Androgen levels increase by intratumoral de novo steroidogenesis during progression of castration-resistant prostate cancer

Although systemic androgen deprivation prolongs life in advanced prostate cancer, remissions are temporary because patients almost uniformly progress to a state of a castration-resistant prostate cancer (CRPC) as indicated by recurring PSA. This complex process of progression does not seem to be stochastic as the timing and phenotype are highly predictable, including the observation that most androgen-regulated genes are reactivated despite castrate levels of serum androgens. Recent evidence indicates that intraprostatic levels of androgens remain moderately high following systemic androgen deprivation therapy, whereas the androgen receptor (AR) remains functional, and silencing the AR expression following castration suppresses tumor growth and blocks the expression of genes known to be regulated by androgens. From these observations, we hypothesized that CRPC progression is not independent of androgen-driven activity and that androgens may be synthesized de novo in CRPC tumors leading to AR activation. Using the LNCaP xenograft model, we showed that tumor androgens increase during CRPC progression in correlation to PSA up-regulation. We show here that all enzymes necessary for androgen synthesis are expressed in prostate cancer tumors and some seem to be up-regulated during CRPC progression. Using an ex vivo radiotracing assays coupled to high-performance liquid chromatography-radiometric/mass spectrometry detection, we show that tumor explants isolated from CRPC progression are capable of de novo conversion of [(14)C]acetic acid to dihydrotestosterone and uptake of [(3)H]progesterone allows detection of the production of six other steroids upstream of dihydrotestosterone. This evidence suggests that de novo androgen synthesis may be a driving mechanism leading to CRPC progression following castration.

Required hours of practice for learner drivers : a comparison between two Australian jurisdictions

Problem: This study considers whether requiring learner drivers to complete a set number of hours while on a learner licence affects the amount of hours of supervised practice that they undertake. It compares the amount of practice that learners in Queensland and New South Wales report undertaking. At the time the study was conducted, learner drivers in New South Wales were required to complete 50 hours of supervised practice while those from Queensland were not. Method: Participants were approached outside driver licensing centres after they had just completed their practical driving test to obtain their provisional (intermediate) licence. Those agreeing to participate were interviewed over the phone later and asked a range of questions to obtain information including socio-demographic details and amount of supervised practice completed. Results: There was a significant difference in the amount of practice that learners reported undertaking. Participants from New South Wales reported completing a significantly greater amount of practice (M = 73.3 hours, sd = 29.12 hours) on their learner licence than those from Queensland (M = 64.1 hours, sd = 51.05 hours). However, the distribution of hours of practice among the Queensland participants was bimodal in nature. Participants from Queensland reported either completing much less or much more practice than the New South Wales average. Summary: While it appears that the requirement that learner drivers complete a set number of hours may increase the average amount of hours of practice obtained, it may also serve to discourage drivers from obtaining additional practice, over and above the required hours. Impact on Industry: The results of this study suggest that the implications of requiring learner drivers to complete a set number of hours of supervised practice are complex. In some cases, policy makers may inadvertently limit the amount of hours learners obtain to the mandated amount rather than encouraging them to obtain as much practice as possible.

Submission to Travelsafe : vehicle impoundment for drink drivers

This submission has been prepared in response to the Parliamentary Travelsafe Committee's Inquiry into vehicle impoundment for drink drivers to address research relevant to the committee’s investigation into whether: • Drink drivers in Queensland continue to drive illegally after being apprehended by police or disqualified from driving by the courts; • The incidence of repeat drink driving undermines the effectiveness of existing penalties for drink driving offences; and • Vehicle impoundment and/or ignition key confiscation are cost-effective deterrents that will reduce drink driving recidivism, relating to other existing or potential methods of managing offenders.

The speed paradox : the misalignment between driver attitudes and speeding behaviour

This paper reports on a study investigating preferred driving speeds and frequency of speeding of 320 Queensland drivers. Despite growing community concern about speeding and extensive research linking it to road trauma, speeding remains a pervasive, and arguably, socially acceptable behaviour. This presents an apparent paradox regarding the mismatch between beliefs and behaviours, and highlights the necessity to better understand the factors contributing to speeding. Utilising self-reported behaviour and attitudinal measures, results of this study support the notion of a speed paradox. Two thirds of participants agreed that exceeding the limit is not worth the risks nor is it okay to exceed the posted limit. Despite this, more than half (58.4%) of the participants reported a preference to exceed the 100km/hour speed limit, with one third preferring to do so by 10 to 20 km/hour. Further, mean preferred driving speeds on both urban and open roads suggest a perceived enforcement tolerance of 10%, suggesting that posted limits have limited direct influence on speed choice. Factors that significantly predicted the frequency of speeding included: exposure to role models who speed; favourable attitudes to speeding; experiences of punishment avoidance; and the perceived certainty of punishment for speeding. These findings have important policy implications, particularly relating to the use of enforcement tolerances.

Impact of cognitive load and frustration on drivers’ speech [Abstract]

Secondary tasks such as cell phone calls or interaction with automated speech dialog systems (SDSs) increase the driver’s cognitive load as well as the probability of driving errors. This study analyzes speech production variations due to cognitive load and emotional state of drivers in real driving conditions. Speech samples were acquired from 24 female and 17 male subjects (approximately 8.5 h of data) while talking to a co-driver and communicating with two automated call centers, with emotional states (neutral, negative) and the number of necessary SDS query repetitions also labeled. A consistent shift in a number of speech production parameters (pitch, first format center frequency, spectral center of gravity, spectral energy spread, and duration of voiced segments) was observed when comparing SDS interaction against co-driver interaction; further increases were observed when considering negative emotion segments and the number of requested SDS query repetitions. A mel frequency cepstral coefficient based Gaussian mixture classifier trained on 10 male and 10 female sessions provided 91% accuracy in the open test set task of distinguishing co-driver interactions from SDS interactions, suggesting—together with the acoustic analysis—that it is possible to monitor the level of driver distraction directly from their speech.

Head and eye movements and lane keeping in drivers with hemianopia and quadrantanopia compared to controls

Purpose: To compare the eye and head movements and lane-keeping of drivers with hemianopia and quadrantanopia with that of age-matched controls when driving under real world conditions. Methods: Participants included 22 hemianopes and 8 quadrantanopes (M age 53 yrs) and 30 persons with normal visual fields (M age 52 yrs) who were ≥ 6 months from the brain injury date and either a current driver or aiming to resume driving. All participants drove an instrumented dual-brake vehicle along a 14-mile route in traffic that included non-interstate city driving and interstate driving. Driving performance was scored using a standardised assessment system by two “backseat” raters and the Vigil Vanguard system which provides objective measures of speed, braking and acceleration, cornering, and video-based footage from which eye and head movements and lane-keeping can be derived. Results: As compared to drivers with normal visual fields, drivers with hemianopia or quadrantanopia on average were significantly more likely to drive slower, to exhibit less excessive cornering forces or acceleration, and to execute more shoulder movements off the seat. Those hemianopic and quadrantanopic drivers rated as safe to drive by the backseat evaluator made significantly more excursive eye movements, exhibited more stable lane positioning, less sudden braking events and drove at higher speeds than those rated as unsafe, while there was no difference between safe and unsafe drivers in head movements. Conclusions: Persons with hemianopic and quadrantanopic field defects rated as safe to drive have different driving characteristics compared to those rated as unsafe when assessed using objective measures of driving performance.

Curriculum design innovation in flexible science teaching

In this paper you will be introduced to a number of principles which can be used to inform good teaching practice and rigorous curriculum design. Principles relate to: * Application of a common sequence of events for how learners learn; * Accommodating different learning styles; * Adopting a purposeful approach to teaching and learning; * Using assessment as a central driving force in the curriculum and as an organising structure leading to coherence of teaching and learning approach; and * The increasing emphasis that is being placed on the development of generic graduate competencies over and above discipline content knowledge. The principles are particularly significant in relation to adult learning. The paper will use three specific applications as illustrations to help you to learn how these principles can be applied. The illustrations are taken from a second year subject in supercomputing that uses scientific case studies. The subject has been developed (with support from Silicon Graphics Inc. and Intel) to be taught entirely via the Internet.

Investigation of highly regulated promoters for the production of recombinant proteins in plants

