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.

3-D reconstruction of an ancient Egyptian mummy using X-ray computer tomography

Computer tomography has been used to image and reconstruct in 3-D an Egyptian mummy from the collection of the British Museum. This study of Tjentmutengebtiu, a priestess from the 22nd dynasty (945-715 BC) revealed invaluable information of a scientific, Egyptological and palaeopathological nature without mutilation and destruction of the painted cartonnage case or linen wrappings. Precise details on the removal of the brain through the nasal cavity and the viscera from the abdominal cavity were obtained. The nature and composition of the false eyes were investigated. The detailed analysis of the teeth provided a much closer approximation of age at death. The identification of materials used for the various amulets including that of the figures placed in the viscera was graphically demonstrated using this technique.

Small Business and entrepreneurship policy

There are two key approaches to entrepreneurship, each of which has different implications for small business policy (Danson 2002). The first conceives of entrepreneurship as an economic process and can be traced to the work of Joseph Schumpeter who developed the concept of creative destruction to describe the entrepreneurial process that led to the simultaneous elimination of old industries and activities and the creation of new activities through the commercial application of new ideas. While entrepreneurship as a process of creative destruction might include start up activity amongst small firms, it does not exclusively involve small firms as large firms may contribute to the entrepreneurial process through the generation of new knowledge and by assisting in financing the development of new ideas amongst small firms. Although innovation occurs in large as well as small firms, the literature on small enterprise innovation draws heavily on Schumpeter’s depiction of the central role of the entrepreneur in the process of creative destruction, whereby the economic system is transformed from within and new cycles in economic life emerge in which new industries and markets replace old industries and markets. Schumpeter argued that entrepreneurs drove the process of innovation and that innovation was a stimulus to economic development and involved the development of new products, processes, methods of production or new forms of commercial or financial organisation (Schumpeter 1911). At a time when technological development and structuraleconomic change are occurring at a rapid pace, small firm innovation is seen to be critically important because empirical evidence, although not undisputed, indicates that SMEs make an important contribution to radical innovations in new industries (Nooteboom 1994). The second view of entrepreneurship focuses on the individual entrepreneur more than the entrepreneurial process. The entrepreneur is depicted as an owner of small businesses, and is regarded as having particular personal characteristics such as self-reliance, individual initiative and self-motivation. Entrepreneurs are also considered to have a behavioural orientation towards the exploitation of new ideas and opportunities. They are the risk takers who are able to see an opportunity and pursue it commercially despite the uncertainty of rewards. The capacity to plan, manage and lead is also seen to be identifying characteristics of entrepreneurs. Different small business policy approaches arise from these different perspectives on entrepreneurship. Small business policy approaches that emphasise the process by which new ideas are generated and applied commercially arise from the first and broader view of entrepreneurship. Policies designed to generate a population of risk taking and self-motivated individuals with highly developed management and commercial skills are more in keeping with the second approach, which is focused on the individual entrepreneur rather than the entrepreneurial process.

