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

Validating denial of service vulnerabilities in web services

The loosely-coupled and dynamic nature of web services architectures has many benefits, but also leads to an increased vulnerability to denial of service attacks. While many papers have surveyed and described these vulnerabilities, they are often theoretical and lack experimental data to validate them, and assume an obsolete state of web services technologies. This paper describes experiments involving several denial of service vulnerabilities in well-known web services platforms, including Java Metro, Apache Axis, and Microsoft .NET. The results both confirm and deny the presence of some of the most well-known vulnerabilities in web services technologies. Specifically, major web services platforms appear to cope well with attacks that target memory exhaustion. However, attacks targeting CPU-time exhaustion are still effective, regardless of the victim’s platform.

Analysis of distrubances in large interconnected power systems

World economies increasingly demand reliable and economical power supply and distribution. To achieve this aim the majority of power systems are becoming interconnected, with several power utilities supplying the one large network. One problem that occurs in a large interconnected power system is the regular occurrence of system disturbances which can result in the creation of intra-area oscillating modes. These modes can be regarded as the transient responses of the power system to excitation, which are generally characterised as decaying sinusoids. For a power system operating ideally these transient responses would ideally would have a “ring-down” time of 10-15 seconds. Sometimes equipment failures disturb the ideal operation of power systems and oscillating modes with ring-down times greater than 15 seconds arise. The larger settling times associated with such “poorly damped” modes cause substantial power flows between generation nodes, resulting in significant physical stresses on the power distribution system. If these modes are not just poorly damped but “negatively damped”, catastrophic failures of the system can occur. To ensure system stability and security of large power systems, the potentially dangerous oscillating modes generated from disturbances (such as equipment failure) must be quickly identified. The power utility must then apply appropriate damping control strategies. In power system monitoring there exist two facets of critical interest. The first is the estimation of modal parameters for a power system in normal, stable, operation. The second is the rapid detection of any substantial changes to this normal, stable operation (because of equipment breakdown for example). Most work to date has concentrated on the first of these two facets, i.e. on modal parameter estimation. Numerous modal parameter estimation techniques have been proposed and implemented, but all have limitations [1-13]. One of the key limitations of all existing parameter estimation methods is the fact that they require very long data records to provide accurate parameter estimates. This is a particularly significant problem after a sudden detrimental change in damping. One simply cannot afford to wait long enough to collect the large amounts of data required for existing parameter estimators. Motivated by this gap in the current body of knowledge and practice, the research reported in this thesis focuses heavily on rapid detection of changes (i.e. on the second facet mentioned above). This thesis reports on a number of new algorithms which can rapidly flag whether or not there has been a detrimental change to a stable operating system. It will be seen that the new algorithms enable sudden modal changes to be detected within quite short time frames (typically about 1 minute), using data from power systems in normal operation. The new methods reported in this thesis are summarised below. The Energy Based Detector (EBD): The rationale for this method is that the modal disturbance energy is greater for lightly damped modes than it is for heavily damped modes (because the latter decay more rapidly). Sudden changes in modal energy, then, imply sudden changes in modal damping. Because the method relies on data from power systems in normal operation, the modal disturbances are random. Accordingly, the disturbance energy is modelled as a random process (with the parameters of the model being determined from the power system under consideration). A threshold is then set based on the statistical model. The energy method is very simple to implement and is computationally efficient. It is, however, only able to determine whether or not a sudden modal deterioration has occurred; it cannot identify which mode has deteriorated. For this reason the method is particularly well suited to smaller interconnected power systems that involve only a single mode. Optimal Individual Mode Detector (OIMD): As discussed in the previous paragraph, the energy detector can only determine whether or not a change has occurred; it cannot flag which mode is responsible for the deterioration. The OIMD seeks to address this shortcoming. It uses optimal detection theory to test for sudden changes in individual modes. In practice, one can have an OIMD operating for all modes within a system, so that changes in any of the modes can be detected. Like the energy detector, the OIMD is based on a statistical model and a subsequently derived threshold test. The Kalman Innovation Detector (KID): This detector is an alternative to the OIMD. Unlike the OIMD, however, it does not explicitly monitor individual modes. Rather it relies on a key property of a Kalman filter, namely that the Kalman innovation (the difference between the estimated and observed outputs) is white as long as the Kalman filter model is valid. A Kalman filter model is set to represent a particular power system. If some event in the power system (such as equipment failure) causes a sudden change to the power system, the Kalman model will no longer be valid and the innovation will no longer be white. Furthermore, if there is a detrimental system change, the innovation spectrum will display strong peaks in the spectrum at frequency locations associated with changes. Hence the innovation spectrum can be monitored to both set-off an “alarm” when a change occurs and to identify which modal frequency has given rise to the change. The threshold for alarming is based on the simple Chi-Squared PDF for a normalised white noise spectrum [14, 15]. While the method can identify the mode which has deteriorated, it does not necessarily indicate whether there has been a frequency or damping change. The PPM discussed next can monitor frequency changes and so can provide some discrimination in this regard. The Polynomial Phase Method (PPM): In [16] the cubic phase (CP) function was introduced as a tool for revealing frequency related spectral changes. This thesis extends the cubic phase function to a generalised class of polynomial phase functions which can reveal frequency related spectral changes in power systems. A statistical analysis of the technique is performed. When applied to power system analysis, the PPM can provide knowledge of sudden shifts in frequency through both the new frequency estimate and the polynomial phase coefficient information. This knowledge can be then cross-referenced with other detection methods to provide improved detection benchmarks.

