Middle India as revealed by Chetan Bhagat

The middle classes form the bulk of Indian migrants who head for Australian shores today. Yet, within Australia, general knowledge of the conditions that drive Indians’ determined search for opportunities overseas is limited to the few who have contact with international students and migrants from the sub-continent, and the skewed, melodramatic antics of Bollywood. It is my suggestion that a broader understanding of the underlying reasons that push Indians to migrate to societies like Australia can be had through readings of Chetan’s Bhagat’s four hugely popular novels: Five Point Someone, One night @the Call Center, The 3 mistakes of My life and Two States. Bhagat is a graduate of India’s famed Indian Institute of Technology and a former Non-Resident Indian investment banker who has since returned to live in Delhi. His experiences make him the perfect mouthpiece for middle India and his paperbacks depict that stratum of Indian society’s obsessions with social mobility, marriage, regional and religious divides with great sympathy and conviction. Drawing on observations made during a recent visit to India, I illustrate what an exploration of Bhagat’s paperbacks reveals about everyday, contemporary India and what it adds to Australian understandings of Indians and India today.

designing creative clusters : some indicators

This paper explores how the design of creative clusters as a key strategy in promoting the urban creative economy has played out in Shanghai. Creative Clusters in Europe and North America context have emerged ‘organically’. They developed spontaneously in those cities which went through a period of post-industrial decline. Creative Industries grew up in these cities as part of a new urban economy in the wake of old manufacturing industries. Artists and creative entrepreneurs moved into vacant warehouses and factories and began the trend of ‘creative clusters’. Such clusters facilitate the transfer of tacit knowledge through informal learning, the efficient sourcing of skills and information, competition, collaboration and learning, inter-cluster trading and networking. This new urban phenomenon was soon targeted by local economic development policy in charge of re-generating and re-structuralizing industrial activities in cities. Rising interest from real estate and local economic development has led to more and more planned creative clusters. In the aim of catching up with the world’s creative cities, Shanghai has planned over 100 creative clusters since 2005. Along with these officially designed creative clusters, there are organically emerged creative clusters that are much smaller in scale and much more informal in terms of the management. And they emerged originally in old residential areas just outside the CBD and expand to include French concession the most sort after residential area at the edge of CBD. More recently, office buildings within CBD are made available for creative usages. From fringe to CBD, these organic creative clusters provide crucial evidences for the design of creative clusters. This paper will be organized in 2 parts. In the first part, I will present a case study of 8 ‘official’ clusters (title granted by local govenrment) in Shanghai through which I am hoping to develop some key indicators of the success/failure of creative clusters as well as link them with their physical, social and operational efficacies. In the second part, a variety of ‘alternative’ clusters (organicly formed clusters most of which are not recongnized by the government) supplies with us the possibilities of rethinking the so-called ‘cluster development strategy’ in terms of what kind of spaces are appropriate for use by clusters? Who should manage them and in what format? And ultimately what are their relationship with the rest of the city should be defined?

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

Fuzzy methods for analysis of microarrays and networks

Bioinformatics involves analyses of biological data such as DNA sequences, microarrays and protein-protein interaction (PPI) networks. Its two main objectives are the identification of genes or proteins and the prediction of their functions. Biological data often contain uncertain and imprecise information. Fuzzy theory provides useful tools to deal with this type of information, hence has played an important role in analyses of biological data. In this thesis, we aim to develop some new fuzzy techniques and apply them on DNA microarrays and PPI networks. We will focus on three problems: (1) clustering of microarrays; (2) identification of disease-associated genes in microarrays; and (3) identification of protein complexes in PPI networks. The first part of the thesis aims to detect, by the fuzzy C-means (FCM) method, clustering structures in DNA microarrays corrupted by noise. Because of the presence of noise, some clustering structures found in random data may not have any biological significance. In this part, we propose to combine the FCM with the empirical mode decomposition (EMD) for clustering microarray data. The purpose of EMD is to reduce, preferably to remove, the effect of noise, resulting in what is known as denoised data. We call this method the fuzzy C-means method with empirical mode decomposition (FCM-EMD). We applied this method on yeast and serum microarrays, and the silhouette values are used for assessment of the quality of clustering. The results indicate that the clustering structures of denoised data are more reasonable, implying that genes have tighter association with their clusters. Furthermore we found that the estimation of the fuzzy parameter m, which is a difficult step, can be avoided to some extent by analysing denoised microarray data. The second part aims to identify disease-associated genes from DNA microarray data which are generated under different conditions, e.g., patients and normal people. We developed a type-2 fuzzy membership (FM) function for identification of diseaseassociated genes. This approach is applied to diabetes and lung cancer data, and a comparison with the original FM test was carried out. Among the ten best-ranked genes of diabetes identified by the type-2 FM test, seven genes have been confirmed as diabetes-associated genes according to gene description information in Gene Bank and the published literature. An additional gene is further identified. Among the ten best-ranked genes identified in lung cancer data, seven are confirmed that they are associated with lung cancer or its treatment. The type-2 FM-d values are significantly different, which makes the identifications more convincing than the original FM test. The third part of the thesis aims to identify protein complexes in large interaction networks. Identification of protein complexes is crucial to understand the principles of cellular organisation and to predict protein functions. In this part, we proposed a novel method which combines the fuzzy clustering method and interaction probability to identify the overlapping and non-overlapping community structures in PPI networks, then to detect protein complexes in these sub-networks. Our method is based on both the fuzzy relation model and the graph model. We applied the method on several PPI networks and compared with a popular protein complex identification method, the clique percolation method. For the same data, we detected more protein complexes. We also applied our method on two social networks. The results showed our method works well for detecting sub-networks and give a reasonable understanding of these communities.

