Non-motorized public transport : a global review and analysis of trends and issues

Over recent decades there has been growing interest in the role of non-motorized modes in the overall transport system (especially walking and cycling for private purposes) and many government initiatives have been taken to encourage these active modes. However there has been relatively little research attention given to the paid form of non-motorized travel which can be called non-motorized public transport (NMPT). This involves cycle-powered vehicles which can carry several passengers (plus the driver) and a small amount of goods; and which provide flexible hail-and-ride services. Effectively they are non-motorized taxis. Common forms include cycle-rickshaw (Bangladesh, India), becak (Indonesia), cyclos (Vietnam, Cambodia), bicitaxi (Columbia, Cuba), velo-taxi (Germany, Netherland), and pedicabs (UK, Japan, USA). --------- The popularity of NMPT is widespread in developing countries, where it caters for a wide range of mobility needs. For instance in Dhaka, Bangladesh, rickshaws are the preferred mode for non-walk trips and have a higher mode share than cars or buses. Factors that underlie the continued existence and popularity of NMPT in many developing countries include positive contribution to social equity, micro-macro economic significance, employment creation, and suitability for narrow and crowded streets. Although top speeds are lower than motorized modes, NMPT is competitive and cost-effective for short distance door-to-door trips that make up the bulk of travel in many developing cities. In addition, NMPT is often the preferred mode for vulnerable groups such as females, children and elderly people. NMPT is more prominent in developing countries but its popularity and significance is also gradually increasing in several developed countries of Asia, Europe and parts of North America, where there is a trend for the NMPT usage pattern to broaden from tourism to public transport. This shift is due to a number of factors including the eco-sustainable nature of NMPT; its operating flexibility (such as in areas where motorized vehicle access is restricted or discouraged through pricing); and the dynamics that it adds to the urban fabric. Whereas NMPT may have been seen as a “dying” mode, in many cities it is maintaining or increasing its significance and with potential for further growth. --------- This paper will examine and analyze global trends in NMPT incorporating both developing and developed country contexts and issues such as usage patterns; NMPT policy and management practices; technological development; and operational integration of NMPT into the overall transport system. It will look at how NMPT policies, practices and usage have changed over time and the differing trends in developing and developed countries. In particular, it will use Dhaka, Bangladesh as a case study in recognition of its standing as the major NMPT city in the world. The aim is to highlight NMPT issues and trends and their significance for shaping future policy towards NMPT in developing and developed countries. The paper will be of interest to transport planners, traffic engineers, urban and regional planners, environmentalists, economists and policy makers.

Current child restraint practice in Queensland, new legislation and future challenges

Correct use of child restraints reduces the risk of death and injury. Use of adult seat belts is better than being unrestrained but can result in injury to children who are too small. New Australian legislation extends the requirement for using child-specific restraints until children are 7 years old and thus requires more appropriate levels of protection for these children. As part of a larger study of injury prevention in Queensland, parents of children 0-9 years old were surveyed regarding their restraint practices before the introduction of the new legislation. The restraint status of 18% of the children would not be compliant with the new legislation, with the problem being more prevalent for 5-9 year olds (22%) than 0-4 year olds (16%). A high proportion of older children used an adult seat belt. Very few children aged 0-4 (1.3%) usually travelled in the front seat in contravention of the new requirement, but around 11% of this age group were reported as ever having done so. Usual travel in the front seat was higher among 5-9 year olds (8.5%), with more than half of the 5-9 year olds reported as ever having done so. Given the widespread use of adult seat belts by older children, there is a need to consider improving protection of children in the ‘gap’ between when the requirement for the child to use a booster ceases (effectively age 7) and when the adult belt is likely to actually fit the child (closer to age 9 or 10).

Colours Unknown

Colours Unknown was originally published online by Bradt Travel Guides in July, 2009. On February 7th, 2010, it was published nationally in the Sunday Telegraph, the Sunday Mail Brisbane, the Sunday Mail Adelaide, the Sunday Tasmanian and the Sunday Herald Sun. The piece won the unpublished section of the 2009 Independent on Sunday and Bradt Travel Guides Travel Writing Competition - an international writing prize based in London.

