Establishing design thinking : accident, program frameworks and personal practices

Distribution through electronic media provides an avenue for promotion, recognition and an outlet of display for graphic designers. The emergence of available media technologies have enabled graphic designers to extend these boundaries of their practice. In this context the designer is constantly striving for aesthetic success and is strongly influenced by the fashion and trends of contemporary design work. The designer is always in a state of inquiry, finding pathways of discovery that lead to innovation and originality that are highly valued criteria for self-evaluation. This research is based on an analysis of the designer perspective and the processes used within an active graphic design practice specializing entirely within a digital collage domain. Contemporary design methodologies were critically examined, compared and refined to reflect the self-practice of the researcher. The refined methodology may assist designers in maintaining systematic work practices, as well as promote the importance of exploration and experimentation processes. Research findings indicate some differences in the identified methodologies and the design practice of the researcher in the sense that many contemporary designers are not confined to a client-base but are self-generating design images influenced by contemporary practitioners. As well as confirming some aspects of more conventional design processes, the researcher found that accidental discoveries and the designer’s interaction with technology plays a significant part in the design process.

Improving ultrasound excitation systems using a flexible power supply with adjustable voltage and frequency to drive piezoelectric transducers

The ability of a piezoelectric transducer in energy conversion is rapidly expanding in several applications. Some of the industrial applications for which a high power ultrasound transducer can be used are surface cleaning, water treatment, plastic welding and food sterilization. Also, a high power ultrasound transducer plays a great role in biomedical applications such as diagnostic and therapeutic applications. An ultrasound transducer is usually applied to convert electrical energy to mechanical energy and vice versa. In some high power ultrasound system, ultrasound transducers are applied as a transmitter, as a receiver or both. As a transmitter, it converts electrical energy to mechanical energy while a receiver converts mechanical energy to electrical energy as a sensor for control system. Once a piezoelectric transducer is excited by electrical signal, piezoelectric material starts to vibrate and generates ultrasound waves. A portion of the ultrasound waves which passes through the medium will be sensed by the receiver and converted to electrical energy. To drive an ultrasound transducer, an excitation signal should be properly designed otherwise undesired signal (low quality) can deteriorate the performance of the transducer (energy conversion) and increase power consumption in the system. For instance, some portion of generated power may be delivered in unwanted frequency which is not acceptable for some applications especially for biomedical applications. To achieve better performance of the transducer, along with the quality of the excitation signal, the characteristics of the high power ultrasound transducer should be taken into consideration as well. In this regard, several simulation and experimental tests are carried out in this research to model high power ultrasound transducers and systems. During these experiments, high power ultrasound transducers are excited by several excitation signals with different amplitudes and frequencies, using a network analyser, a signal generator, a high power amplifier and a multilevel converter. Also, to analyse the behaviour of the ultrasound system, the voltage ratio of the system is measured in different tests. The voltage across transmitter is measured as an input voltage then divided by the output voltage which is measured across receiver. The results of the transducer characteristics and the ultrasound system behaviour are discussed in chapter 4 and 5 of this thesis. Each piezoelectric transducer has several resonance frequencies in which its impedance has lower magnitude as compared to non-resonance frequencies. Among these resonance frequencies, just at one of those frequencies, the magnitude of the impedance is minimum. This resonance frequency is known as the main resonance frequency of the transducer. To attain higher efficiency and deliver more power to the ultrasound system, the transducer is usually excited at the main resonance frequency. Therefore, it is important to find out this frequency and other resonance frequencies. Hereof, a frequency detection method is proposed in this research which is discussed in chapter 2. An extended electrical model of the ultrasound transducer with multiple resonance frequencies consists of several RLC legs in parallel with a capacitor. Each RLC leg represents one of the resonance frequencies of the ultrasound transducer. At resonance frequency the inductor reactance and capacitor reactance cancel out each other and the resistor of this leg represents power conversion of the system at that frequency. This concept is shown in simulation and test results presented in chapter 4. To excite a high power ultrasound transducer, a high power signal is required. Multilevel converters are usually applied to generate a high power signal but the drawback of this signal is low quality in comparison with a sinusoidal signal. In some applications like ultrasound, it is extensively important to generate a high quality signal. Several control and modulation techniques are introduced in different papers to control the output voltage of the multilevel converters. One of those techniques is harmonic elimination technique. In this technique, switching angles are chosen in such way to reduce harmonic contents in the output side. It is undeniable that increasing the number of the switching angles results in more harmonic reduction. But to have more switching angles, more output voltage levels are required which increase the number of components and cost of the converter. To improve the quality of the output voltage signal with no more components, a new harmonic elimination technique is proposed in this research. Based on this new technique, more variables (DC voltage levels and switching angles) are chosen to eliminate more low order harmonics compared to conventional harmonic elimination techniques. In conventional harmonic elimination method, DC voltage levels are same and only switching angles are calculated to eliminate harmonics. Therefore, the number of eliminated harmonic is limited by the number of switching cycles. In the proposed modulation technique, the switching angles and the DC voltage levels are calculated off-line to eliminate more harmonics. Therefore, the DC voltage levels are not equal and should be regulated. To achieve this aim, a DC/DC converter is applied to adjust the DC link voltages with several capacitors. The effect of the new harmonic elimination technique on the output quality of several single phase multilevel converters is explained in chapter 3 and 6 of this thesis. According to the electrical model of high power ultrasound transducer, this device can be modelled as parallel combinations of RLC legs with a main capacitor. The impedance diagram of the transducer in frequency domain shows it has capacitive characteristics in almost all frequencies. Therefore, using a voltage source converter to drive a high power ultrasound transducer can create significant leakage current through the transducer. It happens due to significant voltage stress (dv/dt) across the transducer. To remedy this problem, LC filters are applied in some applications. For some applications such as ultrasound, using a LC filter can deteriorate the performance of the transducer by changing its characteristics and displacing the resonance frequency of the transducer. For such a case a current source converter could be a suitable choice to overcome this problem. In this regard, a current source converter is implemented and applied to excite the high power ultrasound transducer. To control the output current and voltage, a hysteresis control and unipolar modulation are used respectively. The results of this test are explained in chapter 7.

