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Breast cancer is the second most common cancer worldwide after lung cancer with the vast majority of early stage breast cancers being hormone-dependent. One of the major therapeutic advances in the clinical treatment of breast cancer has been the introduction of selective estrogen receptor modulators (SERMs). We describe the design and synthesis of novel SERM type ligands based on the 2-arylindole scaffold to selectively target the estrogen receptor in hormone dependent breast cancers. Some of these novel compounds are designed as bisindole type structures, while others are conjugated to a cytotoxic agent based on combretastatin A4 (CA4) which is a potent inhibitor of tubulin polymerisation. The indole compounds synthesised within this project such as 31 and 86 demonstrate estrogen receptor (ER) binding and strong antiproliferative activity in the ER positive MCF-7 breast cancer cell line with IC 50 values of 2.71 μM and 1.86 μM respectively. These active compounds induce apoptotic activity in MCF-7 cells with minimal effects on normal peripheral blood cells. Their strong anti-cancer effect is likely mediated by the presence of two ER binding ligands for 31 and an ER binding ligand combined with a cytotoxic agent for 86 . [ABSTRACT FROM AUTHOR]

The paper reviews the current knowledge and understanding of the crystallographic features of phase transformations in solid materials – metals, ceramics and alloys. It covers both of the broad classes of phase transformations in crystalline solids – martensitic or ‘displacive’ and ‘diffusional’ or ‘reconstructive’. The factors that govern the crystallographic features of these two classes of transformations are compared and contrasted. This provides an appropriate basis for examining the ‘diffusional–displacive’ transformations that appear to exhibit the characteristics of both classes. After a brief summary of the considerable body of experimental data available on the crystallographic characteristics of these various types of phase transformation, the different models/theories advanced to account for these observations are discussed. The main emphasis is on those models/theories that are capable of predicting, rather than just rationalising or explaining, these crystallographic features. The review purposely adopts a unifying approach and attempts to reconcile the controversy that has on occasions existed between the ‘displacive’ group and the ‘diffusional’ group – particularly in respect of the ‘diffusional–displacive’ transformation. Developing a comprehensive understanding of the crystallographic features of all classes of phase transformations is obviously the ultimate goal. The review concludes by assessing how close we are to this final achievement, identifies the gaps in current knowledge and suggests future work. [Copyright &y& Elsevier]

Following the successful application of the edge-to-edge matching model to the self-assembled DySi2 nanostructures on Si(001), the interfacial structure is fully described by a coincidence site lattice/complete pattern shift lattice model and the Δg parallelism criterion in this paper. The stepped interface with the terrace plane contains a higher density of near coincidence site clusters than the substrate Si(001). The one-to-one coincidence of steps and secondary misfit dislocations further reduces the interfacial energy. The calculated results are completely consistent with the previous experimental observations. [Copyright &y& Elsevier]

This paper reviews the current knowledge and understanding of martensitic transformations in ceramics — the tetragonal to monoclinic transformation in zirconia in particular. This martensitic transformation is the key to transformation toughening in zirconia ceramics. A very considerable body of experimental data on the characteristics of this transformation is now available. In addition, theoretical predictions can be made using the phenomenological theory of martensitic transformations. As the paper will illustrate, the phenomenological theory is capable of explaining all the reported microstructural and crystallographic features of the transformation in zirconia and in some other ceramic systems. Hence the theory, supported by experiment, can be used with considerable confidence to provide the quantitative data that is essential for developing a credible, comprehensive understanding of the transformation toughening process.A critical feature in transformation toughening is the shape strain that accompanies the transformation. This shape strain, or nucleation strain, determines whether or not the stress-induced martensitic transformation can occur at the tip of a potentially dangerous crack. If transformation does take place, then it is the net transformation strain left behind in the transformed region that provides toughening by hindering crack growth. The fracture mechanics based models for transformation toughening, therefore, depend on having a full understanding of the characteristics of the martensitic transformation and, in particular, on being able to specify both these strains. A review of the development of the models for transformation toughening shows that their refinement and improvement over the last couple of decades has been largely a result of the inclusion of more of the characteristics of the stress-induced martensitic transformation. The paper advances an improved model for the stress-induced martensitic transformation and the strains resulting from the transformation. This model, which separates the nucleation strain from the subsequent net transformation strain, is shown to be superior to any of the constitutive models currently available. [Copyright &y& Elsevier]

Abstract: The crystallographic features of surface α precipitates accompanied by surface tilt(s) in a Ti–5.26wt.% Cr alloy have been comprehensively studied by transmission electron microscopy of samples prepared using a focused ion beam. For comparison, the bulk precipitates formed far below the free surface in the same alloy have also been examined. It is found that both the surface and the bulk α precipitates exhibit a lath-shaped morphology and their habit plane always contains a single set of misfit dislocations with the Burgers vector . However, the surface precipitates differ from the bulk ones in terms of their orientation relationship with the matrix, the habit plane and the long axis direction. As a result, the interphase interface between the surface precipitates and matrix contains glissile dislocations and the interface of bulk precipitates is associated with sessile dislocations. Such a glissile interface is one of the major common features of displacive-diffusional and martensitic transformations and can be used to further understand the mechanism of bainitic transformation in steels and other alloy systems. [Copyright &y& Elsevier]

Based on electron backscatter diffraction, a novel and simple method was developed to determine orientation relationships (ORs) between phases in solids. The method was successful in explaining the crystallography of heterogeneous nucleation of Mg grains grown on Al2Y nucleation particles in an Mg–10wt.% Y alloy. Two reproducible ORs were identified and they completely agree with previous predictions from the edge-to-edge matching model. This confirms that Al2Y is an effective grain refiner for this type of alloy. [Copyright &y& Elsevier]