The effectiveness of marketing communication within the immersive environment

Immersive environments are part of a recent media innovation that allow users to become so involved within a computer-based simulated environment that they feel part of that virtual world (Grigorovici, 2003). A specific example is Second Life, which is an internet-based, three-dimensional immersive virtual world in which users create an online representation of themselves (an avatar) to play games and interact socially with thousands of people simultaneously. This study focuses on Second Life as an example of an immersive environment, as it is the largest adult freeform virtual world, home to 12 million avatars (IOWA State University, 2008). Already in Second Life there are more than 100 real-life brands from a range of industries, including automotive, professional services, and consumer goods and travel, among others (KZero, 2007; New Business Horizons, 2009). Compared to traditional advertising media, this interactive media can immerse users in the environment. As a result of this interactivity, users can become more involved with a virtual environment, resulting in prolonged usage over weeks, months and even years. Also, it can facilitate presence. Despite these developments, little is known about the effectiveness of marketing messages in a virtual world context. Marketers are incorporating products into Second Life using a strategy of online product placement. This study, therefore, explores the perceived effectiveness of online product placement in Second Life in terms of effects on product/brand recall, purchase intentions and trial. This research examines the association between individuals’ involvement with Second Life and online product placement effectiveness, as well as the relationship between individuals’ Second Life involvement and the effectiveness of online product placement. In addition, it investigates the association of immersion and product placement involvement. It also examines the impact of product placement involvement on online product placement effectiveness and the role of presence in affecting this relationship. An exploratory study was conducted for this research using semi-structured in-depth interviews face-to-face, email-based and in-world. The sample comprised 24 active Second Life users. Results indicate that product placement effectiveness is not directly associated with Second Life involvement, but rather effectiveness is impacted through the effect of Second Life involvement on product placement involvement. A positive relationship was found between individuals’ product placement involvement and online product placement effectiveness. Findings also indicate that online product placement effectiveness is not directly associated with immersion. Rather, it appears that effectiveness is impacted through the effect of immersion on product placement involvement. Moreover, higher levels of presence appear to have a positive impact on the relationship between product placement involvement and product placement effectiveness. Finally, a model was developed from this qualitative study for future testing. In terms of theoretical contributions, this study provides a new model for testing the effectiveness of product placement within immersive environments. From a methodological perspective, in-world interviews as a new research method were undertaken. In terms of a practical contribution, findings identified useful information for marketers and advertising agencies that aim to promote their products in immersive virtual environments like Second Life.

The effect of traffic lane widths on the safety of cyclists in urban areas

This literature review examines the relationship between traffic lane widths on the safety of road users. It focuses on the impacts of lane widths on motor vehicle behaviour and cyclists’ safety. The review commenced with a search of available databases. Peer reviewed articles and road authority reports were reviewed, as well as current engineering guidelines. Research shows that traffic lane width influences drivers’ perceived difficulty of the task, risk perception and possibly speed choices. Total roadway width, and the presence of onroad cycling facilities, influence cyclists’ positioning on the road. Lateral displacement between bicycles and vehicles is smallest when a marked bicycle facility is present. Reduced motor vehicle speeds can significantly improve the safety of vulnerable road users, particularly pedestrians and cyclists. It has been shown that if road lane widths on urban roads were reduced, through various mechanisms, it could result in a safety environment for all road users.

Pollutant characteristics on roof surfaces for evaluation as a stormwater harvesting catchment

This paper presents the outcomes of a study which focused on evaluating roof surfaces as stormwater harvesting catchments. Build-up and wash-off samples were collected from model roof surfaces. The collected build-up samples were separated into five different particle size ranges prior to the analysis of physico-chemical parameters. Study outcomes showed that roof surfaces are efficient catchment surfaces for the deposition of fine particles which travel over long distances. Roof surfaces contribute relatively high pollutant loads to the runoff and hence significantly influence the quality of the harvested rainwater. Pollutants associated with solids build-up on roof surfaces can vary with time, even with minimal changes to total solids load and particle size distribution. It is postulated that this variability is due to changes in distant atmospheric pollutant sources and wind patterns. The study highlighted the requirement for first flush devices to divert the highly polluted initial portion of roof runoff. Furthermore, it is highly recommended to not to harvest runoff from small intensity rainfall events since there is a high possibility that the runoff would contain a significant amount of pollutants even after the initial runoff fraction.

Virtual fencing applications : Implementing and testing an automated cattle control system

Managing livestock movement in extensive systems has environmental and production benefits. Currently permanent wire fencing is used to control cattle; this is both expensive and inflexible. Cattle are known to respond to auditory and visual cues and we investigated whether these can be used to manipulate their behaviour. Twenty-five Belmont Red steers with a mean live weight of 270kg were each randomly assigned to one of five treatments. Treatments consisted of a combination of cues (audio, tactile and visual stimuli) and consequence (electrical stimulation). The treatments were electrical stimulation alone, audio plus electrical stimulation, vibration plus electrical stimulation, light plus electrical stimulation and electrified electric fence (6kV) plus electrical stimulation. Cue stimuli were administered for 3s followed immediately by electrical stimulation (consequence) of 1kV for 1s. The experiment tested the operational efficacy of an on-animal control or virtual fencing system. A collar-halter device was designed to carry the electronics, batteries and equipment providing the stimuli, including audio, vibration, light and electrical of a prototype virtual fencing device. Cattle were allowed to travel along a 40m alley to a group of peers and feed while their rate of travel and response to the stimuli were recorded. The prototype virtual fencing system was successful in modifying the behaviour of the cattle. The rate of travel of cattle along the alley demonstrated the large variability in behavioural response associated with tactile, visual and audible cues. The experiment demonstrated virtual fencing has potential for controlling cattle in extensive grazing systems. However, larger numbers of cattle need to be tested to derive a better understanding of the behavioural variance. Further controlled experimental work is also necessary to quantify the interaction between cues, consequences and cattle learning.