Vibrational spectroscopic studies of wool

Fourier transfonn (FT) Raman, Raman microspectroscopy and Fourier transform infrared (FTIR) spectroscopy have been used for the structural analysis and characterisation of untreated and chemically treated wool fibres. For FT -Raman spectroscopy novel methods of sample presentation have been developed and optimised for the analysis of wool. No significant fluorescence was observed and the spectra could be obtained routinely. The stability of wool keratin to the laser source was investigated and the visual and spectroscopic signs of sample damage were established. Wool keratin was found to be extremely robust with no signs of sample degradation observed for laser powers of up to 600 m W and for exposure times of up to seven and half hours. Due to improvements in band resolution and signal-to-noise ratio, several previously unobserved spectral features have become apparent. The assignment of the Raman active vibrational modes of wool have been reviewed and updated to include these features. The infrared spectroscopic techniques of attenuated total reflectance (ATR) and photoacoustic (P A) have been used to examine shrinkproofed and mothproofed wool samples. Shrinkproofing is an oxidative chemical treatment used to selectively modifY the surface of a wool fibre. Mothproofing is a chemical treatment applied to wool for the prevention of insect attack. The ability of PAS and A TR to vary the penetration depth by varying certain instrumental parameters was used to obtain spectra of the near surface regions of these chemically treated samples. These spectra were compared with those taken with a greater penetration depth, which therefore represent more of the bulk wool sample. The PA and ATR spectra demonstrated that oxidation was restricted to the near-surface layer of wool. Extensive curve fitting of ATR spectra of untreated wool indicated that cuticle was composed of a mixed protein conformation, but was predominately that of an a.-helix. The cortex was proposed to be a mixture of both a.helical and ~-pleated sheet protein conformations. These findings were supported by PAS depth profiling results. Raman microspectroscopy was used in an extensive investigation of the molecular structure of the wool fibre. This included determining the orientation of certain functional groups within the wool fibre and the symmetry of particular vibrations. The orientation ofbonds within the wool fibre was investigated by orientating the wool fibre axis parallel and then perpendicular to the plane of polarisation of the electric vector of the incident radiation. It was experimentally determined that the majority of C=O and N-H bonds of the peptide bond of wool lie parallel to the fibre axis. Additionally, a number of the important vibrations associated with the a-helix were also found to lie parallel to the fibre axis. Further investigation into the molecular structure of wool involved determining what effect stretching the wool fibre had on bond orientation. Raman spectra of stretched and unstretched wool fibres indicated that extension altered the orientation ofthe aromatic rings, the CH2 and CH3 groups of the amino acids. Curve fitting results revealed that extension resulted in significant destruction of the a-helix structure a substantial increase in the P-pleated sheet structure. Finally, depolarisation ratios were calculated for Raman spectra. The vibrations associated with the aromatic rings of amino acids had very low ratios which indicated that the vibrations were highly symmetrical.

