Protein associated with SMAD1 (PAWS1/FAM83G) is a substrate for type I bone morphogenetic protein receptors and modulates bone morphogenetic protein signalling

Bone morphogenetic proteins (BMPs) control multiple cellular processes in embryos and adult tissues. BMPs signal through the activation of type I BMP receptor kinases, which then phosphorylate SMADs 1/5/8. In the canonical pathway, this triggers the association of these SMADs with SMAD4 and their translocation to the nucleus, where they regulate gene expression. BMPs can also signal independently of SMAD4, but this pathway is poorly understood. Here, we report the discovery and characterization of PAWS1/FAM83G as a novel SMAD1 interactor. PAWS1 forms a complex with SMAD1 in a SMAD4-independent manner, and BMP signalling induces the phosphorylation of PAWS1 through BMPR1A. The phosphorylation of PAWS1 in response to BMP is essential for activation of the SMAD4-independent BMP target genes NEDD9 and ASNS. Our findings identify PAWS1 as the first non-SMAD substrate for type I BMP receptor kinases and as a novel player in the BMP pathway. We also demonstrate that PAWS1 regulates the expression of several non-BMP target genes, suggesting roles for PAWS1 beyond the BMP pathway

The influence of primary Cu6Sn5 size on the shear impact properties of Sn-Cu/Cu BGA Joints

A method is presented to control the size of primary Cu6Sn5 in ball grid array (BGA) joints while keeping all other microstructural features near-constant, enabling a direct study of the size of primary Cu6Sn5 on impact properties. For Sn-2Cu/Cu BGA joints, it is shown that larger primary Cu6Sn5 particles have a clear negative effect on the shear impact properties. Macroscopic fracture occurred by a combination of the brittle fracture of embedded primary Cu6Sn5 rods and ductile fracture of the matrix βSn. Cleavage of the Cu6Sn5 rods occurred mostly along (0001) or perpendicular to (0001) with some crack deflection between the two. The deterioration of shear impact properties with increasing Cu6Sn5 size is attributed to (1) the larger microcracks introduced by the brittle fracture of larger embedded Cu6Sn5 crystals, and (2) the less numerous and more widely spaced rods when the Cu6Sn5 crystals are larger, which makes them poor strengtheners

Nucleation and twinning in tin droplet solidification on single crystal intermetallic compounds

βSn nucleation is a key step in the formation of microstructure in electronic solder joints. Here, the heterogeneous nucleation of βSn is studied in undercooled tin droplets spread on the facets of various intermetallic compounds (IMCs). Nucleation undercoolings are measured in solidifying droplets and are linked to orientation relationships (ORs) measured by electron backscatter diffraction (EBSD). Preferred ORs developed on all IMCs studied. For the more potent nucleants (αCoSn3, IrSn4, PtSn4, PdSn4) the ORs represent relatively simple atomic matches. ORs with lower potency nucleants (Cu6Sn5, Ag3Sn, Ni3Sn4) had more complex atomic matches that are explored based on matching of the closest packed atomic rows. βSn solidification twinning is shown to be more complex than has been reported previously: both nucleation on an IMC facet and cyclic twinning of that grain occurred in many droplets on Cu6Sn5, Ag3Sn, Ni3Sn4; in all twinned droplets the Sn twinning axis occurred along a direction on the IMC with the lowest linear atomic disregistry; and interrelated cyclic twins formed consisting of up to five rings of cyclic twins all related by shared Sn axes

Solidification behavior of intensively sheared hypoeutectic Al-Si alloy liquid

The official published version of this article can be found at the link below.The effect of the processing temperature on the microstructural and mechanical properties of Al-Si (hypoeutectic) alloy solidified from intensively sheared liquid metal has been investigated systematically. Intensive shearing gives a significant refinement in grain size and intermetallic particle size. It also is observed that the morphology of intermetallics, defect bands, and microscopic defects in high-pressure die cast components are affected by intensive shearing the liquid metal. We attempt to discuss the possible mechanism for these effects.Funded by the EPSRC

Patient-specific blood flow simulations in the pulmonary bifurcation of patients with tetralogy of fallot

Dysfunction of the pulmonary valve and narrowing of the branch pulmonary arteries are common chronic complications in adult patients with tetralogy of Fallot; the most common cyanotic congenital heart disease with an estimate prevalence 1 in 3000 live births. Clinical consequences include, but are not limited to, abnormal lung development and elevated pulmonary vascular resistance. It is, therefore, crucial to better understand and characterise the haemodynamic environment in the pulmonary bifurcation to better diagnose and treat these patients. In this study, we have focused on investigating the blood flow dynamics in patient-specific geometries of the pulmonary bifurcation by means of computational models