Towards sustainable urban futures : evaluating urban sustainability performance of the Gold coast, Australia

Creating sustainable urban environments is one of the challenging issues that need a clear vision and implementation strategies involving changes in governmental values and decision making process for local governments. Particularly, internalisation of environmental externalities of daily urban activities (e.g. manufacturing, transportation and so on) has immense importance for which local policies are formulated to provide better living conditions for the people inhabiting urban areas. Even if environmental problems are defined succinctly by various stakeholders, complicated nature of sustainability issues demand a structured evaluation strategy and well-defined sustainability parameters for efficient and effective policy making. Following this reasoning, this study involves assessment of sustainability performance of urban settings mainly focusing on environmental problems caused by rapid urban expansion and transformation. By taking into account land-use and transportation interaction, it tries to reveal how future urban developments would alter daily urban travel behaviour of people and affect the urban and natural environments. The paper introduces a grid-based indexing method developed for this research and trailed as a GIS-based decision support tool to analyse and model selected spatial and aspatial indicators of sustainability in the Gold Coast. This process reveals parameters of site specific relationship among selected indicators that are used to evaluate index-based performance characteristics of the area. The evaluation is made through an embedded decision support module by assigning relative weights to indicators. Resolution of selected grid-based unit of analysis provides insights about service level of projected urban development proposals at a disaggregate level, such as accessibility to transportation and urban services, and pollution. The paper concludes by discussing the findings including the capacity of the decision support system to assist decision-makers in determining problematic areas and developing intervention policies for sustainable outcomes of future developments.

A decision support system for sustainable urban development : the integrated land use and transportation indexing model

Broad, early definitions of sustainable development have caused confusion and hesitation among local authorities and planning professionals. This confusion has arisen because loosely defined principles of sustainable development have been employed when setting policies and planning projects, and when gauging the efficiencies of these policies in the light of designated sustainability goals. The question of how this theory-rhetoric-practice gap can be filled is the main focus of this chapter. It examines the triple bottom line approach–one of the sustainability accounting approaches widely employed by governmental organisations–and the applicability of this approach to sustainable urban development. The chapter introduces the ‘Integrated Land Use and Transportation Indexing Model’ that incorporates triple bottom line considerations with environmental impact assessment techniques via a geographic, information systems-based decision support system. This model helps decision-makers in selecting policy options according to their economic, environmental and social impacts. Its main purpose is to provide valuable knowledge about the spatial dimensions of sustainable development, and to provide fine detail outputs on the possible impacts of urban development proposals on sustainability levels. In order to embrace sustainable urban development policy considerations, the model is sensitive to the relationship between urban form, travel patterns and socio-economic attributes. Finally, the model is useful in picturing the holistic state of urban settings in terms of their sustainability levels, and in assessing the degree of compatibility of selected scenarios with the desired sustainable urban future.

Examining psychosocial influences on speeding in Australian and Chinese contexts : a social learning approach

Speeding remains a significant contributing factor to road trauma internationally, despite increasingly sophisticated speed management strategies being adopted around the world. Increases in travel speed are associated with increases in crash risk and crash severity. As speed choice is a voluntary behaviour, driver perceptions are important to our understanding of speeding and, importantly, to designing effective behavioural countermeasures. The four studies conducted in this program of research represent a comprehensive approach to examining psychosocial influences on driving speeds in two countries that are at very different levels of road safety development: Australia and China. Akers’ social learning theory (SLT) was selected as the theoretical framework underpinning this research and guided the development of key research hypotheses. This theory was chosen because of its ability to encompass psychological, sociological, and criminological perspectives in understanding behaviour, each of which has relevance to speeding. A mixed-method design was used to explore the personal, social, and legal influences on speeding among car drivers in Queensland (Australia) and Beijing (China). Study 1 was a qualitative exploration, via focus group interviews, of speeding among 67 car drivers recruited from south east Queensland. Participants were assigned to groups based on their age and gender, and additionally, according to whether they self-identified as speeding excessively or rarely. This study aimed to elicit information about how drivers conceptualise speeding as well as the social and legal influences on driving speeds. The findings revealed a wide variety of reasons and circumstances that appear to be used as personal justifications for exceeding speed limits. Driver perceptions of speeding as personally and socially acceptable, as well as safe and necessary were common. Perceptions of an absence of danger associated with faster driving speeds were evident, particularly with respect to driving alone. An important distinction between the speed-based groups related to the attention given to the driving task. Rare speeders expressed strong beliefs about the need to be mindful of safety (self and others) while excessive speeders referred to the driving task as automatic, an absent-minded endeavour, and to speeding as a necessity in order to remain alert and reduce boredom. For many drivers in this study, compliance with speed limits was expressed as discretionary rather than mandatory. Social factors, such as peer and parental influence were widely discussed in Study 1 and perceptions of widespread community acceptance of speeding were noted. In some instances, the perception that ‘everybody speeds’ appeared to act as one rationale for the need to raise speed limits. Self-presentation, or wanting to project a positive image of self was noted, particularly with respect to concealing speeding infringements from others to protect one’s image as a trustworthy and safe driver. The influence of legal factors was also evident. Legal sanctions do not appear to influence all drivers to the same extent. For instance, fear of apprehension appeared to play a role in reducing speeding for many, although previous experiences of detection and legal sanctions seemed to have had limited influence on reducing speeding among some drivers. Disregard for sanctions (e.g., driving while suspended), fraudulent demerit point use, and other strategies to avoid detection and punishment were widely and openly discussed. In Study 2, 833 drivers were recruited from roadside service stations in metropolitan and regional locations in Queensland. A quantitative research strategy assessed the relative contribution of personal, social, and legal factors to recent and future self-reported speeding (i.e., frequency of speeding and intentions to speed in the future). Multivariate analyses examining a range of factors drawn from SLT revealed that factors including self-identity (i.e., identifying as someone who speeds), favourable definitions (attitudes) towards speeding, personal experiences of avoiding detection and punishment for speeding, and perceptions of family and friends as accepting of speeding were all significantly associated with greater self-reported speeding. Study 3 was an exploratory, qualitative investigation of psychosocial factors associated with speeding among 35 Chinese drivers who were recruited from the membership of a motoring organisation and a university in Beijing. Six focus groups were conducted to explore similar issues to those examined in Study 1. The findings of Study 3 revealed many similarities with respect to the themes that arose in Australia. For example, there were similarities regarding personal justifications for speeding, such as the perception that posted limits are unreasonably low, the belief that individual drivers are able to determine safe travel speeds according to personal comfort with driving fast, and the belief that drivers possess adequate skills to control a vehicle at high speed. Strategies to avoid detection and punishment were also noted, though they appeared more widespread in China and also appeared, in some cases, to involve the use of a third party, a topic that was not reported by Australian drivers. Additionally, higher perceived enforcement tolerance thresholds were discussed by Chinese participants. Overall, the findings indicated perceptions of a high degree of community acceptance of speeding and a perceived lack of risk associated with speeds that were well above posted speed limits. Study 4 extended the exploratory research phase in China with a quantitative investigation involving 299 car drivers recruited from car washes in Beijing. Results revealed a relatively inexperienced sample with less than 5 years driving experience, on average. One third of participants perceived that the certainty of penalties when apprehended was low and a similar proportion of Chinese participants reported having previously avoided legal penalties when apprehended for speeding. Approximately half of the sample reported that legal penalties for speeding were ‘minimally to not at all’ severe. Multivariate analyses revealed that past experiences of avoiding detection and punishment for speeding, as well as favourable attitudes towards speeding, and perceptions of strong community acceptance of speeding were most strongly associated with greater self-reported speeding in the Chinese sample. Overall, the results of this research make several important theoretical contributions to the road safety literature. Akers’ social learning theory was found to be robust across cultural contexts with respect to speeding; similar amounts of variance were explained in self-reported speeding in the quantitative studies conducted in Australia and China. Historically, SLT was devised as a theory of deviance and posits that deviance and conformity are learned in the same way, with the balance of influence stemming from the ways in which behaviour is rewarded and punished (Akers, 1998). This perspective suggests that those who speed and those who do not are influenced by the same mechanisms. The inclusion of drivers from both ends of the ‘speeding spectrum’ in Study 1 provided an opportunity to examine the wider utility of SLT across the full range of the behaviour. One may question the use of a theory of deviance to investigate speeding, a behaviour that could, arguably, be described as socially acceptable and prevalent. However, SLT seemed particularly relevant to investigating speeding because of its inclusion of association, imitation, and reinforcement variables which reflect the breadth of factors already found to be potentially influential on driving speeds. In addition, driving is a learned behaviour requiring observation, guidance, and practice. Thus, the reinforcement and imitation concepts are particularly relevant to this behaviour. Finally, current speed management practices are largely enforcement-based and rely on the principles of behavioural reinforcement captured within the reinforcement component of SLT. Thus, the application