Vulnerable and invisible : depictions of trafficking victims in public awareness campaigns

Public concern about the crime of human trafficking has dramatically risen over the last two decades. . This concern and panic has both spawned and been fuelled by an array of public awareness campaigns that aim to educate the public about this crime. Campaigns such as the Blue Blindfold Campaign in the UK, the UN-driven Blue Heart Campaign, and the worldwide Body Shop campaign have contributed to the public’s awareness and, to an extent, understanding of the phenomenon of human trafficking. This research explores these and other government and non-government campaigns aimed at raising public awareness of human trafficking. It questions the rationale, call to action and impact of these efforts, and analyses the depiction of trafficking victims in these campaigns. In particular, this research argues that some of these campaigns perpetuate an understanding of a hierarchy of victimisation of trafficking. A public focus on sex trafficking often results in the conflation of prostitution and trafficking, and renders invisible the male and female victims of trafficking for other forms of labour.

Really really

In “Really Really”, a series of words float through animated star constellations. While apparently drifting aimlessly, the words can be rearranged in numerous ways to recount roughly the same sappy avowal of long-distance love. The many combinations of words, and their predictable associations, call attention to the thresholds of verbal expression. When some sincere words are needed most it seems as if they’ve all been said before. And so, this declaration of love is both enabled and haunted by the tension between sentiment and formula. “Really Really” continues my interests in how meaning is constructed and circulated, and in particular, how common models of communication continue to frame and yet fall short of our personal experiences.

Unlocking black box models of leadership effectiveness: Exploring alternative research and policy metaphors

There is an intimate interconnectivity between policy guidelines defining reform and the delineation of what research methods would be subsequently applied to determine reform success. Research is guided as much by the metaphors describing it as by the ensuing empirical definition of actions of results obtained from it. In a call for different reform policy metaphors Lumby and English (2010) note, “The primary responsibility for the parlous state of education... lies with the policy makers that have racked our schools with reductive and dehumanizing processes, following the metaphors of market efficiency, and leadership models based on accounting and the characteristics of machine bureaucracy” (p. 127)

Reframing the design of context-aware computing

From location-aware computing to mining the social web, representations of context have promised to make better software applications. The opportunities and challenges of context-aware computing from representational, situated and interactional perspectives have been well documented, but arguments from the perspective of design are somewhat disparate. This paper draws on both theoretical perspectives and a design framing, using the problem of designing a social mobile agile ridesharing system, in order to reflect upon and call for broader design approaches for context-aware computing and human-computer Interaction research in general.

Privacy compliance verification in cryptographic protocols

To provide privacy protection, cryptographic primitives are frequently applied to communication protocols in an open environment (e.g. the Internet). We call these protocols privacy enhancing protocols (PEPs) which constitute a class of cryptographic protocols. Proof of the security properties, in terms of the privacy compliance, of PEPs is desirable before they can be deployed. However, the traditional provable security approach, though well-established for proving the security of cryptographic primitives, is not applicable to PEPs. We apply the formal language of Coloured Petri Nets (CPNs) to construct an executable specification of a representative PEP, namely the Private Information Escrow Bound to Multiple Conditions Protocol (PIEMCP). Formal semantics of the CPN specification allow us to reason about various privacy properties of PIEMCP using state space analysis techniques. This investigation provides insights into the modelling and analysis of PEPs in general, and demonstrates the benefit of applying a CPN-based formal approach to the privacy compliance verification of PEPs.

