MTI-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression

Membrane type 1 metalloprotease (MT1-MMP) is a transmembrane metalloprotease that plays a major role in the extracellular matrix remodeling, directly by degrading several of its components and indirectly by activating pro-MMP2. We investigated the effects of MT1-MMP overexpression on in vitro and in vivo properties of human breast adenocarcinoma MCF7 cells, which do not express MT1-MMP or MMP-2. MT1-MMP and MMP-2 cDNAs were either transfected alone or cotransfected. All clones overexpressing MT1-MMP 1) were able to activate endogenous or exogenous pro-MMP-2, 2) displayed an enhanced in vitro invasiveness through matrigel-coated filters independent of MMP-2 transfection, 3) induced the rapid development of highly vascularized tumors when injected subcutanously in nude mice, and 4) promoted blood vessels sprouting in the rat aortic ring assay. These effects were observed in all clones overexpressing MT1-MMP regardless of MMP-2 expression levels, suggesting that the production of MMP-2 by tumor cells themselves does not play a critical role in these events. The angiogenic phenotype of MT1-MMP-producing cells was associated with an up-regulation of VEGF expression. These results emphasize the importance of MT1-MMP during tumor angiogenesis and open new opportunities for the development of antiangiogenic strategies combining inhibitors of MT1-MMP and VEGF antagonists. - Sounni, N. E., Devy, L., Hajitou, A., Frankenne, F., Munaut, C., Gilles, C., Deroanne, C., Thompson, E. W., Foidart, J. M., Noel, A. MT1-MMP expression promotes tumor growth and angiogenesis through an up-regulation of vascular endothelial growth factor expression.

New particle formation and growth at a remote, sub-tropical coastal location

A month-long intensive measurement campaign was conducted in March/April 2007 at Agnes Water, a remote coastal site just south of the Great Barrier Reef on the east coast of Australia. Particle and ion size distributions were continuously measured during the campaign. Coastal nucleation events were observed in clean, marine air masses coming from the south-east on 65% of the days. The events usually began at ~10:00 local time and lasted for 1-4 hrs. They were characterised by the appearance of a nucleation mode with a peak diameter of ~10 nm. The freshly nucleated particles grew within 1-4 hrs up to sizes of 20-50 nm. The events occurred when solar intensity was high (~1000 W m-2) and RH was low (~60%). Interestingly, the events were not related to tide height. The volatile and hygroscopic properties of freshly nucleated particles (17-22.5 nm), simultaneously measured with a volatility-hygroscopicity-tandem differential mobility analyser (VH-TDMA), were used to infer chemical composition. The majority of the volume of these particles was attributed to internally mixed sulphate and organic components. After ruling out coagulation as a source of significant particle growth, we conclude that the condensation of sulphate and/or organic vapours was most likely responsible for driving particle growth during the nucleation events. We cannot make any direct conclusions regarding the chemical species that participated in the initial particle nucleation. However, we suggest that nucleation may have resulted from the photo-oxidation products of unknown sulphur or organic vapours emitted from the waters of Hervey Bay, or from the formation of DMS-derived sulphate clusters over the open ocean that were activated to observable particles by condensable vapours emitted from the nutrient rich waters around Fraser Island or Hervey Bay. Furthermore, a unique and particularly strong nucleation event was observed during northerly wind. The event began early one morning (08:00) and lasted almost the entire day resulting in the production of a large number of ~80 nm particles (average modal concentration during the event was 3200 cm-3). The Great Barrier Reef was the most likely source of precursor vapours responsible for this event.

Percutaneous insertion of Dual Growth Rods using a new mobile bearing implant

Growth rods are commonly used for the treatment of scoliosis in the immature spine. Many variations have been proposed but breakage of implants is a common problem. Growth rod insertion commonly involves large exposures at initial insertion followed by multiple smaller procedures for lengthening. We present our early experiences using a percutaneous technique of insertion of a new titanium mobile bearing implant (Medtronic Inc). The implant allows some rotatory motion in the middle of the construct thus reducing construct stresses and thus possibly reducing rod breakage risk. Based on this small initial series with 12 months follow-up, percutaneous insertion of growth rods using the new implant is a safe and reliable technique although the infection rate in our sample was of note. This may be related to the titanium wear and inflammation seen in the soft tissues at time of operation and visualised on histology. No implants have required removal due to infection, and all infections were treated with debridement at next lengthening and suppressive antibiotics. Propionibacterium is one of the commonest infections seen with spinal implants and sometimes does not respond to simple antibiotic suppression. The technique allows preservation of the soft tissues until definitive fusion is needed and may lead to a decrease in hospital stay. The implant is low profile and seems to offer advantages over other systems on the market. Further follow up is needed to look at longer term outcomes with this new implant type.