of SLT to a behaviour such as speeding offers promise in advancing our understanding of the factors that influence speeding, as well as extending our knowledge of the application of SLT. Moreover, SLT could act as a valuable theoretical framework with which to examine other illegal driving behaviours that may not necessarily be seen as deviant by the community (e.g., mobile phone use while driving). This research also made unique contributions to advancing our understanding of the key components and the overall structure of Akers’ social learning theory. The broader SLT literature is lacking in terms of a thorough structural understanding of the component parts of the theory. For instance, debate exists regarding the relevance of, and necessity for including broader social influences in the model as captured by differential association. In the current research, two alternative SLT models were specified and tested in order to better understand the nature and extent of the influence of differential association on behaviour. Importantly, the results indicated that differential association was able to make a unique contribution to explaining self-reported speeding, thereby negating the call to exclude it from the model. The results also demonstrated that imitation was a discrete theoretical concept that should also be retained in the model. The results suggest a need to further explore and specify mechanisms of social influence in the SLT model. In addition, a novel approach was used to operationalise SLT variables by including concepts drawn from contemporary social psychological and deterrence-based research to enhance and extend the way that SLT variables have traditionally been examined. Differential reinforcement was conceptualised according to behavioural reinforcement principles (i.e., positive and negative reinforcement and punishment) and incorporated concepts of affective beliefs, anticipated regret, and deterrence-related concepts. Although implicit in descriptions of SLT, little research has, to date, made use of the broad range of reinforcement principles to understand the factors that encourage or inhibit behaviour. This approach has particular significance to road user behaviours in general because of the deterrence-based nature of many road safety countermeasures. The concept of self-identity was also included in the model and was found to be consistent with the definitions component of SLT. A final theoretical contribution was the specification and testing of a full measurement model prior to model testing using structural equation modelling. This process is recommended in order to reduce measurement error by providing an examination of the psychometric properties of the data prior to full model testing. Despite calls for such work for a number of decades, the current work appears to be the only example of a full measurement model of SLT. There were also a number of important practical implications that emerged from this program of research. Firstly, perceptions regarding speed enforcement tolerance thresholds were highlighted as a salient influence on driving speeds in both countries. The issue of enforcement tolerance levels generated considerable discussion among drivers in both countries, with Australian drivers reporting lower perceived tolerance levels than Chinese drivers. It was clear that many drivers used the concept of an enforcement tolerance in determining their driving speed, primarily with the desire to drive faster than the posted speed limit, yet remaining within a speed range that would preclude apprehension by police. The quantitative results from Studies 2 and 4 added support to these qualitative findings. Together, the findings supported previous research and suggested that a travel speed may not be seen as illegal until that speed reaches a level over the prescribed enforcement tolerance threshold. In other words, the enforcement tolerance appears to act as a ‘de facto’ speed limit, replacing the posted limit in the minds of some drivers. The findings from the two studies conducted in China (Studies 2 and 4) further highlighted the link between perceived enforcement tolerances and a ‘de facto’ speed limit. Drivers openly discussed driving at speeds that were well above posted speed limits and some participants noted their preference for driving at speeds close to ‘50% above’ the posted limit. This preference appeared to be shaped by the perception that the same penalty would be imposed if apprehended, irrespective of what speed they travelling (at least up to 50% above the limit). Further research is required to determine whether the perceptions of Chinese drivers are mainly influenced by the Law of the People’s Republic of China or by operational practices. Together, the findings from both studies in China indicate that there may be scope to refine enforcement tolerance levels, as has happened in other jurisdictions internationally over time, in order to reduce speeding. Any attempts to do so would likely be assisted by the provision of information about the legitimacy and purpose of speed limits as well as risk factors associated with speeding because these issues were raised by Chinese participants in the qualitative research phase. Another important practical implication of this research for speed management in China is the way in which penalties are determined. Chinese drivers described perceptions of unfairness and a lack of transparency in the enforcement system because they were unsure of the penalty that they would receive if apprehended. Steps to enhance the perceived certainty and consistency of the system to promote a more equitable approach to detection and punishment would appear to be welcomed by the general driving public and would be more consistent with the intended theoretical (deterrence) basis that underpins the current speed enforcement approach. The use of mandatory, fixed penalties may assist in this regard. In many countries, speeding attracts penalties that are dependent on the severity of the offence. In China, there may be safety benefits gained from the introduction of a similar graduated scale of speeding penalties and fixed penalties might also help to address the issue of uncertainty about penalties and related perceptions of unfairness. Such advancements would be in keeping with the principles of best practice for speed management as identified by the World Health Organisation. Another practical implication relating to legal penalties, and applicable to both cultural contexts, relates to the issues of detection and punishment avoidance. These two concepts appeared to strongly influence speeding in the current samples. In Australia, detection avoidance strategies reported by participants generally involved activities that are not illegal (e.g., site learning and remaining watchful for police vehicles). The results from China were similar, although a greater range of strategies were reported. The most common strategy reported in both countries for avoiding detection when speeding was site learning, or familiarisation with speed camera locations. However, a range of illegal practices were also described by Chinese drivers (e.g., tampering with or removing vehicle registration plates so as to render the vehicle unidentifiable on camera and use of in-vehicle radar detectors). With regard to avoiding punishment when apprehended, a range of strategies were reported by drivers from both countries, although a greater range of strategies were reported by Chinese drivers. As the results of the current research indicated that detection avoidance was strongly associated with greater self-reported speeding in both samples, efforts to reduce avoidance opportunities are strongly recommended. The practice of randomly scheduling speed camera locations, as is current practice in Queensland, offers one way to minimise site learning. The findings of this research indicated that this practice should continue. However, they also indicated that additional strategies are needed to reduce opportunities to evade detection. The use of point-to-point speed detection (also known as sectio