Optimising a coal rail network under capacity constraints

This research deals with an innovative methodology for optimising the coal train scheduling problem. Based on our previously published work, generic solution techniques are developed by utilising a “toolbox” of standard well-solved standard scheduling problems. According to our analysis, the coal train scheduling problem can be basically modelled a Blocking Parallel-Machine Job-Shop Scheduling (BPMJSS) problem with some minor constraints. To construct the feasible train schedules, an innovative constructive algorithm called the SLEK algorithm is proposed. To optimise the train schedule, a three-stage hybrid algorithm called the SLEK-BIH-TS algorithm is developed based on the definition of a sophisticated neighbourhood structure under the mechanism of the Best-Insertion-Heuristic (BIH) algorithm and Tabu Search (TS) metaheuristic algorithm. A case study is performed for optimising a complex real-world coal rail system in Australia. A method to calculate the lower bound of the makespan is proposed to evaluate results. The results indicate that the proposed methodology is promising to find the optimal or near-optimal feasible train timetables of a coal rail system under network and terminal capacity constraints.

Scheduling a flow-shop with combined buffer conditions

In this paper, No-Wait, No-Buffer, Limited-Buffer, and Infinite-Buffer conditions for the flow-shop problem (FSP) have been investigated. These four different buffer conditions have been combined to generate a new class of scheduling problem, which is significant for modelling many real-world scheduling problems. A new heuristic algorithm is developed to solve this strongly NP-hard problem. Detailed numerical implementations have been analysed and promising results have been achieved.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

Individuals in a mass market environment: Australian bequest donors seek better communication from charities

Swelling social need and competing calls on government funds have heightened the philanthropic dollar’s value. Yet, Australia is not regarded as having a robust giving culture: while 86% of adults give, a mere 16% plan their giving with those who do donating four times as much as spontaneous givers (Giving Australia, 2005). Traditionally, the prime planned giving example is a charitable bequest, a revenue stream not prevalent here (Baker, 2007). In fact, Baker’s Victorian probate data shows under 5% of estates provide a charitable bequest and just over 1% of estate assets is bequeathed. The UK, in contrast, sources 30% and the US 10% of charitable income through bequests (NCVO, 2004; Sargeant, Wymer and Hilton,2006). Australian charities could boost bequest giving. Understanding the donor market, which has or may remember them in their will is critical. This paper reports donor perceptions of Australian charities’ bequest communication/ marketing. The data forms part of a wider study of Australian donors’ bequest attitudes and behaviour. Charities spend heavily on bequest promotion, from advertising to personal selling to public relations and promotion. Infrastructure funds are scarce so guidance on what works for donors is important. Guy and Patton (1988) made their classic call for a nonprofit marketing perspective and identify the need for charities to better understand the motivations and behaviour of their supporters. In similar vein, this study aims to improve the way nonprofits and givers interact; and ultimately, enhance the giving experience and thus multiply planned giving participation. Academically, it offers insights to Australian bequest motivations and attitudes not studied empirically before.

Foresight practice in Australia: a meta-scan of practitioners and organisations

This critical review of foresight professionals seeks to analyse their social interests, methodology, epistemological focal domains, capacitating focus, geography and organisational type. The call for a deeper understanding of the practice in the Australian context is made in order for the foundations for a National Foresight Strategy to be laid.

eBILITY : from tool use to partnerships

In this article we identify how computational automation achieved through programming has enabled a new class of music technologies with generative music capabilities. These generative systems can have a degree of music making autonomy that impacts on our relationships with them; we suggest that this coincides with a shift in the music-equipment relationship from tool use to a partnership. This partnership relationship can occur when we use technologies that display qualities of agency. It raises questions about the kinds of skills and knowledge that are necessary to interact musically in such a partnership. These are qualities of musicianship we call eBility. In this paper we seek to define what eBility might consist of and how consideration of it might effect music education practice. The 'e' in eBility refers not only to the electronic nature of computing systems but also to the ethical, enabling, experiential and educational dimensions of the creative relationship with technologies with agency. We hope to initiate a discussion around differentiating what we term representational technologies from those with agency and begin to uncover the implications of these ideas for music educators in schools and communities. We hope also to elucidate the emergent theory and practice that has enabled the development of strategies for optimising this kind of eBility where the tool becomes partner. The identification of musical technologies with agency adds to the authors’ list of metaphors for technology use in music education that previously included tool, medium and instrument. We illustrate these ideas with examples and with data from our work with the jam2jam interactive music system. In this discussion we will outline our experiences with jam2jam as an example of a technology with agency and describe the aspects of eBility that interaction with it promotes.