Modelling photochemical production of fine particulates in a toluene/NOx/water vapour system

This work investigates the computer modelling of the photochemical formation of smog products such as ozone and aerosol, in a system containing toluene, NOx and water vapour. In particular, the problem of modelling this process in the Commonwealth Scientific and Industrial Research Organization (CSIRO) smog chambers, which utilize outdoor exposure, is addressed. The primary requirement for such modelling is a knowledge of the photolytic rate coefficients. Photolytic rate coefficients of species other than N02 are often related to JNo2 (rate coefficient for the photolysis ofN02) by a simple factor, but for outdoor chambers, this method is prone to error as the diurnal profiles may not be similar in shape. Three methods for the calculation of diurnal JNo2 are investigated. The most suitable method for incorporation into a general model, is found to be one which determines the photolytic rate coefficients for N02, as well as several other species, from actinic flux, absorption cross section and quantum yields. A computer model was developed, based on this method, to calculate in-chamber photolysis rate coefficients for the CSIRO smog chambers, in which ex-chamber rate coefficients are adjusted by accounting for variation in light intensity by transmittance through the Teflon walls, albedo from the chamber floor and radiation attenuation due to clouds. The photochemical formation of secondary aerosol is investigated in a series of toluene-NOx experiments, which were performed in the CSIRO smog chambers. Three stages of aerosol formation, in plots of total particulate volume versus time, are identified: a delay period in which no significant mass of aerosol is formed, a regime of rapid aerosol formation (regime 1) and a second regime of slowed aerosol formation (regime 2). Two models are presented which were developed from the experimental data. One model is empirically based on observations of discrete stages of aerosol formation and readily allows aerosol growth profiles to be calculated. The second model is based on an adaptation of published toluene photooxidation mechanisms and provides some chemical information about the oxidation products. Both models compare favorably against the experimental data. The gross effects of precursor concentrations (toluene, NOx and H20) and ambient conditions (temperature, photolysis rate) on the formation of secondary aerosol are also investigated, primarily using the mechanism model. An increase in [NOx]o results in increased delay time, rate of aerosol formation in regime 1 and volume of aerosol formed in regime 1. This is due to increased formation of dinitrocresol and furanone products. An increase in toluene results in a decrease in the delay time and an increase in the rate of aerosol formation in regime 1, due to enhanced reactivity from the toluene products, such as the radicals from the photolysis of benzaldehyde. Water vapor has very little effect on the formation of aerosol volume, except that rates are slightly increased due to more OH radicals from reaction with 0(1D) from ozone photolysis. Increased temperature results in increased volume of aerosol formed in regime 1 (increased dinitrocresol formation), while increased photolysis rate results in increased rate of aerosol formation in regime 1. Both the rate and volume of aerosol formed in regime 2 are increased by increased temperature or photolysis rate. Both models indicate that the yield of secondary particulates from hydrocarbons (mass concentration aerosol formed/mass concentration hydrocarbon precursor) is proportional to the ratio [NOx]0/[hydrocarbon]0

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.

