Implication of collagen type I-induced membrane-type 1-matrix metalloproteinase expression and matrix metalloproteinase-2 activation in the metastatic progression of breast carcinoma

We have previously demonstrated that fibroblasts and invasive human breast carcinoma (HBC) cells specifically activate matrix metalloproteinase- 2 (MMP-2) when cultured on 3-dimensional gels of type I collagen but not a range of other substrates. We show here the constitutive expression of membrane-type 1 (MT1)-MMP in both fibroblasts, and invasive HBC cell lines, that have fibroblastic attributes presumably acquired through an epithelial- to-mesenchymal transition (EMT). Treatment with collagen type I increased the steady-state MT1-MMP mRNA levels in these cells but did not induce either MT1-MMP expression or MMP-2 activation in noninvasive breast carcinoma cell lines, which retain epithelial features. Basal MT3-MMP mRNA expression had a pattern similar to that of MT1-MMP but was not up-regulated by collagen. MT4- MMP mRNA was seen in both invasive and noninvasive HBC cell lines and was also not collagen-regulated, and MT2-MMP mRNA was not detected in any of the HBC cell lines tested. These data support a role for MT1-MMP in the collagen- induced MMP-2-activation seen in these cells. In situ hybridization analysis of archival breast cancer specimens revealed a close parallel in expression of both collagen type I and MT1-MMP mRNA in peritumoral fibroblasts, which was correlated with aggressiveness of the lesion. Relatively high levels of expression of both mRNA species were seen in fibroblasts close to invasive tumor nests and, although only focally, in certain areas close to preinvasive tumors. These foci may represent hot spots for local degradation and invasive progression. Collectively, these results implicate MT1-MMP in collagen- stimulated MMP-2 activation and suggest that this mechanism may be employed in vivo by both tumor-associated fibroblasts and EMT-derived carcinoma cells to facilitate increased invasion and/or metastasis.

The type I collagen induction of MT1-MMP-mediated MMP-2 activation is repressed by αVβ3 integrin in human breast cancer cells

The influence of αVβ3 integrin on MT1-MMP functionality was studied in human breast cancer cells of differing β3 integrin status. Overexpression of β3 integrin caused increased cell surface expression of αV integrin and increased cellular adhesion to extracellular matrix (ECM) substrates in BT-549, MDA-MB-231 and MCF-7 cells. β3 integrin expression also enhanced the migration of breast cancer cells on ECM substrates and enhanced collagen gel contraction. In vivo, αVβ3 cooperated with MT1-MMP to increase the growth of MCF-7 cells after orthotopic inoculation in immunocompromised mice, but had no influence on in vitro proliferation. Despite these stimulatory effects, overexpression of β3 integrin suppressed the type I collagen (Col I) induced MMP-2 activation in all breast cancer cell lines analyzed. This was also evident in extracts from the MCF-7 tumors in vivo, where MMP-2 activation was stimulated by MT1-MMP transfection, but attenuated with β3 integrin expression. Although our studies confirm important biological effects of αVβ3 integrin on enhancing cell adhesion and migration, ECM remodeling and tumor growth, β3 integrin caused reduced MMP-2 activation in response to Col I in vitro, which appears to be physiologically relevant, as it was also seen in tumor xenografts in vivo. The reduction of MMP-2 activation (and thus MT1-MMP activity) by αVβ3 in response to Col I may be important in scenarios where cells which are activated for matrix degradation need to preserve some pericellular collagen, perhaps as a substrate for cell adhesion and migration, thus maintaining a balanced level of proteolysis required for efficient tumor growth.

