Examination of coating failure by acoustic emission

Coatings of NiCrAlY bond coat with a zirconia - 12 wt percent yttria overlay were applied to disc-shaped specimens of U-700 alloy. A waveguide of 1 mm diameter platinum was TIG welded to the specimen and allowed it to be suspended in a tubular furnace. The specimen was thermally cycled to 1150 C, and the acoustic emission (AE) monitored. The weight gain per thermal cycle was also measured. A computer system based on the IBM-XT microcomputer was used extensively to acquire the AE data with respect to temperature. This system also controlled the temperature by using a PD software loop. Several different types of AE analyses were performed. A major feature of these tests, not addressed by previous work in this area, was that the coatings covered 100 percent of the specimen and also that the AE was amplified at two different levels. It is believed that this latter feature allows a qualitative appraisal of the relative number of cracks per AE event. The difference in AE counts between the two channels is proportional to the number of cracks per AE event, and this parameter may be thought of as the crack density. The ratio of the AE count difference to the AE count magnitude of one channel is inversely proportional to the crack growth. Both of these parameters allow the crack distribution and crack growth within each specimen to be qualitatively followed during the thermal cycling operation. Recent results which used these principles will be presented

Sputtered Hydroxyapatite Nanocoatings on Novel Titanium Alloys for Biomedical Applications

Titanium and titanium alloys have been extensively studied for many applications in the area of bone tissue engineering. It was believed that the excellent properties of titanium alloys, e.g. lightweight, excellent corrosion resistance, high mechanical strength and low elastic modulus compared to other metallic biomaterials such as stainless steels and Cr-Co alloys, would provide enhanced stability for load-bearing implants. However, they usually lack sufficient osseointegration for implant longevity, and their biocompatibility is also an important concern in these applications due to the potential adverse reactions of metallic ions with the surrounding tissues once these metallic ions are released from the implant surfaces. One approach for consideration to improve the healing process is the application of a hydroxyapatite nanocoating onto the surface of biomedical devices and implants. Hydroxyapatite, with its excellent biocompatibility, and similar chemistry and structure to the mineral component of bone, provides a bioactive surface for direct bone formation and apposition with adjacent hard tissues. The deposition of a SiO2 interlayer between the implant surface and the hydroxyapatite nanocoating is necessary to further improve the biocompatibility of metal implants, as SiO2 has its own excellent compatibility with living tissues, and high chemical inertness, which lead to enhanced osteointegrative and functional properties of the system as a whole. Therefore, SiO2 and hydroxyapatite nanocoatings were deposited onto titanium alloys using electron beam evaporation and magnetron sputtering techniques, respectively, with different process parameters to optimize the deposition conditions and so achieve desired properties. Surface characteristics are essential due to their role in enhancing osseointegration. Surface morphology and microstructure were observed using a scanning electron micro-scope (SEM) and elemental analysis was performed by the energy dispersive X-ray spectroscopy method (EDS). The crystal structure was examined using X-ray diffractometer (XRD) to identify the phase components, while nanocoating thickness was measured using profilometer. This chapter is divided into five major parts. First is an overview of bone and bone implants, including their structure and mechanical properties. The second part highlights the importance of nanocoatings for bone implants longevity. Various coatings and surface modification techniques of titanium and its alloys are also elucidated. The advantages and drawbacks of each technique are reviewed. The last part focuses on the study of sputtered hydroxyapatite and SiO2 nanocoatings on titanium. A thorough discussion of the results is presented

Improved Imputation of Common and Uncommon Single Nucleotide Polymorphisms (SNPs) with a New Reference Set

Statistical imputation of genotype data is an important technique for analysis of genome-wide association studies (GWAS). We have built a reference dataset to improve imputation accuracy for studies of individuals of primarily European descent using genotype data from the Hap1, Omni1, and Omni2.5 human SNP arrays (Illumina). Our dataset contains 2.5-3.1 million variants for 930 European, 157 Asian, and 162 African/African-American individuals. Imputation accuracy of European data from Hap660 or OmniExpress array content, measured by the proportion of variants imputed with R^2^>0.8, improved by 34%, 23% and 12% for variants with MAF of 3%, 5% and 10%, respectively, compared to imputation using publicly available data from 1,000 Genomes and International HapMap projects. The improved accuracy with the use of the new dataset could increase the power for GWAS by as much as 8% relative to genotyping all variants. This reference dataset is available to the scientific community through the NCBI dbGaP portal. Future versions will include additional genotype data as well as non-European populations

Longer telomere length in peripheral white blood cells is associated with risk of lung cancer and the rs2736100 (CLPTM1L-TERT) polymorphism in a prospective cohort study among women in China.

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women's Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8-2.5], and 2.2 [1.2-4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

Female Chromosome X Mosaicism is Age-Related and Preferentially Affects the Inactivated X Chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events 4 2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases