Clathrin-independent carriers form a high capacity endocytic sorting system at the leading edge of migrating cells

Although the importance of clathrin- and caveolin-independent endocytic pathways has recently emerged, key aspects of these routes remain unknown. Using quantitative ultrastructural approaches, we show that clathrin-independent carriers (CLICs) account for approximately three times the volume internalized by the clathrin-mediated endocytic pathway, forming the major pathway involved in uptake of fluid and bulk membrane in fibroblasts. Electron tomographic analysis of the 3D morphology of the earliest carriers shows that they are multidomain organelles that form a complex sorting station as they mature. Proteomic analysis provides direct links between CLICs, cellular adhesion turnover, and migration. Consistent with this, CLIC-mediated endocytosis of key cargo proteins, CD44 and Thy-1, is polarized at the leading edge of migrating fibroblasts, while transient ablation of CLICs impairs their ability to migrate. These studies provide the first quantitative ultrastructural analysis and molecular characterization of the major endocytic pathway in fibroblasts, a pathway that provides rapid membrane turnover at the leading edge of migrating cells.

Texture for Script identification

The problem of determining the script and language of a document image has a number of important applications in the field of document analysis, such as indexing and sorting of large collections of such images, or as a precursor to optical character recognition (OCR). In this paper, we investigate the use of texture as a tool for determining the script of a document image, based on the observation that text has a distinct visual texture. An experimental evaluation of a number of commonly used texture features is conducted on a newly created script database, providing a qualitative measure of which features are most appropriate for this task. Strategies for improving classification results in situations with limited training data and multiple font types are also proposed.

A Petrov-Galerkin method for a singularly perturbed ordinary differential equation with non-smooth data

In this paper, a singularly perturbed ordinary differential equation with non-smooth data is considered. The numerical method is generated by means of a Petrov-Galerkin finite element method with the piecewise-exponential test function and the piecewise-linear trial function. At the discontinuous point of the coefficient, a special technique is used. The method is shown to be first-order accurate and singular perturbation parameter uniform convergence. Finally, numerical results are presented, which are in agreement with theoretical results.

Less popular but more democratic? Corrie, Clarkson and the dancing Cru

The central cultural experience of modernity has been change, both the ‘creative destruction’ of existing structures, and the growth, often exponential, of new knowledge. During the twentieth century, the central cultural platform for the collective experience of modernising societies changed too, from page and stage to the screen – from publishing, the press and radio to cinema, television and latterly computer screens. Despite the successive dominance of new media, none has lasted long at the top. The pattern for each was to give way to a successor platform in popularity, but to continue as part of an increasingly crowded media menu. Modern media are supplemented not supplanted by their successors.

Pornography and erotica: Definitions and prevalence

In this paper, we offer some observations regarding the sex industry, in particular the pornography and erotica sectors. Marketing literature observing pornography and erotica is scant. We find that following exponential growth of the sex industry (given use of the Internet) an evaluation of consumer behaviour and marketing practices is justified. In order to begin a study of these industry sectors, we find it necessary to define both pornography and erotica. Following the development of definitions, we consider these industries from a marketing perspective in the hope that we may encourage research into these areas.

The role of land use and psycho-social factors in high density residents' work travel mode choices : implications for sustainable transport policy

Imperatives to improve the sustainability of cities often hinge upon plans to increase urban residential density to facilitate greater reliance on sustainable forms of transport and minimise car use. However there is ongoing debate about whether high residential density land use in isolation results in sustainable transport outcomes. Findings from surveys with residents of inner-urban high density dwellings in Brisbane, Australia, suggest that solo car travel accounts for the greatest modal share of typical work journeys and attitudes toward dwelling and neighbourhood transport-related features, residential sorting factors and socio-demographics, alongside land use such as public transport availability, are significantly associated with work travel mode choice. We discuss the implications of our findings for transport policy and management including encouraging relatively sustainable intermodal forms of transport for work journeys.