Contemporary public spaces in urban knowledge precincts : observations from Brisbane, Australia

The advanced era of knowledge-based urban development has led to an unprecedented increase in mobility of people and the subsequent growth in the new typology of agglomerated enclaves of knowledge such as urban knowledge precincts. A new role has been assigned to contemporary public spaces of these precincts to attract and retain the mobile knowledge workforce for long by creating a sense of place for them. This paper sheds light over the place making in the globalised knowledge economy world which develops a sense of permanence spatio-temporally to knowledge workers displaying a set of particular characteristics and simultaneously is process-dependent getting developed by the internal and external flows and contributing substantially in the development of the broader context it stands in relation with. The paper highlights the observations from Australia’s new world city Brisbane to outline the application of urban design as a tool to create and sustain this bipartite place making in urban knowledge precincts, which caters diverse range of social, cultural and democratic needs. It seeks to analyse the modified permeable typology of public spaces that makes it more viable and adaptive as per the changing needs of the contemporary globalised or in other words knowledge society. This research has taken an overall process-based approach reflecting how urban design is an assemblage of the encompassing processes that underlay the resultant place making. It explores how the permeable design typology of these contemporary precincts in Brisbane develops a progressive sense of place that makes them stimulating, effervescent and vibrant.

A variant of the breast cancer type 2 susceptibility protein (BRC) repeat is essential for the RECQL5 Helicase to interact with RAD51 Recombinase for genome stabilization

The BRC repeat is a structural motif in the tumor suppressor BRCA2 (breast cancer type 2 susceptibility protein), which promotes homologous recombination (HR) by regulating RAD51 recombinase activity. To date, the BRC repeat has not been observed in other proteins, so that its role in HR is inferred only in the context of BRCA2. Here, we identified a BRC repeat variant, named BRCv, in the RECQL5 helicase, which possesses anti-recombinase activity in vitro and suppresses HR and promotes cellular resistance to camptothecin-induced replication stress in vivo. RECQL5-BRCv interacted with RAD51 through two conserved motifs similar to those in the BRCA2-BRC repeat. Mutations of either motif compromised functions of RECQL5, including association with RAD51, inhibition of RAD51-mediated D-loop formation, suppression of sister chromatid exchange, and resistance to camptothecin-induced replication stress. Potential BRCvs were also found in other HR regulatory proteins, including Srs2 and Sgs1, which possess anti-recombinase activities similar to that of RECQL5. A point mutation in the predicted Srs2-BRCv disrupted the ability of the protein to bind RAD51 and to inhibit D-loop formation. Thus, BRC is a common RAD51 interaction module that can be utilized by different proteins to either promote HR, as in the case of BRCA2, or to suppress HR, as in RECQL5.

p-type doping of ZnO by means of high-density inductively coupled plasmas

A custom-designed inductively coupled plasma assisted radio-frequency magnetron sputtering deposition system has been used to fabricate N-doped p-type ZnO (ZnO:N) thin films on glass substrates from a sintered ZnO target in a reactive Ar + N2 gas mixture. X-ray diffraction and scanning electron microscopy analyses show that the ZnO:N films feature a hexagonal crystal structure with a preferential (002) crystallographic orientation and grow as vertical columnar structures. Hall effect and X-ray photoelectron spectroscopy analyses show that N-doped ZnO thin films are p-type with a hole concentration of 3.32 × 1018 cm- 3 and mobility of 1.31 cm2 V- 1 s- 1. The current-voltage measurement of the two-layer structured ZnO p-n homojunction clearly reveals the rectifying ability of the p-n junction. The achievement of p-type ZnO:N thin films is attributed to the high dissociation ability of the high-density inductively coupled plasma source and effective plasma-surface interactions during the growth process.

Aluminum-assisted crystallization and p-type doping of polycrystalline Si

Aluminum-doped p-type polycrystalline silicon thin films have been synthesized on glass substrates using an aluminum target in a reactive SiH 4+Ar+H2 gas mixture at a low substrate temperature of 300∈°C through inductively coupled plasma-assisted RF magnetron sputtering. In this process, it is possible to simultaneously co-deposit Si-Al in one layer for crystallization of amorphous silicon, in contrast to the conventional techniques where alternating metal and amorphous Si layers are deposited. The effect of aluminum target power on the structural and electrical properties of polycrystalline Si films is analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and Hall-effect analysis. It is shown that at an aluminum target power of 100 W, the polycrystalline Si film features a high crystalline fraction of 91%, a vertically aligned columnar structure, a sheet resistance of 20.2 kΩ/□ and a hole concentration of 6.3×1018 cm-3. The underlying mechanism for achieving the semiconductor-quality polycrystalline silicon thin films at a low substrate temperature of 300∈°C is proposed.