Crosstalk between developmental and tumour-specific signalling pathways : kallikrein-related serine peptidases and nodal in prostrate cancer

Prostate cancer is an important male health issue. The strategies used to diagnose and treat prostate cancer underscore the cell and molecular interactions that promote disease progression. Prostate cancer is histologically defined by increasingly undifferentiated tumour cells and therapeutically targeted by androgen ablation. Even as the normal glandular architecture of the adult prostate is lost, prostate cancer cells remain dependent on the androgen receptor (AR) for growth and survival. This project focused on androgen-regulated gene expression, altered cellular differentiation, and the nexus between these two concepts. The AR controls prostate development, homeostasis and cancer progression by regulating the expression of downstream genes. Kallikrein-related serine peptidases are prominent transcriptional targets of AR in the adult prostate. Kallikrein 3 (KLK3), which is commonly referred to as prostate-specific antigen, is the current serum biomarker for prostate cancer. Other kallikreins are potential adjunct biomarkers. As secreted proteases, kallikreins act through enzyme cascades that may modulate the prostate cancer microenvironment. Both as a panel of biomarkers and cascade of proteases, the roles of kallikreins are interconnected. Yet the expression and regulation of different kallikreins in prostate cancer has not been compared. In this study, a spectrum of prostate cell lines was used to evaluate the expression profile of all 15 members of the kallikrein family. A cluster of genes was co-ordinately expressed in androgenresponsive cell lines. This group of kallikreins included KLK2, 3, 4 and 15, which are located adjacent to one another at the centromeric end of the kallikrein locus. KLK14 was also of interest, because it was ubiquitously expressed among the prostate cell lines. Immunohistochemistry showed that these 5 kallikreins are co-expressed in benign and malignant prostate tissue. The androgen-regulated expression of KLK2 and KLK3 is well-characterised, but has not been compared with other kallikreins. Therefore, KLK2, 3, 4, 14 and 15 expression were all measured in time course and dose response experiments with androgens, AR-antagonist treatments, hormone deprivation experiments and cells transfected with AR siRNA. Collectively, these experiments demonstrated that prostatic kallikreins are specifically and directly regulated by the AR. The data also revealed that kallikrein genes are differentially regulated by androgens; KLK2 and KLK3 were strongly up-regulated, KLK4 and KLK15 were modestly up-regulated, and KLK14 was repressed. Notably, KLK14 is located at the telomeric end of the kallikrein locus, far away from the centromeric cluster of kallikreins that are stimulated by androgens. These results show that the expression of KLK2, 3, 4, 14 and 15 is maintained in prostate cancer, but that these genes exhibit different responses to androgens. This makes the kallikrein locus an ideal model to investigate AR signalling. The increasingly dedifferentiated phenotype of aggressive prostate cancer cells is accompanied by the re-expression of signalling molecules that are usually expressed during embryogenesis and foetal tissue development. The Wnt pathway is one developmental cascade that is reactivated in prostate cancer. The canonical Wnt cascade regulates the intracellular levels of β-catenin, a potent transcriptional co-activator of T-cell factor (TCF) transcription factors. Notably, β-catenin can also bind to the AR and synergistically stimulate androgen-mediated gene expression. This is at the expense of typical Wnt/TCF target genes, because the AR:β-catenin and TCF:β-catenin interactions are mutually exclusive. The effect of β-catenin on kallikrein expression was examined to further investigate the role of β-catenin in prostate cancer. Stable knockdown of β-catenin in LNCaP prostate cancer cells attenuated the androgen-regulated expression of KLK2, 3, 4 and 15, but not KLK14. To test whether KLK14 is instead a TCF:β-catenin target gene, the endogenous levels of β-catenin were increased by inhibiting its degradation. Although KLK14 expression was up-regulated by these treatments, siRNA knockdown of β-catenin demonstrated that this effect was independent of β-catenin. These results show that β-catenin is required for maximal expression of KLK2, 3, 4 and 15, but not KLK14. Developmental cells and tumour cells express a similar repertoire of signalling molecules, which means that these different cell types are responsive to one another. Previous reports have shown that stem cells and foetal tissues can reprogram aggressive cancer cells to less aggressive phenotypes by restoring the balance to developmental signalling pathways that are highly dysregulated in cancer. To investigate this phenomenon in prostate cancer, DU145 and PC-3 prostate cancer cells were cultured on matrices pre-conditioned with human embryonic stem cells (hESCs). Soft agar assays showed that prostate cancer cells exposed to hESC conditioned matrices had reduced clonogenicity compared with cells harvested from control matrices. A recent study demonstrated that this effect was partially due to hESC-derived Lefty, an antagonist of Nodal. A member of the transforming growth factor β (TGFβ) superfamily, Nodal regulates embryogenesis and is re-expressed in cancer. The role of Nodal in prostate cancer has not previously been reported. Therefore, the expression and function of the Nodal signalling pathway in prostate cancer was investigated. Western blots confirmed that Nodal is expressed in DU145 and PC-3 cells. Immunohistochemistry revealed greater expression of Nodal in malignant versus benign glands. Notably, the Nodal inhibitor, Lefty, was not expressed at the mRNA level in any prostate cell lines tested. The Nodal signalling pathway is functionally active in prostate cancer cells. Recombinant Nodal treatments triggered downstream phosphorylation of Smad2 in DU145 and LNCaP cells, and stably-transfected Nodal increased the clonogencity of LNCaP cells. Nodal was also found to modulate AR signalling. Nodal reduced the activity of an androgen-regulated KLK3 promoter construct in luciferase assays and attenuated the endogenous expression of AR target genes including prostatic kallikreins. These results demonstrate that Nodal is a novel example of a developmental signalling molecule that is reexpressed in prostate cancer and may have a functional role in prostate cancer progression. In summary, this project clarifies the role of androgens and changing cellular differentiation in prostate cancer by characterising the expression and function of the downstream genes encoding kallikrein-related serine proteases and Nodal. Furthermore, this study emphasises the similarities between prostate cancer and early development, and the crosstalk between developmental signalling pathways and the AR axis. The outcomes of this project also affirm the utility of the kallikrein locus as a model system to monitor tumour progression and the phenotype of prostate cancer cells.