Imagining neighbourhood-based community : an autoethnography

This research is an autoethnographic investigation of consumption experiences, public and quasi-public spaces, and their relationship to community within an inner city neighbourhood. The research specifically focuses on the gentrifying inner city, where class-based processes of change can have implications for people’s abilities to remain within, or feel connected to place. However, the thesis draws on broader theories of the throwntogetherness of the contemporary city (e.g., Amin and Thrift, 2002; Massey 2005) to argue that the city is a space where place-based meanings cannot be seen to be fixed, and are instead better understood as events of place – based on ever shifting interrelations between the trajectories of people and things. This perspective argues the experience of belonging to community is not just born of a social encounter, but also draws on the physical and symbolic elements of the context in which it is situated. The thesis particularly explores the ways people construct identifications within this shifting urban environment. As such, consumption practices and spaces offer one important lens through which to explore the interplay of the physical, social and symbolic. Consumer research tells us that consumption practices can facilitate experiences in which identity-defining meaning can be generated and shared. Consumption spaces can also support different kinds of collective identification – as anchoring realms for specific cultural groups or exposure realms that enable individuals to share in the identification practices of others with limited risk (Aubert-Gamet & Cova, 1999). Furthermore, the consumption-based lifestyles that gentrifying inner city neighbourhoods both support and encourage can also mean that consumption practices may be a key reason that people are moving through public space. That is, consumption practices and spaces may provide a purpose for which – and spatial frame against which – our everyday interactions and connections with people and objects are undertaken within such neighbourhoods. The purpose of this investigation then was to delve into the subjectivities at the heart of identifying with places, using the lens of our consumption-based experiences within them. The enquiry describes individual and collective identifications and emotional connections, and explores how these arise within and through our experiences within public and quasi-public spaces. It then theorises these ‘imaginings’ as representative of an experience of community. To do so, it draws on theories of imagination and its relation to community. Theories of imagined community remind us that both the values and identities of community are held together by projections that create relational links out of objects and shared practices (e.g., Benedict Anderson, 2006; Urry, 2000). Drawing on broader theories of the processes of the imagination, this thesis suggests that an interplay between reflexivity and fantasy – which are products of the critical and the fascinated consciousness – plays a role in this imagining of community (e.g., Brann, 1991; Ricoeur, 1994). This thesis therefore seeks to explore how these processes of imagining are implicated within the construction of an experience of belonging to neighbourhood-based community through consumption practices and the public and quasi-public spaces that frame them. The key question of this thesis is how do an individual’s consumption practices work to construct an imagined presence of neighbourhood-based community? Given the focus on public and quasi-public spaces and our experiences within them, the research also asked how do experiences in the public and quasi-public spaces that frame these practices contribute to the construction of this imagined presence? This investigation of imagining community through consumption practices is based on my own experiences of moving to, and attempting to construct community connections within, an inner city neighbourhood in Melbourne, Australia. To do so, I adopted autoethnographic methodology. This is because autoethnography provides the methodological tools through which one can explore and make visible the subjectivities inherent within the lived experiences of interest to the thesis (Ellis, 2004). I describe imagining community through consumption as an extension of a placebased self. This self is manifest through personal identification in consumption spaces that operate as anchoring realms for specific cultural groups, as well as through a broader imagining of spaces, people, and practices as connected through experiences within realms of exposure. However, this is a process that oscillates through cycles of identification; these anchor one within place personally, but also disrupt those attachments. This instability can force one to question the orientation and motives of these imaginings, and reframe them according to different spaces and reference groups in ways that can also work to construct a more anonymous and, conversely, more achievable collective identification. All the while, the ‘I’ at the heart of this identification is in an ongoing process of negotiation, and similarly, the imagined community is never complete. That is, imagining community is a negotiation, with people and spaces – but mostly with the different identifications of the self. This thesis has been undertaken by publication, and thus the process of imagining community is explored and described through four papers. Of these, the first two focus on specific types of consumption spaces – a bar and a shopping centre – and consider the ways that anchoring and exposure within these spaces support the process of imagining community. The third paper examines the ways that the public and quasi-public spaces that make up the broader neighbourhood context are themselves throwntogether as a realm of exposure, and considers the ways this shapes my imaginings of this neighbourhood as community. The final paper develops a theory of imagined community, as a process of comparison and contrast with imagined others, to provide a summative conceptualisation of the first three papers. The first paper, chapter five, explores this process of comparison and contrast in relation to authenticity, which in itself is a subjective assessment of identity. This chapter was written as a direct response to the recent work of Zukin (2010), and draws on theories of authenticity as applied to personal and collective identification practices by consumer researchers Arnould and Price (2000). In this chapter, I describe how my assessments of the authenticity of my anchoring experiences within one specific consumption space, a neighbourhood bar, are evaluated in comparison to my observations of and affective reactions to the social practices of another group of residents in a different consumption space, the local shopping centre. Chapter five also provides an overview of the key sites and experiences that are considered in more detail in the following two chapters. In chapter six, I again draw on my experiences within the bar introduced in chapter five, this time to explore the process of developing a regular identity within a specific consumption space. Addressing the popular theory of the cafe or bar as third place (Oldenburg, 1999), this paper considers the purpose of developing anchored relationships with people within specific consumption spaces, and explores the different ways this may be achieved in an urban context where the mobilities and lifestyle practices of residents complicate the idea of a consumption space as an anchoring or third place. In doing so, this chapter also considers the manner in which this type of regular identification may be seen to be the beginning of the process of imagining community. In chapter seven, I consider the ways the broader public spaces of the neighbourhood work cumulatively to expose different aspects of its identity by following my everyday movements through the neighbourhood’s shopping centre and main street. Drawing on the theories of Urry (2000), Massey (2005), and Amin (2007, 2008), this chapter describes how these spaces operate as exposure realms, enabling the expression of different senses of the neighbourhood’s spaces, times, cultures, and identities through their physical, social, and symbolic elements. Yet they also enable them to be united: through habitual pathways, group practices of appropriation of space, and memory traces that construct connections between objects and experiences. This chapter describes this as a process of exposure to these different elements. Our imagination begins to expand the scope of the frames onto which it projects an imagined presence; it searches for patterns within the physical, social, and symbolic environment and draws connections between people and practices across spaces. As the final paper, chapter eight, deduces, it is in making these connections that one constructs the objects and shared practices of imagined community. This chapter describes this as an imagining of neighbourhood as a place-based extension of the self, and then explores the ways in which I drew on physical, social, and symbolic elements in an attempt to construct a fit between the neighbourhood’s offerings and my desires for place-based identity definition. This was as a cumulative but fragmented process, in which positive and negative experiences of interaction and identification with people and things were searched for their potential to operate as the objects and shared practices of imagined community. This chapter describes these connections as constructed through interplay between reflexivity and fantasy, as the imagination seeks balance between desires for experiences of belonging, and the complexities of constructing them within the throwntogether context of the contemporary city. The conclusion of the thesis describes the process of imagining community as a reflexive fantasy, that is, as a product of both the critical and fascinated consciousness (Ricoeur, 1994). It suggests that the fascinated consciousness imbues experiences with hope and desire, which the reflexive imagining can turn to disappointment and shame as it critically reflects on the reality of those fascinated projections. At the same time, the reflexive imagination also searches the practices of others for affirmation of those projections, effectively seeking to prove the reality of the fantasy of the imagined community.

A conversation approach to business model innovation

Sense making through conversation plays a key role in channelling and furthering participatory business model innovation. The designer as facilitator, with conversation as a core tool, is an emerging area of interest within the design research literature. This paper will discuss preliminary findings of a case study of Second Road, a strategy and innovation consultancy that employed a design thinking approach and conversational methods to redesign a client’s business development model. Through this study conversation based co-creation emerged as the primary method for participatory innovation.

Hyperlipidemia impaired innate immune response to periodontal pathogen Porphyromonas gingivalis in apolipoprotein E knockout mice

A finely-tuned innate immune response plays a pivotal role in protecting host against bacterial invasion during periodontal disease progression. Hyperlipidemia has been suggested to exacerbate periodontal health condition. However, the underlying mechanism has not been addressed. In the present study, we investigated the effect of hyperlipidemia on innate immune responses to periodontal pathogen Porphyromonas gingivalis infection. Apolipoprotein E-deficient and wild-type mice at the age of 20 weeks were used for the study. Peritoneal macrophages were isolated and subsequently used for the study of viable P. gingivalis infection. ApoE−/− mice demonstrated inhibited iNOS production and impaired clearance of P. gingivalis in vitro and in vivo; furthermore, ApoE−/− mice displayed disrupted cytokine production pattern in response to P. gingivalis, with a decreased production of tumor necrosis factor-α, interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein-1. Microarray data demonstrated that Toll-like receptor (TLR) and NOD-like receptor (NLR) pathway were altered in ApoE−/− mice macrophages; further analysis of pattern recognition receptors (PRRs) demonstrated that expression of triggering receptors on myeloid cells-1 (TREM-1), an amplifier of the TLR and NLR pathway, was decreased in ApoE−/− mice macrophages, leading to decreased recruitment of NF-κB onto the promoters of the TNF-α and IL-6. Our data suggest that in ApoE−/− mice hyperlipidemia disrupts the expression of PRRs, and cripples the host’s capability to generate sufficient innate immune response to P. gingivalis, which may facilitate immune evasion, subgingival colonization and establishment of P. gingivalis in the periodontal niche.

Preparing culturally and linguistically diverse nursing students for clinical practice in the health care setting

The number of culturally and linguistically diverse (CALD) students seeking enrollment in higher education courses in Western countries where English is the predominant language has grown considerably in the past decade, especially in undergraduate health care courses. When enrolled in nursing courses, students are required to complete clinical placements. Such experiences can create significant challenges for CALD students where language, cultural differences, and interpretation of cultural norms complicate the learning process. To assist CALD nursing students to transition successfully, an extracurricular integrated curriculum program was developed and implemented at a university in Queensland, Australia. The program is a series of interactive workshops based on the principles of caring pedagogy and student-centered learning. The program applies strategies that combine small-group discussions with peers, role-plays, and interactions with final-year nursing student volunteers. Evaluation of the program suggests it has assisted most of the students surveyed to be successful in their clinical studies.

