Kallikrein-related peptidase 4 activation of protease-activated receptor family members and association with prostate cancer

Two areas of particular importance in prostate cancer progression are primary tumour development and metastasis. These processes involve a number of physiological events, the mediators of which are still being discovered and characterised. Serine proteases have been shown to play a major role in cancer invasion and metastasis. The recently discovered phenomenon of their activation of a receptor family known as the protease activated receptors (PARs) has extended their physiological role to that of signaling molecule. Several serine proteases are expressed by malignant prostate cancer cells, including members of the kallikreinrelated peptidase (KLK) serine protease family, and increasingly these are being shown to be associated with prostate cancer progression. KLK4 is highly expressed in the prostate and expression levels increase during prostate cancer progression. Critically, recent studies have implicated KLK4 in processes associated with cancer. For example, the ectopic over-expression of KLK4 in prostate cancer cell lines results in an increased ability of these cells to form colonies, proliferate and migrate. In addition, it has been demonstrated that KLK4 is a potential mediator of cellular interactions between prostate cancer cells and osteoblasts (bone forming cells). The ability of KLK4 to influence cellular behaviour is believed to be through the selective cleavage of specific substrates. Identification of relevant in vivo substrates of KLK4 is critical to understanding the pathophysiological roles of this enzyme. Significantly, recent reports have demonstrated that several members of the KLK family are able to activate PARs. The PARs are relatively new members of the seven transmembrane domain containing G protein coupled receptor (GPCR) family. PARs are activated through proteolytic cleavage of their N-terminus by serine proteases, the resulting nascent N-terminal binds intramolecularly to initiate receptor activation. PARs are involved in a number of patho-physiological processes, including vascular repair and inflammation, and a growing body of evidence suggests roles in cancer. While expression of PAR family members has been documented in several types of cancers, including prostate, the role of these GPCRs in prostate cancer development and progression is yet to be examined. Interestingly, several studies have suggested potential roles in cellular invasion through the induction of cytoskeletal reorganisation and expression of basement membrane-degrading enzymes. Accordingly, this program of research focussed on the activation of the PARs by the prostate cancer associated enzyme KLK4, cellular processing of activated PARs and the expression pattern of receptor and agonist in prostate cancer. For these studies KLK4 was purified from the conditioned media of stably transfected Sf9 insect cells expressing a construct containing the complete human KLK4 coding sequence in frame with a V5 epitope and poly-histidine encoding sequences. The first aspect of this study was the further characterisation of this recombinant zymogen form of KLK4. The recombinant KLK4 zymogen was demonstrated to be activatable by the metalloendopeptidase thermolysin and amino terminal sequencing indicated that thermolysin activated KLK4 had the predicted N-terminus of mature active KLK4 (31IINED). Critically, removal of the pro-region successfully generated a catalytically active enzyme, with comparable activity to a previously published recombinant KLK4 produced from S2 insect cells. The second aspect of this study was the activation of the PARs by KLK4 and the initiation of signal transduction. This study demonstrated that KLK4 can activate PAR-1 and PAR-2 to mobilise intracellular Ca2+, but failed to activate PAR-4. Further, KLK4 activated PAR-1 and PAR-2 over distinct concentration ranges, with KLK4 activation and mobilisation of Ca2+ demonstrating higher efficacy through PAR-2. Thus, the remainder of this study focussed on PAR-2. KLK4 was demonstrated to directly cleave a synthetic peptide that mimicked the PAR-2 Nterminal activation sequence. Further, KLK4 mediated Ca2+ mobilisation through PAR-2 was accompanied by the initiation of the extra-cellular regulated kinase (ERK) cascade. The specificity of intracellular signaling mediated through PAR-2 by KLK4 activation was demonstrated by siRNA mediated protein depletion, with a reduction in PAR-2 protein levels correlating to a reduction in KLK4 mediated Ca2+mobilisation and ERK phosphorylation. The third aspect of this study examined cellular processing of KLK4 activated PAR- 2 in a prostate cancer cell line. PAR-2 was demonstrated to be expressed by five prostate derived cell lines including the prostate cancer cell line PC-3. It was also demonstrated by flow cytometry and confocal microscopy analyses that activation of PC-3 cell surface PAR-2 by KLK4 leads to internalisation of this receptor in a time dependent manner. Critically, in vivo relevance of the interaction between KLK4 and PAR-2 was established by the observation of the co-expression of receptor and agonist in primary prostate cancer and prostate cancer bone lesion samples by immunohistochemical analysis. Based on the results of this study a number of exciting future studies have been proposed, including, delineating differences in KLK4 cellular signaling via PAR-1 and PAR-2 and the role of PAR-1 and PAR-2 activation by KLK4 in prostate cancer cells and bone cells in prostate cancer progression.

The nature and extent of policing alcohol related crime and reducing violence in and around late night entertainment areas

The misuse of alcohol is well documented in Australia and has been associated with disorders and harms that often require police attention. The extent of alcohol-related incidents requiring police attention has been recorded as substantial in some Australian cities (Arro, Crook, & Fenton, 1992; Davey & French, 1995; Ireland & Thommeny, 1993). A significant proportion of harmful drinking occurs in and around licensed premises (Jochelson, 1997; Stockwell, Masters, Phillips, Daly, Gahegan, Midford, & Philp, 1998; Borges, Cherpitel, & Rosovsky, 1998) and most of these incidents are not reported to police (Bryant & Williams, 2000; Lister, Hobbs, Hall, & Winlow, 2000). Alcohol-related incidents have also been found to be concentrated in certain places at certain times (Jochelson, 1997) and therefore manipulating the context in which these incidents occur may provide a means to prevent and reduce the harm associated with alcohol misuse. One of the major objectives of the present program of research was to investigate the occurrence and resource impact of alcohol-related incidents on operational (general duties) policing across a large geographical area. A second objective of the thesis was to examine the characteristics and temporal/spatial dynamics of police attended alcohol incidents in the context of Place Based theories of crime. It was envisaged that this approach would reveal the patterns of the most prevalent offences and demonstrate the relevance of Place Based theories of crime to understanding these patterns. In addition, the role of alcohol, time and place were also explored in order to examine the association between non criminal traffic offences and other types of criminal offences. A final objective of the thesis was to examine the impact of a situational crime prevention strategy that had been initiated to reduce the violence and disorder associated with late-night liquor trading premises. The program of research in this doctorate thesis has been undertaken through the presentation of published papers. The research was conducted in three stages which produced six manuscripts, five of which were submitted to peer reviewed journals and one that was published in a peer reviewed conference proceedings. Stage One included two studies (Studies 1 & 2) both of which involved a cross sectional approach to examine the prevalence and characteristics of alcohol-related incidents requiring police attendance across three large geographical areas that included metropolitan cities, provincial regions and rural areas. Stage Two of the program of research also comprised two cross sectional quantitative studies (Studies 3 & 4) that investigated the temporal and spatial dynamics of the major offence categories attended by operational police in a specific Police District (Gold Coast). Stage Three of the program of research involved two studies (Studies 5 & 6) that assessed the effectiveness of a situational crime prevention strategy. The studies employed a pre-post design to assess the impact on crime, disorder and violence by preventing patrons from entering late-night liquor trading premises between 3 a.m. and 5 a.m. (lockout policy). Although Study Five was solely quantitative in nature, Study Six included both quantitative and qualitative aspects. The approach adopted in Study Six, therefore facilitated not only a quantative comparison of the impact of the lockout policy on different policing areas, but also enabled the processes related to the implementation of the lockout policy to be examined. The thesis reports a program of research involving a common data collection method which then involved a series of studies being conducted to explore different aspects of the data. The data was collected from three sources. Firstly a pilot phase was undertaken to provide participants with training. Secondly a main study period was undertaken immediately following the pilot phase. The first and second sources of data were collected between 29th March 2004 and 2nd May 2004. Thirdly, additional data was collected between the 1st April 2005 and 31st May 2005. Participants in the current program of research were first response operational police officers who completed a modified activity log over a 9 week period (4 week pilot phase & 5 week survey study phase), identifying the type, prevalence and characteristics of alcohol-related incidents that were attended. During the study period police officers attended 31,090 alcohol-related incidents. Studies One and Two revealed that a substantial proportion of current police work involves attendance at alcohol-related incidents (i.e., 25% largely involving young males aged between 17 and 24 years). The most common incidents police attended were vehicle and/or traffic matters, disturbances and offences against property. The major category of offences most likely to involve alcohol included vehicle/traffic matters, disturbances and offences against the person (e.g., common & serious assaults). These events were most likely to occur in the late evenings and early hours of the morning on the weekends, and importantly, usually took longer for police to complete than non alcohol-related incidents. The findings in Studies Three and Four suggest that serious traffic offences, disturbances and offences against the person share similar characteristics and occur in concentrated places at similar times. In addition, it was found that time, place and incident type all have an influence on whether an incident attended by a police officer is alcohol-related. Alcohol-related incidents are more likely to occur in particular locations in the late evenings and early mornings on the weekends. In particular, there was a strong association between the occurrence of alcohol-related disturbances and alcohol-related serious traffic offences in regards to place and time. In general, stealing and property offences were not alcohol-related and occurred in daylight hours during weekdays. The results of Studies Five and Six were mixed. A number of alcohol-related offences requiring police attention were significantly reduced for some policing areas and for some types of offences following the implementation of the lockout policy. However, in some locations the lockout policy appeared to have a negative or minimal impact. Interviews with licensees revealed that although all were initially opposed to the lockout policy as they believed it would have a negative impact on business, most perceived some benefits from its introduction. Some of the benefits included, improved patron safety and the development of better business strategies to increase patron numbers. In conclusion, the overall findings of the six studies highlight the pervasive nature of alcohol across a range of criminal incidents, demonstrating the tremendous impact alcohol-related incidents have on police. The findings also demonstrate the importance of time and place in predicting the occurrence of alcohol-related offences. Although this program of research did not set out to test Place Based theories of crime, these theories were used to inform the interpretation of findings. The findings in the current research program provide evidence for the relevance of Place Based theories of crime to understanding the factors contributing to violence and disorder, and designing relevant crime prevention strategies. For instance, the results in Studies Five and Six provide supportive evidence that this novel lockout initiative can be beneficial for public safety by reducing some types of offences in particular areas in and around late-night liquor trading premises. Finally, intelligent-led policing initiatives based on problem oriented policing, such as the lockout policy examined in this thesis, have potential as a major crime prevention technique to reduce specific types of alcohol-related offences.

Does the summative assessment of real world learning using criterion-referenced assessment need to be discipline specific?

This paper synthesises the existing literature on the contemporary conception of ‘real world’ and compares it with similar notions such as ‘authentic’ and ‘work integrated learning’. While the term ‘real world’ may be partly dependent on the discipline, it does not necessarily follow that the criterion-referenced assessment of ‘real world’ assessment must involve criteria and performance descriptors that are discipline specific. Two examples of summative assessment (court report and trial process exercise) from a final year core subject at the Queensland University of Technology, LWB432 Evidence, emphasise real world learning, are authentic, innovative and better prepare students for the transition into the workplace than more generic forms of assessment such as tutorial participation or oral presentations. The court report requires students to attend a criminal trial in a Queensland Court and complete a two page report on what they saw in practice compared with what they learned in the classroom. The trial process exercise is a 50 minute written closed book activity conducted in tutorials, where students plan questions that they would ask their witness in examination-in-chief, plan questions that they would ask their opponent’s witness in cross-examination, plan questions that they would ask in reexamination given what their opponent asked in cross-examination, and prepare written objections to their opponent’s questions. The trial process exercise simulates the real world, whereas the court report involves observing the real world, and both assessment items are important to the role of counsel. The design of the criterion-referenced assessment rubrics for the court report and trial process exercise is justified by the literature. Notably, the criteria and performance descriptors are not necessarily law specific and this paper highlights the parts that may be easily transferred to other disciplines.

Embedded engagements : the challenge of creative practice research to the humanities

This article explores the opportunities and challenges surrounding a viable cross-disciplinary engagement between the Humanities disciplines and the Creative Practice disciplines within the innovative context of the Creative Industries Faculty at the Queensland University of Technology. This will involve a charting of the intersection of the emerging field of creative practice-led research with various disciplines in the Humanities such as cultural studies. The potential for a reciprocal, transformative process in these creative fields will be addressed. Several examples of postgraduate students’ research will be foregrounded as case studies of the issues involved in fostering a genuine cultural critique both within and through creative practice. Some observers may argue that the research higher degree creative practitioner in effect looks outward from the symbolic material forms being created, in search of an interpretative paradigm, thereby trawling the Humanities for a theory. Several current debates within the postgraduate research arena regarding the balance between the theoretical exegesis and the creative work (e.g. performance, drama, dance, visual art, creative writing, film and screen production, music, interactive media etc) will also be critically examined.

Bend and stretch : pedagogical callisthenics in creative practice honours

The supervision of research higher degree (RHD) candidates in creative practice-led programs poses challenges for both candidates and supervisors. Changes in international postgraduate training agendas have complicated this ever-shifting terrain. This paper investigates the honours research training year. This fourth year is made up of a project and coursework and is a traditional entry point for doctoral study. At Creative Industries, honours acts as a precursor and model for supervisory practice in postgraduate creative arts in an interdisciplinary faculty. The findings indicate that best practice may involve ‘bending and stretching’ existing pedagogical approaches for an increasingly interdisciplinary and mobile research environment. This discussion considers the supervision of candidates enrolled in Queensland University of Technology Faculty of Creative Industries honours courses that encompass a range of disciplines including creative writing, fashion, animation and performance studies. We present results of an analysis of the work of honours students who are creative practitioners (many of whom will, or have, moved into the RHD environment). This examination was undertaken in order to develop an understanding of the dynamics of creative practice at this level, particularly in light of the growing emphasis on early research training in Australian universities. Specific pedagogical strategies mooted include establishing a common research vocabulary, an increasing focus on research design, and a linking of theory and practice.

Translation and news making : a study of contemporary arabic television

Arabic satellite television has recently attracted tremendous attention in both the academic and professional worlds, with a special interest in Aljazeera as a curious phenomenon in the Arab region. Having made a household name for itself worldwide with the airing of the Bin Laden tapes, Aljazeera has set out to deliberately change the culture of Arabic journalism, as it has been repeatedly stated by its current General Manager Waddah Khanfar, and to shake up the Arab society by raising awareness to issues never discussed on television before and challenging long-established social and cultural values and norms while promoting, as it claims, Arab issues from a presumably Arab perspective. Working within the meta-frame of democracy, this Qatari-based network station has been received with mixed reactions ranging from complete support to utter rejection in both the west and the Arab world. This research examines the social semiotics of Arabic television and the socio-cultural impact of translation-mediated news in Arabic satellite television, with the aim to carry out a qualitative content analysis, informed by framing theory, critical linguistic analysis, social semiotics and translation theory, within a re-mediation framework which rests on the assumption that a medium “appropriates the techniques, forms and social significance of other media and attempts to rival or refashion them in the name of the real" (Bolter and Grusin, 2000: 66). This is a multilayered research into how translation operates at two different yet interwoven levels: translation proper, that is the rendition of discourse from one language into another at the text level, and translation as a broader process of interpretation of social behaviour that is driven by linguistic and cultural forms of another medium resulting in new social signs generated from source meaning reproduced as target meaning that is bound to be different in many respects. The research primarily focuses on the news media, news making and reporting at Arabic satellite television and looks at translation as a reframing process of news stories in terms of content and cultural values. This notion is based on the premise that by its very nature, news reporting is a framing process, which involves a reconstruction of reality into actualities in presenting the news and providing the context for it. In other words, the mediation of perceived reality through a media form, such as television, actually modifies the mind’s ordering and internal representation of the reality that is presented. The research examines the process of reframing through translation news already framed or actualized in another language and argues that in submitting framed news reports to the translation process several alterations take place, driven by the linguistic and cultural constraints and shaped by the context in which the content is presented. These alterations, which involve recontextualizations, may be intentional or unintentional, motivated or unmotivated. Generally, they are the product of lack of awareness of the dynamics and intricacies of turning a message from one language form into another. More specifically, they are the result of a synthesis process that consciously or subconsciously conforms to editorial policy and cultural interpretive frameworks. In either case, the original message is reproduced and the news is reframed. For the case study, this research examines news broadcasts by the now world-renowned Arabic satellite television station Aljazeera, and to a lesser extent the Lebanese Broadcasting Corporation (LBC) and Al- Arabiya where access is feasible, for comparison and crosschecking purposes. As a new phenomenon in the Arab world, Arabic satellite television, especially 24-hour news and current affairs, provides an interesting area worthy of study, not only for its immediate socio-cultural and professional and ethical implications for the Arabic media in particular, but also for news and current affairs production in the western media that rely on foreign language sources and translation mediation for international stories.

An experimental and finite element investigation of the biomechanics of vertebral compression fractures