Heating mechanism of self-interaction of surface polaritons at n-type semiconductor-metal interface

The influence of electron heating in the high-frequency surface polariton (SP) field on the dispersion properties of the SPs considered is investigated. High frequency SPs propagate at the interface between an n-type semiconductor with finite electron pressure, and a metal. The nonlinear dispersion relation for the SPs is derived and investigated.

Self-interaction of surface polaritons at the narrow-gap n-type semiconductor metal interface

The non-linear self-interaction of the potential surface polaritons (SP) which is due to the free carriers dispersion law where nonparabolicity is studied. The SP propagate at the interface between n-type semiconductor and a metal. The self interaction of the SP is shown to be different in semiconductors with normal and inverse zone structures. The results of the SP field envelope evolution are given. The obtained nonlinear frequency shift has been compared with shifts which are due to another self-interaction mechanisms. This comparison shows that the nonlinear self-interaction mechanism, which is due to free carriers spectrum nonparabolicity, is especially significant in narrow-gap semiconductor materials.

Controlling current and voltage type interfaces in power-hardware-in-the-loop simulations

The usual practice to study a large power system is through digital computer simulation. However, the impact of large scale use of small distributed generators on a power network cannot be evaluated strictly by simulation since many of these components cannot be accurately modelled. Moreover, the network complexity makes the task of practical testing on a physical network nearly impossible. This study discusses the paradigm of interfacing a real-time simulation of a power system to real-life hardware devices. This type of splitting a network into two parts and running a real-time simulation with a physical system in parallel is usually termed as power-hardware-in-the-loop (PHIL) simulation. The hardware part is driven by a voltage source converter that amplifies the signals of the simulator. In this paper, the effects of suitable control strategy on the performance of PHIL and the associated stability aspects are analysed in detail. The analyses are validated through several experimental tests using an real-time digital simulator.

Evaluation of resonant damping techniques for Z-source current-type inverter

For the renewable energy sources whose outputs vary continuously, a Z-source current-type inverter has been proposed as a possible buck-boost alternative for grid-interfacing. With a unique X-shaped LC network connected between its dc power source and inverter topology, Z-source current-type inverter is however expected to suffer from compounded resonant complications in addition to those associated with its second-order output filter. To improve its damping performance, this paper proposes the careful integration of Posicast or three-step compensators before the inverter pulse-width modulator for damping triggered resonant oscillations. In total, two compensators are needed for wave-shaping the inverter boost factor and modulation ratio, and they can conveniently be implemented using first-in first-out stacks and embedded timers of modern digital signal processors widely used in motion control applications. Both techniques are found to damp resonance of ac filter well, but for cases of transiting from current-buck to boost state, three-step technique is less effective due to the sudden intermediate discharging interval introduced by its non-monotonic stepping (unlike the monotonic stepping of Posicast damping). These findings have been confirmed both in simulations and experiments using an implemented laboratory prototype.

Networking iPads into Preschool Spaces

This chapter explores preschools as networked spaces into which iPads were introduced, which involved the mediation of complex relationships between children and adults, physical and virtual technology and other materials like toys, play spaces, art materials and books. The chapter aims to explain how these human and non-human ‘actors’ come to coexist and lead to the development of literacy and creativity in specific ways. This approach particularly draws attention to specific challenges faced by the teachers as they negotiated a range of complex demands and obstacles to make the iPads available to the children for play and learning.

