The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 Å crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix α10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site, thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation.

a b s t r a c tAn FE model of the solution heat treatment, forming and in-die quenching (HFQ) process was developed. Good correlation with a deviation of less than 5% was achieved between the thickness distribution of the simulated and experimentally formed parts, verifying the model. Subsequently, the model was able to provide a more detailed understanding of the HFQ process, and was used to study the effects of forming temperature and speed on the thickness distribution of the HFQ formed part. It was found that a higher forming speed is beneficial for HFQ forming, as it led to less thinning and improved thickness homogeneity.

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a b s t r a c tAluminium alloy 2024 (AA2024) is extensively used as a structural material in the aircraft industry because of its good combination of strength and fatigue resistance. However, complex shaped components, particularly those made from sheet, are extremely difficult to form by traditional cold forming due to its low ductility at room temperature. A possible solution of this problem is to form sheet workpieces at elevated temperature. The aim of the work described in this paper is to determine the relationship between formability and temperature for AA2024 by conducting a series of tensile tests at elevated temperatures ranging from 350 to 493 • C. Ductility of AA2024 was found to increase gradually with increasing temperature up to 450 • C, followed by a sharp decrease with further increase in temperature. So-called cup tests confirmed that the formability of AA2024 is very high at a temperature of about 450 • C. Fracture surfaces and longitudinal sections of formed samples were examined by scanning electron microscope. It was found that fracture occurred in three different modes depending upon the temperature, and the sharp decrease in ductility when the temperature exceeds 450 • C was caused by softening of grain boundaries by solute enrichment (at higher heating rates liquation may be involved) and softening of the matrix around inclusion particles.

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