A peptidomimetic inhibitor of matrix metalloproteinases containing a tetherable linker group

Successful wound repair and normal turnover of the extracellular matrix relies on a balance between matrix metalloproteinases (MMPs) and their natural inhibitors (the TIMPs). When over-expression of MMPs and abnormally high levels of activation or low expression of TIMPs are encountered, excessive degradation of connective tissue and the formation of chronic ulcers can occur. One strategy to rebalance MMPs and TIMPs is to use inhibitors. We have designed a synthetic pseudopeptide inhibitor with an amine linker group based on a known high-affinity peptidomimetic MMP inhibitor have demonstrated inhibition of MMP-1, -2, -3 and -9 activity in standard solutions. The inhibitor was also tethered to a polyethylene glycol hydrogel using a facile reaction between the linker unit on the inhibitor and the hydrogel precursors. After tethering, we observed inhibition of the MMPs although there was an increase in the IC50s which was attributed to poor diffusion of the MMPs into the hydrogels, reduced activity of the tethered inhibitor or incomplete incorporation of the inhibitor into the hydrogels. When the tethered inhibitors were tested against chronic wound fluid we observed significant inhibition in proteolytic activity suggesting our approach may prove useful in rebalancing MMPs within chronic wounds.

Ordering of Ge islands on Si(001) substrates patterned by nanoindentation

Spatial organization of Ge islands, grown by physical vapor deposition, on prepatterned Si(001) substrates has been investigated. The substrates were patterned prior to Ge deposition by nanoindentation. Characterization of Ge dots is performed by atomic force microscopy and scanning electron microscopy. The nanoindents act as trapping sites, allowing ripening of Ge islands at those locations during subsequent deposition and diffusion of Ge on the surface. The results show that island ordering is intrinsically linked to the nucleation and growth at indented sites and it strongly depends on pattern parameters.

Applying the open innovation system concept to infrastructure projects

Purpose: The goal of this conceptual paper is to provide tools to help maximise the value delivered by infrastructure projects, by developing methods to increase adoption of innovative products during construction. Methods: The role of knowledge flows in determining innovation adoption rates is conceptually examined. A promising new approach is developed. Open innovation system theory is extended, by reviewing the role of three frameworks: (1) knowledge intermediaries, (2) absorptive capacity and (3) governance arrangements. Originality: We develop a novel open innovation system model to guide further research in the area of adoption of innovation on infrastructure projects. The open innovation system model currently lacks definition of core concepts, especially with regard to the impact of different degrees and types of openness. The three frameworks address this issue and add substance to the open innovation system model, addressing widespread criticism that it is underdeveloped. The novelty of our model is in the combination of the three frameworks to explore the system. These frameworks promise new insights into system dynamics and facilitate the development of new methods to optimise the diffusion of innovation. Practical Implications: The framework will help to reveal gaps in knowledge flows that impede the uptake of innovations. In the past, identifying these gaps has been difficult given the lack of nuance in existing theory. The knowledge maps proposed will enable informed policy advice to effectively harness the power of knowledge networks, increase innovation diffusion and improve the performance of infrastructure projects. The models developed in this paper will be used in planned empirical research into innovation on large scale infrastructure projects in the Australian built environment.

The role of the built environment in the creation, cultivation and acquisition of a knowledge-base

This chapter explores the role of the built environment in the creation, cultivation and acquisition of a knowledge base by people populating the urban landscape. It examines McDonald’s restaurants as a way to comprehend the relevance of the physical design in the diffusion of codified and tacit knowledge at an everyday level. Through an examination of space at a localised level, this chapter describes the synergies of space and the significance of this relationship in navigating the global landscape.

In situ preparation and protein delivery of silicate/alginate composite microspheres with core-shell structure