Some applications of logic to feasibility in higher types

While it is commonly accepted that computability on a Turing machine in polynomial time represents a correct formalization of the notion of a feasibly computable function, there is no similar agreement on how to extend this notion on functionals, that is, what functionals should be considered feasible. One possible paradigm was introduced by Mehlhorn, who extended Cobham's definition of feasible functions to type 2 functionals. Subsequently, this class of functionals (with inessential changes of the definition) was studied by Townsend who calls this class POLY, and by Kapron and Cook who call the same class basic feasible functionals. Kapron and Cook gave an oracle Turing machine model characterisation of this class. In this article, we demonstrate that the class of basic feasible functionals has recursion theoretic properties which naturally generalise the corresponding properties of the class of feasible functions, thus giving further evidence that the notion of feasibility of functionals mentioned above is correctly chosen. We also improve the Kapron and Cook result on machine representation.Our proofs are based on essential applications of logic. We introduce a weak fragment of second order arithmetic with second order variables ranging over functions from NN which suitably characterises basic feasible functionals, and show that it is a useful tool for investigating the properties of basic feasible functionals. In particular, we provide an example how one can extract feasible programs from mathematical proofs that use nonfeasible functions.

A grounded theory study of technology appropriation in anaesthesia

The human-technology nexus is a strong focus of Information Systems (IS) research; however, very few studies have explored this phenomenon in anaesthesia. Anaesthesia has a long history of adoption of technological artifacts, ranging from early apparatus to present-day information systems such as electronic monitoring and pulse oximetry. This prevalence of technology in modern anaesthesia and the rich human-technology relationship provides a fertile empirical setting for IS research. This study employed a grounded theory approach that began with a broad initial guiding question and, through simultaneous data collection and analysis, uncovered a core category of technology appropriation. This emergent basic social process captures a central activity of anaesthestists and is supported by three major concepts: knowledge-directed medicine, complementary artifacts and culture of anaesthesia. The outcomes of this study are: (1) a substantive theory that integrates the aforementioned concepts and pertains to the research setting of anaesthesia and (2) a formal theory, which further develops the core category of appropriation from anaesthesia-specific to a broader, more general perspective. These outcomes fulfill the objective of a grounded theory study, being the formation of theory that describes and explains observed patterns in the empirical field. In generalizing the notion of appropriation, the formal theory is developed using the theories of Karl Marx. This Marxian model of technology appropriation is a three-tiered theoretical lens that examines appropriation behaviours at a highly abstract level, connecting the stages of natural, species and social being to the transition of a technology-as-artifact to a technology-in-use via the processes of perception, orientation and realization. The contributions of this research are two-fold: (1) the substantive model contributes to practice by providing a model that describes and explains the human-technology nexus in anaesthesia, and thereby offers potential predictive capabilities for designers and administrators to optimize future appropriations of new anaesthetic technological artifacts; and (2) the formal model contributes to research by drawing attention to the philosophical foundations of appropriation in the work of Marx, and subsequently expanding the current understanding of contemporary IS theories of adoption and appropriation.

