White-etching matter in bearing steel. Part II: Distinguishing cause and effect in bearing steel failure

The premature failure of large bearings of the type used in wind turbines, possibly through a mechanism called “white-structure flaking”, has triggered many studies of microstructural damage associated with “white-etching areas” created during rolling contact fatigue, although whether they are symptoms or causes of failure is less clear. Therefore, some special experiments have been conducted to prove that white-etching areas are the consequence, and not the cause, of damage. By artificially introducing a fine dispersion of microcracks in the steel through heat treatment and then subjecting the sample to rolling contact fatigue, manifestations of hard white-etching matter have been created to a much greater extent than samples similarly tested without initial cracks. A wide variety of characterization tools has been used to corroborate that the white areas thus created have the same properties as reported observations on real bearings. Evidence suggests that the formation mechanism of the white-etching regions involves the rubbing and beating of the free surfaces of cracks, debonded inclusions, and voids under repeated rolling contact. It follows that the focus in avoiding early failure should be in enhancing the toughness of the bearing steel in order to avoid the initial microscopic feature event.Funding by CONACyT, the Cambridge Overseas Trust, and the Roberto Rocca Education Programme is highly appreciated and acknowledged.This is the accepted manuscript version. The final published version is available from Springer at http://link.springer.com/article/10.1007%2Fs11661-014-2431-x

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe

Analysis of shared heritability in common disorders of the brain

Paroxysmal Cerebral Disorder

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Synthesis and Solid-State NMR Studies of Proton-Conducting Mesoporous Niobium Oxide Polymer Composites with Nafion-Like Thermal Durability

Proton conductivity and thermal durability studies were performed on a series of mesoporous Nb2O5 composites with naphthalene sulfonate formaldehyde resin polymerized within the pores. The proximity of the sulfonate groups of the polymer to the walls of the oxide mesostructure was deliberately tailored to ensure superior dehydration resistance crucial to proton conductivity. Initially characterized by nitrogen adsorption, XRD, TGA and STEM, subsequent study using impedance spectroscopy over a temperature range of 20–150 °C established their proton conductivity performance. The most promising sample displayed a conductivity of 21.77 mS cm−1 at 80 °C surpassing the literature value for Nafion 117 (8 mS cm−1) as measured in our labs using the same setup. Subsequent thermal durability tests demonstrated that this composite maintains superior conductivity to Nafion 117 at 80 °C for the length of the study (24 h). These observations were rationalized by in depth solid-state NMR studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei