Gelatinase A (MMP-2) activation by skin fibroblasts : dependence on MT1-MMP expression and fibrillar collagen form

The respective requirements of collagen and MT1-MMP in the activation of MMP-2 by primary fibroblast cultures were explored further. Three-dimensional gels enriched in human collagen types I and III or composed of recombinant human type II or III collagen, caused increased MT1-MMP production (mRNA and protein) and induced MMP-2 activation. Only marginal induction was seen with dried monomeric collagen confirming the need for collagen fibrillar organisation for activation. To our surprise, relatively low amounts (as low as 25 μg/ml) of acid soluble type I collagen added to fibroblast cultures also induced potent MMP-2 activation. However, the requirement for collagen fibril formation by the added collagen was indicated by the inhibition seen when the collagen was pre-incubated with a fibril-blocking peptide, and the reduced activation seen with alkali-treated collagen preparations known to have impaired fibrilisation. Pre-treatment of the collagen with sodium periodate also abrogated MMP-2 activation induction. Further evidence of the requirement for collagen fibril formation was provided by the lack of activation when type IV collagen, which does not form collagen fibrils, was added in the cultures. Fibroblasts derived from MT1-MMP-deficient mice were unable to activate MMP-2 in response to either three-dimensional collagen gel or added collagen solutions, compared to their littermate controls. Collectively, these data indicate that the fibrillar structure of collagen and MT1-MMP are essential for the MMP-2 activational response in fibroblasts.

Optimising the cell source and biomaterials for the generation of vascularized adipose tissue in vivo

We initially described a rat chamber model with an inserted arteriovenous pedicle which spontaneously generates 3-dimensional vascularized connective tissue (Tanaka Y et al., Br J Plast Surg 2000; 53: 51-7). More recently we have developed a murine chamber model containing reconstituted basement membrane (Matrigel®) and FGF-2 that generates vascularized adipose tissue in vivo (Cronin K et al., Plast Reconstr Surg 2004; in press). We have extended this work to assess the cellular and matrix requirements for the Matrigel®- induced neo-adipogenesis. We found that chambers sealed to host fat were unable to grow new adipose tissue. In these chambers the Matrigel® became vascularized with maximal outgrowth of vessels extending to the periphery at 6 weeks. A small amount of adipose tissue was found adjacent to the vessels, most likely arising from periadventitial adipose tissue. In contrast, chambers open to interaction with endogenous adipose tissue showed abundant new fat, and partial exposure to adjacent adipose tissue clearly showed neo-adipogenesis only in this area. Addition of small amounts of free fat to the closed chamber containing Matrigel® was able to induce neo-adipogenesis. Addition of small pieces of human fat also caused neo-adipogenesis in immunocompromised (SCID) mice. Also, we found Matrigel® to induce adipogenesis of Lac-Z-tagged (Rosa-26) murine bone marrow-derived mesenchymal stem cells, and cells similar to these have been isolated from human adipose tissue. Given that Matrigel® is a mouse product and cannot be used in humans, we have started investigating alternative matrix scaffolds for adipogenesis such as the PDA-approved PLGA, collagen and purified components derived from Matrigel®, such as laminin-1. The optimal conditions for adipogenesis with these matrices are still being elucidated. In conclusion, we have demonstrated that a precursor cell source inside the chamber is essential for the generation of vascularized adipose tissue in vivo. This technique offers unique potential for the reconstruction of soft tissue defects and may enable the generation of site-specific tissue using the correct microenvironment.

A Bayesian hurdle model for analysis of an insect resistance monitoring database

Motivated by the analysis of the Australian Grain Insect Resistance Database (AGIRD), we develop a Bayesian hurdle modelling approach to assess trends in strong resistance of stored grain insects to phosphine over time. The binary response variable from AGIRD indicating presence or absence of strong resistance is characterized by a majority of absence observations and the hurdle model is a two step approach that is useful when analyzing such a binary response dataset. The proposed hurdle model utilizes Bayesian classification trees to firstly identify covariates and covariate levels pertaining to possible presence or absence of strong resistance. Secondly, generalized additive models (GAMs) with spike and slab priors for variable selection are fitted to the subset of the dataset identified from the Bayesian classification tree indicating possibility of presence of strong resistance. From the GAM we assess trends, biosecurity issues and site specific variables influencing the presence of strong resistance using a variable selection approach. The proposed Bayesian hurdle model is compared to its frequentist counterpart, and also to a naive Bayesian approach which fits a GAM to the entire dataset. The Bayesian hurdle model has the benefit of providing a set of good trees for use in the first step and appears to provide enough flexibility to represent the influence of variables on strong resistance compared to the frequentist model, but also captures the subtle changes in the trend that are missed by the frequentist and naive Bayesian models.