A fully Bayesian approach to inference for Coxian phase-type distributions with covariate dependent mean

Phase-type distributions represent the time to absorption for a finite state Markov chain in continuous time, generalising the exponential distribution and providing a flexible and useful modelling tool. We present a new reversible jump Markov chain Monte Carlo scheme for performing a fully Bayesian analysis of the popular Coxian subclass of phase-type models; the convenient Coxian representation involves fewer parameters than a more general phase-type model. The key novelty of our approach is that we model covariate dependence in the mean whilst using the Coxian phase-type model as a very general residual distribution. Such incorporation of covariates into the model has not previously been attempted in the Bayesian literature. A further novelty is that we also propose a reversible jump scheme for investigating structural changes to the model brought about by the introduction of Erlang phases. Our approach addresses more questions of inference than previous Bayesian treatments of this model and is automatic in nature. We analyse an example dataset comprising lengths of hospital stays of a sample of patients collected from two Australian hospitals to produce a model for a patient's expected length of stay which incorporates the effects of several covariates. This leads to interesting conclusions about what contributes to length of hospital stay with implications for hospital planning. We compare our results with an alternative classical analysis of these data.

Downtime reduction analysis of the Australia Post flat mail optical character reader

Machine downtime, whether planned or unplanned, is intuitively costly to manufacturing organisations, but is often very difficult to quantify. The available literature showed that costing processes are rarely undertaken within manufacturing organisations. Where cost analyses have been undertaken, they generally have only valued a small proportion of the affected costs, leading to an overly conservative estimate. This thesis aimed to develop a cost of downtime model, with particular emphasis on the application of the model to Australia Post’s Flat Mail Optical Character Reader (FMOCR). The costing analysis determined a cost of downtime of $5,700,000 per annum, or an average cost of $138 per operational hour. The second section of this work focused on the use of the cost of downtime to objectively determine areas of opportunity for cost reduction on the FMOCR. This was the first time within Post that maintenance costs were considered along side of downtime for determining machine performance. Because of this, the results of the analysis revealed areas which have historically not been targeted for cost reduction. Further exploratory work was undertaken on the Flats Lift Module (FLM) and Auto Induction Station (AIS) Deceleration Belts through the comparison of the results against two additional FMOCR analysis programs. This research has demonstrated the development of a methodical and quantifiable cost of downtime for the FMOCR. This has been the first time that Post has endeavoured to examine the cost of downtime. It is also one of the very few methodologies for valuing downtime costs that has been proposed in literature. The work undertaken has also demonstrated how the cost of downtime can be incorporated into machine performance analysis with specific application to identifying high costs modules. The outcome of this report has both been the methodology for costing downtime, as well as a list of areas for cost reduction. In doing so, this thesis has outlined the two key deliverables presented at the outset of the research.

Free will, moral responsibility and ADHD

One of the oldest problems in philosophy concerns the relationship between free will and moral responsibility. If we adopt the position that we lack free will, in the absolute sense—as have most philosophers who have addressed this issue—how can we truly be held accountable for what we do? This paper will contend that the most significant and interesting challenge to the long-standing status-quo on the matter comes not from philosophy, jurisprudence, or even physics, but rather from psychology. By examining this debate through the lens of contemporary behaviour disorders, such as ADHD, it will be argued that notions of free will, along with its correlate, moral responsibility, are being eroded through the logic of psychology which is steadily reconfiguring large swathes of familiar human conduct as pathology. The intention of the paper is not only to raise some concerns over the exponential growth of behaviour disorders, but also, and more significantly, to flag the ongoing relevance of philosophy for prying open contemporary educational problems in new and interesting ways.

Risk-assessment practices in the private rental sector : implications for low-income renters (Final Report)