It is predicted that with increased life expectancy in the developed world, there will be a greater demand for synthetic materials to repair or regenerate lost, injured or diseased bone (Hench & Thompson 2010). There are still few synthetic materials having true bone inductivity, which limits their application for bone regeneration, especially in large-size bone defects. To solve this problem, growth factors, such as bone morphogenetic proteins (BMPs), have been incorporated into synthetic materials in order to stimulate de novo bone formation in the center of large-size bone defects. The greatest obstacle with this approach is that the rapid diffusion of the protein from the carrier material, leading to a precipitous loss of bioactivity; the result is often insufficient local induction or failure of bone regeneration (Wei et al. 2007). It is critical that the protein is loaded in the carrier material in conditions which maintains its bioactivity (van de Manakker et al. 2009). For this reason, the efficient loading and controlled release of a protein from a synthetic material has remained a significant challenge. The use of microspheres as protein/drug carriers has received considerable attention in recent years (Lee et al. 2010; Pareta & Edirisinghe 2006; Wu & Zreiqat 2010). Compared to macroporous block scaffolds, the chief advantage of microspheres is their superior protein-delivery properties and ability to fill bone defects with irregular and complex shapes and sizes. Upon implantation, the microspheres are easily conformed to the irregular implant site, and the interstices between the particles provide space for both tissue and vascular ingrowth, which are important for effective and functional bone regeneration (Hsu et al. 1999). Alginates are natural polysaccharides and their production does not have the implicit risk of contamination with allo or xeno-proteins or viruses (Xie et al. 2010). Because alginate is generally cytocompatible, it has been used extensively in medicine, including cell therapy and tissue engineering applications (Tampieri et al. 2005; Xie et al. 2010; Xu et al. 2007). Calcium cross-linked alginate hydrogel is considered a promising material as a delivery matrix for drugs and proteins, since its gel microspheres form readily in aqueous solutions at room temperature, eliminating the need for harsh organic solvents, thereby maintaining the bioactivity of proteins in the process of loading into the microspheres (Jay & Saltzman 2009; Kikuchi et al. 1999). In addition, calcium cross-linked alginate hydrogel is degradable under physiological conditions (Kibat PG et al. 1990; Park K et al. 1993), which makes alginate stand out as an attractive candidate material for the protein carrier and bone regeneration (Hosoya et al. 2004; Matsuno et al. 2008; Turco et al. 2009). However, the major disadvantages of alginate microspheres is their low loading efficiency and also rapid release of proteins due to the mesh-like networks of the gel (Halder et al. 2005). Previous studies have shown that a core-shell structure in drug/protein carriers can overcome the issues of limited loading efficiencies and rapid release of drug or protein (Chang et al. 2010; Molvinger et al. 2004; Soppimath et al. 2007). We therefore hypothesized that introducing a core-shell structure into the alginate microspheres could solve the shortcomings of the pure alginate. Calcium silicate (CS) has been tested as a biodegradable biomaterial for bone tissue regeneration. CS is capable of inducing bone-like apatite formation in simulated body fluid (SBF) and its apatite-formation rate in SBF is faster than that of Bioglass® and A-W glass-ceramics (De Aza et al. 2000; Siriphannon et al. 2002). Titanium alloys plasma-spray coated with CS have excellent in vivo bioactivity (Xue et al. 2005) and porous CS scaffolds have enhanced in vivo bone formation ability compared to porous β-tricalcium phosphate ceramics (Xu et al. 2008). In light of the many advantages of this material, we decided to prepare CS/alginate composite microspheres by combining a CS shell with an alginate core to improve their protein delivery and mineralization for potential protein delivery and bone repair applications

Investigation of electrophoretic loading and enhanced mechanical properties of hydrogels for delivery of therapeutic proteins

Hydrogels, which are three-dimensional crosslinked hydrophilic polymers, have been used and studied widely as vehicles for drug delivery due to their good biocompatibility. Traditional methods to load therapeutic proteins into hydrogels have some disadvantages. Biological activity of drugs or proteins can be compromised during polymerization process or the process of loading protein can be really timeconsuming. Therefore, different loading methods have been investigated. Based on the theory of electrophoresis, an electrochemical gradient can be used to transport proteins into hydrogels. Therefore, an electrophoretic method was used to load protein in this study. Chemically and radiation crosslinked polyacrylamide was used to set up the model to load protein electrophoretically into hydrogels. Different methods to prepare the polymers have been studied and have shown the effect of the crosslinker (bisacrylamide) concentration on the protein loading and release behaviour. The mechanism of protein release from the hydrogels was anomalous diffusion (i.e. the process was non-Fickian). The UV-Vis spectra of proteins before and after reduction show that the bioactivities of proteins after release from hydrogel were maintained. Due to the concern of cytotoxicity of residual monomer in polyacrylamide, poly(2-hydroxyethyl- methacrylate) (pHEMA) was used as the second tested material. In order to control the pore size, a polyethylene glycol (PEG) porogen was introduced to the pHEMA. The hydrogel disintegrated after immersion in water indicating that the swelling forces exceeded the strength of the material. In order to understand the cause of the disintegration, several different conditions of crosslinker concentration and preparation method were studied. However, the disintegration of the hydrogel still occurred after immersion in water principally due to osmotic forces. A hydrogel suitable for drug delivery needs to be biocompatible and also robust. Therefore, an approach to improving the mechanical properties of the porogen-containing pHEMA hydrogel by introduction of an inter-penetrating network (IPN) into the hydrogel system has been researched. A double network was formed by the introduction of further HEMA solution into the system by both electrophoresis and slow diffusion. Raman spectroscopy was used to observe the diffusion of HEMA into the hydrogel prior to further crosslinking by ã-irradiation. The protein loading and release behaviour from the hydrogel showing enhanced mechanical property was also studied. Biocompatibility is a very important factor for the biomedical application of hydrogels. Different hydrogels have been studied on both a three-dimensional HSE model and a HSE wound model for their biocompatibilities. They did not show any detrimental effect to the keratinocyte cells. From the results reported above, these hydrogels show good biocompatibility in both models. Due to the advantage of the hydrogels such as the ability to absorb and deliver protein or drugs, they have potential to be used as topical materials for wound healing or other biomedical applications.