Osteoporosis is a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Osteoporosis affects over 200 million people worldwide, with an estimated 1.5 million fractures annually in the United States alone, and with attendant costs exceeding $10 billion dollars per annum. Osteoporosis reduces bone density through a series of structural changes to the honeycomb-like trabecular bone structure (micro-structure). The reduced bone density, coupled with the microstructural changes, results in significant loss of bone strength and increased fracture risk. Vertebral compression fractures are the most common type of osteoporotic fracture and are associated with pain, increased thoracic curvature, reduced mobility, and difficulty with self care. Surgical interventions, such as kyphoplasty or vertebroplasty, are used to treat osteoporotic vertebral fractures by restoring vertebral stability and alleviating pain. These minimally invasive procedures involve injecting bone cement into the fractured vertebrae. The techniques are still relatively new and while initial results are promising, with the procedures relieving pain in 70-95% of cases, medium-term investigations are now indicating an increased risk of adjacent level fracture following the procedure. With the aging population, understanding and treatment of osteoporosis is an increasingly important public health issue in developed Western countries. The aim of this study was to investigate the biomechanics of spinal osteoporosis and osteoporotic vertebral compression fractures by developing multi-scale computational, Finite Element (FE) models of both healthy and osteoporotic vertebral bodies. The multi-scale approach included the overall vertebral body anatomy, as well as a detailed representation of the internal trabecular microstructure. This novel, multi-scale approach overcame limitations of previous investigations by allowing simultaneous investigation of the mechanics of the trabecular micro-structure as well as overall vertebral body mechanics. The models were used to simulate the progression of osteoporosis, the effect of different loading conditions on vertebral strength and stiffness, and the effects of vertebroplasty on vertebral and trabecular mechanics. The model development process began with the development of an individual trabecular strut model using 3D beam elements, which was used as the building block for lattice-type, structural trabecular bone models, which were in turn incorporated into the vertebral body models. At each stage of model development, model predictions were compared to analytical solutions and in-vitro data from existing literature. The incremental process provided confidence in the predictions of each model before incorporation into the overall vertebral body model. The trabecular bone model, vertebral body model and vertebroplasty models were validated against in-vitro data from a series of compression tests performed using human cadaveric vertebral bodies. Firstly, trabecular bone samples were acquired and morphological parameters for each sample were measured using high resolution micro-computed tomography (CT). Apparent mechanical properties for each sample were then determined using uni-axial compression tests. Bone tissue properties were inversely determined using voxel-based FE models based on the micro-CT data. Specimen specific trabecular bone models were developed and the predicted apparent stiffness and strength were compared to the experimentally measured apparent stiffness and strength of the corresponding specimen. Following the trabecular specimen tests, a series of 12 whole cadaveric vertebrae were then divided into treated and non-treated groups and vertebroplasty performed on the specimens of the treated group. The vertebrae in both groups underwent clinical-CT scanning and destructive uniaxial compression testing. Specimen specific FE vertebral body models were developed and the predicted mechanical response compared to the experimentally measured responses. The validation process demonstrated that the multi-scale FE models comprising a lattice network of beam elements were able to accurately capture the failure mechanics of trabecular bone; and a trabecular core represented with beam elements enclosed in a layer of shell elements to represent the cortical shell was able to adequately represent the failure mechanics of intact vertebral bodies with varying degrees of osteoporosis. Following model development and validation, the models were used to investigate the effects of progressive osteoporosis on vertebral body mechanics and trabecular bone mechanics. These simulations showed that overall failure of the osteoporotic vertebral body is initiated by failure of the trabecular core, and the failure mechanism of the trabeculae varies with the progression of osteoporosis; from tissue yield in healthy trabecular bone, to failure due to instability (buckling) in osteoporotic bone with its thinner trabecular struts. The mechanical response of the vertebral body under load is highly dependent on the ability of the endplates to deform to transmit the load to the underlying trabecular bone. The ability of the endplate to evenly transfer the load through the core diminishes with osteoporosis. Investigation into the effect of different loading conditions on the vertebral body found that, because the trabecular bone structural changes which occur in osteoporosis result in a structure that is highly aligned with the loading direction, the vertebral body is consequently less able to withstand non-uniform loading states such as occurs in forward flexion. Changes in vertebral body loading due to disc degeneration were simulated, but proved to have little effect on osteoporotic vertebra mechanics. Conversely, differences in vertebral body loading between simulated invivo (uniform endplate pressure) and in-vitro conditions (where the vertebral endplates are rigidly cemented) had a dramatic effect on the predicted vertebral mechanics. This investigation suggested that in-vitro loading using bone cement potting of both endplates has major limitations in its ability to represent vertebral body mechanics in-vivo. And lastly, FE investigation into the biomechanical effect of vertebroplasty was performed. The results of this investigation demonstrated that the effect of vertebroplasty on overall vertebra mechanics is strongly governed by the cement distribution achieved within the trabecular core. In agreement with a recent study, the models predicted that vertebroplasty cement distributions which do not form one continuous mass which contacts both endplates have little effect on vertebral body stiffness or strength. In summary, this work presents the development of a novel, multi-scale Finite Element model of the osteoporotic vertebral body, which provides a powerful new tool for investigating the mechanics of osteoporotic vertebral compression fractures at the trabecular bone micro-structural level, and at the vertebral body level.

Developing an integrated decision model for the enhancement of sustainability deliverables for Australian road infrastructure projects

Road and highway infrastructure provides the backbone for a nation's economic growth. The versatile dispersion of population in Australia, from sparsely settled communities in remote areas to regenerated inner city suburbs with high density living in metropolitans, calls for continuing development and improvement on roads infrastructure under the current federal government policies and state governments' strategic plans. As road infrastructure projects involve large resources and mechanism, achieving sustainability not only in economic scales but also through environmental and social responsibility becomes a crucial issue. Current efforts are often impeded by different interpretation on sustainability agenda by stakeholders involved in these types of projects. As a result, sustainability deliverables at the project level is not often as transparent and measurable, compared to promises in project briefs and designs. This paper reviews the past studies on sustainable infrastructure construction, focusing on roads and highway projects. Through literature study and consultation with the industry, key sustainability indicators specific to road infrastructure projects have been identified. Based on these findings, this paper introduces an on-going research project aimed at identifying and integrating the different perceptions and priority needs of the stakeholders, and issues that impact on the gap between sustainability foci and its actual realization at project end level. The exploration helps generate an integrated decision-making model for sustainable road infrastructure projects. The research will promote to the industry more systematic and integrated approaches to decision-making on the implementation of sustainability strategies to achieve deliverable goals throughout the development and delivery process of road infrastructure projects in Australia.