From the consciousness industry to the creative industries : consumer-created content, social network markets, & the growth of knowledge

In studies of media industries, too much attention has been paid to providers and firms, too little to consumers and markets. But with user-created content, the question first posed more than a generation ago by the uses & gratifications method and taken up by semiotics and the active audience tradition (‘what do audiences do with media?’), has resurfaced with renewed force. What’s new is that where this question (of what the media industries and audiences did with each other) used to be individualist and functionalist, now, with the advent of social networks using Web 2.0 affordances, it can be re-posed at the level of systems and populations as well.

The big brother : monitoring urban growth and change for sustainable infrastructure provision

Monitoring urban growth and land-use change is an important issue for sustainable infrastructure planning. Rapid urban development, sprawl and increasing population pressure, particularly in developing nations, are resulting in deterioration of infrastructure facilities, loss of productive agricultural lands and open spaces, pollution, health hazards and micro-climatic changes. In addressing these issues effectively, it is crucial to collect up-to-date and accurate data and monitor the changing environment at regular intervals. This chapter discusses the role of geospatial technologies for mapping and monitoring the changing environment and urban structure, where such technologies are highly useful for sustainable infrastructure planning and provision.

Posttraumatic growth in Australian populations

It is easy to assume that because Australia and the United States are both predominantly English speaking countries that are relatively young and share many similarities in terms of their historical beginnings, they elicit the same results when investigating psychological constructs. In recent years this has been questioned across a number of domains (e.g., personality and stereotyping) and research has demonstrated that although many constructs are universal, there are differences between these nations; some subtle and others quite stark (McCrae et al., 2005; Terraciano et al., 2005). In this chapter we discuss research that has investigated Posttraumatic Growth (PTG) in various populations in Australia and highlight the similarities and differences that have been found between Australian samples and those published in other countries, especially the US. Data are drawn from quantitative and qualitative investigations conducted with groups who have experienced diverse traumatic events as either direct survivors (e.g., rape, armed hold-up, bereavement) or vicarious survivors (e.g., paramedics). A description of the Australian context sets the scene for the ensuing discussion about PTG in Australian populations.

Port of Brisbane stormwater quality : stage 1 rainfall simulation to evaluate pollutant build-up and wash-off from selected land uses

Background: The quality of stormwater runoff from ports is significant as it can be an important source of pollution to the marine environment. This is also a significant issue for the Port of Brisbane as it is located in an area of high environmental values. Therefore, it is imperative to develop an in-depth understanding of stormwater runoff quality to ensure that appropriate strategies are in place for quality improvement. ---------------- The Port currently has a network of stormwater sample collection points where event based samples together with grab samples are tested for a range of water quality parameters. Whilst this information provides a ‘snapshot’ of the pollutants being washed from the catchment/s, it does not allow for a quantifiable assessment of total contaminant loads being discharged to the waters of Moreton Bay. It also does not represent pollutant build-up and wash-off from the different land uses across a broader range of rainfall events which might be expected. As such, it is difficult to relate stormwater quality to different pollutant sources within the Port environment. ----------------- Consequently, this would make the source tracking of pollutants to receiving waters extremely difficult and in turn the ability to implement appropriate mitigation measures. Also, without this detailed understanding, the efficacy of the various stormwater quality mitigation measures implemented cannot be determined with certainty. --------------- Current knowledge on port stormwater runoff quality Currently, little knowledge exists with regards to the pollutant generation capacity specific to port land uses as these do not necessarily compare well with conventional urban industrial or commercial land use due to the specific nature of port activities such as inter-modal operations and cargo management. Furthermore, traffic characteristics in a port area are different to a conventional urban area. Consequently, as data inputs based on an industrial and commercial land uses for modelling purposes is questionable. ------------------ A comprehensive review of published research failed to locate any investigations undertaken with regards to pollutant build-up and wash-off for port specific land uses. Furthermore, there is very limited information made available by various ports worldwide about the pollution generation potential of their facilities. Published work in this area has essentially focussed on the water quality or environmental values in the receiving waters such as the downstream bay or estuary. ----------------- The Project: The research project is an outcome of the collaborative Partnership between the Port of Brisbane Corporation (POBC) and Queensland University of Technology (QUT). A key feature of this Partnership is the undertaking of ‘cutting edge’ research to strengthen the environmental custodianship of the Port area. This project aims to develop a port specific stormwater quality model to allow informed decision making in relation to stormwater quality improvement in the context of the increased growth of the Port. --------------- Stage 1 of the research project focussed on the assessment of pollutant build-up and wash-off using rainfall simulation from the current Port of Brisbane facilities with the longer-term objective of contributing to the development of ecological risk mitigation strategies for future expansion scenarios. Investigation of complex processes such as pollutant wash-off using naturally occurring rainfall events has inherent difficulties. These can be overcome using simulated rainfall for the investigations. ----------------- The deliverables for Stage 1 included the following: * Pollutant build-up and wash-off profiles for six primary land uses within the Port of Brisbane to be used for water quality model development. * Recommendations with regards to future stormwater quality monitoring and pollution mitigation measures. The outcomes are expected to deliver the following benefits to the Port of Brisbane: * The availability of Port specific pollutant build-up and wash-off data will enable the implementation of customised stormwater pollution mitigation strategies. * The water quality data collected would form the baseline data for a Port specific water quality model for mitigation and predictive purposes. * To be at the cutting-edge in terms of water quality management and environmental best practice in the context of port infrastructure. ---------------- Conclusions: The important conclusions from the study are: * It confirmed that the Port environment is unique in terms of pollutant characteristics and is not comparable to typical urban land uses. * For most pollutant types, the Port land uses exhibited lower pollutant concentrations when compared to typical urban land uses. * The pollutant characteristics varied across the different land uses and were not consistent in terms of the land use. Hence, the implementation of stereotypical structural water quality improvement devices could be of limited value. * The <150m particle size range was predominant in suspended solids for pollutant build-up as well as wash-off. Therefore, if suspended solids are targeted as the surrogate parameter for water quality improvement, this specific particle size range needs to be removed. ------------------- Recommendations: Based on the study results the following preliminary recommendations are made: * Due to the appreciable variation in pollutant characteristics for different port land uses, any water quality monitoring stations should preferably be located such that source areas can be easily identified. * The study results having identified significant pollutants for the different land uses should enable the development of a more customised water quality monitoring and testing regime targeting the critical pollutants. * A ‘one size fits all’ approach may not be appropriate for the different port land uses due to the varying pollutant characteristics. As such, pollution mitigation will need to be specifically tailored to suit the specific land use. * Any structural measures implemented for pollution mitigation to be effective should have the capability to remove suspended solids of size <150m. * Based on the results presented and the particularly the fact that the Port land uses cannot be compared to conventional urban land uses in relation to pollutant generation, consideration should be given to the development of a port specific water quality model.