Basin analysis and economic geology of the Northern Mount Isa Basin

The Mount Isa Basin is a new concept used to describe the area of Palaeo- to Mesoproterozoic rocks south of the Murphy Inlier and inappropriately described presently as the Mount Isa Inlier. The new basin concept presented in this thesis allows for the characterisation of basin-wide structural deformation, correlation of mineralisation with particular lithostratigraphic and seismic stratigraphic packages, and the recognition of areas with petroleum exploration potential. The northern depositional margin of the Mount Isa Basin is the metamorphic, intrusive and volcanic complex here referred to as the Murphy Inlier (not the "Murphy Tectonic Ridge"). The eastern, southern and western boundaries of the basin are obscured by younger basins (Carpentaria, Eromanga and Georgina Basins). The Murphy Inlier rocks comprise the seismic basement to the Mount Isa Basin sequence. Evidence for the continuity of the Mount Isa Basin with the McArthur Basin to the northwest and the Willyama Block (Basin) at Broken Hill to the south is presented. These areas combined with several other areas of similar age are believed to have comprised the Carpentarian Superbasin (new term). The application of seismic exploration within Authority to Prospect (ATP) 423P at the northern margin of the basin was critical to the recognition and definition of the Mount Isa Basin. The Mount Isa Basin is structurally analogous to the Palaeozoic Arkoma Basin of Illinois and Arkansas in southern USA but, as with all basins it contains unique characteristics, a function of its individual development history. The Mount Isa Basin evolved in a manner similar to many well described, Phanerozoic plate tectonic driven basins. A full Wilson Cycle is recognised and a plate tectonic model proposed. The northern Mount Isa Basin is defined as the Proterozoic basin area northwest of the Mount Gordon Fault. Deposition in the northern Mount Isa Basin began with a rift sequence of volcaniclastic sediments followed by a passive margin drift phase comprising mostly carbonate rocks. Following the rift and drift phases, major north-south compression produced east-west thrusting in the south of the basin inverting the older sequences. This compression produced an asymmetric epi- or intra-cratonic clastic dominated peripheral foreland basin provenanced in the south and thinning markedly to a stable platform area (the Murphy Inlier) in the north. The fmal major deformation comprised east-west compression producing north-south aligned faults that are particularly prominent at Mount Isa. Potential field studies of the northern Mount Isa Basin, principally using magnetic data (and to a lesser extent gravity data, satellite images and aerial photographs) exhibit remarkable correlation with the reflection seismic data. The potential field data contributed significantly to the unravelling of the northern Mount Isa Basin architecture and deformation. Structurally, the Mount Isa Basin consists of three distinct regions. From the north to the south they are the Bowthorn Block, the Riversleigh Fold Zone and the Cloncurry Orogen (new names). The Bowthom Block, which is located between the Elizabeth Creek Thrust Zone and the Murphy Inlier, consists of an asymmetric wedge of volcanic, carbonate and clastic rocks. It ranges from over 10 000 m stratigraphic thickness in the south to less than 2000 min the north. The Bowthorn Block is relatively undeformed: however, it contains a series of reverse faults trending east-west that are interpreted from seismic data to be down-to-the-north normal faults that have been reactivated as thrusts. The Riversleigh Fold Zone is a folded and faulted region south of the Bowthorn Block, comprising much of the area formerly referred to as the Lawn Hill Platform. The Cloncurry Orogen consists of the area and sequences equivalent to the former Mount Isa Orogen. The name Cloncurry Orogen clearly distinguishes this area from the wider concept of the Mount Isa Basin. The South Nicholson Group and its probable correlatives, the Pilpah Sandstone and Quamby Conglomerate, comprise a later phase of now largely eroded deposits within the Mount Isa Basin. The name South Nicholson Basin is now outmoded as this terminology only applied to the South Nicholson Group unlike the original broader definition in Brown et al. (1968). Cored slimhole stratigraphic and mineral wells drilled by Amoco, Esso, Elf Aquitaine and Carpentaria Exploration prior to 1986, penetrated much of the stratigraphy and intersected both minor oil and gas shows plus excellent potential source rocks. The raw data were reinterpreted and augmented with seismic stratigraphy and source rock data from resampled mineral and petroleum stratigraphic exploration wells for this study. Since 1986, Comalco Aluminium Limited, as operator of a joint venture with Monument Resources Australia Limited and Bridge Oil Limited, recorded approximately 1000 km of reflection seismic data within the basin and drilled one conventional stratigraphic petroleum well, Beamesbrook-1. This work was the first reflection seismic and first conventional petroleum test of the northern Mount Isa Basin. When incorporated into the newly developed foreland basin and maturity models, a grass roots petroleum exploration play was recognised and this led to the present thesis. The Mount Isa Basin was seen to contain excellent source rocks coupled with potential reservoirs and all of the other essential aspects of a conventional petroleum exploration play. This play, although high risk, was commensurate with the enormous and totally untested petroleum potential of the basin. The basin was assessed for hydrocarbons in 1992 with three conventional exploration wells, Desert Creek-1, Argyle Creek-1 and Egilabria-1. These wells also tested and confrrmed the proposed basin model. No commercially viable oil or gas was encountered although evidence of its former existence was found. In addition to the petroleum exploration, indeed as a consequence of it, the association of the extensive base metal and other mineralisation in the Mount Isa Basin with hydrocarbons could not be overlooked. A comprehensive analysis of the available data suggests a link between the migration and possible generation or destruction of hydrocarbons and metal bearing fluids. Consequently, base metal exploration based on hydrocarbon exploration concepts is probably. the most effective technique in such basins. The metal-hydrocarbon-sedimentary basin-plate tectonic association (analogous to Phanerozoic models) is a compelling outcome of this work on the Palaeo- to Mesoproterozoic Mount lsa Basin. Petroleum within the Bowthom Block was apparently destroyed by hot brines that produced many ore deposits elsewhere in the basin.

Transition of synthetic chromium oxide gel to crystalline chromium oxide : a hot stage Raman spectroscopic study

Chromium oxide gel material was synthesised and appeared to be X-ray amorphous. The changes in the structure of the synthetic chromium oxide gel were investigated using hot-stage Raman spectroscopy based upon the results of thermogravimetric analysis. The thermally decomposed product of the synthetic chromium oxide gel in nitrogen atmosphere was confirmed to be crystalline Cr2O3 as determined by the hot-stage Raman spectra. Two bands were observed at 849 and 735 cm-1 in the Raman spectrum at 25 °C, which were attributed to the symmetric stretching modes of O-CrIII-OH and O-CrIII-O. With temperature increase, the intensity of the band at 849 cm-1 decreased, while the band at 735 cm-1 increased. These changes in intensity are attributed to the loss of OH groups and formation of O-CrIII-O units in the structure. A strongly hydrogen bonded water H-O-H bending band was found at 1704 cm-1 in the Raman spectrum of the chromium oxide gel, however this band shifted to around 1590 cm-1 due to destruction of the hydrogen bonds upon thermal treatment. Six new Raman bands were observed at 578, 540, 513, 390, 342 and 303 cm-1 attributed to the thermal decomposed product Cr2O3. The use of the hot-stage Raman microscope enabled low-temperature phase changes brought about through dehydration and dehydroxylation to be studied.

