Mathematical modeling of the cancer cell’s control circuitry : paving the way to individualized therapeutic strategies

Cancer is a disease of signal transduction in which the dysregulation of the network of intracellular and extracellular signaling cascades is sufficient to thwart the cells finely-tuned biochemical control mechanisms. A keen interest in the mathematical modeling of cell signaling networks and the regulation of signal transduction has emerged in recent years, and has produced a glimmer of insight into the sophisticated feedback control and network regulation operating within cells. In this review, we present an overview of published theoretical studies on the control aspects of signal transduction, emphasizing the role and importance of mechanisms such as ‘ultrasensitivity’ and feedback loops. We emphasize that these exquisite and often subtle control strategies represent the key to orchestrating ‘simple’ signaling behaviors within the complex intracellular network, while regulating the trade-off between sensitivity and robustness to internal and external perturbations. Through a consideration of these apparent paradoxes, we explore how the basic homeostasis of the intracellular signaling network, in the face of carcinogenesis, can lead to neoplastic progression rather than cell death. A simple mathematical model is presented, furnishing a vivid illustration of how ‘control-oriented’ models of the deranged signaling networks in cancer cells may enucleate improved treatment strategies, including patient-tailored combination therapies, with the potential for reduced toxicity and more robust and potent antitumor activity.

Decision strategies for automated visual collision avoidance

This paper provides a preliminary analysis of an autonomous uncooperative collision avoidance strategy for unmanned aircraft using image-based visual control. Assuming target detection, the approach consists of three parts. First, a novel decision strategy is used to determine appropriate reference image features to track for safe avoidance. This is achieved by considering the current rules of the air (regulations), the properties of spiral motion and the expected visual tracking errors. Second, a spherical visual predictive control (VPC) scheme is used to guide the aircraft along a safe spiral-like trajectory about the object. Lastly, a stopping decision based on thresholding a cost function is used to determine when to stop the avoidance behaviour. The approach does not require estimation of range or time to collision, and instead relies on tuning two mutually exclusive decision thresholds to ensure satisfactory performance.

Cultural development strategies and urban revitalization

Municipal governments around the globe increasingly turn to museums, performing arts centers, arts districts, and other cultural activities to promote and revitalize their cities. While a significant body of literature examines revitalization strategies that focus primarily around entertainment and commerce, the empirical body of research that specifically investigates the role of cultural strategies in urban redevelopment is still growing. This paper first discusses the development of municipal cultural strategies in the United States, and draws from the literature to outline the characteristics of three different models of such strategies. Second, the paper presents findings from a national survey distributed to municipal agencies involved in the promotion and development of cultural activities and facilities in large and medium‐sized US cities. The survey data indicate that although most agencies are guided by a varied set of goals, entrepreneurial objectives continue to guide the development and support of cultural activities in most cities.

Doctoral research training : encouraging timely completion – case study reflections of one university on how it supports a vibrant research training culture

This is a case study of a young university striving to generate and sustain a vibrant Research Training culture. The university’s research training framework is informed by a belief in a project management approach to achieving successful research candidature. This has led to the definition and reporting of key milestones during candidature. In turn, these milestones have generated a range of training programs to support Higher Degree Research (HDR) students to meet these milestones in a timely fashion. Each milestone focuses on a specific set of skills blended with supporting the development of different parts of the doctoral thesis. Data on student progress and completion has provided evidence in highlighting the role that the milestones and training are playing in supporting timely completion. A university-wide reporting cycle generated data on the range of workshops and training provided to Higher Degree Research students and supervisors. The report provided details of thesis topic and format, as well as participation in research training events and participant evaluation of those events. Analysis of the data led to recommendations and comments on the strengths and weaknesses of the current research training program. Discussion considered strategies and drivers for enhancements into the future. In particular, the paper reflects on the significant potential role of centrally curated knowledge systems to support HDR student and supervisor access, and engagement and success. The research training program was developed using blended learning as a model. It covered face-to-face workshops as well as online modules. These were supplemented by web portals that offered a range of services to inform and educate students and supervisors and included opportunities for students to interact with each other. Topics ranged from the research life cycle, writing and publication, ethics, managing research data, managing copyright, and project management to use of software and the University’s Code of Conduct for Research. The challenges discussed included: How to reach off campus students and those studying in external modes? How best to promote events to potential participants? How long and what format is best for face-to-face sessions? What online resources best supplement face-to-face offerings? Is there a place for peer-based learning and what form should this take? These questions are raised by a relatively young university seeking to build and sustain a vibrant research culture. The rapid growth in enrolments in recent years has challenged previous one-to-one models of support. This review of research training is timely in seeking strategies to address changing research training support capacity and student needs. Part of the discussion will focus on supervisory training, noting that good supervision is the one remaining place where one-to-one support is provided. Ensuring that supervisors are appropriately equipped to address student expectations is considered in the context of the research training provisions. The paper concludes with reflection on the challenges faced, and recommended ways forward as the number of research students grows into the future.

