Monitoring and regulatory role of the balanced scorecard in controlling organisational identities

This thesis employs the theoretical fusion of disciplinary knowledge, interlacing an analysis from both functional and interpretive frameworks and applies these paradigms to three concepts—organisational identity, the balanced scorecard performance measurement system, and control. As an applied thesis, this study highlights how particular public sector organisations are using a range of multi-disciplinary forms of knowledge constructed for their needs to achieve practical outcomes. Practical evidence of this study is not bound by a single disciplinary field or the concerns raised by academics about the rigorous application of academic knowledge. The study’s value lies in its ability to explore how current communication and accounting knowledge is being used for practical purposes in organisational life. The main focus of this thesis is on identities in an organisational communication context. In exploring the theoretical and practical challenges, the research questions for this thesis were formulated as: 1. Is it possible to effectively control identities in organisations by the use of an integrated performance measurement system—the balanced scorecard—and if so, how? 2. What is the relationship between identities and an integrated performance measurement system—the balanced scorecard—in the identity construction process? Identities in the organisational context have been extensively discussed in graphic design, corporate communication and marketing, strategic management, organisational behaviour, and social psychology literatures. Corporate identity is the self-presentation of the personality of an organisation (Van Riel, 1995; Van Riel & Balmer, 1997), and organisational identity is the statement of central characteristics described by members (Albert & Whetten, 2003). In this study, identity management is positioned as a strategically complex task, embracing not only logo and name, but also multiple dimensions, levels and facets of organisational life. Responding to the collaborative efforts of researchers and practitioners in identity conceptualisation and methodological approaches, this dissertation argues that analysis can be achieved through the use of an integrated framework of identity products, patternings and processes (Cornelissen, Haslam, & Balmer, 2007), transforming conceptualisations of corporate identity, organisational identity and identification studies. Likewise, the performance measurement literature from the accounting field now emphasises the importance of ‘soft’ non-financial measures in gauging performance—potentially allowing the monitoring and regulation of ‘collective’ identities (Cornelissen et al., 2007). The balanced scorecard (BSC) (Kaplan & Norton, 1996a), as the selected integrated performance measurement system, quantifies organisational performance under the four perspectives of finance, customer, internal process, and learning and growth. Broadening the traditional performance measurement boundary, the BSC transforms how organisations perceived themselves (Vaivio, 2007). The rhetorical and communicative value of the BSC has also been emphasised in organisational self-understanding (Malina, Nørreklit, & Selto, 2007; Malmi, 2001; Norreklit, 2000, 2003). Thus, this study establishes a theoretical connection between the controlling effects of the BSC and organisational identity construction. Common to both literatures, the aspects of control became the focus of this dissertation, as ‘the exercise or act of achieving a goal’ (Tompkins & Cheney, 1985, p. 180). This study explores not only traditional technical and bureaucratic control (Edwards, 1981), but also concertive control (Tompkins & Cheney, 1985), shifting the locus of control to employees who make their own decisions towards desired organisational premises (Simon, 1976). The controlling effects on collective identities are explored through the lens of the rhetorical frames mobilised through the power of organisational enthymemes (Tompkins & Cheney, 1985) and identification processes (Ashforth, Harrison, & Corley, 2008). In operationalising the concept of control, two guiding questions were developed to support the research questions: 1.1 How does the use of the balanced scorecard monitor identities in public sector organisations? 1.2 How does the use of the balanced scorecard regulate identities in public sector organisations? This study adopts qualitative multiple case studies using ethnographic techniques. Data were gathered from interviews of 41 managers, organisational documents, and participant observation from 2003 to 2008, to inform an understanding of organisational practices and members’ perceptions in the five cases of two public sector organisations in Australia. Drawing on the functional and interpretive paradigms, the effective design and use of the systems, as well as the understanding of shared meanings of identities and identifications are simultaneously recognised. The analytical structure guided by the ‘bracketing’ (Lewis & Grimes, 1999) and ‘interplay’ strategies (Schultz & Hatch, 1996) preserved, connected and contrasted the unique findings from the multi-paradigms. The ‘temporal bracketing’ strategy (Langley, 1999) from the process view supports the comparative exploration of the analysis over the periods under study. The findings suggest that the effective use of the BSC can monitor and regulate identity products, patternings and processes. In monitoring identities, the flexible BSC framework allowed the case study organisations to monitor various aspects of finance, customer, improvement and organisational capability that included identity dimensions. Such inclusion legitimises identity management as organisational performance. In regulating identities, the use of the BSC created a mechanism to form collective identities by articulating various perspectives and causal linkages, and through the cascading and alignment of multiple scorecards. The BSC—directly reflecting organisationally valued premises and legitimised symbols—acted as an identity product of communication, visual symbols and behavioural guidance. The selective promotion of the BSC measures filtered organisational focus to shape unique identity multiplicity and characteristics within the cases. Further, the use of the BSC facilitated the assimilation of multiple identities by controlling the direction and strength of identifications, engaging different groups of members. More specifically, the tight authority of the BSC framework and systems are explained both by technical and bureaucratic controls, while subtle communication of organisational premises and information filtering is achieved through concertive control. This study confirms that these macro top-down controls mediated the sensebreaking and sensegiving process of organisational identification, supporting research by Ashforth, Harrison and Corley (2008). This study pays attention to members’ power of self-regulation, filling minor premises of the derived logic of their organisation through the playing out of organisational enthymemes (Tompkins & Cheney, 1985). Members are then encouraged to make their own decisions towards the organisational premises embedded in the BSC, through the micro bottom-up identification processes including: enacting organisationally valued identities; sensemaking; and the construction of identity narratives aligned with those organisationally valued premises. Within the process, the self-referential effect of communication encouraged members to believe the organisational messages embedded in the BSC in transforming collective and individual identities. Therefore, communication through the use of the BSC continued the self-producing of normative performance mechanisms, established meanings of identities, and enabled members’ self-regulation in identity construction. Further, this research establishes the relationship between identity and the use of the BSC in terms of identity multiplicity and attributes. The BSC framework constrained and enabled case study organisations and members to monitor and regulate identity multiplicity across a number of dimensions, levels and facets. The use of the BSC constantly heightened the identity attributes of distinctiveness, relativity, visibility, fluidity and manageability in identity construction over time. Overall, this research explains the reciprocal controlling relationships of multiple structures in organisations to achieve a goal. It bridges the gap among corporate and organisational identity theories by adopting Cornelissen, Haslam and Balmer’s (2007) integrated identity framework, and reduces the gap in understanding between identity and performance measurement studies. Parallel review of the process of monitoring and regulating identities from both literatures synthesised the theoretical strengths of both to conceptualise and operationalise identities. This study extends the discussion on positioning identity, culture, commitment, and image and reputation measures in integrated performance measurement systems as organisational capital. Further, this study applies understanding of the multiple forms of control (Edwards, 1979; Tompkins & Cheney, 1985), emphasising the power of organisational members in identification processes, using the notion of rhetorical organisational enthymemes. This highlights the value of the collaborative theoretical power of identity, communication and performance measurement frameworks. These case studies provide practical insights about the public sector where existing bureaucracy and desired organisational identity directions are competing within a large organisational setting. Further research on personal identity and simple control in organisations that fully cascade the BSC down to individual members would provide enriched data. The extended application of the conceptual framework to other public and private sector organisations with a longitudinal view will also contribute to further theory building.