Creative industry and world city construction : Beijing as a creative world city

The study of the creative industries is not much more than a decade old. What makes it fascinating is that it is dealing with a rapidly evolving process, where a good deal of Schumpeterian ‘creative destruction’ – of old industries, business models, and some familiar cultural and creative pursuits – can already be observed. What happens next – and who will be the winner – is hard to predict. Furthermore, the creative industries encompass both large-scale ‘industry’ (media, publishing, digital applications) and individual creative talent; both economic and cultural values, and both global reach and local context. Thus, the challenge is to integrate ‘top-down’ policy and planning with ‘bottom-up’ experimentation and innovation. There is always the promise that this new creative ecology will provide some novel answers to problems of wealth-creation for emergent economies, new solutions to problems of intellectual emancipation for individuals, and sustainable development for that most intense incubator of creative ideas, the city.

Ecological sustainable development: a study of the obstacles in Australia's construction industry

Ecological sustainable development (ESD), defined as that which meets the needs of the present without compromising the ability of future generations to meet their own needs, has much to offer in enhancing the quality of life of people and maintaining the environment for future generations by reducing the pollution of water, air and land, minimizing the destruction of irreplaceable ecosystems and cutting down the amount of toxic materials released. However, there is still much to do to achieve full implementation world-wide. This paper reports on three factors-design, attitudes and financial constraints - that are likely barriers to the implementation of ESD within the built environment in Australian industry. A postal questionnaire survey is described aimed at soliciting views on detailed aspects of the factors. This shows that ESD in the Australian built environment has also not been successfully implemented. The main reason is found to be due to the perceived costs involved - the cost of using environmental materials being a predominant factor. The design of ESD, being more sophisticated, also is perceived as involving stakeholders in more expense. There also appears to be a lack of knowledge and a lack of specialised and interdisciplinary design teams available in the Australian context.

Paradigm shifters : tricksters and cultural science

This paper seeks to link anthropological and economic treatments of the process of innovation and change, not only within a given ‘complex system’ (e.g. a cosmology; an industry) but also between systems (e.g. cultural and economic systems; but also divine and human systems). The role of the ‘Go-Between’ is considered, both in the anthropological figure of the Trickster (Hyde 1998) and in the Schumpeterian entrepreneur. Both figures parlay appetite (economic wants) into meaning (cultural signs). Both practice a form of creativity based on deception, ‘creative destruction’; renewal by disruption and needs-must adaptation. The disciplinary purpose of the paper is to try to bridge two otherwise disconnected domains – cultural studies and evolutionary economics – by showing that the traditional methods of the humanities (e.g. anthropological, textual and historical analysis) have explanatory force in the context of economic actions and complex-system evolutionary dynamics. The objective is to understand creative innovation as a general cultural attribute rather than one restricted only to accredited experts such as artists; thus to theorise creativity as a form of emergence for dynamic adaptive systems. In this context, change is led by ‘paradigm shifters’ – tricksters and entrepreneurs who create new meanings out of the clash of difference, including the clash of mutually untranslatable communication systems (language, media, culture).

Nonverbal Learning Disability explained : the link to shunted hydrocephalus

A Nonverbal Learning Disability is believed to be caused by damage, disorder or destruction of neuronal white matter in the brain’s right hemisphere and may be seen in persons experiencing a wide range of neurological diseases such as hydrocephalus and other types of brain injury (Harnadek & Rourke 1994). This article probes the relationship between shunted hydrocephalus and Nonverbal Learning Disability. Description of hydrocephalus and intelligence associated with hydrocephalus concludes with explication of the ‘final common pathway’ that links residual damage caused by the hydrocephalic condition to a Nonverbal Learning Disability (Rourke & Del Dotto 1994, p. 37). The paper seeks to assist teachers, teacher aides, psychologists, guidance officers, support workers, parents and disability service providers whose role is to understand and advocate for individuals with shunted hydrocephalus and spina bifida.

