Search

Abstract Immunoglobulin G (IgG) is the main isotype of antibody in human blood. IgG consists of four subclasses (IgG1 to IgG4), encoded by separate constant region genes within the Ig heavy chain locus (IGH). Here, we report a genome-wide association study on blood IgG subclass levels. Across 4334 adults and 4571 individuals under 18 years, we discover ten new and identify four known variants at five loci influencing IgG subclass levels. These variants also affect the risk of asthma, autoimmune diseases, and blood traits. Seven variants map to the IGH locus, three to the Fcγ receptor (FCGR) locus, and two to the human leukocyte antigen (HLA) region, affecting the levels of all IgG subclasses. The most significant associations are observed between the G1m (f), G2m(n) and G3m(b*) allotypes, and IgG1, IgG2 and IgG3, respectively. Additionally, we describe selective associations with IgG4 at 16p11.2 (ITGAX) and 17q21.1 (IKZF3, ZPBP2, GSDMB, ORMDL3). Interestingly, the latter coincides with a highly pleiotropic signal where the allele associated with lower IgG4 levels protects against childhood asthma but predisposes to inflammatory bowel disease. Our results provide insight into the regulation of antibody-mediated immunity that can potentially be useful in the development of antibody based therapeutics.

Bifilms have been proposed to be critical for forming casting defects. The reduced pressure test (RPT) and bifilm index (BI) have been widely studied and used in industry for melt quality assessment. However, the BI remains challenged in predicting the mechanical properties. This work investigated the usage of RPT for elongation prediction by analyzing the melt in two foundries. The results showed that the BI could be valid when the bifilms exist as fully inflated pores. In reality, bifilms present as pores with various morphology and distribution, generating local stress concentrations under tension. Consequently, the parameter areaeff, which considers the pores’ morphology and distribution, was proposed, and the resultant f eff showed a good correlation with the elongation of the castings. These results guide the foundry to predict the elongation of the final castings and give directions for further research on the bifilm defects.

The influence of Na-Based flux on the melt quality assessment was studied using Density index (DI), bifilm index (BI) and tensile test. The melt was prepared with scrap and ingot with and/or without the addition of Na-based flux. The results show that the addition of Na-based flux decreases the accuracy of the correlation between BI/DI and the hydrogen content due to the increased shrinkage pores. The addition of flux promotes the formation of shrinkage pores by either altering the eutectic solidification behavior or generating more and bigger oxide films which leads to insufficient feeding. Moreover, the addition of flux improves the ductility of specimens by modifying the eutectic phase rather than improving the melt quality.

Endothelial cells play an important role in several vascular diseases, and molecular analysis of these cells could provide valuable information on underlying tissue status. However, no clinically established procedure for harvesting endothelial cells exists. A micro‐3D‐printed device adapted for endovascular techniques to harvest endothelial cells for transcriptomic analysis is presented. In vivo evaluation in swine (n = 6) yielded tissue samples in 60 out of 65 cases, of which 80% show a substantial amount of tissue. The cytological evaluation indicates high selectivity towards endothelial cells, and RNA‐sequencing shows gene expression signatures consistent with vascular tissue. It is found that there are no short‐term safety risks compared to operation with a control wire of equal dimensions and acute complications are not detected. If translated to clinical use, the device could enable increased understanding of early‐stage endothelial cell‐mediated disease progression and earlier diagnosis of diseases such as atherosclerosis.

Metal casting is an industrially important manufacturing process offering a superior combination of design flexibility, productivity and cost-effectiveness, but has limitations due to filling related defects. Several semisolid casting processes are available capable of casting at a range of solid fractions to overcome this. The current communication aims to review the filling front behaviour and give a new perspective to the gate design in semisolid processing compared to conventional high-pressure die-casting. It is shown that solid fraction and gate widths are critical to avoid instability and spraying.