Listening in to others : in between noise and silence

Since the launch of the ‘Clean Delhi, Green Delhi’ campaign in 2003, slums have become a significant social and political issue in India’s capital city. Through this campaign, the state, in collaboration with Delhi’s middle class through the ‘Bhagidari system’ (literally translated as ‘participatory system’), aims to transform Delhi into a ‘world-class city’ that offers a sanitised, aesthetically appealing urban experience to its citizens and Western visitors. In 2007, Delhi won the bid to host the 2010 Commonwealth Games; since then, this agenda has acquired an urgent, almost violent, impetus to transform Delhi into an environmentally friendly, aesthetically appealing and ‘truly international city’. Slums and slum-dwellers, with their ‘filth, dirt, and noise’, have no place in this imagined city. The violence inflicted upon slum-dwellers, including the denial of their judicial rights, is justified on these accounts. In addition, the juridical discourse since 2000 has ‘re-problematised slums as ‘nuisance’. The rising antagonism of the middle-classes against the poor, supported by the state’s ambition to have a ‘world-class city’, has allowed a new rhetoric to situate the slums in the city. These representations articulate slums as homogenised spaces of experience and identity. The ‘illegal’ status of slum-dwellers, as encroachers upon public space, is stretched to involve ‘social, cultural, and moral’ decadence and depravity. This thesis is an ethnographic exploration of everyday life in a prominent slum settlement in Delhi. It sensually examines the social, cultural and political materiality of slums, and the relationship of slums with the middle class. In doing so, it highlights the politics of sensorial ordering of slums as ‘filthy, dirty, and noisy’ by the middle classes to calcify their position as ‘others’ in order to further segregate, exclude and discriminate the slums. The ethnographic experience in the slums, however, highlights a complex sensorial ordering and politics of its own. Not only are the interactions between diverse communities in slums highly restricted and sensually ordained, but the middle class is identified as a sensual ‘other’, and its sensual practices prohibited. This is significant in two ways. First, it highlights the multiplicity of social, cultural experience and engagement in the slums, thereby challenging its homogenised representation. Second, the ethnographic exploration allowed me to frame a distinct sense of self amongst the slums, which is denied in mainstream discourses, and allowed me to identify the slums’ own ’others’, middle class being one of them. This thesis highlights sound – its production, performances and articulations – as an act with social, cultural, and political implications and manifestations. ‘Noise’ can be understood as a political construct to identify ‘others’ – and both slum-dwellers and the middle classes identify different sonic practices as noise to situate the ‘other’ sonically. It is within this context that this thesis frames the position of Listener and Hearer, which corresponds to their social-political positions. These positions can be, and are, resisted and circumvented through sonic practices. For instance, amplification tactics in the Karimnagar slums, which are understood as ‘uncultured, callous activities to just create more noise’ by the slums’ middle-class neighbours, also serve definite purposes in shaping and navigating the space through the slums’ soundscapes, asserting a presence that is otherwise denied. Such tactics allow the residents to define their sonic territories and scope of sonic performances; they are significant in terms of exerting one’s position, territory and identity, and they are very important in subverting hierarchies. The residents of the Karimnagar slums have to negotiate many social, cultural, moral and political prejudices in their everyday lives. Their identity is constantly under scrutiny and threat. However, the sonic cultures and practices in the Karimnagar slums allow their residents to exert a definite sonic presence – which the middle class has to hear. The articulation of noise and silence is an act manifesting, referencing and resisting social, cultural, and political power and hierarchies.

An obsession with storytelling : conducting oral history interviews for creative writing

Anna Hirsch and Clare Dixon (2008, 190) state that creative writers’ ‘obsession with storytelling…might serve as an interdisciplinary tool for evaluating oral histories.’ This paper enters a dialogue with Hirsch and Dixon’s statement by documenting an interview methodology for a practice-led PhD project, The Artful Life Story: Oral History and Fiction, which investigates the fictionalising of oral history. ----- ----- Alistair Thomson (2007, 62) notes the interdisciplinary nature of oral history scholarship from the 1980s onwards. As a result, oral histories are being used and understood in a variety of arts-based settings. In such contexts, oral histories are not valued so much for their factual content but as sources that are at once dynamic, emotionally authentic and open to a multiplicity of interpretations. How can creative writers design and conduct interviews that reflect this emphasis? ----- ----- The paper briefly maps the growing trend of using oral histories in fiction and ethnographic novels, in order to establish the need to design interviews for arts-based contexts. I describe how I initially designed the interviews to suit the aims of my practice. Once in the field, however, I found that my original methods did not account for my experiences. I conclude with the resulting reflection and understanding that emerged from these problematic encounters, focusing on the technique of steered monologue (Scagliola 2010), sometimes referred to as the Biographic Narrative Interpretative Method (Wengraf 2001, Jones 2006).