The expression of ADAM-9 and -10 in prostate cancer and their regulation by dihydrotestosterone, insulin-like growth Factor-1 and epidermal growth factor

Prostrate Cancer(PCa)is the most common cause of cancer death amongst Western males. PCa occurs in two distinct stages. In its early stage, growth and development is dependent primarily on male sex hormones (androgens) such as testosterone, although other growth factors have roles maintaining PCa cell survival in this stage. In the later stage of PCa development, growth and.maintenance is independent of androgen stimulation and growth factors including Insulin-like Growth Factor -1 (IGf.:·l) and Epidermal Growth Factor (EGF) are thought to have more crucial roles in cell survival and PCa progression. PCa, in its late stages, is highly aggressive and metastatic, that is, tumorigenic cells migrate from the primary site of the body (prostate) and travel via the systemic and lymphatic circulation, residing and colonising in the bone, lymph node, lung, and in more rare cases, the brain. Metastasis involves both cell migration and tissue degradation activities. The degradation of the extracellular matrix (ECM), the tissue surrounding the organ, is mediated in part by members of a family of 26 proteins called the Matrix Metalloproteases (MMPs), whilst ceil adhesion molecules, of which proteins known as Integrins are included, mediate ce11 migration. A family of proteins known as the ADAMs (A Disintegrin . And Metalloprotease domain) were a recently characterised family at the commencement of this study and now comprise 34 members. Because of their dual nature, possessing an active metaiioprotease domain, homologous to that of the MMPs, and an integrin-binding domain capable of regulating cell-cell and cell-ECM contacts, it was thought likely that members of the ADAMs family may have implications for the progression of aggressive cancers such as those ofthe prostate. This study focussed on two particular ADAMs -9 and -10. ADAM-9 has an active metalloprotease domain, which has been shown to degrade constituents of the ECM, including fibronectin, in vitro. It also has an integrin-binding capacity through association with key integrins involved in PCa progression, such as a6~1. ADAM-10 has no such integrin binding activities, but its bovine orthologue, MADM, is able to degrade coHagen type IV, a major component of basement membranes. It is likely human ADAM-10 has the same activity. It is also known to cleave Ll -a protein involved in cell anchorage activities - and collagen type XVII - which is a principal component of the hemidesmosomes of cellular tight junctions. The cleavage of these proteins enables the cell to be released from the surrounding environment and commence migratory activities, as required in metastasis. Previous studies in this laboratory showed the mRNA expression of the five ADAMs -9,- 10, -11, -15 and -17 in PCa cell lines, characteristic of androgen-dependent and androgen independent disease. These studies were furthered by the characterisation of AD AM-9, -10 and -17 mRNA regulation by Dihydrotestosterone (DHT) in the androgen-responsive cell line (LNCaP). ADAM-9 and -10 mRNA levels were elevated in response to DHT stimulation. Further to these observations, the expression of ADAM-9 and -10 was shown in primary prostate biopsies from patients with PCa. ADAM-1 0 was expressed in the cytoplasm and on the ceH membrane in epithelial and basal cells ofbenign prostate glands, but in high-grade PCa glands, ADAM-I 0 expression was localised to the nucleus and its expression levels appeared to be elevated when compared to low-grade PCa glands. These studies provided a strong background for the hypothesis that ADAM-9 and -10 have key roles in the development ofPCa and provided a basis for further studies.The aims of this study were to: 1) characterise the expression, localisation and levels, of ADAM-9 and -10 mRNA and protein in cell models representing characteristics of normal through androgen-dependent to androgen-independent PCa, as well as to expand the primary PCa biopsy data for ADAM-9 and ADAM-10 to encompass PCa bone metastases 2) establish an in vitro cell system, which could express elevated levels of ADAM-1 0 so that functional cell-based assays such as cell migration, invasion and attachment could be carried out, and 3) to extend the previous hormonal regulation data, to fully characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in the hormonal/growth factor responsive cell line LNCaP. For aim 1 (expression of ADAM-9 and -10 mRNA and protein), ADAM-9 and -10 mRNA were characterised by R T -PCR, while their protein products were analysed by Western blot. Both ADAM-9 and -10 mRNA and protein were expressed at readily detectable levels across progressively metastatic PCa cell lines model that represent characteristics of low-grade,. androgen-dependent (LNCaP and C4) to high-grade, androgen-independent (C4-2 and C4-2B) PCa. When the non-tumorigenic prostate cell line RWPE-1 was compared with the metastatic PCa cell line PC-3, differential expression patterns were seen by Western blot analysis. For ADAM-9, the active form was expressed at higher levels in RWPE-1, whilst subcellular fractionation showed that the active form of ADAM-9 was predominantly located in the cell nucleus. For ADAM-I 0, in both of the cell Jines, a nuclear specific isoform of the mature, catalytically active ADAM-I 0 was found. This isoforrn differed by -2 kDa in Mr (smaller) than the cytoplasmic specific isoform. Unprocessed ADAM-I 0 was readily detected in R WPE-1 cell lines but only occasionally detected in PC-3 cell lines. Immunocytochemistry using ADAM-9 and -10 specific antibodies confirmed