TR) segmentation and filtering, and the estimation and correction of the tumor purity and ploidy. Then, this study evaluated the rationality of segmentation and genotype identification by the GSA algorithm and compared with other two algorithms, PureCN and ASCAT, found that the segmentation result of GSA algorithm was more logical. In addition, the results indicated that the GSA algorithm had an excellent predictive effect on tumor purity and ploidy, if the tumor purity was more than 20%. Furtherly, this study evaluated the HRD scores and BRCA1/2 deficiency status of 195 clinical samples, and the results indicated that the accuracy was 0.98 (comparing with Affymetrix OncoScan™ assay) and the sensitivity was 95.2% (comparing with BRCA1/2 deficiency status), both were well-behaved. Finally, HRD scores and 16 genes mutations (TP53 and 15 HRR pathway genes) were analyzed in 17 cell lines, the results showed that there was higher frequency in HRR pathway genes in high HRD score samples. CONCLUSIONS: This new algorithm, named as GSA, could effectively and accurately calculate the purity and ploidy of tumor samples through NGS data, and then reflect the degree of genomic instability and large-scale copy number variations of tumor samples.

Experiments and identification of the unbalance of aerostatic guideways on the micro-scale.

In order to diagnose the unbalance of aerostatic guideways, displacement and acceleration sensors were used to measure the vibration signals of the unbalance of the aerostatic guideways caused by the gas fluctuation. The frequency characteristics for the unbalance of aerostatic guideways caused by gas fluctuation has been extracted from the measured signals by power spectral density, and the basic frequencies of the guideway system have been diagnosed according to spectral characteristics, in agreement with the results calculated by the corresponding motion equations and the finite element method.

Homologous recombination deficiency status predicts response to platinum-based chemotherapy in Chinese patients with high-grade serous ovarian carcinoma.

BACKGROUND: Homologous Recombination Deficiency (HRD) is a predictive biomarker for ovarian cancer treated with PARP inhibitors or for breast cancer treated with first-line platinum-based chemotherapy. However, limited research is documented on platinum-based treatment prediction with HRD as a biomarker in ovarian cancer patients, especially in the Chinese population. METHODS: We investigated the association between HRD status and the response of platinum-based chemotherapy in 240 Chinese HGSOC patients. RESULTS: The Pt-sensitive patients showed higher HRD scores than Pt-resistant ones, but this was not significant(median: 42.6 vs. 31.6, p = 0.086). (Pt)-sensitive rate was higher in HRD + BRCAm tumors and in HRD + BRCAwt tumors (HRD + BRCAm: 97%, p = 0.004 and HRD + BRCAwt: 90%, p = 0.04) compared with 74% in the HRD-BRCAwt tumors. We also found Pt-sensitive patients tend to be enriched in patients with BRCA mutations or non-BRCA HRR pathway gene mutations (BRCA: 93.6% vs 75.4%, p < 0.001; non-BRCA HRR: 88.6% vs 75.4%, p = 0.062). Patients with HRD status positive had significantly improved PFS compared with those with HRD status negative (median PFS: 30.5 months vs. 16.8 months, Log-rank p = 0.001). Even for BRCAwt patients, positive HRD was also associated with better PFS than the HRD-negative group (median: 27.5 months vs 16.8 months, Log-rank p = 0.010). Further, we found patients with pathogenic mutations located in the DNA-binding domain (DBD) of BRCA1 had improved FPS, compared to those with mutations in other domains. (p = 0.03). CONCLUSIONS: The HRD status can be identified as an independent significance in Chinese HGSOC patients treated with first-line platinum-based chemotherapy.

Carriage error identification based on cross-correlation analysis and wavelet transformation.

This paper proposes a novel method for identifying carriage errors. A general mathematical model of a guideway system is developed, based on the multi-body system method. Based on the proposed model, most error sources in the guideway system can be measured. The flatness of a workpiece measured by the PGI1240 profilometer is represented by a wavelet. Cross-correlation analysis performed to identify the error source of the carriage. The error model is developed based on experimental results on the low frequency components of the signals. With the use of wavelets, the identification precision of test signals is very high.

Effect of KDP-Crystal Material Properties on Surface Morphology in Ultra-Precision Fly Cutting.

To study the effect of material properties on the surface morphology of potassium dihydrogen phosphate (KDP) crystals, an ultra-precision fly cutting machine tool with a single-point diamond tool was used to perform a cutting experiment on (100) crystal plane of the KDP crystal. The elastic modulus, shear modulus, hardness, and dislocation of KDP crystals are taken into the cutting force model by introducing the strain gradient plasticity theory. Since the size effect and dynamic response will affect the surface roughness during ultra-precision machining, the surface roughness of workpieces in ultra-precision fly cutting is hard to predict. Based on the previously established strain gradient plasticity theoretical model, cutting force model, and the dynamic characteristics of the ultra-precision fly cutting system, a surface morphology prediction model under the influence of KDP crystal material properties was established. Finally, the accuracy of the surface morphology prediction model was verified by ultra-precision fly cutting experiments, and identified the frequency range of the characteristic signal caused by the anisotropy of the KDP crystal from the frequency, thereby verifying the KDP crystal material properties has a significant effect on the surface of the machined workpiece roughness.

Morphological Analysis of KDP-Crystal Workpiece Surfaces Machined by Ultra-Precision Fly Cutting.