Keeping House : a novel and novel companion

The creative work of this study is a novel-length work of literary fiction called Keeping House (published as Grace's Table, by University of Queensland Press, April 2014). Grace has not had twelve people at her table for a long time. Hers isn't the kind of family who share regular Sunday meals. As Grace prepares the feast, she reflects on her life, her marriage and her friendships. When the three generations of her family come together, simmering tensions from the past threaten to boil over. The one thing that no one can talk about is the one thing that no one can forget. Grace's Table is a moving and often funny novel using food as a language to explore the power of memory and the family rituals that define us. The exegetical component of this study does not adhere to traditional research pedagogies. Instead, it follows the model of what the literature describes as fictocriticism. It is the intention that the exegesis be read as a hybrid genre; one that combines creative practice and theory and blurs the boundaries between philosophy and fiction. In offering itself as an alternative to the exegetical canon it provides a model for the multiplicity of knowledge production suited to the discipline of practice-led research. The exegesis mirrors structural elements of the creative work by inviting twelve guests into the domestic space of the novel to share a meal. The guests, chosen for their diverse thinking, enable examination of the various agents of power involved in the delivery of food. Their ideas cross genders, ages and time periods; their motivations and opinions often collide. Some are more concerned with the spatial politics of where food is consumed, others with its actual preparation and consumption. Each, however, provides a series of creative reflective conversations throughout the meal which help to answer the research question: How can disempowered women take authority within their domestic space? Michel de Certeau must defend his "operational tactics" or "art of the weak" 1 as a means by which women can subvert the colonisation of their domestic space against Michel Foucault's ideas about the functions of a "disciplinary apparatus". 2 Erving Goffman argues that the success of de Certeau's "tactics" depends upon his theories of "performance" and "masquerade" 3; a claim de Certeau refutes. Doreen Massey and the author combine forces in arguing for space, time and politics to be seen as interconnected, non-static and often contested. The author calls for identity, or sense of self, to be considered a further dimension which impacts on the function of spatial models. Yu-Fi Tuan speaks of the intimacy of kitchens; Gaston Bachelard the power of daydreams; and Jean Anthelme Brillat-Savarin gives the reader a taste of the nourishing arts. Roland Barthes forces the author to reconsider her function as a writer and her understanding of the reader's relationship with a text. Fictional characters from two texts have a place at the table – Marian from The Edible Woman by Margaret Atwood 4 and Lilian from Lilian's Story by Kate Grenville. 5 Each explores how they successfully subverted expectations of their gender. The author interprets and applies elements of the conversations to support Grace's tactics in the novel as well as those related to her own creative research practice. Grace serves her guests, reflecting on what is said and how it relates to her story. Over coffee, the two come together to examine what each has learned.