Repair of calvarial defects with customized tissue-engineered bone grafts - I. Evaluation of osteogenesis in a three-dimensional culture system

Bone generation by autogenous cell transplantation in combination with a biodegradable scaffold is one of the most promising techniques being developed in craniofacial surgery. The objective of this combined in vitro and in vivo study was to evaluate the morphology and osteogenic differentiation of bone marrow derived mesenchymal progenitor cells and calvarial osteoblasts in a two-dimensional (2-D) and three-dimensional (3-D) culture environment (Part I of this study) and their potential in combination with a biodegradable scaffold to reconstruct critical-size calvarial defects in an autologous animal model [Part II of this study; see Schantz, J.T., et al. Tissue Eng. 2003;9(Suppl. 1):S-127-S-139; this issue]. New Zealand White rabbits were used to isolate osteoblasts from calvarial bone chips and bone marrow stromal cells from iliac crest bone marrow aspirates. Multilineage differentiation potential was evaluated in a 2-D culture setting. After amplification, the cells were seeded within a fibrin matrix into a 3-D polycaprolactone (PCL) scaffold system. The constructs were cultured for up to 3 weeks in vitro and assayed for cell attachment and proliferation using phase-contrast light, confocal laser, and scanning electron microscopy and the MTS cell metabolic assay. Osteogenic differentiation was analyzed by determining the expression of alkaline phosphatase (ALP) and osteocalcin. The bone marrow-derived progenitor cells demonstrated the potential to be induced to the osteogenic, adipogenic, and chondrogenic pathways. In a 3-D environment, cell-seeded PCL scaffolds evaluated by confocal laser microscopy revealed continuous cell proliferation and homogeneous cell distribution within the PCL scaffolds. On osteogenic induction mesenchymal progenitor cells (12 U/L) produce significantly higher (p < 0.05) ALP activity than do osteoblasts (2 U/L); however, no significant differences were found in osteocalcin expression. In conclusion, this study showed that the combination of a mechanically stable synthetic framework (PCL scaffolds) and a biomimetic hydrogel (fibrin glue) provides a potential matrix for bone tissue-engineering applications. Comparison of osteogenic differentiation between the two mesenchymal cell sources revealed a similar pattern.

A novel winding structure in planar inductors to decrease the overall capacitive couplings

This paper presents a new method for winding configuration in planar magnetic elements with more than two layers. It has been proven by 3D Finite Element method and mathematical modeling that this suggested configuration results in reduction of the equivalent capacitive coupling in the planar inductor

A framework for improved adolescent and child safety in MMOs

This paper presents an approach to providing better safety for adolescents playing online games. We highlight an emerging paedophile presence in online games and offer a general framework for the design of monitoring and alerting tools. Our method is to monitor and detect relationships forming with a child in online games, and alert if the relationship indicates an offline meeting with the child has been arranged or has the potential to occur. A prototype implementation with demonstrative components of the framework has been created and is introduced. The prototype demonstration and evaluation uses a teen rated online relationship-building environment for its case study, specifically the predominant Massive Multiplayer Online Game (MMO) World of Warcraft.