Modulation of dermal microvascular endithelial cell responses to growth factors and haemostatic factors in the presence of vitronectin

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Economic growth, inequality and technology adoption in transitional economies

The stylized facts that motivate this thesis include the diversity in growth patterns that are observed across countries during the process of economic development, and the divergence over time in income distributions both within and across countries. This thesis constructs a dynamic general equilibrium model in which technology adoption is costly and agents are heterogeneous in their initial holdings of resources. Given the households‟ resource level, this study examines how adoption costs influence the evolution of household income over time and the timing of transition to more productive technologies. The analytical results of the model constructed here characterize three growth outcomes associated with the technology adoption process depending on productivity differences between the technologies. These are appropriately labeled as „poverty trap‟, „dual economy‟ and „balanced growth‟. The model is then capable of explaining the observed diversity in growth patterns across countries, as well as divergence of incomes over time. Numerical simulations of the model furthermore illustrate features of this transition. They suggest that that differences in adoption costs account for the timing of households‟ decision to switch technology which leads to a disparity in incomes across households in the technology adoption process. Since this determines the timing of complete adoption of the technology within a country, the implications for cross-country income differences are obvious. Moreover, the timing of technology adoption appears to be impacts on patterns of growth of households, which are different across various income groups. The findings also show that, in the presence of costs associated with the adoption of more productive technologies, inequalities of income and wealth may increase over time tending to delay the convergence in income levels. Initial levels of inequalities in the resources also have an impact on the date of complete adoption of more productive technologies. The issue of increasing income inequality in the process of technology adoption opens up another direction for research. Specifically increasing inequality implies that distributive conflicts may emerge during the transitional process with political- economy consequences. The model is therefore extended to include such issues. Without any political considerations, taxes would leads to a reduction in inequality and convergence of incomes across agents. However this process is delayed if politico-economic influences are taken into account. Moreover, the political outcome is sub optimal. This is essentially due to the fact that there is a resistance associated with the complete adoption of the advanced technology.

Towards a controlled growth of self-assembled nanostructures: shaping, ordering and localization in Ge/Si heteroepitaxy.