Gifted young adolescents : voices of self

Despite the challenges that giftedness can add to self-formation during early adolescence, gifted young adolescents seldom are asked about their lives outside of counselling and educational contexts. The study considers the complexities that face gifted young adolescents in the process of self-discovery and self-representation, thereby building a case for seeking their own viewpoints. A guiding assumption for the study was that gifted young adolescents may respond positively to the opportunity to share their own perspectives and their own versions of “who they are”. The theoretical underpinnings for this study drew from Dialogical Self Theory. The study resides within an interactive view of self as a dynamic construction rather than a static state, where “who we are” is formed in everyday exchanges with self and others. Self-making as a process among gifted young adolescents is presented as an interactive network of “I” voices interpreted to reflect internal and external dialogue. In this way, self is understood within dialogical concepts of voices as multiple expressions. The study invited twelve gifted young adolescents to write freely about themselves over a six month period in an email journal project. Participants were recruited online and by word-of-mouth and they were able to negotiate their own levels of involvement. Access to the lives of individual young adolescents was sought in an out-of-school setting using narrative methods of personal writing in the form of journals sent as emails to the researcher. The role of the researcher was to act as a supportive listener who responded to participant-led emails and thereby facilitated the process of authoring that occurred across the data-gathering phase. The listening process involved responses that were affirming and designed to build trust. Data in the form of email texts were analysed using a close listening method that uncovered patterns of voices that were explicitly or subtly expressed by participants. The interpretation of voices highlighted the tensions and contradictions involved in the process of participants forming a “self” that emerged as multiple “I” voices. There were three key findings of the study. First, the gifted young adolescent participants each constructed a self around four key voices of Author, Achiever, Resistor/Co-operator and Self-Innovator. These voices were dialogical selfconstructions that showed multiplicity as a normal way of being. Second, the selfmaking processes of the gifted young adolescent participants were guided by a hierarchy of voices that were directed through self-awareness. Third, authoring in association with a responsive adult listener emerged as a dialogic space for promoting self-awareness and a language of self-expression among gifted young adolescents. The findings of the study contribute to knowledge about gifted young adolescents by presenting their own versions of “who” they are, perspectives that might differ from mainstream perceptions. Participants were shown to have highly diverse, complex and individual expressions that have implications for how well they are understood and supported by others. The use of email journals helped to create a synergy for self-disclosure and a safe space for self-expression where participants’ abilities to be themselves were encouraged. Increased self-awareness and selfknowledge among gifted young adolescents is vital to their self-formation and their management of self and others’ expectations. This study makes an original contribution to the field of self-study by highlighting the processes and complexities of young adolescents’ self-constructions. Through the innovative use of narrative methods and an inter-disciplinary approach, the voices of gifted young adolescents were privileged. At a practical level, the study can inform educators, policy-makers, parents and all those who seek to contribute to the well-being of gifted young adolescents.

Boundary weaving : the social structure and processes of organizational boundaries

Boundaries are an important field of study because they mediate almost every aspect of organizational life. They are becoming increasingly more important as organizations change more frequently and yet, despite the endemic use of the boundary metaphor in common organizational parlance, they are poorly understood. Organizational boundaries are under-theorized and researchers in related fields often simply assume their existence, without defining them. The literature on organizational boundaries is fragmented with no unifying theoretical basis. As a result, when it is recognized that an organizational boundary is "dysfunctional". there is little recourse to models on which to base remediating action. This research sets out to develop just such a theoretical model and is guided by the general question: "What is the nature of organizational boundaries?" It is argued that organizational boundaries can be conceptualised through elements of both social structure and of social process. Elements of structure include objects, coupling, properties and identity. Social processes include objectification, identification, interaction and emergence. All of these elements are integrated by a core category, or basic social process, called boundary weaving. An organizational boundary is a complex system of objects and emergent properties that are woven together by people as they interact together, objectifying the world around them, identifying with these objects and creating couplings of varying strength and polarity as well as their own fragmented identity. Organizational boundaries are characterised by the multiplicity of interconnections, a particular domain of objects, varying levels of embodiment and patterns of interaction. The theory developed in this research emerged from an exploratory, qualitative research design employing grounded theory methodology. The field data was collected from the training headquarters of the New Zealand Army using semi-structured interviews and follow up observations. The unit of analysis is an organizational boundary. Only one research context was used because of the richness and multiplicity of organizational boundaries that were present. The model arose, grounded in the data collected, through a process of theoretical memoing and constant comparative analysis. Academic literature was used as a source of data to aid theory development and the saturation of some central categories. The final theory is classified as middle range, being substantive rather than formal, and is generalizable across medium to large organizations in low-context societies. The main limitation of the research arose from the breadth of the research with multiple lines of inquiry spanning several academic disciplines, with some relevant areas such as the role of identity and complexity being addressed at a necessarily high level. The organizational boundary theory developed by this research replaces the typology approaches, typical of previous theory on organizational boundaries and reconceptualises the nature of groups in organizations as well as the role of "boundary spanners". It also has implications for any theory that relies on the concept of boundaries, such as general systems theory. The main contribution of this research is the development of a holistic model of organizational boundaries including an explanation of the multiplicity of boundaries . no organization has a single definable boundary. A significant aspect of this contribution is the integration of aspects of complexity theory and identity theory to explain the emergence of higher-order properties of organizational boundaries and of organizational identity. The core category of "boundary weaving". is a powerful new metaphor that significantly reconceptualises the way organizational boundaries may be understood in organizations. It invokes secondary metaphors such as the weaving of an organization's "boundary fabric". and provides managers with other metaphorical perspectives, such as the management of boundary friction, boundary tension, boundary permeability and boundary stability. Opportunities for future research reside in formalising and testing the theory as well as developing analytical tools that would enable managers in organizations to apply the theory in practice.

