Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Development of ferrous laminated composites with unique microstructures by control of carbon diffusion

A novel method is described for preparing ferrous laminated composites, containing ultrahigh carbon steel as one of the components, which results in hard and soft layers bounded by sharp and discrete interfaces. The method is based on increasing the activity of carbon in iron by silicon addition; in this manner, the carbon is made to segregate into specific layers by heat treatment at low temperatures (∼770 °C). The results are ferrous laminated composites with discrete and sharp interfaces that consist of hard layers containing spherical carbide particles embedded in a matrix of ultrafine martensite or ferrite adjoining soft layers of a coarse grained iron alloy. In addition, the high activity of carbon is shown to result in total depletion of carbon in a silicon containing UHC steel ribbon bonded to mild steel.Peer reviewe

Interface effects on the fracture mechanism of a high toughness aluminum composite laminate

The microstructure and the mechanical properties of a multilayer composite laminate based on aluminum 7075 and 2024 alloys produced by hot roll-bonding were examined. The composite laminate has been tested at room temperature under impact Charpy tests, three-point bend tests and shear tests on the interfaces. The toughness of the post-rolling tempered and T6 treated composite laminate, measured by impact absorbed energy in the crack arrester orientation, was more than twenty times higher than that of the monolithic Al 7075 alloy and seven times higher than that of Al 2024 alloy. The outstanding toughness increase of the composite laminate in the post-rolling tempered and T6 treated condition is mainly due to the mechanism of “interface predelamination”. By this fracture mechanism the interfaces are debonded before the main crack reaches them, warranting delamination in all interfaces. Therefore, delamination and crack renucleation in every layer are responsible for the improvement in toughness.Financial support from CICYT (Project MAT2003-01172) is gratefully acknowledged. C.M. Cepeda-Jiménez and J.M. García-Infanta thank the Spanish Ministry of Education and Science for a Juan de la Cierva contract and a FPI fellowship respectively. We also thank L. del Real-Alarcón for the welding work, F.F. González-Rodríguez for assistance during hot rolling and J. Chao-Hermida for assistance with the Charpy impact test.Peer reviewe

Superplastic behavior of two ultrahigh boron steels

The high-temperature deformation behavior of two ultrahigh boron steels containing 2.2 pct and 4.9 pct B was investigated. Both alloys were processedvia powder metallurgy involving gas atomization and hot isostatic pressing (hipping) at various temperatures. After hipping at 700 °C, the Fe-2.2 pct B alloy showed a fine microstructure consisting of l-µm grains and small elongated borides (less than 1µm) . At 1100 °C, a coarser microstructure with rounded borides was formed. This alloy was superplastic at 850 °C with stress exponents of about two and tensile elongations as high as 435 pct. The microstructure of the Fe-4.9 pct B alloy was similar to that of the Fe-2.2 pct B alloy showing, in addition, coarse borides. This alloy also showed low stress exponent values but lacked high tensile elongation (less than 65 pct), which was attributed to the presence of stress accumulation at the interface between the matrix and the large borides. A change in the activation energy value at theα-γ transformation temperature was seen in the Fe-2.2 pct B alloy. The plastic flow data were in agreement with grain boundary sliding and slip creep models.Peer reviewe

Notch Impact Behavior of Oxide Dispersion Strengthened (ODS) Fe20Cr5Al alloy

In this paper tensile tests and LS and LT notched Charpy impact tests were performed at the temperature range between -196 and 200 °C on an oxide dispersion strengthened (ODS) Fe20Cr6Al0.5Y2O3 hot-rolled tube. The absorbed energy values in the range of high-temperatures of LS notched specimens is considerably higher than those of LT notched specimens; however such values tend to converge as temperature increases. Ductile fracture on the normal planes to RD with delaminations parallel to the tube surface were observed in the temperature range between RT and 200 °C. Delaminations of crack divider type were observed in LT specimens, whereas delaminations of crack arrester type were observed in LS specimens. The yttria particles in the grain boundaries and the transverse plastic anisotropy are the possible causes of that the delaminations were parallel to the tube surfacePM 2000 is a trademark of Plansee GmbH. The authors acknowledge the financial support of the Spanish Ministerio de Economia e Innovacio´ n (MINECO) in the form of a Coordinate Project in the Energy Area of Plan Nacional 2009 (ENE2009-13766-C04-01). G.P. acknowledges MINECO for financial support in the form of PhD Research Grant (FPI). This research was supported by ORNL’s Shared Research Equipment (SHaRE) User Facility, which is sponsored by the Office of Basic Energy Sciences, U.S. Department of EnergyPeer reviewe

Structural superplasticity at higher strain rates of hypereutectoid Fe-5.5Al-1Sn-1Cr-1.3C steel

A fine-grained ultra-high-carbon steel—UHC steel—containing 1.35 wt pct carbon, 5.5 wt pct aluminum, 1 wt pct tin, and 1 wt pct chromium exhibits fine-structure superplasticity in the temperature regime between 775 °C and 900 °C at higher strain rates up to 10−2 s−1. Thermomechanical processing was performed in order to achieve a fine-grained equiaxed microstructure consisting of κ-carbides of about 0.7 to 2.5 µm in size finely distributed within the ferritic Fe(Al, Sn, Cr) solid solution matrix with a linear intercept grain size of 3 to 5 µm. Superplasticity occurred in the strain rate regime of 10−4<- [(e)\dot]≤10−2 s−1 with m values of 0.5 to 0.6 (stress exponent n=1.6 to 2). Tensile elongations of more than 900 pct were recorded. From thermal activation analysis, activation energies of Q=230 to 243 kJ/mole were determined, which clearly reveal a contribution of the alloying elements Al and Sn to the lattice diffusion of iron. The governing deformation mechanism is grain boundary sliding accommodated by dislocation climb controlled by lattice diffusion sustained by chemical diffusion. At very high strain rates of [(e)\dot]≳2 · 10−2 s−1, the strain-rate-sensitivity exponent decreases to about 0.2≤m≤0.27, which indicates class II solid solution behavior of this material.Peer reviewe