This report focuses on risk-assessment practices in the private rental market, with particular consideration of their impact on low-income renters. It is based on the fieldwork undertaken in the second stage of the research process that followed completion of the Positioning Paper. The key research question this study addressed was: What are the various factors included in ‘risk-assessments’ by real estate agents in allocating ‘affordable’ tenancies? How are these risks quantified and managed? What are the key outcomes of their decision-making? The study builds on previous research demonstrating that a relatively large proportion of low-cost private rental accommodation is occupied by moderate- to high-income households (Wulff and Yates 2001; Seelig 2001; Yates et al. 2004). This is occurring in an environment where the private rental sector is now the de facto main provider of rental housing for lower-income households across Australia (Seelig et al. 2005) and where a number of factors are implicated in patterns of ‘income–rent mismatching’. These include ongoing shifts in public housing assistance; issues concerning eligibility for rent assistance; ‘supply’ factors, such as loss of low-cost rental stock through upgrading and/or transfer to owner-occupied housing; patterns of supply and demand driven largely by middle- to high-income owner-investors and renters; and patterns of housing need among low-income households for whom affordable housing is not appropriate. In formulating a way of approaching the analysis of ‘risk-assessment’ in rental housing management, this study has applied three sociological perspectives on risk: Beck’s (1992) formulation of risk society as entailing processes of ‘individualisation’; a socio-cultural perspective which emphasises the situated nature of perceptions of risk; and a perspective which has drawn attention to different modes of institutional governance of subjects, as ‘carriers of specific indicators of risk’. The private rental market was viewed as a social institution, and the research strategy was informed by ‘institutional ethnography’ as a method of enquiry. The study was based on interviews with property managers, real estate industry representatives, tenant advocates and community housing providers. The primary focus of inquiry was on ‘the moment of allocation’. Six local areas across metropolitan and regional Queensland, New South Wales, and South Australia were selected as case study localities. In terms of the main findings, it is evident that access to private rental housing is not just a matter of ‘supply and demand’. It is also about assessment of risk among applicants. Risk – perceived or actual – is thus a critical factor in deciding who gets housed, and how. Risk and its assessment matter in the context of housing provision and in the development of policy responses. The outcomes from this study also highlight a number of salient points: 1.There are two principal forms of risk associated with property management: financial risk and risk of litigation. 2. Certain tenant characteristics and/or circumstances – ability to pay and ability to care for the rented property – are the main factors focused on in assessing risk among applicants for rental housing. Signals of either ‘(in)ability to pay’ and/or ‘(in)ability to care for the property’ are almost always interpreted as markers of high levels of risk. 3. The processing of tenancy applications entails a complex and variable mix of formal and informal strategies of risk-assessment and allocation where sorting (out), ranking, discriminating and handing over characterise the process. 4. In the eyes of property managers, ‘suitable’ tenants can be conceptualised as those who are resourceful, reputable, competent, strategic and presentable. 5. Property managers clearly articulated concern about risks entailed in a number of characteristics or situations. Being on a low income was the principal and overarching factor which agents considered. Others included: - unemployment - ‘big’ families; sole parent families - domestic violence - marital breakdown - shift from home ownership to private rental - Aboriginality and specific ethnicities - physical incapacity - aspects of ‘presentation’. The financial vulnerability of applicants in these groups can be invoked, alongside expressed concerns about compromised capacities to manage income and/or ‘care for’ the property, as legitimate grounds for rejection or a lower ranking. 6. At the level of face-to-face interaction between the property manager and applicants, more intuitive assessments of risk based upon past experience or ‘gut feelings’ come into play. These judgements are interwoven with more systematic procedures of tenant selection. The findings suggest that considerable ‘risk’ is associated with low-income status, either directly or insofar as it is associated with other forms of perceived risk, and that such risks are likely to impede access to the professionally managed private rental market. Detailed analysis suggests that opportunities for access to housing by low-income householders also arise where, for example: - the ‘local experience’ of an agency and/or property manager works in favour of particular applicants - applicants can demonstrate available social support and financial guarantors - an applicant’s preference or need for longer-term rental is seen to provide a level of financial security for the landlord - applicants are prepared to agree to specific, more stringent conditions for inspection of properties and review of contracts - the particular circumstances and motivations of landlords lead them to consider a wider range of applicants - In particular circumstances, property managers are prepared to give special consideration to applicants who appear worthy, albeit ‘risky’. The strategic actions of demonstrating and documenting on the part of vulnerable (low-income) tenant applicants can improve their chances of being perceived as resourceful, capable and ‘savvy’. Such actions are significant because they help to persuade property managers not only that the applicant may have sufficient resources (personal and material) but that they accept that the onus is on themselves to show they are reputable, and that they have valued ‘competencies’ and understand ‘how the system works’. The parameters of the market do shape the processes of risk-assessment and, ultimately, the strategic relation of power between property manager and the tenant applicant. Low vacancy rates and limited supply of lower-cost rental stock, in all areas, mean that there are many more tenant applicants than available properties, creating a highly competitive environment for applicants. The fundamental problem of supply is an aspect of the market that severely limits the chances of access to appropriate and affordable housing for low-income rental housing applicants. There is recognition of the impact of this problem of supply. The study indicates three main directions for future focus in policy and program development: providing appropriate supports to tenants to access and sustain private rental housing, addressing issues of discrimination and privacy arising in the processes of selecting suitable tenants, and addressing problems of supply.