The question concerning (Internet) time

Spatial representations, metaphors and imaginaries (cyberspace, web pages) have been the mainstay of internet research for a long time. Instead of repeating these themes, this paper seeks to answer the question of how we might understand the concept of time in relation to internet research. After a brief excursus on the general history of the concept, this paper proposes three different approaches to the conceptualisation of internet time. The common thread underlying all the approaches is the notion of time as an assemblage of elements such as technical artefacts, social relations and metaphors. By drawing out time in this way, the paper addresses the challenge of thinking of internet time as coexistence, a clash of fluxes, metaphors, lived experiences and assemblages. In other words, this paper proposes a way to articulate internet time as a multiplicity.

The impact of tenure type on the desire for retirement village living

In 2005 17.3% of Australians were aged 60 years and older (Australian Bureau of Statistics). A consequence of this aging population is the increased use of self-contained independent living units (SCILU) in Retirement Villages by older Australians. The retirement village sector has thus become a significant sector within the residential property market. In seeking to determine the impact of tenure type on the desirability of RV living this paper first profiles a typical SCILU in Australia, before explaining and examining the various tenure types offered by the market. This paper concludes that the multiplicity of offerings of the SCILU product with respect to tenure type, when combined with deferred management fees and participation in capital gains/losses, may be contributing to a lack of clarity in what the SCILU product entails and the security of investment it offers. This perception is supported by litigated disputes and may be damaging the reputation, ongoing viability and desirability of SCILUs.

Outlearning

Making the University Matter investigates how academics situate themselves simultaneously in the university and the world and how doing so affects the viability of the university setting. The university stands at the intersection of two sets of interests, needing to be at one with the world while aspiring to stand apart from it. In an era that promises intensified political instability, growing administrative pressures, dwindling economic returns and questions about economic viability, lower enrolments and shrinking programs, can the university continue to matter into the future? And if so, in which way? What will help it survive as an honest broker? What are the mechanisms for ensuring its independent voice? Barbie Zelizer brings together some of the leading names in the field of media and communication studies from around the globe to consider a multiplicity of answers from across the curriculum on making the university matter, including critical scholarship, interdisciplinarity, curricular blends of the humanities and social sciences, practical training and policy work. The collection is introduced with an essay by the editor and each section has a brief introduction to contextualise the essays and highlight the issues they raise.

African Burkitt Lymphoma: Age-Specific Risk and Correlations with Malaria Biomarkers

African Burkitt lymphoma is an aggressive B-cell, non-Hodgkin lymphoma linked to Plasmodium falciparum malaria. Malaria biomarkers related to onset of African Burkitt lymphoma are unknown. We correlated age-specific patterns of 2,602 cases of African Burkitt lymphoma (60% male, mean ± SD age = 7.1 ± 2.9 years) from Uganda, Ghana, and Tanzania with malaria biomarkers published from these countries. Age-specific patterns of this disease and mean multiplicity of P. falciparum malaria parasites, defined as the average number of distinct genotypes per positive blood sample based on the merozoite surface protein-2 assessed by polymerase chain reaction, were correlated and both peaked between 5 and 9 years. This pattern, which was strong and consistent across regions, contrasted parasite prevalence, which peaked at 2 years and decreased slightly, and geometric mean parasite density, which peaked between 2 and 3 years and decreased sharply. Our findings suggest that concurrent infection with multiple malaria genotypes may be related to onset of African Burkitt lymphoma.

