Integrated genomic analyses of ovarian carcinoma

A catalogue of molecular aberrations that cause ovarian cancer is critical for developing and deploying therapies that will improve patients’ lives. The Cancer Genome Atlas project has analysed messenger RNA expression, microRNA expression, promoter methylation and DNA copy number in 489 high-grade serous ovarian adenocarcinomas and the DNA sequences of exons from coding genes in 316 of these tumours. Here we report that high-grade serous ovarian cancer is characterized by TP53 mutations in almost all tumours (96%); low prevalence but statistically recurrent somatic mutations in nine further genes including NF1, BRCA1, BRCA2, RB1 and CDK12; 113 significant focal DNA copy number aberrations; and promoter methylation events involving 168 genes. Analyses delineated four ovarian cancer transcriptional subtypes, three microRNA subtypes, four promoter methylation subtypes and a transcriptional signature associated with survival duration, and shed new light on the impact that tumours with BRCA1/2 (BRCA1 or BRCA2) and CCNE1 aberrations have on survival. Pathway analyses suggested that homologous recombination is defective in about half of the tumours analysed, and that NOTCH and FOXM1 signalling are involved in serous ovarian cancer pathophysiology.National Institutes of Health (U.S.) (Grant U54HG003067)National Institutes of Health (U.S.) (Grant U54HG003273)National Institutes of Health (U.S.) (Grant U54HG003079)National Institutes of Health (U.S.) (Grant U24CA126543)National Institutes of Health (U.S.) (Grant U24CA126544)National Institutes of Health (U.S.) (Grant U24CA126546)National Institutes of Health (U.S.) (Grant U24CA126551)National Institutes of Health (U.S.) (Grant U24CA126554)National Institutes of Health (U.S.) (Grant U24CA126561)National Institutes of Health (U.S.) (Grant U24CA126563)National Institutes of Health (U.S.) (Grant U24CA143882)National Institutes of Health (U.S.) (Grant U24CA143731)National Institutes of Health (U.S.) (Grant U24CA143835)National Institutes of Health (U.S.) (Grant U24CA143845)National Institutes of Health (U.S.) (Grant U24CA143858)National Institutes of Health (U.S.) (Grant U24CA144025)National Institutes of Health (U.S.) (Grant U24CA143866)National Institutes of Health (U.S.) (Grant U24CA143867)National Institutes of Health (U.S.) (Grant U24CA143848)National Institutes of Health (U.S.) (Grant U24CA143843)National Institutes of Health (U.S.) (Grant R21CA135877

Vibroacoustic Optimization Study for the Volute Casing of a Centrifugal Fan

A numerical optimization is presented to reduce the vibrational noise of a centrifugal fan volute. Minimal vibrational radiated sound power was considered as the aim of the optimization. Three separate parts of volute panel thickness (ST: the side panel thickness; BT: the back panel thickness; FT: the front panel thickness) were taken as the design variables. Then, a vibrational noise optimization control method for the volute casing was proposed that considered the influence of vibroacoustic coupling. The optimization method was mainly divided into three main parts. The first was based on the simulation of unsteady flow to the fan to obtain the vibrational noise source. The second used the design of experiments (DoE) method and a weighted-average surrogate model (radial basis function, or RBF) with three design variables related to the geometries of the three-part volute panel thickness, which was used to provide the basic mathematical model for the optimization of the next part. The third part, implementing the low vibrational noise optimization for the fan volute, applied single-objective (taking volute radiated acoustical power as the objective function) and multi-objective (taking the volute radiated acoustical power and volute total mass as the objective function) methods. In addition, the fan aerodynamic performance, volute casing surface fluctuations, and vibration response were validated by experiments, showing good agreement. The optimization results showed that the vibrational noise optimization method proposed in this study can effectively reduce the vibration noise of the fan, obtaining a maximum value of noise reduction of 7.3 dB. The optimization in this study provides an important technical reference for the design of low vibroacoustic volute centrifugal compressors and fans whose fluids should be strictly kept in the system without any leakage

Determination of lead elemental concentration and isotopic ratios in coal ash and coal fly ash reference materials using isotope dilution thermal ionization mass spectrometry

The rapid expansion of coal-fired power plants around the world has produced a huge volume of toxic elements associated with combustion residues such as coal fly ash (CFA) and coal ash (CA), which pose great threats to the global environment. It is therefore crucial for environmental science to monitor the migration and emission pathway of toxic elements such as CFA and CA. Lead isotopes have proved to be powerful tracers capable of dealing with this issue. Unfortunately, up to now, few high precision lead isotope data of CFA and CA certified reference materials (CRMs) determined by using the double spike technique have been reported. Hence, to facilitate the application of lead isotopes in environmental science, it is indispensable and urgent to determine a suite of high precision Pb isotope ratios and Pb elemental contents for CFA and CA CRMs. Here, we measured lead isotope ratios from four CFA and CA CRMs using thermal ionization mass spectrometry (TIMS) combined with the Pb–Pb double spike method. Lead isotope ratios values of CRMs (GBW11124, GBW08401, GBW11125d, and JCFA-1) covered wide variation ranges from 17.993 to 19.228 for Pb/Pb, from 15.513 to 15.675 for Pb/Pb, and from 38.184 to 39.067 for Pb/Pb. Lead isotope ratios of these CRMs, except for GBW11124, show good external reproducibility (2 RSD, n = 8), which is better than 0.05% for Pb/Pb and Pb/Pb, 0.07% forPb/Pb, 0.04% for Pb/Pb, and 0.05% for Pb/Pb. The Pb concentrations of these CRMs were determined using Pb single spike method. The reproducibility (1 RSD, n = 4) of Pb elemental content wa

Sliding and Fretting Wear Behavior of Biomedical Ultrafine-Grained TiNbZrTaFe/Si Alloys in Simulated Physiological Solution

This work investigated the wear behavior of ultrafine-grained Ti65Nb23.33Zr5Ta1.67Fe5 (at.%, TNZTF) and Ti65Nb23.33Zr5Ta1.67Si5 (at.%, TNZTS) alloys fabricated by high-energy ball milling and spark plasma sintering. Wear tests were conducted in a simulated physiological solution under both reciprocating sliding and fretting wear conditions with different loads, frequencies, and stroke lengths. The microstructures, mechanical properties, and anti-wear properties of the investigated alloys were characterized. The results showed that the TNZTF and TNZTS alloys had much less wear volume than the commonly used Ti-6Al-4V (TC4) alloy and commercially pure titanium (CP-Ti). The TNZTF and TNZTS alloys exhibited much more smooth wear surfaces and shallower wear scars compared with TC4 and CP-Ti. The investigated alloys exhibited different wear mechanisms under the reciprocating sliding wear conditions, while they were similar under the fretting wear conditions. Compared with TC4 and CP-Ti, the fabricated TNZTF and TNZTS alloys showed a substantially higher wear resistance, owing to their ultrafine-grained microstructure and superior hardness. Additionally, the addition of Nb and Zr further enhanced the wear resistance by forming a protective Nb2O5 and ZrO2 oxide film. This work provides guidance for designing new biomedical titanium alloys with excellent wear resistance

The role of an active surveillance strategy of targeting household and neighborhood contacts related to leprosy cases released from treatment in a low-endemic area of China.

OBJECTIVE:Early diagnosis remains the primary goal for leprosy management programs. This study aims to determine whether active surveillance of patients with leprosy and their contact individuals increased identification of latent leprosy cases in the low-endemic areas. METHODS:This cross-sectional survey was carried out between October 2014 and August 2016 in 21 counties throughout Shandong Province. The survey was conducted among patients with leprosy released from treatment (RFT) and their contacts from both household and neighbors. RESULTS:A total of 2,210 RFT patients and 9,742 contacts comprising 7877 household contacts (HHCs), including 5,844 genetic related family members (GRFMs) and 2033 non-genetic related family members and 1,865 contacts living in neighboring houses (neighbor contacts, NCs), were recruited. Among identified individuals, one relapsed and 13 were newly diagnosed, giving a detection rate of 0.12%, corresponding to 120 times the passive case detection rate. Detection rates were similar for HHCs and NCs (0.114% vs. 0.214%, P = 0.287). Analysis of the family history of leprosy patients revealed clustering of newly diagnosed cases and association with residential coordinates of previously-diagnosed multibacillary leprosy cases. CONCLUSION:Active case-finding programs are feasible and contributes to early case detection by tracking HHCs and NCs in low-endemic areas