The expression, regulation and function of kallikrein 4 in prostate cancer

Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor  and  (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.

Ingroup and role identity influences on the initiation and maintenance of students' voluntary attendance at peer study sessions for statistics

Background: Although class attendance is linked to academic performance, questions remain about what determines students’ decisions to attend or miss class. Aims: In addition to the constructs of a common decision-making model, the theory of planned behaviour, the present study examined the influence of student role identity and university student (in-group) identification for predicting both the initiation and maintenance of students’ attendance at voluntary peer-assisted study sessions in a statistics subject. Sample: University students enrolled in a statistics subject were invited to complete a questionnaire at two time points across the academic semester. A total of 79 university students completed questionnaires at the first data collection point, with 46 students completing the questionnaire at the second data collection point. Method: Twice during the semester, students’ attitudes, subjective norm, perceived behavioural control, student role identity, in-group identification, and intention to attend study sessions were assessed via on-line questionnaires. Objective measures of class attendance records for each half-semester (or ‘term’) were obtained. Results: Across both terms, students’ attitudes predicted their attendance intentions, with intentions predicting class attendance. Earlier in the semester, in addition to perceived behavioural control, both student role identity and in-group identification predicted students’ attendance intentions, with only role identity influencing intentions later in the semester. Conclusions: These findings highlight the possible chronology that different identity influences have in determining students’ initial and maintained attendance at voluntary sessions designed to facilitate their learning.

Development and piloting of a brain tumour-specific question prompt list

The objective of this research was to develop a question prompt list aimed at increasing question asking and reducing the unmet information needs of adults with primary brain tumours, and to pilot the question prompt list to determine its suitability for the intended population. Thematic analysis of existing resources was used to create a draft which was refined via interviews with 12 brain tumour patients and six relatives, readability testing and review by health professionals. A non-randomised before–after pilot study with 20 brain tumour patients was used to assess the acceptability and usefulness of the question prompt list, compared with a ‘standard brochure’, and the feasibility of evaluation strategies. The question prompt list developed covered seven main topics (diagnosis, prognosis, symptoms and changes, treatment, support, after treatment finishes and the health professional team). Pilot study participants provided with the question prompt list agreed that it was helpful (7/7), contained questions that were useful to them (7/7) and prompted them to ask their medical oncologist questions (5/7). The question prompt list is acceptable to patients and contains questions relevant to them. Research is now needed to assess its effectiveness in increasing question asking and reducing unmet information needs.

Learnability and discriminability of melodic medical equipment alarms

Melodic alarms proposed in the IEC 60601-1-8 standard for medical electrical equipment were tested for learnability and discriminability. Thirty-three non-anaesthetist participants learned the alarms over two sessions of practice, with or without mnemonics suggested in the standard. Fewer than 30% of participants could identify the alarms with 100% accuracy at the end of practice. Confusions persisted between pairs of alarms, especially if mnemonics were used during learning (p = 0.011). Participants responded faster (p < 0.00001) and more accurately (p = 0.002) to medium priority alarms than to high priority alarms, even though they rated the high priority alarms as sounding more urgent (p < 0.00001). Participants with at least 1 year of formal musical training identified the alarms more accurately (p = 0.0002) than musically untrained participants, and found the task easier overall (p < 0.00001). More intensive studies of the IEC 60601-1-8 alarms are needed for their effectiveness to be determined.

Perceptions of visibility and conspicuity of biomotion clothing configurations for road workers at road work sites

Aims: This study determined whether the visibility benefits of positioning retroreflective strips in biological motion configurations were evident at real world road worker sites. Methods: 20 visually normal drivers (M=40.3 years) participated in this study that was conducted at two road work sites (one suburban and one freeway) on two separate nights. At each site, four road workers walked in place wearing one of four different clothing options: a) standard road worker night vest, b) standard night vest plus retroreflective strips on thighs, c) standard night vest plus retroreflective strips on ankles and knees, d) standard night vest plus retroreflective strips on eight moveable joints (full biomotion). Participants seated in stationary vehicles at three different distances (80m, 160m, 240m) rated the relative conspicuity of the four road workers using a series of a standardized visibility and ranking scales. Results: Adding retroreflective strips in the full biomotion configuration to the standard night vest significantly (p<0.001) enhanced perceptions of road worker visibility compared to the standard vest alone, or in combination with thigh retroreflective markings. These visibility benefits were evident at all distances and at both sites. Retroreflective markings at the ankles and knees also provided visibility benefits compared to the standard vest, however, the full biomotion configuration was significantly better than all of the other configurations. Conclusions: These data provide the first evidence that the benefits of biomotion retroreflective markings that have been previously demonstrated under laboratory and closed- and open-road conditions are also evident at real work sites.

Contextualising the teaching and learning of measurement in Torres Strait Islander schools

This paper reports on a mathematics project conducted with six Torres Strait Islander schools and communities by the research team at the YuMi Deadly Centre at QUT. Data collected is from a small focus group of six teachers and two teacher aides. We investigated how measurement is taught and learned by students, their teachers and teacher aides in the community schools. A key focus of the project was that the teaching and learning of measurement be contextualised to the students’ culture, community and home languages. A significant finding from the project was that the teachers had differing levels of knowledge and understanding about how to contextualise measurement to support student learning. For example, an Indigenous teacher identified that mathematics and the environment are relational, that is, they are not discrete and in isolation from one another, rather they mesh together, thus affording the articulation and interchange among and between mathematics and Torres Strait Islander culture.