Art spaces in community and economic development : connections to neighborhoods, artists, and the cultural economy

There is growing interest in the arts in community and economic development, yet little research examines the dynamics of community-based arts institutions to inform urban planning and policy. Drawing on interviews with participants and organizers of small and midsized art spaces, the study explores the factors that influence their involvement in neighborhood revitalization and outreach, support for artistic communities, and efforts to build bridges to commercial cultural sectors. Art spaces function as a conduit for building social networks that contribute to both community revitalization and artistic development. But issues pertaining to the location, organization, and management of art spaces may limit their community and economic development potential. The article concludes with proposals to craft stronger arts-based community and economic development programs.

Art spaces, public space, and the link to community development

Recent literature credits community art spaces with both enhancing social interaction and engagement and generating economic revitalization. This article argues that the ability of art spaces to realize these outcomes is linked to their role as public spaces and that their community development potential can be expanded with greater attention to this role. An analysis of the public space characteristics is useful because it encourages consideration of sometimes overlooked issues, particularly the effect of the physical environment on outcomes related to community development. I examine the relationship between public space and community development at various types of art spaces including artist cooperatives, ethnic-specific art spaces, and city-sponsored art centers in central city and suburban locations. This study shows that through their programming and other activities, art spaces serve various public space roles related to community development. However, the ability of many to perform as public spaces is hindered by facility design issues and poor physical connections in their surrounding area. This article concludes with proposals for enhancing the community development role of the art spaces through their function as public spaces.

Development and evaluation of the Ontrack Diabetes Program : an automated, web-based type 2 diabetes self-management and dysphoria intervention

This research was conducted in the area of Clinical and Health Psychology. The study involved the development and evaluation of a novel, web-based program aimed to improve Type 2 diabetes self-management and mood. The program was developed as an original technological intervention aimed to improve access to support for rural and remote communities, and is currently being trialled across Australia with a larger sample size. The researcher aims to continue research into the field of clinical psychology, and in particular is interested in working on further interventions to support those with comorbid physical and mental health conditions.

Designing schools as effective 21st C learning spaces : a review

The Queensland Centre for Social Science Innovation was formed in 2012 to develop collaborations among the Queensland Government and five Queensland universities—The University of Queensland, Griffith University, Queensland University of Technology, James Cook University and Central Queensland University. Three priorities for initial projects were established by the Queensland Government with response by the participating universities. This project addressed the identified priority area: factors affecting educational achievement and investigation of the link between school design, refurbishment and educational outcomes. The proposal for this project indicated that a Review of research literature would be undertaken that linked school and classroom design with educational outcomes for learners in the 21st century. Further, research would be examined for impact of technology on staff and students, as well as learning spaces that addressed the diversity of student learners. Specific investigation of research on effective design to enhance learning outcomes for Aboriginal and Torres Strait Islander students was to be undertaken. The project therefore consists of a Review of research literature to provide an evidence base on the impact of school and classroom on educational outcomes. The original proposal indicated that indicators of successful school and classroom design would be student learning outcomes on a range of variables, with input, the specific architectural design elements. The review was undertaken during the period July 2012 to June 2013. A search was undertaken of journals, databases, and websources to identify relevant material. These were examined for evidence-based statements and design of learning spaces to enhance learning. The Review is comprehensive, and representative of issues raised in research, and conceptualisations and debates informing modern educational design. Initial findings indicated two key findings central to reading this Review. The first key finding is that the predominant focus of modern design of learning space is on process and the engagement of stakeholders. Schools are social institutions and development of a school as a learning space to suit 21st century learning needs necessarily involves the staff, students and other members of the community as key participants. The concept of social aspects of design is threaded throughout the Review. The second key finding is that little research explicitly examined the relationship between the design of learning spaces and educational outcomes. While some research does exist, the most explicitly-focused research uses narrow test-based achievement as the learning outcomes. These are not sympathetic to the overall framings of the research on 21st century learning, future schooling and the needs of the new generation of learners and society.