The role of customer gratitude in making relationship marketing investments successful

This paper recognises that customer loyalty is important for many competitive organisations, and that retail firms make investments to build and maintain loyal relationships with their existing and potential customers (e.g. loyalty programs). However, there has been little focus on the mechanisms by which these relationship investments operate to achieve customer loyalty. This paper examines one mechanism, namely customer gratitude, which works to make a firm’s relationship marketing investment a success or a failure. Using data from 1600 undergraduate students, this study empirically confirms the mediating role of customer gratitude between the customers’ perceptions a firm’s relationship marketing investments and customers’ perceptions of the value of the relationship with the firm. Further, a significant moderating effect of perceived benevolence on the relationship between customers’ perceptions a firm’s relationship marketing investments and customer gratitude was identified. For theorists, this customer gratitude model offers a better psychological explanation of how relationship marketing investments operate to improve the value that customers place on their relationships with retailers. Our research suggests that managers should invest resources to stimulate customer gratitude in order to build strong customer–seller relationships.

Computational strategies for surface fitting using thin plate spline finite element methods

Thin plate spline finite element methods are used to fit a surface to an irregularly scattered dataset [S. Roberts, M. Hegland, and I. Altas. Approximation of a Thin Plate Spline Smoother using Continuous Piecewise Polynomial Functions. SIAM, 1:208--234, 2003]. The computational bottleneck for this algorithm is the solution of large, ill-conditioned systems of linear equations at each step of a generalised cross validation algorithm. Preconditioning techniques are investigated to accelerate the convergence of the solution of these systems using Krylov subspace methods. The preconditioners under consideration are block diagonal, block triangular and constraint preconditioners [M. Benzi, G. H. Golub, and J. Liesen. Numerical solution of saddle point problems. Acta Numer., 14:1--137, 2005]. The effectiveness of each of these preconditioners is examined on a sample dataset taken from a known surface. From our numerical investigation, constraint preconditioners appear to provide improved convergence for this surface fitting problem compared to block preconditioners.

Biogas in Bangladesh : challenges and strategies

The people of Bangladesh are underprivileged from continuous grid electricity. Despite the plentiful supply of renewable sources of energy in Bangladesh, currently their contribution to the electricity supply remains inconsequential. Use of renewable energy is considered an indispensable component of sustainable energy systems, as renewable energy resources emit less greenhouse gas emissions compared to other non-renewable energy systems. Out of the various renewable sources, solar and biogas and to a limited extend, wind and hydro-power are effectively used. Though the biogas production was the leading and most appropriate renewable energy resource in our country, it has become notably insignificant due to the lack of appropriate strategies and institutional settings. To address this, this article examines Bangladesh's current energy strategies and institutional settings and investigates future strategies for the advancement of biogas production. This article argues that further significant efforts could be made toward energy sustainability in Bangladesh and the development for a national sustainable energy policy.

Recovering Functional Integrity in Pastures Dominated by an Invasive Grass Species