Transcutaneous immunization with novel lipid-based adjuvants induces protection against gastric Helicobacter pylori infection

The development of vaccines to combat pathogens that infect across mucosal surfaces has been a major goal of vaccine research. Successful mucosal vaccination requires the co-administration of adjuvants that can overcome the state of immune tolerance normally associated with mucosal application of proteins. In the case of oral immunization, delivery systems are also required to protect vaccine antigens against destruction by gastric pH and digestive enzymes. Furthermore, adjuvants used for mucosal delivery must be free of neurotoxic effects like those induced by the commonly used experimental mucosal adjuvant cholera toxin. Maintenance of the "cold chain" is also essential for the effectiveness of any vaccine and adjuvants/delivery systems that enhance the stability of a vaccine would offer a significant advantage. Needle-free methods of vaccination that induce protective immunity at multiple mucosal surfaces are also desirable for rapid vaccination of large populations. In the present study we show that transcutaneous immunization (TCI) using Lipid C, a novel lipid-based matrix originally developed for oral immunization, containing soluble Helicobacter sonicate significantly reduces the gastric bacterial burden in mice following gastric challenge with live Helicobacter pylori. Protection is associated with the production of splenic gamma interferon and gastric IgA and was achieved without the co-administration of potent and potentially toxic adjuvants, although protection was further enhanced by inclusion of CpG-ODN and cholera toxin in the lipid delivery system.

Assessing population limits : a carrying capacity approach to planning

While purporting to enhance Australia’s sustainability, the federal government’s Population Strategy rejects the assessment of the limiting factors to future population growth, thus avoiding urgent threshold issues such as resource depletion and environmental destruction. A more forward-thinking and whole-system perspective would assess and incorporate critical biophysical limits into governance processes with suitable prioritisation. It would encourage communities to examine their individual and collective responsibilities in the context of these limits in order to most equitably optimise outcomes; and it would employ both a resource-based examination of minimum population requirements, and an impact-based assessment of maximum thresholds. This carrying capacity approach to planning could help guide society towards a more sustainable future.

Swimming but drowning

This single-channel digital video work documents a performative event, the disintegrative process as a drawing-object is progressively submerged within water. This work forms part of a series of video works examining ephemerality within art and the iconoclastic impulse. This is informed by Gustav Metzger’s conceptualisation of auto-destructive art (1959) as that which contains within itself an agent, which automatically leads to its destruction. Here, the ontological moment of the work corresponds to its demise, investigating a symbiotic relationship between creation and destruction. It addresses the phenomenology and epistemology of destruction in art when presented by the artist, as both a process and an ethical position. The work was included in the group show 'The Construct', curated by Kris Carlon for Artworkers' Residency and Exhibition Project 2006 at the State Library of Queensland.

Thermal stability of newberyite Mg(PO3OH)•3H2O – a cave mineral from Skipton lava tubes, Victoria, Australia.

The mineral newberyite Mg(PO3OH)•3H2O is a mineral that has been found in caves such as the Skipton Lava Tubes (SW of Ballarat, Victoria, Australia), Moorba cave, Jurien Bay, Western Australia, and in the Petrogale Cave (Madura , Eucla, Western Australia). Because these minerals contain water, the minerals lend themselves to thermal analysis. The mineral newberyite is found to decompose at 145°C with a water loss of 31.96%, a result which is very close to the theoretical value. The result shows that the mineral is not stable in caves where the temperature exceeds this value. The implication of this result rests with the removal of kidney stones, which have the same composition as newberyite. Point heating focussing on the kidney stone results in the destruction of the kidney stone.

Unlocking risk allocation and equitable conversion : reform of the passing of risk in the sale of land

The principles relating to the passing of risk under a contract for the sale of real property would seem to have been long settled. The rule under the general law is that the risk of loss of the subject matter under a contract for the sale of real property passes to the buyer upon the creation of a valid and binding contract. This article considers the origin of that rule, how it developed with the growth of equity, and advances the view that it is anomalous in a modern context of property dealings. In doing so, the article adverts to the variety of statutory mechanisms used to subvert the rule, few of which are of practical value. It concludes that the rule is outmoded in many respects and suggests a number of reforms which might be implemented nationally to bring consistency and simplicity to the issue of damage or destruction of improvements which are the subject of a land contract.