Insurance and trust : lessons from the Christchurch Cathedral

This article examines important insurance and trust law issues that may confront trustees charged with the governance and protection of unique properties with broad community and heritage significance. Often trustee roles are assumed by community leaders without full appreciation of the potential difficulties and consequences when unforeseen circumstances arise. Three recent New Zealand court decisions in relation to the deconstruction and repair of the Christchurch Cathedral and to the interim construction of a transitional"cardboard Cathedral" highlight how difficult - and legally exposed - the role of trustee can be. The Cathedral cases go to the heart of defining the core purpose for which a Trust is created and examine the scope of discretion in fulfilling this charge its Trustees carry. Arising in the wake of the devastating Christchurch earthquakes, the Cathedral's Trustees were called upon to consider the best directions forward for a criplled and dangerous building subject to potential demolition, the wellbeing of the Cathedral's direct community, and the broader heritage and identity factors that this 'heart' of Christchurch represented. In the context of a seemingly grossly underinsured material damage cover - and faced with broader losses across the Diocese's holdings - the Trustees found that their sense of mission failed to gel with that of a community-based heritage buildings preservation trust. The High Court had to consider how monies received under the material damage policy could be applied by the Trustee in deconstructing, reinstating or repairing the Cathedral and if monies could be partly deployed to create an interim solution in the former of a transitional cathedral - all this in the context of the site-specific purpose of the Cathedral trust. The cases emphasise further the need to assess professionally the nature and quantum of cover effected to protect against various risks. In addition, in the case of historic or unusual buildings extra care must be exercised to take account additional costs associated with reinstatement so as to substantially retain the character and intrinsic value of such properties.

BRAF inhibitors : from the laboratory to clinical trials

BRAF is one of the most commonly mutated proto-oncogenes and plays a significant role in the development of numerous cancers of high clinical impact. Due to the commonality of BRAF mutations, a number of BRAF inhibitors have been developed as tools in the management of patients with cancers dependent on the action of mutant BRAF to drive cellular proliferation. In this review, we examine the current state of clinical trials and laboratory research concerning BRAF inhibitors in development and available for clinical use. We contrast the effectiveness of type-I and type-II BRAF inhibitors, the former typically showing much more restricted inhibitory selectivity and greater patient response rates.

Enterprise system lifecycle-wide innovation - research in progress

Enterprise Systems purport to bring innovation to organizations. Yet, no past studies, neither from innovation nor from ES disciplines have merged their knowledge to understand how ES could facilitate lifecycle-wide innovation. Therefore, this study forms conceptual bridge between the two disciplines. In this research, we seek to understand how ES could facilitate innovation across its lifecycle phases. We associate classifications of innovation such as radical vs. incremental, administrative vs. technical innovation with the three phases of ES lifecycle. We introduce Continuous Restrained Innovation (CRI) as a new type of innovation specific to ES, considering restraints of technology, business processes and organization. Our empirical data collection at the implementation phase, using data from both the client and implementation partner, shows preliminary evidence of CRI. In addition, we state that both parties consider the implementation of ES as a radical innovation yet, are less interest in seeking further innovations through the system.

Electrical characteristics of lateral heterostructure organic field-effect bipolar transistors

We describe and discuss the unique electrical characteristics of an organic field-effect transistor in which the active layer consists of a type II lateral heterojunction located approximately midway between the source and drain. The two active semiconductors on either side of the junction transport only one carrier type each, with the other becoming trapped, which leads to devices that operate in only the steady state when there is balanced electron and hole injections from the drain and source. We describe the unique transfer characteristics of such devices in two material systems.

The road we're on

The creative development and direction of THE ROAD WE'RE ON (Book by Stephen Carleton, Music by Scott Saunders), commissioned by the Queensland Music Festival and the Murweh Shire Council. The was a site-specific, community-driven music theatre production produced and performed in Charleville and involved over 100 local artists and the communities of western Queensland.

Guardians of hidden universes

“Guardians of Hidden Universes” is a playful story for experiencing on your phone in the street. You’re a Guardian of Hidden Universes, and when you check your Communication Terminal you find the Guild has made a terrible mistake they need you to repair. The experience lasts about 15-25 minutes, and takes you around whatever city you happen to be in. That’s right – you can play it in any city in the world! The app was launched at Popup Playground‘s 2013 Fresh Air Festival – a new pervasive gaming festival in Melbourne, Australia. This playful story is inspired by the idea of creating a locative-experience that is not site-specific. How can we have an experience than engages with the environment that also can work worldwide? The story is also playing with the idea of engaging with a character and a space and intuition within a short period of time. The short and playful experience is a Universe Creation 101 production. It was conceived, written, and designed by Christy Dena; with artwork, coding, and interface design by Elroy.