Geekdom for Grrrls health : Australian undergraduate experiences developing and promoting women’s health in cyberspace

There is an increasing global reliance on the Internet for retrieving information on health, illness, and recovery (Sillence et al, 2007; Laurent et al, 2009; Adams, 2010). People suffering from a vast array of illnesses, conditions, and complaints, as well as healthy travelers seeking advice about safe practices abroad, and teens seeking information about safe sexual practices are all now more likely to go to the internet for information than they are to rely solely on a general practitioner or physician (Santor et al, 2007; Moreno et al, 2009; Bartlett et al, 2010). Women in particular seek advice and support online for a number of health-related concerns regarding issues such as puberty, conception, pregnancy, postnatal depression, mothering, breast-cancer recovery, and ageing healthily (van Zutphen, 2008; Raymond et al, 2005). In keeping with this increasing socio-technological trend, the Women’s Health Unit at the Queensland University of Technology (Q.U.T), Brisbane, Australia, introduced the research, design, and development of online information resources for issues affecting the health of Australian women as an assessment item for students in the undergraduate Public Health curriculum. Students were required to research a particular health issue affecting Australian women, including pregnancy, pregnancy terminations, postnatal depression, returning to the work force after having a baby, breast cancer recovery, chronic disease prevention, health and safety for sex-workers, and ageing healthily. Students were required to design and develop websites that supported people living with these conditions, or who were in these situations. The websites were designed for communicating effectively with both women seeking information about their health, and their health practitioners. The pedagogical challenge inherent in this exercise was twofold: firstly, to encourage students to develop the skills to design and maintain software for online health forums; and secondly, to challenge public health students to go beyond generating ‘awareness’ and imparting health information to developing a nuanced understanding of the worlds and perspectives of their audiences, who require supportive networks and options that resonate with their restrictions, capabilities, and dispositions. This latter challenge spanned the realms of research, communication, and aesthetic design. This paper firstly, discusses an increasing reliance on the Internet by women seeking health-related information and the potential health risks and benefits of this trend. Secondly, it applies a post-structural analysis of the de-centred and mobile female self, as online social ‘spaces’ and networks supersede geographical ‘places’ and hierarchies, with implications for democracy, equality, power, and ultimately women’s health. Thirdly, it depicts the processes (learning reflections) and products (developed websites) created within this Women’s Health Unit by the students. Finally, we review this development in the undergraduate curriculum in terms of the importance of providing students with skills in research, communication, and technology in order to share and implement improved health care and social marketing for women as both recipients and providers of health care in the Internet Age.

Optimal track access rights allocation for agent negotiation in an open railway market

In open railway access markets, a train service provider (TSP) negotiates with an infrastructure provider (IP) for track access rights. This negotiation has been modeled by a multi-agent system (MAS) in which the IP and TSP are represented by separate software agents. One task of the IP agent is to generate feasible (and preferably optimal) track access rights, subject to the constraints submitted by the TSP agent. This paper formulates an IP-TSP transaction and proposes a branch-and-bound algorithm for the IP agent to identify the optimal track access rights. Empirical simulation results show that the model is able to emulate rational agent behaviors. The simulation results also show good consistency between timetables attained from the proposed methods and those derived by the scheduling principles adopted in practice.

Fuzzy logic power system stabilizer in multimachine stability studies

Power system stabilizers (PSS) work well at the particular network configuration and steady state conditions for which they were designed. Once conditions change, their performance degrades. This can be overcome by an intelligent nonlinear PSS based on fuzzy logic. Such a fuzzy logic power system stabilizer (FLPSS) is developed, using speed and power deviation as inputs, and provides an auxiliary signal for the excitation system of a synchronous motor in a multimachine power system environment. The FLPSS's effect on the system damping is then compared with a conventional power system stabilizer's (CPSS) effect on the system. The results demonstrate an improved system performance with the FLPSS and also that the FLPSS is robust

Invention and business performance in the tissue-engineering industry

Tissue engineering is a young and interdisciplinary scientific discipline but it offers exciting opportunities to improve the quality of health care for hundreds of thousands of patients. Lured by its potential, several start-up companies, pharmaceutical corporations, and medical device enterprises alike are investing heavily in this sector. Invention is a key driver of competition in this sector. In this study, we aim to explain the variation in inventive output across the different firms in the sector. Our major premise is that firms that forge alliances will be able to tap into the expertise of their partners and thus improve their chances of inventive output. We further argue that alliances that enable technology acquisition or learning will enhance the inventive output of firms more than other kinds of alliances. We measure the inventive output of a company by the number of patents filed. On the basis of a preliminary analysis of seven companies, we find support for the hypotheses. We also argue that, to achieve commercial success, firms need to manage time to market (through alliances or otherwise), have a global outlook, nurture their financial resources, and attain critical mass through mergers.