Potassium dihydrogen phosphate crystals exhibit excellent nonlinear optical properties that are significantly affected by the surface morphology of the crystal. To comprehensively examine and characterize the morphological features of these crystals, the machined surfaces of workpieces are analyzed using wavelet, fractal, and power spectral density (PSD) methods. First, the fractal method is employed to analyze the features of the machined surfaces of different materials and examine the relationship between the surface roughness and fractal dimension of different materials. Then, the morphological anisotropy of the machined surfaces is analyzed using the two-dimensional PSD method. Based on the orientation of the machined surfaces of the workpieces, the tangential waves on the surfaces are analyzed using wavelet-transform and PSD methods. From a frequency-domain perspective, the scales of various influencing factor signals are identified. Additionally, the frequency range of the spindle vibration is determined based on the machining experiment. On this basis, the cause of the machined surface waviness errors is revealed.

Porous Membrane with High Selectivity for Alkaline Quinone-Based Flow Batteries.

Aqueous organic-based flow batteries are increasingly receiving attention owing to their appealing traits of high safety and low cost. An economic and high-performance membrane is always regarded as the heart of the batteries. Here, we introduce a cost-effective, homemade porous membrane with high performance for alkaline quinone-based flow batteries. The membrane is constituted by highly stable poly(ether sulfone) (PES) and sulfonated poly(ether ether ketone) (SPEEK) that serves dual functions of (1) adjusting the membrane microstructure and (2) endowing the membrane with a charge trait. Benefiting from the well-tuned structure and charge property of the membrane, a high ion selectivity and transport of OH- with much higher mobility serving as the primary charge-balancing ion can be realized. By employing alkaline alizarin red (ARS)/ferro-ferricyanide flow battery as the platform, a battery delivers a coulombic efficiency (CE) of 98.28% and an energy efficiency (EE) of 85.81% at 40 mA cm-2, which is higher than that of the battery with a Nafion 212 membrane (CE ∼ 99.19%, EE ∼ 84.60%), however, with much lower cost. The successful application of homemade porous membrane may provide a new strategy to engineer and fabricate membranes with high efficiency for alkaline quinone-based flow batteries and further decrease the batteries' cost.

Effect of confinement on droplet coalescence in shear flow.

The effect of confinement on the coalescence of Newtonian (polydimethylsiloxane) droplets in a Newtonian (polyisobutylene) matrix is investigated experimentally. A counter rotating parallel plate device, equipped with a microscopy setup, is used to visualize two interacting droplets during shear flow. The ratio of droplet-to-matrix viscosity is kept constant at 1.1. Droplet collisions are studied for a range of droplet sizes, both in bulk conditions and for gap spacings that are comparable to the droplet size. As a result, we present the first quantitative experimental data set for the coalescence of two equal-sized droplets in a pure shear flow with varying degrees of confinement. Compared to bulk conditions, for droplets smaller than roughly 0.2 times the gap spacing, a slight degree of confinement only decreases the orientation angle at which the droplets coalesce whereas the critical conditions for coalescence remain unaltered. For more confined conditions, the critical capillary number up to which coalescence can occur, increases. Therefore, confinement clearly promotes coalescence. In addition, the droplet trajectories, the time-dependent orientation angle of the droplet pair, and the droplet deformation prior to the coalescence event are systematically studied, and a comparison between the confined and the unconfined situation is provided. It is shown that the presence of two parallel walls can induce changes in the flow field around the droplet pair, which cause an increase of the interaction time between the droplets. Moreover, for sufficiently confined droplets, the additional force originating from the presence of the walls becomes comparable to the hydrodynamic force on the droplet pair, thus influencing the drainage of the matrix film between the droplet surfaces.

Bioconversion of conjugated linoleic acid by Lactobacillus plantarum CGMCC8198 supplemented with Acer truncatum bunge seeds oil.

Conjugated linoleic acid (CLA) isomers, c9, t11-CLA and t10, c12-CLA, have been proved to exhibit excellent biomedical properties for potential use in anti-cancer applications and in reducing obesity. Acer truncatum Bunge (ATB), which is rich in unsaturated fatty acids, including oleic acid, linoleic acid, and nervonic acid, is a new resource for edible oil. In the present study, we developed a new method for producing two CLA isomers from ATB-seed oil by fermentation using Lactobacillus plantarum CGMCC8198 (LP8198), a novel probiotics strain. Polymerase chain reaction results showed that there was a conserved linoleate isomerase (LIase) gene in LP8198, and its transcription could be induced by ATB-seed oil. Analyses by gas chromatography-mass spectrometry showed that the concentration of c9, t11-CLA and t10, c12-CLA in ATB-seed oil could be increased by about 9- and 2.25-fold, respectively, after being fermented by LP8198.

Effect of SMYD3 on the microRNA expression profile of MCF-7 breast cancer cells.

SET and MYND domain containing 3 (SMYD3) is a histone methyltransferase (HMT) and transcription factor, which serves important roles in carcinogenesis. Numerous downstream target genes of SMYD3 have been identified in previous studies. However, the downstream microRNA (miRNA) s regulated by SMYD3 are yet to be elucidated. In the present study, the results of miRNA microarray demonstrated that 30 miRNA expression profiles were upregulated, whilst 24 miRNAs were downregulated by >2.0-fold in the SMYD3-overexpressed MCF-7 breast cancer cells. The HMT activity was demonstrated to be essential for SMYD3-mediated transactivation of miR-200c-3p and the overexpression of miR-200c-3p inhibited the transactivation effects of SMYD3 on myocardin-related transcription factor-A-dependent migration-associated genes. To our best knowledge, the current study is the first to report on the transcriptional regulation of SMYD3 on miRNAs, and miR-200c may be a downstream negative regulator of the SMYD3-mediated pathway in the migration of breast cancer cells. These results may provide a novel theoretical basis to understand the mechanisms underlying the initiation, progression, diagnosis, prevention and therapy of breast cancer.