Exotic grasses have been introduced in countries worldwide for pasture improvement, soil stabilisation and ornamental purposes. Some of these introductions have proven successful, but many have not (Cook & Dias 2006). In Australia, the Commonwealth Plant Introduction Scheme was initiated in 1929, and over-time introduced more than 5000 species of grasses, legumes and other forage and browse plants (Cook & Dias 2006). Lonsdale (1994) suggested that, in tropical Australia, 13% of introductions have become a problem, with only 5% being considered useful for agriculture. Low (1997) suggested that 5 out of 18 of Australia's worst tropical environmental weeds were intentionally introduced as pasture grasses. The spread and dominance of invasive grass species that degrade the quality of pastures for production can impact significantly on the livelihoods of small proprietors. Although Livestock grazing contributes only a small percentage to the world's GDP (1.5%), maintaining the long-term stability of this industry is crucial because of the high social and environmental consequence of a collapse. One billion of the world's poor are dependent on livestock grazing for food and income with this industry occupying more than 25% of the world's land base (Steinfeld et al. 2006). The ling-term sustainability of livestock grazing is also crucial for the environment. A recent FAO report attributed livestock production as a major cause of five of the most serious environmental problems: global warming, land degredation, air and water pollution, and the loss of biodiversity (Steinfeld et al. 2006). For these reasons, finding more effective approaches that guide the sustainable management of pastures is urgently needed. In Australia more than 55% of land use is for livestock grazing by sheelp and/or cattle. This land use dominate in the semi-arid and arid regions where rainfall and soil conditions are marginal for production (Commonwealth of Australia 2004). Although the level of agriculture production by conglomerates is increasing, the majority of livestock grazing within Australia remains family owned and operated (Commonwealth of Australia 2004). The sustainability of production from a grazed pasture is dependent on its botanical composition (Kemp & Dowling 1991, Kemp et al. 1996). In a grazed pasture, the dominance of an invasive grass species can impact on the functional integrity of the ecosystem, including production and nutrient cycling; wwhich will in turn, affect the income of proprietors and the ability of the system to recover from disturbance and environmental change. In Australia, $0.3 billion is spent on weed control in livestock production, but despite this substantial investment $1.9 billion is still lost in yield as a result of weeds (Sinden et al. 2004). In this paper, we adaprt a framework proposed for the restoration of degraded rainforest communities (Lamb & Gilmour 2003, Lamb et al. 2005) to compare and contrast options for recovering function integrity (i.e. a diverse set of desirable plant species that maintain key ecological processes necessary for sustainable production and nutrient cycling) within pasture communities dominated by an invasive grass species. To do this, we uase a case-study of the invasion of Eragrostis curvula (Africal lovegrss; hereafter, Lovegrass), a serious concern in Australian agricultural communities (Parsons and Cuthbertson 1992). The spread and dominance of Lovegrass is a problem because its low palatability, low nutritional content and competitiveness affect the livelihood of graziers by reducing the diversity of other plant species. We conclude by suggesting modifications to this framework for pasture ecosystems to help increase the effiency of strategies to protect functional integrity and balance social/economic and biodiversity values.

Learning in and out of university : Aboriginal and Torres Strait Islander students’ conceptions and strategies used to learn

Research suggests that students’ approaches to learning and learning outcomes are closely related to their conceptions of learning. This paper describes a phenomenographically inspired investigation into conceptions of formal learning held by 22 Aboriginal and Torres Strait Islander students from three Australian universities in Queensland; experiences of informal learning, reasons for studying and strategies used to learn were also investigated. The attrition rate for these students in tertiary education is higher than that of any other group of students. It was hoped that information gained may delineate factors that contribute to high attrition rates and therefore inform courses of action that may lead to improved teaching and learning practices for these students. Additionally, success in tertiary education for Aboriginal and Torres Strait Islander students may increase their involvement in mainstream society. Results showed that they view and approach university learning in much the same way as other university students. It was also apparent that, generally, the strategies these students used did not match the conceptions of learning they held. An interesting result was the difference between the conceptions of formal learning and explanations of informal learning

Learning in formal and informal contexts : conceptions and strategies of Aboriginal and Torres Strait Islander university students

Research suggests that students' approaches to learning and hence learning outcomes are closely related to their conceptions of learning. This paper describes an investigation into conceptions of formal learning held by 22 Aboriginal and Torres Strait Islander students from three Australian universities in Queensland; categories of informal learning, reasons for studying and strategies used to learn were also investigated. The attrition rate for these students in tertiary education is higher than that of any other group of students. The main aim of this study was to determine their conceptions of learning in order to provide information that might facilitate instruction more suited to their needs in order to address the high attrition rate. Results showed that these students view and approach university learning in much the same way as other university students. It was also apparent that, for the most part, the strategies these students used did not match the conceptions of learning they held. An interesting result was the difference between the conceptions of formal learning and perceptions of informal learning.