Exploring Indigenous representations in Australian film and literature for the Australian Curriculum

The Australian Curriculum: English, v.5 (ACARA, 2013) now being implemented in Queensland asks teachers and curriculum designers to incorporate the cross curriculum priority (CCP)of Indigenous issues through Aboriginal and Torres Strait Islander histories and cultures. In the Australian Curriculum English, (AC:E) one way to address this CCP is by including texts by and about Aboriginal and Torres Strait Islander people. With the rise of promising and accomplished young, Indigenous filmmakers such as Ivan Sen, Rachael Perkins, Wayne Blair and Warwick Thornton, this guide focuses on the suitable films for schools implementing the Australian Curriculum in terms of cultural representations. This annotated guide suggests some films suitable for inclusion in classroom study and suggests some companion texts (novels, plays, television series and animations, documentaries, poetry and short stories) that may be studied alongside the films. Some of these are by Indigenous filmmakers and writers, and others features Aboriginal and Torres Strait Island representations in character and/or themes.

The roles of Australian chairs in clinical nursing

Australian chairs in clinical nursing have been established in order to achieve more effective partnerships between academia and the health care sector in education, research and quality of nursing care. The aim of this study was to describe the goals, obstacles, supports and outcomes of such appointments. The study explored the perceptions of a purposive sample of Australian professors holding clinical chairs, stratified to ensure representation of both the geographical and clinical specialty diversity of the population. Eight professors were interviewed using semi-structured telephone interviews. The interviews covered three phases: role establishment, current foci and future developments. Qualitative analysis for common themes and areas of divergence was conducted with concurrent analysis providing the opportunity to seek confirmation for emerging themes. The participants highlighted the diversity of arrangements between university and health sector partners in establishing their respective roles. Clear communication was crucial to successful partnership arrangements. All roles included components of education, research and politics but the relative contribution of each of these areas depended to a large extent on the priorities of the employing partners. The participants felt the need to secure sustainable income sources and consolidate outcomes to ensure the continued viability of their positions. Clinical professorial nursing appointments provide one means of addressing perceived gaps in the links between the university and health care sectors, academia and clinicians, thus enhancing nursing education, research and politics. Through emphasizing common purpose and mutual respect, these positions can illuminate the crucial role nursing plays in Australian health care delivery.

Review : "The Square" -- Nash Edgerton

Synopsis and review of the Australian crime film The Square (Nash Edgerton, 2009). Includes cast and credits. The Square is the feature film debut of director Nash Edgerton, well-known in Australian film circles not only for his award-winning music videos and short films Deadline (first prize winner at Tropfest in 1997) and Spider, but also for his work as an actor, editor, producer, writer and stuntman on countless Australian films and television programs. The film was co-written by Edgerton’s regular partner and brother Joel, who also plays the arsonist Billy. Joel is familiar to Australian and international audiences for his television work in The Secret Life of Us as well as numerous film roles...

Investigations Into the Significance of Lysine Residues in IGF-I

This PhD thesis presents novel and original research in the field of Insulin-like Growth Factor-I (or IGF-I) biology. IGF-I plays an essential role in promoting normal human growth and development; it also represents both a target and treatment for various diseases. This thesis provides interesting insights into previously uncharacterised mechanisms of action that underlie IGF-I biology. Such findings may lead to improved and novel treatments across a broad range of medical conditions.

Consumers' behavioural responses toward technology-based social products

This thesis examined the determinants of consumers’ use of emerging mental health services delivered via mobile phone technology, which promise to provide cost-effective psychotherapeutic support where and when needed. It builds on the Model of Goal-Directed Behaviour by recognising the role that competition between behavioural alternatives plays in influencing consumers’ decision to use these services. The research employed a three-study, mixed-methodological approach.