Synopolies: The use of cryptographic technologies to impede competition in multiple jurisdictions

Many jurisdictions have developed mature infrastructures, both administratively and legislatively, to promote competition. Substantial funds have been expended to monitor activities that are anticompetitive and many jurisdictions also have adopted a form of "Cartel Leniency Program", first developed by the US Federal Trade Commission, to assist in cartel detection. Further, some jurisdictions are now criminalizing cartel behaviour so that cartel participants can be held criminally liable with substantial custodial penalties imposed. Notwithstanding these multijurisdictional approaches, a new form of possibly anticompetitive behaviour is looming. Synergistic monopolies („synopolies‟) involve not competitors within a horizontal market but complimentors within separate vertical markets. Where two complimentary corporations are monopolists in their own market they can, through various technologies, assist each other to expand their respective monopolies thus creating a barrier to new entrants and/or blocking existing participants from further participation in that market. The nature of the technologies involved means that it is easy for this potentially anti-competitive activity to enter and affect the global marketplace. Competition regulators need to be aware of this potential for abuse and ensure that their respective competition frameworks appropriately address this activity. This paper discusses how new technologies can be used to create a synopoly.

Three-dimensional hydrogen-bonded structures in the 1:1 proton-transfer compounds of L-tartaric acid with the associative-group monosubstituted pyridines 3-minopyridine, 3-carboxypyridine (nicotinic acid) and 2-carboxypyridine (picolinic acid).

The 1:1 proton-transfer compounds of L-tartaric acid with 3-aminopyridine [3-aminopyridinium hydrogen (2R,3R)-tartrate dihydrate, C5H7N2+·C4H5O6-·2H2O, (I)], pyridine-3-carboxylic acid (nicotinic acid) [anhydrous 3-carboxypyridinium hydrogen (2R,3R)-tartrate, C6H6NO2+·C4H5O6-, (II)] and pyridine-2-carboxylic acid [2-carboxypyridinium hydrogen (2R,3R)-tartrate monohydrate, C6H6NO2+·C4H5O6-·H2O, (III)] have been determined. In (I) and (II), there is a direct pyridinium-carboxyl N+-HO hydrogen-bonding interaction, four-centred in (II), giving conjoint cyclic R12(5) associations. In contrast, the N-HO association in (III) is with a water O-atom acceptor, which provides links to separate tartrate anions through Ohydroxy acceptors. All three compounds have the head-to-tail C(7) hydrogen-bonded chain substructures commonly associated with 1:1 proton-transfer hydrogen tartrate salts. These chains are extended into two-dimensional sheets which, in hydrates (I) and (III) additionally involve the solvent water molecules. Three-dimensional hydrogen-bonded structures are generated via crosslinking through the associative functional groups of the substituted pyridinium cations. In the sheet struture of (I), both water molecules act as donors and acceptors in interactions with separate carboxyl and hydroxy O-atom acceptors of the primary tartrate chains, closing conjoint cyclic R44(8), R34(11) and R33(12) associations. Also, in (II) and (III) there are strong cation carboxyl-carboxyl O-HO hydrogen bonds [OO = 2.5387 (17) Å in (II) and 2.441 (3) Å in (III)], which in (II) form part of a cyclic R22(6) inter-sheet association. This series of heteroaromatic Lewis base-hydrogen L-tartrate salts provides further examples of molecular assembly facilitated by the presence of the classical two-dimensional hydrogen-bonded hydrogen tartrate or hydrogen tartrate-water sheet substructures which are expanded into three-dimensional frameworks via peripheral cation bifunctional substituent-group crosslinking interactions.

