Survey of damage mechanisms on PVD coated HSS hobs used in Swedish gear manufacturing industry

Gear hobbing is widely used for production of cylindrical gears in the Swedish transmission industry. The hob, usually consisting of a homogenous HSS (High Speed Steel) body coated with a ceramic PVD (Physical Vapour Deposition) coating, is designed for regrinding and recoating several times without affecting its cutting geometries. Efficient usage of the tool, considering production costs and gear quality, requires reconditioning before wear starts to affect the gear quality negatively and certainly before tool wear renders reconditioning impossible. Hobs of today generally lack in reliability, making it difficult to judge when they have to be taken out for reconditioning. This work presents a survey of wear as observed on today’s state of the art hobs used by Swedish gear manufactures. It aims to identify damage mechanisms and the common problems in order to enable future production of more reliable hobs. The tools were temporarily borrowed from the production and the analyses were made non-destructively using optical microscopes. This was complemented by destructive cross- sectional analysis on two of the hobs.  Wear was most commonly located on the rake faces and the cutting edges of the cutting teeth. It mainly propagates by discrete fractures which appear to originate at local defects in the coating or at the interface. High intrinsic stress in the coating likely promotes coating spallation and accelerates the wear of the cutting edge

Nanoindentation on micro pillars for determination of intrinsic hardness and residual stress in coatings deposited on complex geometries

In this work a procedure to assess the local residual stress in coatings deposited on complex substrate geometries is described. A focused ion beam (FIB) is used to mill structures small enough to relax from residual stress. Nanoindentation is used to measure the change in mechanical properties, most importantly the hardness, in relaxed coating and in as-deposited coating. This change is then related to the residual stress in the coating. This relationship can then be used to calculate the residual stresses, at other positions or at other components, from changes in hardness as measured as before. The procedure is demonstrated on two different PVD coatings; one TiN coating and one nanocomposite TiNiC coating. On a large high speed steel substrate the TiN was measured to a hardness of 28 GPa using conventional techniques. Using this procedure, this could be divided into 23 GPa of intrinsic hardness and an extra 5 GPa induced by the known compressive residual stress of 3.9 GPa. When the same coating was deposited on a thin wire the full procedure allowed the residual stress to be determined to 3.5 GPa in compression

Life path analysis: scaling indicates priming effects of social and habitat factors on dispersal distances

1. Movements of many animals along a life-path can be separated into repetitive ones within home ranges and transitions between home ranges. We sought relationships of social and environmental factors with initiation and distance of transition movements in 114 buzzards Buteo buteo that were marked as nestlings with long-life radio tags. 2. Ex-natal dispersal movements of 51 buzzards in autumn were longer than for 30 later in their first year and than 35 extra-natal movements between home ranges after leaving nest areas. In the second and third springs, distances moved from winter focal points by birds that paired were the same or less than for unpaired birds. No post-nuptial movement exceeded 2 km. 3. Initiation of early ex-natal dispersal was enhanced by presence of many sibs, but also by lack of worm-rich loam soils. Distances travelled were greatest for birds from small broods and with relatively little short grass-feeding habitat near the nest. Later movements were generally enhanced by the absence of loam soils and short grassland, especially with abundance of other buzzards and probable poor feeding habitats (heathland, long grass). 4. Buzzards tended to persist in their first autumn where arable land was abundant, but subsequently showed a strong tendency to move from this habitat. 5. Factors that acted most strongly in ½-km buffers round nests, or round subsequent focal points, usually promoted movement compared with factors acting at a larger scale. Strong relationships between movement distances and environmental characteristics in ½-km buffers, especially during early ex-natal dispersal, suggested that buzzards became primed by these factors to travel far. 6. Movements were also farthest for buzzards that had already moved far from their natal nests, perhaps reflecting genetic predisposition, long-term priming or poor habitat beyond the study area

Climate change effects on phytoplankton depend on cell size and food web structure

We investigated the effects of warming on a natural phytoplankton community from the Baltic Sea, based on six mesocosm experiments conducted 2005–2009. We focused on differences in the dynamics of three phytoplankton size groups which are grazed to a variable extent by different zooplankton groups. While small-sized algae were mostly grazer-controlled, light and nutrient availability largely determined the growth of medium- and large-sized algae. Thus, the latter groups dominated at increased light levels. Warming increased mesozooplankton grazing on medium-sized algae, reducing their biomass. The biomass of small-sized algae was not affected by temperature, probably due to an interplay between indirect effects spreading through the food web. Thus, under the higher temperature and lower light levels anticipated for the next decades in the southern Baltic Sea, a higher share of smaller phytoplankton is expected. We conclude that considering the size structure of the phytoplankton community strongly improves the reliability of projections of climate change effects

Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis

Background: Hypoxia leads to the stabilisation of the hypoxia-inducible factor (HIF) transcription factor that drives the expression of target genes including microRNAs (miRNAs). MicroRNAs are known to regulate many genes involved in tumourigenesis. The aim of this study was to identify hypoxia-regulated miRNAs (HRMs) in bladder cancer and investigate their functional significance. Methods: Bladder cancer cell lines were exposed to normoxic and hypoxic conditions and interrogated for the expression of 384 miRNAs by qPCR. Functional studies were carried out using siRNA-mediated gene knockdown and chromatin immunoprecipitations. Apoptosis was quantified by annexin V staining and flow cytometry. Results: The HRM signature for NMI bladder cancer lines includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 and miR-517a. The most hypoxia-upregulated miRNA was miR-145. The miR-145 was a direct target of HIF-1a and two hypoxia response elements were identified within the promoter region of the gene. Finally, the hypoxic upregulation of miR-145 contributed to increased apoptosis in RT4 cells. Conclusions: We have demonstrated the hypoxic regulation of a number of miRNAs in bladder cancer. We have shown that miR- 145 is a novel, robust and direct HIF target gene that in turn leads to increased cell death in NMI bladder cancer cell lines

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

Genome-Wide Association Study for Incident Myocardial Infarction and Coronary Heart Disease in Prospective Cohort Studies: The CHARGE Consortium

Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stageGWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10-6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with totalmortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10-6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10-3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10-9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10-3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Cardiorespiratory Fitness, Physical Activity, and Insulin Resistance in Children

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.Purpose: Few studies have investigated the independent and joint associations of cardiorespiratory fitness (CRF) and body fat percentage (BF%) with insulin resistance in children. We investigated the independent and combined associations of CRF and BF% with fasting glycaemia and insulin resistance and their interactions with physical activity (PA) and sedentary time among 452 children aged 6¬–8 years. Methods: We assessed CRF with a maximal cycle ergometer exercise test and used allometrically scaled maximal power output (Wmax) for lean body mass (LM1.13) and body mass (BM1) as measures of CRF. BF% and LM were measured by dual-energy X-ray absorptiometry, fasting glycaemia by fasting plasma glucose, and insulin resistance by fasting serum insulin and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). PA energy expenditure (PAEE), moderate-to-vigorous PA (MVPA), and sedentary time were assessed by combined movement and heart rate sensor. Results: Wmax/LM1.13 was not associated with glucose (β=0.065, 95% CI=-0.031 to 0.161), insulin (β=-0.079, 95% CI=-0.172 to 0.015), or HOMA-IR (β=-0.065, 95% CI=-0.161 to 0.030). Wmax/BM1 was inversely associated with insulin (β=-0.289, 95% CI=-0.377 to -0.200) and HOMA-IR (β=-0.269, 95% CI=-0.359 to -0.180). BF% was directly associated with insulin (β=0.409, 95% CI=0.325 to 0.494) and HOMA-IR (β=0.390, 95% CI=0.304 to 0.475). Higher Wmax/BM1, but not Wmax/LM1.13, was associated with lower insulin and HOMA-IR in children with higher BF%. Children with higher BF% and who had lower levels of MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. Conclusion: Children with higher BF% together with less MVPA or higher levels of sedentary time had the highest insulin and HOMA-IR. CRF appropriately controlled for body size and composition using LM was not related to insulin resistance among children.Medical Research CouncilNIH