Volume

In this video, words describing socially awkward conversations float around an animated cloud of gas. A cosmic stock music track accompanies the words. This work examines processes of signification. It emphasizes multiplicity and disconnection as fundamental and generative operations in making meaning. By playing with the simultaneity of internal monologues and external conversations, it draws attention to the seams, gaps and slippages that occur in signifying acts.

A classification framework for design-build variants from an operational perspective

Design-build (DB) is a generic form of construction procurement, and, rather than simply representing a single system, it has evolved in practice into a variety of forms, each of which is similar to, and yet different from each other. Although the importance of selecting an appropriate DB variant has been widely accepted, difficulties occur in practice due to the multiplicity of terms and concepts used. What is needed is some kind of taxonomy or framework within which the individual variants can be placed and their relative attributes identified and understood. Through a comprehensive literature review and content analysis, this paper establishes a systematic classification framework for DB variants based on their operational attributes. In addition to providing much needed support for decision-making, this classification framework provides client/owners with perspectives to understand and examine different categories of DB variants from an operational perspective.

Analytical and numerical solutions of the space and time fractional bloch-torrey equation

Fractional order dynamics in physics, particularly when applied to diffusion, leads to an extension of the concept of Brown-ian motion through a generalization of the Gaussian probability function to what is termed anomalous diffusion. As MRI is applied with increasing temporal and spatial resolution, the spin dynamics are being examined more closely; such examinations extend our knowledge of biological materials through a detailed analysis of relaxation time distribution and water diffusion heterogeneity. Here the dynamic models become more complex as they attempt to correlate new data with a multiplicity of tissue compartments where processes are often anisotropic. Anomalous diffusion in the human brain using fractional order calculus has been investigated. Recently, a new diffusion model was proposed by solving the Bloch-Torrey equation using fractional order calculus with respect to time and space (see R.L. Magin et al., J. Magnetic Resonance, 190 (2008) 255-270). However effective numerical methods and supporting error analyses for the fractional Bloch-Torrey equation are still limited. In this paper, the space and time fractional Bloch-Torrey equation (ST-FBTE) is considered. The time and space derivatives in the ST-FBTE are replaced by the Caputo and the sequential Riesz fractional derivatives, respectively. Firstly, we derive an analytical solution for the ST-FBTE with initial and boundary conditions on a finite domain. Secondly, we propose an implicit numerical method (INM) for the ST-FBTE, and the stability and convergence of the INM are investigated. We prove that the implicit numerical method for the ST-FBTE is unconditionally stable and convergent. Finally, we present some numerical results that support our theoretical analysis.

Optimization of chimeric HIV-1 virus-like particle production in a baculovirus-insect cell expression system

A baculovirus-insect cell expression system potentially provides the means to produce prophylactic HIV-1 virus-like particle (VLP) vaccines inexpensively and in large quantities. However, the system must be optimized to maximize yields and increase process efficiency. In this study, we optimized the production of two novel, chimeric HIV-1 VLP vaccine candidates (GagRT and GagTN) in insect cells. This was done by monitoring the effects of four specific factors on VLP expression: these were insect cell line, cell density, multiplicity of infection (MOI), and infection time. The use of western blots, Gag p24 ELISA, and four-factorial ANOVA allowed the determination of the most favorable conditions for chimeric VLP production, as well as which factors affected VLP expression most significantly. Both VLP vaccine candidates favored similar optimal conditions, demonstrating higher yields of VLPs when produced in the Trichoplusia ni Pro insect cell line, at a cell density of 1 × 106 cells/mL, and an infection time of 96 h post infection. It was found that cell density and infection time were major influencing factors, but that MOI did not affect VLP expression significantly. This work provides a potentially valuable guideline for HIV-1 protein vaccine optimization, as well as for general optimization of a baculovirus-based expression system to produce complex recombinant proteins. © 2009 American Institute of Chemical Engineers.

In vitro primary cell culture as a physiologically relevant method for preclinical testing of human oncolytic adenovirus

Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.