The strain-induced self-assembly of suitable semiconductor pairs is an attractive natural route to nanofabrication. To bring to fruition their full potential for actual applications, individual nanostructures need to be combined into ordered patterns in which the location of each single unit is coupled with others and the surrounding environment. Within the Ge/Si model system, we analyze a number of examples of bottom-up strategies in which the shape, positioning, and actual growth mode of epitaxial nanostructures are tailored by manipulating the intrinsic physical processes of heteroepitaxy. The possibility of controlling elastic interactions and, hence, the configuration of self-assembled quantum dots by modulating surface orientation with the miscut angle is discussed. We focus on the use of atomic steps and step bunching as natural templates for nanodot clustering. Then, we consider several different patterning techniques which allow one to harness the natural self-organization dynamics of the system, such as: scanning tunneling nanolithography, focused ion beam and nanoindentation patterning. By analyzing the evolution of the dot assembly by scanning probe microscopy, we follow the pathway which leads to lateral ordering, discussing the thermodynamic and kinetic effects involved in selective nucleation on patterned substrates.

Professional growth through working together : a study of reciprocal benefits for teacher and education advisor through classroom based professional development

Teacher professional development provided by education advisors as one-off, centrally offered sessions does not always result in change in teacher knowledge, beliefs, attitudes or practice in the classroom. As the mathematics education advisor in this study, I set out to investigate a particular method of professional development so as to influence change in a practising classroom teacher’s knowledge and practices. The particular method of professional development utilised in this study was based on several principles of effective teacher professional development and saw me working regularly in a classroom with the classroom teacher as well as providing ongoing support for her for a full school year. The intention was to document the effects of this particular method of professional development in terms of the classroom teacher’s and my professional growth to provide insights for others working as education advisors. The professional development for the classroom teacher consisted of two components. The first was the co-operative development and implementation of a mental computation instructional program for the Year 3 class. The second component was the provision of ongoing support for the classroom teacher by the education advisor. The design of the professional development and the mental computation instructional program were progressively refined throughout the year. The education advisor fulfilled multiple roles in the study as teacher in the classroom, teacher educator working with the classroom teacher and researcher. Examples of the professional growth of the classroom teacher and the education advisor which occurred as sequences of changes (growth networks, Hollingsworth, 1999) in the domains of the professional world of the classroom teacher and education advisor were drawn from the large body of data collected through regular face-to-face and email communications between the classroom teacher and the education advisor as well as from transcripts of a structured interview. The Interconnected Model of Professional Growth (Clarke & Hollingsworth, 2002; Hollingsworth, 1999) was used to summarise and represent each example of the classroom teacher’s professional growth. A modified version of this model was used to summarise and represent the professional growth of the education advisor. This study confirmed that the method of professional development utilised could lead to significant teacher professional growth related directly to her work in the classroom. Using the Interconnected Model of Professional Growth to summarise and represent the classroom teacher’s professional growth and the modified version for my professional growth assisted with the recognition of examples of how we both changed. This model has potential to be used more widely by education advisors when preparing, implementing, evaluating and following-up on planned teacher professional development activities. The mental computation instructional program developed and trialled in the study was shown to be a successful way of sequencing and managing the teaching of mental computation strategies and related number sense understandings to Year 3 students. This study was conducted in one classroom, with one teacher in one school. The strength of this study was the depth of teacher support provided made possible by the particular method of the professional development, and the depth of analysis of the process. In another school, or with another teacher, this might not have been as successful. While I set out to change my practice as an education advisor I did not expect the depth of learning I experienced in terms of my knowledge, beliefs, attitudes and practices as an educator of teachers. This study has changed the way in which I plan to work as an education advisor in the future.

ACE research vignette 001 : benefits and drawbacks of start-up team heterogeneity

This series of research vignettes is aimed at sharing current and interesting research findings from our team of international Entrepreneurship researchers. In this vignette, Dr. Micheal Stuetzer considers some of the benefits and drawbacks associated with team start-up.

Growth-hormone-stimulated dentinogenesis in Lewis dwarf rat molars

In dentinogenesis, certain growth factors, matrix proteoglycans, and proteins are directly or indirectly dependent on growth hormone. The hypothesis that growth hormone up-regulates the expression of enzymes, sialoproteins, and other extracellular matrix proteins implicated in the formation and mineralization of tooth and bone matrices was tested by the treatment of Lewis dwarf rats with growth hormone over 5 days. The molar teeth were processed for immunohistochemical demonstration of bone-alkaline phosphatase, bone morphogenetic proteins-2 and -4, osteocalcin, osteopontin, bone sialoprotein, and E11 protein. Odontoblasts responded to growth hormone by more cells expressing bone morphogenetic protein, alkaline phosphatase, osteocalcin, and osteopontin. No changes were found in bone sialoprotein or E11 protein expression. Thus, growth hormone may stimulate odontoblasts to express several growth factors and matrix proteins associated with dentin matrix biosynthesis in mature rat molars.