Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

Particle emissions, volatility, and toxicity from an ethanol fumigated compression ignition engine

Particle emissions, volatility, and the concentration of reactive oxygen species (ROS) were investigated for a pre-Euro I compression ignition engine to study the potential health impacts of employing ethanol fumigation technology. Engine testing was performed in two separate experimental campaigns with most testing performed at intermediate speed with four different load settings and various ethanol substitutions. A scanning mobility particle sizer (SMPS) was used to determine particle size distributions, a volatilization tandem differential mobility analyzer (V-TDMA) was used to explore particle volatility, and a new profluorescent nitroxide probe, BPEAnit, was used to investigate the potential toxicity of particles. The greatest particulate mass reduction was achieved with ethanol fumigation at full load, which contributed to the formation of a nucleation mode. Ethanol fumigation increased the volatility of particles by coating the particles with organic material or by making extra organic material available as an external mixture. In addition, the particle-related ROS concentrations increased with ethanol fumigation and were associated with the formation of a nucleation mode. The smaller particles, the increased volatility, and the increase in potential particle toxicity with ethanol fumigation may provide a substantial barrier for the uptake of fumigation technology using ethanol as a supplementary fuel.

The synthesis of novel isoindoline nitroxides bearing water-solubilising functionality

A range of novel tetramethyl- and tetraethylisoindolinenitroxides, possessing aryl-linked carboxylic acids, amines, alcohols and phosphonic acids were prepared. Notably, the chemistry established for the aromatic dibromination of the tetramethylisoindolines was not easily transferred to the corresponding tetraethylisoindoline system. Instead, various tetraethylisoindoline analogues were accessed by the oxidation of methyl groups attached to the aromatic ring to give the carboxylic acids. The increased steric bulk of the tetraethyl structures should limit bio-reduction and these compounds may have potential as antioxidants.

The effective and the evocative : reflecting on practice-led research approaches in art and design

Early in the practice-led research debate, Steven Scrivener (2000, 2002) identified some general differences in the approach of artists and designers undertaking postgraduate research. His distinctions centered on the role of the artefact in problem-based research (associated with design) and creative-production research (associated with artistic practice). Nonetheless, in broader discussions on practice-led research, 'art and design' often continues to be conflated within a single term. In particular, marked differences between art and design methodologies, theoretical framing, research goals and research claims have been underestimated. This paper revisits Scrivener's work and establishes further distinctions between art and design research. It is informed by our own experiences of postgraduate supervision and research methods training, and an empirical study of over sixty postgraduate, practice-led projects completed at the Creative Industries Faculty of QUT between 2002 and 2008. Our reflections have led us to propose that artists and designers work with differing research goals (the evocative and the effective, respectively), which are played out in the questions asked, the creative process, the role of the artefact and the way new knowledge is evidenced. Of course, research projects will have their own idiosyncrasies but, we argue, marking out the poles at each end of the spectrum of art and design provides useful insights for postgraduate candidates, supervisors and methodologists alike.

How relevant is tourism research

One of the definitions of the term myth is ‘an unproved or false collective belief that is used to justify a social institution’ (see http://dictionary.reference.com/browse/myth). Before we are criticized for suggesting such an irreverent thought might apply to tourism academia, readers must recognize that organizations and industries often operate using shared collective myths (see Meyer and Rowan 1977). Institutionalized rules and processes function as myths that provide legitimacy. The question of interest in this paper is not in the context of the quality of tourism academic research output, which is addressed by other papers in this research probe section. Rather, of importance is enhancing understanding of the extent to which our collective knowledge, legitimized through publishing in peer reviewed academic publications, is proving of value to industry stakeholders, an axiom that appears to be largely unquestioned and unproven.

Destination branding case study : tracking brand equity for an emerging destination between 2003 and 2007

Place branding has become a major focus of operations for destination marketing organizations (DMOs) striving for differentiation in cluttered markets. The topic of destination branding has only received attention in the tourism literature since the late 1990s, and there has been relatively little research reported in relations to analyzing destination brand effectiveness over time. This article reports an attempt to oprationalize the concept of consumer-based brand equity (CBBE) for an emerging destination over two points in time. The purpose of the project was to track the effectiveness of the brand in 2007 against benchmarks that were established in a 2003 student at the commencement of a new destination brand campaign. The key finding was there was no change in perceived performance for the destination across the brand's performance indicators and CBBE dimensions. Because of the common challenges faced by DMOs worldwide, it is suggested the CBBE hierarchy provides destination marketers with a practical tool for evaluation brand performance over time.

Generation in context : an exploratory method for musical enquiry

This paper discusses a method, Generation in Context, for interrogating theories of music analysis and music perception. Given an analytic theory, the method consists of creating a generative process that implements the theory in reverse. Instead of using the theory to create analyses from scores, the theory is used to generate scores from analyses. Subjective evaluation of the quality of the musical output provides a mechanism for testing the theory in a contextually robust fashion. The method is exploratory, meaning that in addition to testing extant theories it provides a general mechanism for generating new theoretical insights. We outline our initial explorations in the use of generative processes for music research, and we discuss how generative processes provide evidence as to the veracity of theories about how music is experienced, with insights into how these theories may be improved and, concurrently, provide new techniques for music creation. We conclude that Generation in Context will help reveal new perspectives on our understanding of music.

Evolving interactions : agile design for networked media performance

Network Jamming systems provide real-time collaborative performance experiences for novice or inexperienced users. In this paper we will outline the interaction design considerations that have emerged during through evolutionary development cycles of the jam2jam Network Jamming software that employs generative techniques that require particular attention to the human computer relationship. In particular we describe the co-evolution of features and uses, explore the role of agile development methods in supporting this evolution, and show how the provision of a clear core capability can be matched with options for enhanced features support multi-levelled user experience and skill develop.

Destination branding : tracking brand equity for a competitive set of near-home destinations

In the emerging literature related to destination branding, little has been reported about performance metrics. The focus of most research reported to date has been concerned with the development of destination brand identities and the implementation of campaigns (see for example, Crockett & Wood 1999, Hall 1999, May 2001, Morgan et al 2002). One area requiring increased attention is that of tracking the performance of destination brands over time. This is an important gap in the tourism literature, given: i) the increasing level of investment by destination marketing organisations (DMO) in branding since the 1990s, ii) the complex political nature of DMO brand decision-making and increasing accountability to stakeholders (see Pike, 2005), and iii) the long-term nature of repositioning a destination’s image in the market place (see Gartner & Hunt, 1987). Indeed, a number of researchers in various parts of the world have pointed to a lack of market research monitoring destination marketing objectives, such as in Australia (see Prosser et. al 2000, Carson, Beattie and Gove 2003), North America (Sheehan & Ritchie 1997, Masberg 1999), and Europe (Dolnicar & Schoesser 2003)...