The market structure and characteristics of electronic games

A multi-billion dollar industry, electronic games have been experiencing strong and rapid growth in recent times. The world of games is not only exciting due to the magnificent growth of the industry however, but due to a host of other factors. This chapter explores electronic games, providing an analysis of the industry, key motivators for game play, the game medium and academic research concerning the effects of play. It also reviews the emerging relationship games share with sport, recognizing that they can replicate sports, facilitate sports participation and be played as a sport. These are complex relationships that have not yet been comprehensively studied. The current chapter serves to draw academic attention to the area and presents ideas for future research.

Numerical modelling and design of LiteSteel Beams subject to lateral buckling

The LiteSteel Beam (LSB) is a new hollow flange channel section developed using a patented dual electric resistance welding and cold-forming process. It has a unique geometry consisting of torsionally rigid rectangular hollow flanges and a slender web, and is commonly used as flexural members. However, the LSB flexural members are subjected to a relatively new lateral distortional buckling mode, which reduces their moment capacities. Unlike lateral torsional buckling, the lateral distortional buckling of LSBs is characterised by simultaneous lateral deflection, twist and cross sectional change due to web distortion. Therefore a detailed investigation into the lateral buckling behaviour of LSB flexural members was undertaken using experiments and finite element analyses. This paper presents the details of suitable finite element models developed to simulate the behaviour and capacity of LSB flexural members subject to lateral buckling. The models included all significant effects that influence the ultimate moment capacities of such members, including material inelasticity, lateral distortional buckling deformations, web distortion, residual stresses, and geometric imperfections. Comparison of elastic buckling and ultimate moment capacity results with predictions from other numerical analyses and available buckling moment equations, and experimental results showed that the developed finite element models accurately predict the behaviour and moment capacities of LSBs. The validated model was then used in a detailed parametric study that produced accurate moment capacity data for all the LSB sections and improved design rules for LSB flexural members subject to lateral distortional buckling.

Behaviour and design of cold-formed steel beams subject to lateral-torsional buckling

Cold-formed steel beams are increasingly used as floor joists and bearers in buildings. Their behaviour and moment capacities are influenced by lateral-torsional buckling when they are not laterally restrained adequately. Past research on lateral-torsional buckling has concentrated on hot-rolled steel beams. Hence a numerical study was undertaken to investigate the lateral-torsional buckling behaviour of simply supported cold-formed steel lipped channel beams subjected to uniform bending. For this purpose a finite element model was developed using ABAQUS and its accuracy was verified using available numerical and experimental results. It was then used in a detailed parametric study to simulate the lateral-torsional buckling behaviour and capacity of cold-formed steel beams under varying conditions. The moment capacity results were compared with the predictions from the current design rules in many cold-formed steel codes and suitable recommendations were made. European design rules were found to be conservative while Australian/New Zealand and North American design rules were unconservative. Hence the moment capacity design equations in these codes were modified in this paper based on the available finite element analysis results. This paper presents the details of the parametric study, recommendations to current design rules and the new design rules proposed in this research for lateral-torsional buckling of cold-formed steel lipped channel beams.

Investigation into the transport, behaviour and deposition of combustion aerosols from transport sources

The deterioration of air quality is a significant issue in large and growing cities. This work investigates particulate emissions from transport, the largest source of air pollution in cities today. Emitters such as busy roads and diesel trains are investigated, with specific reference to the evolution of particles over time and distance. Diesel trains are investigated as an alternative to road traffic in investigating evolutionary processes. Higher emissions and solitary sources mean that the emitted plume can be observed over time in a single location. These results represent the first investigation of the evolution of fine and ultrafine aerosol particles from this type of source. Aerosols near a busy road are investigated, with the result that a dependence of total number concentration on distance from the road is shown to be related to the fragmentation of nanoparticle clusters. Local meteorological conditions are also monitored and humidity is shown to vary with distance from the road in a nonmonotonic way. Particles from a busy road were also examined using a scanning electron microscope, with the intention of understanding the make up of the emitted aerosol plume. It was determined that due to significant surface behaviour post-deposition, this method of analysis could not directly classify airborne pollutants. Some interesting results were obtained however, particularly in terms of composite particles and the analysis of deposited patterns. This thesis introduces new work in terms of the analysis of diesel train particulate emissions, as well as adding further evidence towards the fragmentation process of aerosol evolution in both background concentrations and emitted aerosol plumes.

Where do they come from? Prevalence and characteristics of nascent entrepreneurs

This paper reports on a unique study of a large, random sample of business start-ups that were identified prior to the actual, commercial launch of the ventures. The purpose of this paper is two-fold. First, to present frequencies on the involvement of the Swedish population in the small business sector (particularly in start-ups of firms) and to compare these with estimates from Norway and the USA, which are based on studies using a similar research design. The authors also discuss the possible reasons for the differences that emerge between countries. Second, the characteristics of nascent entrepreneurs (i.e. individuals trying to start an independent business) are analysed and compared for sub-groups within the sample and with characteristics of business founders as they appear in theoretical accounts or retrospective empirical studies of surviving all firms. In order to get a representative sample from the working age population, respondents (n = 30,427) were randomly selected and interviewed by telephone. It was found that 2.0% of the Swedish population at the time of the interview were trying to start an independent business. Sweden had a significantly lower prevalence rate of nascent entrepreneurs compared to Norway and the USA. Nascent entrepreneurs were then compared to a control group of people not trying to start a business. The results confirmed findings from previous studies of business founders pointing to the importance of role models and the impression of self-employment obtained through these, employment status, age, education and experience. Marital status, the number of children in the household, and length of employment experience were unrelated to the probability of becoming a nascent entrepreneur. The gender of the respondent was the strongest distinguishing factor. Importantly, the results suggest that while one has a reasonably good understanding of the characteristics associated with men going into business for themselves, the type of variables investigated here have very limited ability to predict nascent entrepreneur status for women.