Influence of physical and chemical parameters on the treatment of heavy metals in polluted stormwater using zeolite : A review

Zeolite-based technology can provide a cost effective solution for stormwater treatment for the removal of toxic heavy metals under increasing demand of safe water from alternative sources. This paper reviews the currently available knowledge relating to the effect of properties of zeolites such as pore size, surface area and Si:Al ratio and the physico-chemical conditions of the system such as pH, temperature, initial metal concentration and zeolite concentration on heavy metal removal performance. The primary aims are, to consolidate available knowledge and identify knowledge gaps. It was established that an in-depth understanding of operational issues such as, diffusion of metal ions into the zeolite pore structure, pore clogging, zeolite surface coverage by particulates in stormwater as well as the effect of pH on stormwater quality in the presence of zeolites is essential for developing a zeolite-based technology for the treatment of polluted stormwater. The optimum zeolite concentration to treat typical volumes of stormwater and initial heavy metal concentrations in stormwater should also be considered as operational issues in this regard. Additionally, leaching of aluminium and sodium ions from the zeolite structure to solution were identified as key issues requiring further research in the effort to develop cost effective solutions for the removal of heavy metals from stormwater.

NMR relaxation behavior and quadrupole coupling constants of 39K and 23Na ions in glycerol. Comparisons with 39K tissue data

The quadrupole coupling constants (qcc) for39K and23Na ions in glycerol have been calculated from linewidths measured as a function of temperature (which in turn results in changes in solution viscosity). The qcc of39K in glycerol is found to be 1.7 MHz, and that of23Na is 1.6 MHz. The relaxation behavior of39K and23Na ions in glycerol shows magnetic field and temperature dependence consistent with the equations for transverse relaxation more commonly used to describe the reorientation of nuclei in a molecular framework with intramolecular field gradients. It is shown, however, that τc is not simply proportional to the ratio of viscosity/temperature (ηT). The 39K qcc in glycerol and the value of 1.3 MHz estimated for this nucleus in aqueous solution are much greater than values of 0.075 to 0.12 MHz calculated from T2 measurements of39K in freshly excised rat tissues. This indicates that, in biological samples, processes such as exchange of potassium between intracellular compartments or diffusion of ions through locally ordered regions play a significant role in determining the effective quadrupole coupling constant and correlation time governing39K relaxation. T1 and T2 measurements of rat muscle at two magnetic fields also indicate that a more complex correlation function may be required to describe the relaxation of39K in tissue. Similar results and conclusions are found for23Na.

The Australian built environment : current challenges and innovative responses

The exploratory research presented in this discussion paper was undertaken as input to a major research grant application for the Australian Research Council. The research looks at the contribution of the Australian built environment to meet social and environmental needs. The paper examines the following research questions: What are the main challenges facing the Australian built environment? What types of building innovations might address those challenges? The research questions were addressed through desk-top research, involving an international review of (1) relevant academic literature in top-tier construction management and general management journals, and (2) high profile industry reports published internationally. Future research will involve assessing the diffusion of the identified building innovations and gauging their impact on social and environmental goals.

Deformation with coupled chemical diffusion

The deformation of rocks is commonly intimately associated with metamorphic reactions. This paper is a step towards understanding the behaviour of fully coupled, deforming, chemically reacting systems by considering a simple example of the problem comprising a single layer system with elastic-power law viscous constitutive behaviour where the deformation is controlled by the diffusion of a single chemical component that is produced during a metamorphic reaction. Analysis of the problem using the principles of non-equilibrium thermodynamics allows the energy dissipated by the chemical reaction-diffusion processes to be coupled with the energy dissipated during deformation of the layers. This leads to strain-rate softening behaviour and the resultant development of localised deformation which in turn nucleates buckles in the layer. All such diffusion processes, in leading to Herring-Nabarro, Coble or “pressure solution” behaviour, are capable of producing mechanical weakening through the development of a “chemical viscosity”, with the potential for instability in the deformation. For geologically realistic strain rates these chemical feed-back instabilities occur at the centimetre to micron scales, and so produce structures at these scales, as opposed to thermal feed-back instabilities that become important at the 100–1000 m scales.