nuclear, cytoplasmic and membrane expression of both ADAMs in these two cell lines. To examine the possibility of ADAM-9 and -10 being shed into the extracellular environment, membrane vesicles that are constitutively shed from the cell surface and contain membrane-associated proteins were collected from the media of the prostate cell lines RWPE-1, LNCaP and PC-3. ADAM-9 was readily detectable in RWPE- 1 and LNCaP cell membrane vesicles by Western blot analysis, but not in PC-3 cells, whilst the expression of ADAM-I 0 was detected in shed vesicles from each of these prostate cell lines. By Laser Capture Microdissection (LCM), secretory epithelial cells of primary prostate gland biopsies were isolated from benign and malignant glands. These secretory cells, by Western blot analysis, expressed similar Mr bands for ADAM-9 and -10 that were found in PCa cell lines in vitro, indicating that the nuclear specific isoforrn of ADAM-I 0 was present in PCa primary tumours and may represent the predominantly nuclear form of ADAM-I 0 expression, previously shown in high-grade PCa by immunohistochemistry (IHC). ADAM-9 and -10 were also examined by IHC in bone metastases taken from PCa patients at biopsy. Both ADAMs could be detected at levels similar to those shown for Prostate Specific Antigen (PSA) in these biopsies. Furthermore, both ADAM-9 and -10 were predominantly membrane- bound with occasional nuclear expression. For aim 2, to establish a cell system that over-expressed levels of ADAM-10, two fulllength ADAM-I 0 mammalian expression vectors were constructed; ADAM-I 0 was cloned into pcDNA3.1, which contains a CMV promoter, and into pMEP4, containing an inducible metallothionine promoter, whose activity is stimulated by the addition of CdC}z. The efficiency of these two constructs was tested by way of transient transfection in the PCa cell line PC-3, whilst the pcDNA3.1 construct was also tested in the RWPE-1 prostate cell line. Resultant Western blot analysis for all transient transfection assays showed that levels of ADAM-I 0 were not significantly elevated in any case, when compared to levels of the housekeeping gene ~-Tubulin, despite testing various levels of vector DNA, and, for pMEP4, the induction of the transfected cell system with different degrees of stimulation with CdCh to activate the metallothionine promoter post-transfection. Another study in this laboratory found similar results when the same full length ADAM-10 sequence was cloned into a Green Fluorescent Protein (GFP) expressing vector, as no fluorescence was observed by means of transient tran sfection in the same, and other, PCa cell lines. It was hypothesised that the Kozak sequence included in the full-length construct (human ADAMI 0 naturally occurring sequence) is not strong enough to initiate translation in an artificial system, in cells, which, as described in Aim 1, are already expressing readily detectable levels of endogenous ADAM-10. As a result, time constraints prevented any further progress with Aim 2 and functional studies including cell attachment, invasion and migration were unable to be explored. For Aim 3, to characterise the response of ADAM-9 and -10 mRNA and protein levels to DHT, IGF-1, DHT plus IGF-1 and EGF in LNCaP cells, the levels of ADAM-9 and -10 mRNA were not stimulated by DHT or IGF-I alone, despite our previous observations that initially characterised ADAM-9 and -10 mRNA as being responsive to DHT. However, IGF-1 in synergy with DHT did significantly elevate mRNA levels ofboth ADAMs. In the case of ADAM-9 and -10 protein, the same trends of stimulation as found at the rnRNA level were shown by Western blot analysis when ADAM-9 and -10 signal intensity was normalised with the housekeeping protein ~-Tubulin. For EGF treatment, both ADAM-9 and -10 mRNA and protein levels were significantly elevated, and further investigation vm found this to be the case for each of these ADAMs proteins in the nuclear fractions of LNCaP cells. These studies are the first to describe extensively, the expression and hormonal/growth factor regulation of two members of the ADAMs family ( -9 and -1 0) in PCa. These observations imply that the expression of ADAM-9 and -10 have varied roles in PCa whilst it develops from androgen-sensitive (early stage disease), through to an androgeninsensitive (late-stage), metastatic disease. Further studies are now required to investigate the several key areas of focus that this research has revealed, including: • Investigation of the cellular mechanisms that are involved in actively transporting the ADAMs to the cell's nuclear compartment and the ADAMs functional roles in the cell nucleus. • The construction of a full-length human ADAM-10 mammalian expression construct with the introduction of a new Kozak sequence, that elevates ADAM-I 0 expression in an in vitro cell system are required, so that functional assays such as cell invasion, migration and attachment may be carried out to fmd the functional consequences of ADAM expression on cellular behaviour. • The regulation studies also need to be extended by confirming the preliminary observations that the nuclear levels of ADAMs may also be elevated by hormones and growth factors such as DHT, IGF-1 and EGF, as well as the regulation of levels of plasma membrany vesicle associated ADAM expression. Given the data presented in this study, it is likely the ADAMs have differential roles throughout the development of PCa due to their differential cellular localisation and synergistic growth-factor regulation. These observations, along with those further studies outlined above, are necessary in identifying these specific components ofPCa metastasis to which the ADAMs may contribute.

