3 resultados para Migrations transnationales

em Aston University Research Archive


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To reveal the moisture migration mechanism of the unsaturated red clays, which are sensitive to water content change and widely distributed in South China, and then rationally use them as a filling material for highway embankments, a method to measure the water content of red clay cylinders using X-ray computed tomography (CT) was proposed and verified. Then, studies on the moisture migrations in the red clays under the rainfall and ground water level were performed at different degrees of compaction. The results show that the relationship between dry density, water content, and CT value determined from X-ray CT tests can be used to nondestructively measure the water content of red clay cylinders at different migration time, which avoids the error reduced by the sample-to-sample variation. The rainfall, ground water level, and degree of compaction are factors that can significantly affect the moisture migration distance and migration rate. Some techniques, such as lowering groundwater table and increasing degree of compaction of the red clays, can be used to prevent or delay the moisture migration in highway embankments filled with red clays.

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Since the first discovery of S100 members in 1965, their expressions have been affiliated with numerous biological functions in all cells of the body. However, in the recent years, S100A4, a member of this superfamily has emerged as the central target in generating new avenue for cancer therapy as its overexpression has been correlated with cancer patients’ mortality as well as established roles as motility and metastasis promoter. As it has no catalytic activity, S100A4 has to interact with its target proteins to regulate such effects. Up to date, more than 10 S100A4 target proteins have been identified but the mechanical process regulated by S100A4 to induce motility remains vague. In this work, we demonstrated that S100A4 overexpression resulted in actin filaments disorganisation, reduction in focal adhesions, instability of filopodia as well as exhibiting polarised morphology. However, such effects were not observed in truncated versions of S100A4 possibly highlighting the importance of C terminus of S100A4 target recognition. In order to assess some of the intracellular mechanisms that may be involved in promoting migrations, different strategies were used, including active pharmaceutical agents, inhibitors and knockdown experiments. Treatment of S100A4 overexpressing cells with blebbistatin and Y-27632, non muscle myosin IIA (NMMIIA) inhibitors, as well as knockdown of NMMIIA, resulted in motility enhancement and focal adhesions reduction proposing that NMMIIA assisted S100A4 in regulating cell motility but its presence is not essential. Further work done using Cos 7 cell lines, naturally lacking NMMIIA, further demonstrated that S100A4 is capable of regulating cell motility independent of NMMIIA, possibly through poor maturation of focal adhesion. Given that all these experiments highlighted the independency of NMMIIA towards migration, a protein that has been put at the forefront of S100A4-induced motility, we aimed to gather further understanding regarding the other molecular mechanisms that may be at play for motility. Using high throughput imaging (HCI), 3 compounds were identified to be capable of inhibiting S100A4-mediated migration. Although we have yet to investigate the underlying mechanism for their effects, these compounds have been shown to target membrane proteins and the externalisation of S100 proteins, for at least one of the compounds, leading us to speculate that preventing externalisation of S100A4 could potentially regulate cell motility.