Association of the microRNA-Single Nucleotide Polymorphism rs2910164 in miR146a with sporadic breast cancer susceptibility: A case control study

Background Breast cancer (BC) is primarily considered a genetic disorder with a complex interplay of factors including age, gender, ethnicity, family history, personal history and lifestyle with associated hormonal and non-hormonal risk factors. The SNP rs2910164 in miR146a (a G to C polymorphism) was previously associated with increased risk of BC in cases with at least a single copy of the C allele in breast cancer, though results in other cancers and populations have shown significant variation. Methods In this study, we examined this SNP in an Australian sporadic breast cancer population of 160 cases and matched controls, with a replicate population of 403 breast cancer cases using High Resolution Melting. Results Our analysis indicated that the rs2910164 polymorphism is associated with breast cancer risk in both primary and replicate populations (p = 0.03 and 0.0013, respectively). In contrast to the results of familial breast cancer studies, however, we found that the presence of the G allele of rs2910164 is associated with increased cancer risk, with an OR of 1.77 (95% CI 1.40–2.23). Conclusions The microRNA miR146a has a potential role in the development of breast cancer and the effects of its SNPs require further inquiry to determine the nature of their influence on breast tissue and cancer.

Cyclic-oxidation behavior of Ti3SiC2-base material at 1100°c

The cyclic-oxidation behavior of Ti3SiC2-base material was studied at 1100°C in air. Scale spallation and weight loss were not observed in the present tests and the weight gain would just continue if the experiments were not interrupted. The present results demonstrated that the scale growth on Ti3SiC2-base material obeyed a parabolic rate law up to 20 cycles. It then changed to a linear rate with further increasing cycles. The scales formed on the Ti3SiC2base material were composed of an inward-growing, fine-grain mixture of Ti022 + SiO2 and an outward-growing, coarse-grain TiO2. Theoretical calculations show that the mismatch in thermal expansion coefficients between the inner scale and Ti3SiC2-base matrix is small. The outer TiO2 layer was under very low compressive stress, while the inner TiO2 + SiO2 layer was under tensile stress during cooling. Scale spaliation is, therefore, not expected and the scale formed on Ti3SiC2-base material is adherent and resistant to cyclic oxidation.

A multiple nucleotide length polymorphism (MNLP) mediates androgen regulation of IRX4 in prostate cancer

Androgens and the androgen receptor (AR) play a crucial role in the initiation and progression of prostate cancer (PCa), regulating the expression of many PCa risk-associated genes. Iroquois Homeobox 4 (IRX4) has been recently identified with PCa risk and overexpressed in PCa. We observed a down-regulation of IRX4 expression in the cells undergoing epithelial to mesenchymal transition, suggesting its potential role in PCa progression and aim to delineate the androgenmediated regulation of IRX4 in PCa.

Improving the selectivity of engineered protease inhibitors: Optimizing the P2 prime residue using a versatile cyclic peptide library

Standard mechanism inhibitors are attractive design templates for engineering reversible serine protease inhibitors. When optimizing interactions between the inhibitor and target protease, many studies focus on the nonprimed segment of the inhibitor's binding loop (encompassing the contact β-strand). However, there are currently few methods for screening residues on the primed segment. Here, we designed a synthetic inhibitor library (based on sunflower trypsin inhibitor-1) for characterizing the P2′ specificity of various serine proteases. Screening the library against 13 different proteases revealed unique P2′ preferences for trypsin, chymotrypsin, matriptase, plasmin, thrombin, four kallikrein-related peptidases, and several clotting factors. Using this information to modify existing engineered inhibitors yielded new variants that showed considerably improved selectivity, reaching up to 7000-fold selectivity over certain off-target proteases. Our study demonstrates the importance of the P2′ residue in standard mechanism inhibition and unveils a new approach for screening P2′ substitutions that will benefit future inhibitor engineering studies.

Characterisation of head-hardened rail steel in terms of cyclic plasticity response and microstructure for improved material modelling

Stress- and strain-controlled tests of heat treated high-strength rail steel (Australian Standard AS1085.1) have been performed in order to improve the characterisation of the said material׳s ratcheting and fatigue wear behaviour. The hardness of the rail head material has also been studied and it has been found that hardness reduces considerably below four-millimetres from the rail top surface. Historically, researchers have used test coupons with circular cross-sections to conduct cyclic load tests. Such test coupons, typically five-millimetres in gauge diameter and ten‐millimetres in grip diameter, are usually taken from the rail head sample. When there is considerable variation of material properties over the cross-section it becomes likely that localised properties of the rail material will be missed. In another case from the literature, disks 47 mm in diameter for a twin-disk rolling contact test machine were obtained directly from the rail sample and used to validate ratcheting and rolling contact fatigue wear models. The question arises: How accurate are such tests, especially when large material property gradients exist? In this research paper, the effects of rail sampling location on the ratcheting behaviour of AS1085.1 rail steel were investigated using rectangular-shaped specimens obtained at four different depths to observe their respective cyclic plasticity behaviour. The microstructural features of the test coupons were also analysed, especially the pearlite inter-lamellar spacing which showed strong correlation with both hardness and cyclic plasticity behaviour of the material. This work ultimately provides new data and testing methodology to aid the selection of valid parameters for material constitutive models to better understand rail surface ratcheting and wear.