Effect of induced airway inflammation in asthma : the expression of trefoil factors, secretoglobins and genes involved in histone acetylation

Asthma is an incapacitating disease of the respiratory system, which causes extensive morbidity and mortality worldwide. Asthma affects more than 300 million people globally(Masoli et al. 2004). In Australia, it affects 10.2% of the population (Masoli et al. 2004) and causes 60,000 people to be hospitalised annually. Health care expenditure due to asthma in Australia was $606 million in 2004–2005. There are four primary biological factors that function in the initiation and exacerbation of asthma. Airway inflammation is important as it is often the first response to an airway insult, initiating the three other components: bronchoconstriction, mucus hyper-secretion and hyper-reactivity. The mediators involved in asthma are still not well understood, and current anti-inflammatory corticosteroid treatments are not effective with all asthmatics. As there is currently no cure for asthma, and airway inflammation is the primary component of the disease, it is important that we understand and investigate the mediators of airway inflammation to look for a potential cure and to produce better therapeutics to treat the inflammation. Trefoil factors (TFFs) and secretoglobins (SCGBs) are small secreted proteins involved in the mediation of inflammation and epithelial restitution. TFFs are pro-inflammatory and SCGBs anti-inflammatory by nature. The hypothesis of this study is that in response to induced acute airway inflammation, the expression of TFF1 and TFF3 will increase and expression of SCGB1A1 and SCGB3A2 will decrease in non-asthmatics (N-A), asthmatics medicating with bronchodilators (A-BD) and asthmatics medicating with corticosteroids (A-ST). When comparing the three groups, we expect to see higher expression of the TFFs in the A-BD group compared to the N-A and A-ST groups, indicating that inflammation is mediated by TFFs in asthma and that corticosteroid medication controls their expression as part of the control of inflammation. We expect to see the opposite with SCGBs, with a greater decrease in the A-BD group compared to the other two groups, suggesting that the A-BD group has the least anti-inflammatory activity in response to inflammatory insult. Epigenetic modification plays a role in the regulation of genes that initiate disease states such as inflammatory conditions and cancers. Histone acetylation is one such modification, which involves the acetylation of histones in chromatin by histone acetyltransferases (HATs). This increases the transcription of genes involved with inflammation or enrols histone deacetylases (HDACs) to down-regulate the transcription of inflammatory genes. These HATs and HDACs work in a homeostatic fashion; however, in the event of inflammation, increased HAT activity can stimulate further inflammation, which is believed to be the mechanism involved in some inflammatory diseases. This study hypothesises that in response to inflammation, the expression of HDACs (HDAC1-5) will decrease and the expression of HATs (NCOA1-3, HAT-1 and CREBBP) will increase in all groups. When comparing the expression between the groups, it was expected that a greater decrease in HDACs and a greater increase in HATs will be seen in the A-BD group compared to the other two groups. This would identify histone acetylation as a mechanism involved in the inflammatory condition of asthma and indicate that corticosteroids may treat the inflammation in asthma at least in part by controlling histone acetylation. The aim of the project was to compare the expression of inflammatory genes TFF1, TFF3, SCGB1A1 and SCGB3A2, as well as to compare the gene expression of HDAC1-5, NCOA1-3, HAT-1 and CREBBP within and between N-A (n=15), A-BD (n=15) and A-ST (n=15) groups in response to inflammation. This was performed by collecting airway cells and proteins by sputum induction in three sessions. The sessions were coordinated into an initial baseline collection (SI-1), followed by a second session at least one week later (SI-2) and a third session, six hours after SI-2 to collect a sample containing the resultant acute inflammation caused in SI-2 (SI-3). Analysis of the SI-1 and SI-2 samples in all three groups had high amounts of variability between samples. The samples were taken at least one weak apart and the environmental stimuli on each participant outside of the testing sessions could not be controlled. For this reason, the SI-1 samples were not used for analysis; instead SI-2 and SI-3 samples were compared as they were same-day collections, reducing the probability of differences being due to anything other than the sputum induction. The gene expressions of the TFFs, SCGBs, HDACs and HATs were analysed using real-time PCR. Western blot analysis was performed to analyse the protein concentrations of the TFFs and SCGBs in secreted fractions of the sputum collection. Both the secreted and intracellular protein fractions collected from the sputum inductions for pre- and post-inflammation (SI-2, SI-3) samples of the N-A and A-BD groups were analysed using a proteomic method called iTRAQ. This allowed the comparison of the change in protein expression as a result of airway inflammation in each group. This technique was used as a discovery method to identify novel proteins that are modulated by induced acute airway inflammation. Any proteins of interest would then be further validated and used for future research. Inflammation was achieved in the SI-3 samples of the N-A group with a 21% unit increase in % neutrophils compared to SI-2 (p=0.01). The N-A group had a marked 5.5-fold decrease in HDAC1 gene expression in SI-3 compared to SI-2 (p=0.03). No differences were seen in any of the TFFs, SCGBs or any of the rest of the HDACs and HATs. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed increases in TFF1 and TFF3, and decreases in SCGB1A1 and SCGB3A2 for the majority of SI-3 samples compared to SI-2. The A-BD group also presented a marked increase in neutrophils in the SI-3 samples compared to SI-2 (27% unit increase, p=0.04). The A-BD group had a significant increase in TFF3 and SCGB1A1 gene expression concomitant with induced acute airway inflammation. A 7.3-fold increase in TFF3 (p=0.05) in SI-3 indicated that TFF3 is linked to inflammation in asthmatics. A 2.8-fold increase in SCGB1A1 (p=0.03) indicated that this gene is also up-regulated, suggesting that this SCGB is expressed to try to combat induced acute airway inflammation. No significant changes were seen in any of the other genes analysed. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. However, non-significant analysis of the data displayed an increase in TFF1 and TFF3, and a decrease in SCGB1A1 and SCGB3A2 in SI-3, similar to that seen in the N-A group. The A-ST group was different from the A-BD group, characterised by the use of inhaled corticosteroid medication to treat asthma symptoms. Inhaled corticosteroids are known to treat asthma symptoms through the control of inflammation. Therefore, it was expected that corticosteroid medication would also control the expression of TFFs, SCGBs, HATs and HDACs. Gene expression results only identified a 7.6-fold decrease in HDAC2 expression in SI-3 (p=0.001), which is proposed to be due to the up-regulation of HDAC2 protein that is known to be a function of corticosteroid use. Western blot data did not display any significant changes in the protein levels of the TFFs and SCGBs analysed. The gene expression in SI-2 and SI-3 in each group was compared. When comparing the A-BD group to the N-A group, a 9-fold increase in TFF3 (p=0.008) and a 34-fold increase in SCGB1A1 (p=0.03) were seen in the SI-3 samples. Comparisons of the A-ST group to the N-A group had an increased expression in SI-2 samples for HDAC5 (3.6-fold, p=0.04), NCOA2 (8.5-fold, p=0.04), NCOA3 (17-fold, p=0.01), HAT-1 (36-fold, p=0.003) and CREBBP (13-fold, p=0.001). The SI-3 samples in the A-ST group compared to the N-A group had increased expression for HDAC1 (6.4-fold, p=0.04), HDAC5 (5.2-fold, p=0.008), NCOA2 (9.6-fold, p=0.03), NCOA3 (16-fold, p=0.06), HAT-1 (41-fold, p<0.001) and CREBBP (31-fold, p=0.001). Comparisons of the A-ST group to the A-BD group had SI-2 increases in HDAC1 (3.8-fold, p=0.03), NCOA3 (4.5-fold, p=0.03), HAT-1 (5.3-fold, p=0.01) and CREBBP (23-fold, p=0.001), while SI-3 comparisons saw a decrease in HDAC2 (41-fold, p=0.008) and increases in HAT-1 (4.3-fold, p=0.003) and CREBBP (40-fold, p=0.001). Results showed that TFF3 and SCGB1A1 expression is higher in asthmatics than non-asthmatics and that histone acetylation is more active in the A-ST group than either the N-A or A-BD group, which suggests that histone acetylation activity may be positively correlated with asthma severity. The iTRAQ proteomic analysis of the secreted protein samples identified the SCGB1A1 protein and found it to be decreased in both the N-A and A-BD groups post-inflammation, but significantly so only in the A-BD group. Although no significant results were obtained from the western blot data, both groups displayed a decrease in SCGB1A1 concentration in SI-3 samples, suggesting a correlation with the proteomic data. Only 31 peptides were identified from the secreted samples. The intracellular iTRAQ analysis successfully identified 664 peptides, eight of which had differential expression in association with induced acute airway inflammation. Significant increases were seen in the A-BD group in SI-3 compared to SI-2 than in the N-A group in chloride intracellular channel protein 1, keratin-19, eosinophil cationic protein, calnexin, peroxiredoxin-5, and ATP-synthase delta subunit, while decreases were seen in cystatin-A and mucin-5AC. The iTRAQ analysis was only a discovery measure and further validation must be performed. In summary, the expression of TFFs and SCGBs differed between non-asthmatics and asthmatics. It is clear that TFF3 is active in the airway inflammation associated with asthma as indicated by an increase associated with inflammation in the A-BD group compared to the N-A group. Results for HDAC and HAT genes showed high HAT expression in the A-ST group compared to the N-A and A-BD groups, suggesting that histone acetyltransferases may be responsible for the characteristic unregulated inflammatory symptoms of asthmatics taking corticosteroids. Interestingly, corticosteroid medication did not seem to silence the expression of the analysed HAT genes, which indicates that corticosteroids may not control inflammation by direct regulation of HATs, but instead by competition, most probably with HDAC2 protein. As a discovery tool, iTRAQ is a potent method to both identify and compare the concentration of proteins between samples. The method is a powerful first step into the identification of novel proteins that are regulated in response to different treatments.