Identification of genes important for growth of asymptomatic bacteriuria Escherichia coli in urine

Escherichia coli is the most important etiological agent of urinary tract infections (UTIs). Unlike uropathogenic E. coli, which causes symptomatic infections, asymptomatic bacteriuria (ABU) E. coli strains typically lack essential virulence factors and colonize the bladder in the absence of symptoms. While ABU E. coli can persist in the bladder for long periods of time, little is known about the genetic determinants required for its growth and fitness in urine. To identify such genes, we have employed a transposon mutagenesis approach using the prototypic ABU E. coli strain 83972 and the clinical ABU E. coli strain VR89. Six genes involved in the biosynthesis of various amino acids and nucleobases were identified (carB, argE, argC, purA, metE, and ilvC), and site-specific mutants were subsequently constructed in E. coli 83972 and E. coli VR89 for each of these genes. In all cases, these mutants exhibited reduced growth rates and final cell densities in human urine. The growth defects could be complemented in trans as well as by supplementation with the appropriate amino acid or nucleobase. When assessed in vivo in a mouse model, E. coli 83972carAB and 83972argC showed a significantly reduced competitive advantage in the bladder and/or kidney during coinoculation experiments with the parent strain, whereas 83972metE and 83972ilvC did not. Taken together, our data have identified several biosynthesis pathways as new important fitness factors associated with the growth of ABU E. coli in human urine.

Collective coverings, communal skin

Collective Coverings, Communal Skin is a large-scale site-specific installation that grows with community contributions created for the 2012 Liverpool Biennial. The work involves transforming objects used in conflict (second hand hunting and camouflage t-shirts) into objects of comfort (hula hoop rag mats) . Many of the shirts were either donated or purchased from thrift stores in Los Angeles and Liverpool. With the massive help of the Liverpool community we transformed individual t-shirts through weaving them into a communal skin that covers the existing internal architecture. There was a workshop space with instruction video, inside the installation where visitors could sit and work on patchwork body-pillows. During structured workshops I talked with the community about meditating while they weave so as to contemplate the spiritual and conceptual dimension of the project. The hula-hoop weavings grew throughout the space for the duration of the 10-week Biennial. The community contributed 770 weavings. This project was funded by the Australia Council for the Arts and FACT.

Development of a flexible design approach for the deflection zone behind road safety barriers

Flexible design practices broadly permit that design values outside the normal range can be accepted as appropriate for a site-specific context providing that the risk is evaluated and is tolerable. Execution of flexible design demands some evaluation of risk. In restoration projects, it may be the case that an immovable object exists within the zone of the expected deflection of a road safety barrier system. Only by design exception can the situation be determined to be acceptable. However, the notion of using flexible design for road safety barrier design is not well developed. The existence of a diminishing return relationship between safety benefits and provision of increased clear zone has been established previously. This paper proposes that a similar rationale might reasonably apply for the deflection zone behind road safety barriers and describes how the risk associated with road safety barriers might be quantified in order that defensible road safety barrier design can exist below the lower bounds of normal design standards. As such, the methodology described in this paper may provide some basis to enable road authorities to make informed design decisions, particularly for restoration, or “Brownfield”, projects.

Soil moisture variability in a temperate deciduous forest: insights from electrical resistivity and throughfall data

Hydrogeophysics is a growing discipline that holds significant promise to help elucidate details of dynamic processes in the near surface, built on the ability of geophysical methods to measure properties from which hydrological and geochemical variables can be derived. For example, bulk electrical conductivity is governed by, amongst others, interstitial water content, fluid salinity, and temperature, and can be measured using a range of geophysical methods. In many cases, electrical resistivity tomography (ERT) is well suited to characterize these properties in multiple dimensions and to monitor dynamic processes, such as water infiltration and solute transport. In recent years, ERT has been used increasingly for ecosystem research in a wide range of settings; in particular to characterize vegetation-driven changes in root-zone and near-surface water dynamics. This increased popularity is due to operational factors (e.g., improved equipment, low site impact), data considerations (e.g., excellent repeatability), and the fact that ERT operates at scales significantly larger than traditional point sensors. Current limitations to a more widespread use of the approach include the high equipment costs, and the need for site-specific petrophysical relationships between properties of interest. In this presentation we will discuss recent equipment advances and theoretical and methodological aspects involved in the accurate estimation of soil moisture from ERT results. Examples will be presented from two studies in a temperate climate (Michigan, USA) and one from a humid tropical location (Tapajos, Brazil).

Novel polymer synthesis methodologies using combination of thermally and photochemically-induced nitroxide mediated polymerisation

The combination of thermally- and photochemically-induced polymerization using light sensitive alkoxyamines was investigated. The thermally driven polymerizations were performed via the cleavage of the alkoxyamine functionality, whereas the photochemically-induced polymerizations were carried out either by nitroxide mediated photo-polymerization (NMP2) or by a classical type II mechanism, depending on the structure of the light-sensitive alkoxyamine employed. Once the potential of the various structures as initiators of thermally- and photo-induced polymerizations was established, their use in combination for block copolymer syntheses was investigated. With each alkoxyamine investigated, block copolymers were successfully obtained and the system was applied to the post-modification of polymer coatings for application in patterning and photografting.

Source characterisation of urban road surface pollutants for enhanced water quality predictions

This study developed a comprehensive research methodology for identification and quantification of sources responsible for pollutant build-up and wash-off from urban road surfaces. The study identified soil and asphalt wear, and non-combusted diesel fuel as the most influential sources for metal and hydrocarbon pollution respectively. The study also developed mathematical models to relate contributions from identified sources to underlying site specific factors such as land use and traffic. Developed mathematical model will play a key role in urban planning practices, enabling the implementation of effective water pollution control strategies.