Coping strategies used by ballet dancers: effects of individual differences in competitive trait anxiety

The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. Relationships between coping strategies and competitive trait anxiety were investigated among 104 classical dancers (81 females and 23 males) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure of 12 dimensions of coping. Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure of three anxiety dimensions. Trait anxiety scores, in particular for Somatic Anxiety and Worry, predicted seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies, some of which are considered to be maladaptive. No effects of gender or status (professional versus students) were identified. Results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet.

Coping strategies used by ballet dancers : effects of individual differences in competitive trait anxiety

The world of classical ballet exerts considerable physical and psychological stress upon those who participate, and yet the process of coping with such stressors is not well understood. The purpose of the present investigation was to examine relationships between coping strategies and competitive trait anxiety among ballet dancers. Participants were 104 classical dancers (81 females and 23 males) ranging in age from 15 to 35 years (M = 19.4 yr., SD = 3.8 yr.) from three professional ballet companies, two private dance schools, and two full-time, university dance courses in Australia. Participants had a mean of 11.5 years of classical dance training (SD = 5.2 yr.), having started dance training at 6.6 years of age (SD = 3.4 yr.). Coping strategies were assessed using the Modified COPE scale (MCOPE: Crocker & Graham, 1995), a 48-item measure comprising 12 coping subscales (Seeking Social Support for Instrumental Reasons, Seeking Social Support for Emotional Reasons, Behavioral Disengagement, Planning, Suppression of Competing Activities, Venting of Emotions, Humor, Active Coping, Denial, Self-Blame, Effort, and Wishful Thinking). Competitive trait anxiety was assessed using the Sport Anxiety Scale (SAS: Smith, Smoll, & Schutz, 1990), a 21-item measure comprising three anxiety subscales (Somatic Anxiety, Worry, Concentration Disruption). Standard multiple regression analyses showed that trait anxiety scores, in particular for Somatic Anxiety and Worry, were significant predictors of seven of the 12 coping strategies (Suppression of Competing Activities: R2 = 27.1%; Venting of Emotions: R2 = 23.2%; Active Coping: R2 = 14.3%; Denial: R2 = 17.7%; Self-Blame: R2 = 35.7%; Effort: R2 = 16.6%; Wishful Thinking: R2 = 42.3%). High trait anxious dancers reported more frequent use of all categories of coping strategies. A separate two-way MANOVA showed no significant main effect for gender nor status (professional versus students) and no significant interaction effect. The present findings are generally consistent with previous research in the sport psychology domain (Crocker & Graham, 1995; Giacobbi & Weinberg, 2000) which has shown that high trait anxious athletes tend, in particular, to use more maladaptive, emotion-focused coping strategies when compared to low trait anxious athletes; a tendency which has been proposed to lead to negative performance effects. The present results emphasize the need for the effectiveness of specific coping strategies to be considered during the process of preparing young classical dancers for a career in professional ballet. In particular, the results suggest that dancers who are, by nature, anxious about performance may need special attention to help them to learn to cope with performance-related stress. Given the absence of differences in coping strategies between student and professional dancers and between males and females, it appears that such educational efforts should begin at an early career stage for all dancers.

Beyond enterprise resource planning projects : Innovative strategies for competitive advantage

ABSTRACT A rapidly changing business environment and legacy IT problems has resulted in many organisations implementing standard package solutions. This 'common systems' approach establishes a common IT and business process infrastructure within organisations and its increasing dominance raises several important strategic issues. These are to what extent do common systems impose common business processes and management systems on competing firms, and what is the source of competitive advantage if the majority of firms employ almost identical information systems and business processes? A theoretical framework based on research into legacy systems and earlier IT strategy literature is used to analyse three case studies in the manufacturing, chemical and IT industries. It is shown that the organisations are treating common systems as the core of their organisations' abilities to manage business transactions. To achieve competitive advantage they are clothing these common systems with information systems designed to capture information about competitors, customers and suppliers, and to provide a basis for sharing knowledge within the organisation and ultimately with economic partners. The importance of these approaches to other organisations and industries is analysed and an attempt is made at outlining the strategic options open to firms beyond the implementation of common business systems.