Experimental and theoretical studies of the redox potentials of cyclic nitroxides

The redox potentials of 25 cyclic nitroxides from four different structural classes (pyrrolidine, piperidine, isoindoline, and azaphenalene) were determined experimentally by cyclic voltammetry in acetonitrile, and also via high-level ab initio molecular orbital calculations. It is shown that the potentials are influenced by the type of ring system, ring substituents and/or groups surrounding the radical moiety. For the pyrrolidine, piperidine, and isoindolines there is excellent agreement (mean absolute deviation of 0.05 V) between the calculated and experimental oxidation potentials; for the azaphenalenes, however, there is an extraordinary discrepancy (mean absolute deviation of 0.60 V), implying that their one-electron oxidation might involve additional processes not considered in the theoretical calculations. This recently developed azaphenalene class of nitroxide represents a new variant of a nitroxide ring fused to an aromatic system and details of the synthesis of five derivatives involving differing aryl substitution are also presented.

A practical approach for reliability prediction of pipeline systems

Pipelines play an important role in the modern society. Failures of pipelines can have great impacts on economy, environment and community. Preventive maintenance (PM) is often conducted to improve the reliability of pipelines. Modern asset management practice requires accurate predictability of the reliability of pipelines with multiple PM actions, especially when these PM actions involve imperfect repairs. To address this issue, a split system approach (SSA) based model is developed in this paper through an industrial case study. This new model enables maintenance personnel to predict the reliability of pipelines with different PM strategies and hence effectively assists them in making optimal PM decisions.

Performance Research in Rangeland Communities

In 2003, Bill Dunstone, John McCallum and Paul Makeham began a collaboration with researchers at the Centre for the Management of Arid Environments (CMAE) in Kalgoorlie, Western Australia. CMAE researchers are keen to develop 'people-oriented' strategies for implementing agricultural extension initiatives in their region. Traditional hierarchies of knowledge-transfer have impeded the 'connectedness' between community and researchers that gives meaning and relevance to useful practice (Ison and Russell, 2000). Our aim is to establish a partnership between the Live Events Research Network (LERN) and CMAE, investigating ways to link creative, performance-based research and practice with the scientific methodologies associated with natural resources management. This accords with recent work undertaken by Deborah Mills and Paul Brown, showing how community cultural development strategies enhance the implementation of policy concerned with community wellbeing. Mills and Brown 'adopted a concept of wellbeing which builds on a social and environmental view of health', and considered such themes as ecological sustainability, rural economic revitalisation, community strengthening, health and wellbeing (Mills, 2003). We propose that rangeland communities can creatively manage some of the challenges confronting them through performance-based projects which: - activate the stories through which a community enacts its sense of place; - facilitate live events in which the community enacts ownership of its culture and identity; - directly involve the community in the formulation of research issues

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.

Mathematical modelling in the early school years

In this article we explore young children's development of mathematical knowledge and reasoning processes as they worked two modelling problems (the Butter Beans Problem and the Airplane Problem). The problems involve authentic situations that need to be interpreted and described in mathematical ways. Both problems include tables of data, together with background information containing specific criteria to be considered in the solution process. Four classes of third-graders (8 years of age) and their teachers participated in the 6-month program, which included preparatory modelling activities along with professional development for the teachers. In discussing our findings we address: (a) Ways in which the children applied their informal, personal knowledge to the problems; (b) How the children interpreted the tables of data, including difficulties they experienced; (c) How the children operated on the data, including aggregating and comparing data, and looking for trends and patterns; (c) How the children developed important mathematical ideas; and (d) Ways in which the children represented their mathematical understandings.