First principle study of hydrogenation of MgB2 : an important step toward reversible hydrogen storage in the coupled LiBH4/MgH2 system

Recent experiments [F. E. Pinkerton, M. S. Meyer, G. P. Meisner, M. P. Balogh, and J. J. Vajo, J. Phys. Chem. C 111, 12881 (2007) and J. J. Vajo and G. L. Olson, Scripta Mater. 56, 829 (2007)] demonstrated that the recycling of hydrogen in the coupled LiBH4/MgH2 system is fully reversible. The rehydrogenation of MgB2 is an important step toward the reversibility. By using ab initio density functional theory calculations, we found that the activation barrier for the dissociation of H2 are 0.49 and 0.58 eV for the B and Mg-terminated MgB2(0001) surface, respectively. This implies that the dissociation kinetics of H2 on a MgB2 (0001) surface should be greatly improved compared to that in pure Mg materials. Additionally, the diffusion of dissociated H atom on the Mg-terminated MgB2(0001) surface is almost barrier-less. Our results shed light on the experimentally-observed reversibility and improved kinetics for the coupled LiBH4/MgH2 system.

The location of Ti atom in sodium alanate : an ab initio spin-polarised study

In this work, ab initio spin-polarised Density Functional Theory (DFT) calculations are performed to study the interaction of a Ti atom with a NaAlH4(001) surface. We confirm that an interstitially located Ti atom in the NaAlH4 subsurface is the most energetically favoured configuration as recently reported (Chem. Comm. (17) 2006, 1822). On the NaAlH4(001) surface, the Ti atom is most stable when adsorbed between two sodium atoms with an AlH4 unit beneath. A Ti atom on top of an Al atom is also found to be an important structure at low temperatures. The diffusion of Ti from the Al-top site to the Na-bridging site has a low activation barrier of 0.20 eV and may be activated at the experimental temperatures (∼323 K). The diffusion of a Ti atom into the energetically favoured subsurface interstitial site occurs via the Na-bridging surface site and is essentially barrierless.

Catalytic effects of subsurface carbon in the chemisorption of hydrogen on a Mg(0001) surface: an ab-initio study

Ab initio density functional theory (DFT) calculations are performed to explore possible catalytic effects on the dissociative chemisorption of hydrogen on a Mg(0001) surface when carbon is incorporated into Mg materials. The computational results imply that a C atom located initially on a Mg(0001) surface can migrate into the subsurface and occupy an fcc interstitial site, with charge transfer to the C atom from neighboring Mg atoms. The effect of subsurface C on the dissociation of H2 on the Mg(0001) surface is found to be relatively marginal: a perfect sublayer of interstitial C is calculated to lower the barrier by 0.16 eV compared with that on a pure Mg(0001) surface. Further calculations reveal, however, that sublayer C may have a significant effect in enhancing the diffusion of atomic hydrogen into the sublayers through fcc channels. This contributes new physical understanding toward rationalizing the experimentally observed improvement in absorption kinetics of H2 when graphite or single walled carbon nanotubes (SWCNT) are introduced into the Mg powder during ball milling.

Social Media Sites as Online Information Grounds : An exploratory study of the ways in which Information Technology (IT) professionals experience social media

Social media tools are often the result of innovations in Information Technology and developed by IT professionals and innovators. Nevertheless, IT professionals, many of whom are responsible for designing and building social media technologies, have not been investigated on how they themselves use or experience social media for professional purposes. This study will use Information Grounds Theory (Pettigrew, 1998) as a framework to study IT professionals’ experience in using social media for professional purposes. Information grounds facilitates the opportunistic discovery of information within social settings created temporarily at a place where people gather for a specific purpose (e.g., doctors’ waiting rooms, office tea rooms etc.), but the social atmosphere stimulates spontaneous sharing of information (Pettigrew, 1999). This study proposes that social media has the qualities that make it a rich information grounds; people participate from separate “places” in cyberspace in a synchronous manner in real-time, making it almost as dynamic and unplanned as physical information grounds. There is limited research on how social media platforms are perceived as a “place,” (a place to go to, a place to gather, or a place to be seen in) that is comparable to physical spaces. There is also no empirical study on how IT professionals use or “experience” social media. The data for this study is being collected through a study of IT professionals who currently use Twitter. A digital ethnography approach is being taken wherein the researcher uses online observations and “follows” the participants online and observes their behaviours and interactions on social media. Next, a sub-set of participants will be interviewed on their experiences with and within social media and how social media compares with traditional methods of information grounds, information communication, and collaborative environments. An Evolved Grounded Theory (Glaser, 1992) approach will be used to analyse tweets data and interviews and to map the findings against the Information Ground Theory. Findings from this study will provide foundational understanding of IT professionals’ experiences within social media, and can help both professionals and researchers understand this fast-evolving method of communications.