Modelling and solving train scheduling problems under capacity constraints

Many large coal mining operations in Australia rely heavily on the rail network to transport coal from mines to coal terminals at ports for shipment. Over the last few years, due to the fast growing demand, the coal rail network is becoming one of the worst industrial bottlenecks in Australia. As a result, this provides great incentives for pursuing better optimisation and control strategies for the operation of the whole rail transportation system under network and terminal capacity constraints. This PhD research aims to achieve a significant efficiency improvement in a coal rail network on the basis of the development of standard modelling approaches and generic solution techniques. Generally, the train scheduling problem can be modelled as a Blocking Parallel- Machine Job-Shop Scheduling (BPMJSS) problem. In a BPMJSS model for train scheduling, trains and sections respectively are synonymous with jobs and machines and an operation is regarded as the movement/traversal of a train across a section. To begin, an improved shifting bottleneck procedure algorithm combined with metaheuristics has been developed to efficiently solve the Parallel-Machine Job- Shop Scheduling (PMJSS) problems without the blocking conditions. Due to the lack of buffer space, the real-life train scheduling should consider blocking or hold-while-wait constraints, which means that a track section cannot release and must hold a train until the next section on the routing becomes available. As a consequence, the problem has been considered as BPMJSS with the blocking conditions. To develop efficient solution techniques for BPMJSS, extensive studies on the nonclassical scheduling problems regarding the various buffer conditions (i.e. blocking, no-wait, limited-buffer, unlimited-buffer and combined-buffer) have been done. In this procedure, an alternative graph as an extension of the classical disjunctive graph is developed and specially designed for the non-classical scheduling problems such as the blocking flow-shop scheduling (BFSS), no-wait flow-shop scheduling (NWFSS), and blocking job-shop scheduling (BJSS) problems. By exploring the blocking characteristics based on the alternative graph, a new algorithm called the topological-sequence algorithm is developed for solving the non-classical scheduling problems. To indicate the preeminence of the proposed algorithm, we compare it with two known algorithms (i.e. Recursive Procedure and Directed Graph) in the literature. Moreover, we define a new type of non-classical scheduling problem, called combined-buffer flow-shop scheduling (CBFSS), which covers four extreme cases: the classical FSS (FSS) with infinite buffer, the blocking FSS (BFSS) with no buffer, the no-wait FSS (NWFSS) and the limited-buffer FSS (LBFSS). After exploring the structural properties of CBFSS, we propose an innovative constructive algorithm named the LK algorithm to construct the feasible CBFSS schedule. Detailed numerical illustrations for the various cases are presented and analysed. By adjusting only the attributes in the data input, the proposed LK algorithm is generic and enables the construction of the feasible schedules for many types of non-classical scheduling problems with different buffer constraints. Inspired by the shifting bottleneck procedure algorithm for PMJSS and characteristic analysis based on the alternative graph for non-classical scheduling problems, a new constructive algorithm called the Feasibility Satisfaction Procedure (FSP) is proposed to obtain the feasible BPMJSS solution. A real-world train scheduling case is used for illustrating and comparing the PMJSS and BPMJSS models. Some real-life applications including considering the train length, upgrading the track sections, accelerating a tardy train and changing the bottleneck sections are discussed. Furthermore, the BPMJSS model is generalised to be a No-Wait Blocking Parallel- Machine Job-Shop Scheduling (NWBPMJSS) problem for scheduling the trains with priorities, in which prioritised trains such as express passenger trains are considered simultaneously with non-prioritised trains such as freight trains. In this case, no-wait conditions, which are more restrictive constraints than blocking constraints, arise when considering the prioritised trains that should traverse continuously without any interruption or any unplanned pauses because of the high cost of waiting during travel. In comparison, non-prioritised trains are allowed to enter the next section immediately if possible or to remain in a section until the next section on the routing becomes available. Based on the FSP algorithm, a more generic algorithm called the SE algorithm is developed to solve a class of train scheduling problems in terms of different conditions in train scheduling environments. To construct the feasible train schedule, the proposed SE algorithm consists of many individual modules including the feasibility-satisfaction procedure, time-determination procedure, tune-up procedure and conflict-resolve procedure algorithms. To find a good train schedule, a two-stage hybrid heuristic algorithm called the SE-BIH algorithm is developed by combining the constructive heuristic (i.e. the SE algorithm) and the local-search heuristic (i.e. the Best-Insertion- Heuristic algorithm). To optimise the train schedule, a three-stage algorithm called the SE-BIH-TS algorithm is developed by combining the tabu search (TS) metaheuristic with the SE-BIH algorithm. Finally, a case study is performed for a complex real-world coal rail network under network and terminal capacity constraints. The computational results validate that the proposed methodology would be very promising because it can be applied as a fundamental tool for modelling and solving many real-world scheduling problems.