Collagen induced MMP-2 activation in human breast cancer

Matrix metalloproteinase-2 (MMP-2), a zymogen requiring proteolytic activation for catalytic activity, has been implicated broadly in the invasion and metastasis of many cancer model systems, including human breast cancer (HBC). MMP-2 has been immunolocalized to carcinomatous human breast, where the degree of activation of MMP-2 correlates well with tumor grade and patient prognosis. Using Matrigel assays, we have stratified HBC cell lines for invasiveness in vitro, and compared this to their potential for metastatic spread in nude mice. HBC cell lines expressing the mesenchymal marker protein vimentin were found to be highly invasive in vitro, and tended to form metastases in nude mice. We have further discovered that culture on collagen-I gels (Vitrogen(TM): Vg) induces MMP-2-activator in highly invasive but not poorly invasive HBC cell lines. As seen for other MMP-2-activator inducing regimens, this induction requires protein synthesis and an intact MMP-2 hemopexin-like domain, appears to be mediated by a cell surface activity, and can be inhibited by metalloproteinase inhibitors. The induction is highly specific to collagen I, and is not seen with thin coatings of collagen I, collagen IV, laminin, or fibronectin, or with 3-dimensional gels of laminin, Matrigel, or gelatin. This review focuses on collagen I and MMP- 2, their localization and source in HBC, and their relationship(s) to MMP-2 activation and HBC metastasis. The relevance of collagen I in activation of MMP-2 in vivo is discussed in terms of stromal cell: tumor cell interaction for collagen I deposition, MMP-2 production and MMP-2-activation. Such cooperativity may exist in vivo for MMP-2 participation in HBC dissemination. A more complete understanding of the regulation of MMP-2-activator by type I collagen may provide new avenues for improved diagnosis and prognosis of human breast cancer.

In-vehicle railway level crossing warning systems : can intelligent transport systems deliver?

Intelligent Transport System (ITS) technology is seen as a cost-effective way to increase the conspicuity of approaching trains and the effectiveness of train warnings at level crossings by providing an in-vehicle warning of an approaching train. The technology is often seen as a potential low-cost alternative to upgrading passive level crossings with traditional active warning systems (flashing lights and boom barriers). ITS platforms provide sensor, localization and dedicated short-range communication (DSRC) technologies to support cooperative applications such as collision avoidance for road vehicles. In recent years, in-vehicle warning systems based on ITS technology have been trialed at numerous locations around Australia, at level crossing sites with active and passive controls. While significant research has been conducted on the benefits of the technology in nominal operating modes, little research has focused on the effects of the failure modes, the human factors implications of unreliable warnings and the technology adoption process from the railway industry’s perspective. Many ITS technology suppliers originate from the road industry and often have limited awareness of the safety assurance requirements, operational requirements and legal obligations of railway operators. This paper aims to raise awareness of these issues and start a discussion on how such technology could be adopted. This paper will describe several ITS implementation cenarios and discuss failure modes, human factors considerations and the impact these scenarios are likely to have in terms of safety, railway safety assurance requirements and the practicability of meeting these requirements. The paper will identify the key obstacles impeding the adoption of ITS systems for the different implementation scenarios and a possible path forward towards the adoption of ITS technology.

Learning experiences for the transition to professional work

A better educated workforce contributes to a more informed and tolerant society with higher economic output, and this is also associated with higher levels of personal health, interpersonal trust and civic and social engagement. Against this backdrop, the role of universities has expanded, as university learning has moved beyond providing an education to preparing students for leadership positions within society. This article examines the effectiveness of final-year learning experiences from the perception of recent graduates. The aim is to improve undergraduate curriculum to facilitate the transition to professional employment. An online quantitative and qualitative survey instrument was developed to investigate graduates’ perceptions of their different learning experiences and assessment types in their senior year. Four hundred and twelve alumni from five universities completed the survey. Our results indicate that graduates value case studies, group work and oral presentations, and that graduates rate lectures and guest lectures from practitioners as the least important in their transition to work. The results validate the use of graduate capability frameworks and mapping the development of the skills over the curriculum. These results are useful for curriculum designers to assist with designing programmes on the transition to professional work.