Free will, moral responsibility and ADHD

One of the oldest problems in philosophy concerns the relationship between free will and moral responsibility. If we adopt the position that we lack free will, in the absolute sense—as have most philosophers who have addressed this issue—how can we truly be held accountable for what we do? This paper will contend that the most significant and interesting challenge to the long-standing status-quo on the matter comes not from philosophy, jurisprudence, or even physics, but rather from psychology. By examining this debate through the lens of contemporary behaviour disorders, such as ADHD, it will be argued that notions of free will, along with its correlate, moral responsibility, are being eroded through the logic of psychology which is steadily reconfiguring large swathes of familiar human conduct as pathology. The intention of the paper is not only to raise some concerns over the exponential growth of behaviour disorders, but also, and more significantly, to flag the ongoing relevance of philosophy for prying open contemporary educational problems in new and interesting ways.

Further evidence for a deficit in switching attention in schizophrenia

In this study, sustained, selective, divided, and switching attention, and reloading of working memory were investigated in schizophrenia by using a newly developed Visual Attention Battery (VAB). Twenty-four outpatients with schizophrenia and 24 control participants were studied using the VAB. Performance on VAB components was correlated with performance of standard tests. Patients with schizophrenia were significantly impaired on VAB tasks that required switching of attention and reloading of working memory but had normal performance on tasks involving sustained attention or attention to multiple stimulus features. Switching attention and reloading of working memory were highly correlated with Trails (B - A) score for patients. The decline in performance on the switching-attention task in patients with schizophrenia met criteria for a differential deficit in switching attention. Future research should examine the neurophysiological basis of the switching deficit and its sensitivity and specificity to schizophrenia.

Population Monte Carlo Algorithm in High Dimensions

The population Monte Carlo algorithm is an iterative importance sampling scheme for solving static problems. We examine the population Monte Carlo algorithm in a simplified setting, a single step of the general algorithm, and study a fundamental problem that occurs in applying importance sampling to high-dimensional problem. The precision of the computed estimate from the simplified setting is measured by the asymptotic variance of estimate under conditions on the importance function. We demonstrate the exponential growth of the asymptotic variance with the dimension and show that the optimal covariance matrix for the importance function can be estimated in special cases.

Protein complementation assay as a display system for screening protein libraries in the intracellular environment

A wide range of screening strategies have been employed to isolate antibodies and other proteins with specific attributes, including binding affinity, specificity, stability and improved expression. However, there remains no high-throughput system to screen for target-binding proteins in a mammalian, intracellular environment. Such a system would allow binding reagents to be isolated against intracellular clinical targets such as cell signalling proteins associated with tumour formation (p53, ras, cyclin E), proteins associated with neurodegenerative disorders (huntingtin, betaamyloid precursor protein), and various proteins crucial to viral replication (e.g. HIV-1 proteins such as Tat, Rev and Vif-1), which are difficult to screen by phage, ribosome or cell-surface display. This study used the β-lactamase protein complementation assay (PCA) as the display and selection component of a system for screening a protein library in the cytoplasm of HEK 293T cells. The colicin E7 (ColE7) and Immunity protein 7 (Imm7) *Escherichia coli* proteins were used as model interaction partners for developing the system. These proteins drove effective β-lactamase complementation, resulting in a signal-to-noise ratio (9:1 – 13:1) comparable to that of other β-lactamase PCAs described in the literature. The model Imm7-ColE7 interaction was then used to validate protocols for library screening. Single positive cells that harboured the Imm7 and ColE7 binding partners were identified and isolated using flow cytometric cell sorting in combination with the fluorescent β-lactamase substrate, CCF2/AM. A single-cell PCR was then used to amplify the Imm7 coding sequence directly from each sorted cell. With the screening system validated, it was then used to screen a protein library based the Imm7 scaffold against a proof-of-principle target. The wild-type Imm7 sequence, as well as mutants with wild-type residues in the ColE7- binding loop were enriched from the library after a single round of selection, which is consistent with other eukaryotic screening systems such as yeast and mammalian cell-surface display. In summary, this thesis describes a new technology for screening protein libraries in a mammalian, intracellular environment. This system has the potential to complement existing screening technologies by allowing access to intracellular proteins and expanding the range of targets available to the pharmaceutical industry.