Modeling obligations with event-calculus

Time plays an important role in norms. In this paper we start from our previously proposed classification of obligations, and point out some shortcomings of Event Calculus (EC) to represent obligations. We proposed an extension of EC that avoids such shortcomings and we show how to use it to model the various types of obligations.

The human μ-opioid receptor gene polymorphism (A118G) is associated with head pain severity in a clinical cohort of female migraine with aura patients

Migraine is a painful and debilitating, neurovascular disease. Current migraine head pain treatments work with differing efficacies in migraineurs. The opioid system plays an important role in diverse biological functions including analgesia, drug response and pain reduction. The A118G single nucleotide polymorphism (SNP) in exon 1 of the μ-opioid receptor gene (OPRM1) has been associated with elevated pain responses and decreased pain threshold in a variety of populations. The aim of the current preliminary study was to test whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. This was a preliminary study to determine whether genotypes of the OPRM1 A118G SNP are associated with head pain severity in a clinical cohort of female migraineurs. A total of 153 chronic migraine with aura sufferers were assessed for migraine head pain using the Migraine Disability Assessment Score instrument and classified into high and low pain severity groups. DNA was extracted and genotypes obtained for the A118G SNP. Logistic regression analysis adjusting for age effects showed the A118G SNP of the OPRM1 gene to be significantly associated with migraine pain severity in the test population (P = 0.0037). In particular, G118 allele carriers were more likely to be high pain sufferers compared to homozygous carriers of the A118 allele (OR = 3.125, 95 % CI = 1.41, 6.93, P = 0.0037). These findings suggest that A118G genotypes of the OPRM1 gene may influence migraine-associated head pain in females. Further investigations are required to fully understand the effect of this gene variant on migraine head pain including studies in males and in different migraine subtypes, as well as in response to head pain medication.

The role of the MTHFR gene in migraine

Migraine is a common neurological disorder and is characterized by debilitating head pain and an assortment of additional symptoms which can include nausea, emesis, photophobia, phonophobia, and occasionally, visual sensory disturbances. A number of genes have been implicated in the pathogenesis of this disease, including genes involved in regulating the vascular system. Of particular importance are the methylenetetrahydrofolate reductase (MTHFR) gene and the role it plays in migraine with aura. Migraine with aura has previously been shown to have a significant comorbidity with stroke, making the vascular class of genes a priority for migraine studies. In this report, we outline the importance of the MTHFR gene in migraine and also discuss the use of a genetic isolate to investigate MTHFR genetic variants. From this study, 3 MTHFR single nucleotide polymorphisms showing association with migraine in the Norfolk Island population have been identified, thus reinforcing the potential role of MTHFR in migraine susceptibility. Further studies will continue to build a gene profile of variants involved in the complex disease migraine and improve understanding of the underlying genetic causes of this disorder.