Plants have been identified as promising expression systems for the commercial production of recombinant proteins. Plant-based protein production or “biofarming” offers a number of advantages over traditional expression systems in terms of scale of production, the capacity for post-translation processing, providing a product free of contaminants and cost effectiveness. A number of pharmaceutically important and commercially valuable proteins, such as antibodies, biopharmaceuticals and industrial enzymes are currently being produced in plant expression systems. However, several challenges still remain to improve recombinant protein yield with no ill effect on the host plant. The ability for transgenic plants to produce foreign proteins at commercially viable levels can be directly related to the level and cell specificity of the selected promoter driving the transgene. The accumulation of recombinant proteins may be controlled by a tissue-specific, developmentally-regulated or chemically-inducible promoter such that expression of recombinant proteins can be spatially- or temporally- controlled. The strict control of gene expression is particularly useful for proteins that are considered toxic and whose expression is likely to have a detrimental effect on plant growth. To date, the most commonly used promoter in plant biotechnology is the cauliflower mosaic virus (CaMV) 35S promoter which is used to drive strong, constitutive transgene expression in most organs of transgenic plants. Of particular interest to researchers in the Centre for Tropical Crops and Biocommodities at QUT are tissue-specific promoters for the accumulation of foreign proteins in the roots, seeds and fruit of various plant species, including tobacco, banana and sugarcane. Therefore this Masters project aimed to isolate and characterise root- and seed-specific promoters for the control of genes encoding recombinant proteins in plant-based expression systems. Additionally, the effects of matching cognate terminators with their respective gene promoters were assessed. The Arabidopsis root promoters ARSK1 and EIR1 were selected from the literature based on their reported limited root expression profiles. Both promoters were analysed using the PlantCARE database to identify putative motifs or cis-acting elements that may be associated with this activity. A number of motifs were identified in the ARSK1 promoter region including, WUN (wound-inducible), MBS (MYB binding site), Skn-1, and a RY core element (seed-specific) and in the EIR1 promoter region including, Skn-1 (seed-specific), Box-W1 (fungal elicitor), Aux-RR core (auxin response) and ABRE (ABA response). However, no previously reported root-specific cis-acting elements were observed in either promoter region. To confirm root specificity, both promoters, and truncated versions, were fused to the GUS reporter gene and the expression cassette introduced into Arabidopsis via Agrobacterium-mediated transformation. Despite the reported tissue-specific nature of these promoters, both upstream regulatory regions directed constitutive GUS expression in all transgenic plants. Further, similar levels of GUS expression from the ARSK1 promoter were directed by the control CaMV 35S promoter. The truncated version of the EIR1 promoter (1.2 Kb) showed some differences in the level of GUS expression compared to the 2.2 Kb promoter. Therefore, this suggests an enhancer element is contained in the 2.2 Kb upstream region that increases transgene expression. The Arabidopsis seed-specific genes ATS1 and ATS3 were selected from the literature based on their seed-specific expression profiles and gene expression confirmed in this study as seed-specific by RT-PCR analysis. The selected promoter regions were analysed using the PlantCARE database in order to identify any putative cis elements. The seed-specific motifs GCN4 and Skn-1 were identified in both promoter regions that are associated with elevated expression levels in the endosperm. Additionaly, the seed-specific RY element and the ABRE were located in the ATS1 promoter. Both promoters were fused to the GUS reporter gene and used to transform Arabidopsis plants. GUS expression from the putative promoters was consitutive in all transgenic Arabidopsis tissue tested. Importantly, the positive control FAE1 seed-specific promoter also directed constitutive GUS expression throughout transgenic Arabidopsis plants. The constitutive nature seen in all of the promoters used in this study was not anticipated. While variations in promoter activity can be caused by a number of influencing factors, the variation in promoter activity observed here would imply a major contributing factor common to all plant expression cassettes tested. All promoter constructs generated in this study were based on the binary vector pCAMBIA2300. This vector contains the plant selection gene (NPTII) under the transcriptional control of the duplicated CaMV 35S promoter. This CaMV 35S promoter contains two enhancer domains that confer strong, constitutive expression of the selection gene and is located immediately upstream of the promoter-GUS fusion. During the course of this project, Yoo et al. (2005) reported that transgene expression is significantly affected when the expression cassette is located on the same T-DNA as the 35S enhancer. It was concluded, the trans-acting effects of the enhancer activate and control transgene expression causing irregular expression patterns. This phenomenon seems the most plausible reason for the constitutive expression profiles observed with the root- and seed-specific promoters assessed in this study. The expression from some promoters can be influenced by their cognate terminator sequences. Therefore, the Arabidopsis ARSK1, EIR1, ATS1 and ATS3 terminator sequences were isolated and incorporated into expression cassettes containing the GUS reporter gene under the control of their cognate promoters. Again, unrestricted GUS activity was displayed throughout transgenic plants transformed with these reporter gene fusions. As previously discussed constitutive GUS expression was most likely due to the trans-acting effect of the upstream CaMV 35S promoter in the selection cassette located on the same T-DNA. The results obtained in this study make it impossible to assess the influence matching terminators with their cognate promoters have on transgene expression profiles. The obvious future direction of research continuing from this study would be to transform pBIN-based promoter-GUS fusions (ie. constructs containing no CaMV 35S promoter driving the plant selection gene) into Arabidopsis in order to determine the true tissue specificity of these promoters and evaluate the effects of their cognate 3’ terminator sequences. Further, promoter truncations based around the cis-elements identified here may assist in determining whether these motifs are in fact involved in the overall activity of the promoter.

The application of the Park & Ride and TOD concepts to develop a new framework that can maximise public transport patronage

With growing concern over the use of the car in our urbanized society, there have emerged a number of lobby groups and professional bodies promoting a return to public transport, walking and cycling, with the urban village as the key driving land use, as a means of making our cities’ transportation systems more sustainable. This research has aimed at developing a framework applicable to the Australian setting that can facilitate increased passenger patronage of rail based urban transport systems from adjacent or associated land uses. The framework specifically tested the application of the Park & Ride and Transit Oriented Development (TOD) concepts and their applicability within the cultural, institutional, political and transit operational characteristics of Australian society. The researcher found that, although the application of the TOD concept had been limited to small pockets of town houses and mixed use developments around stations, the development industry and emerging groups within the community are posed to embrace the concept and bring with it increased rail patronage. The lack of a clear commitment to infrastructure and supporting land uses is a major barrier to the implementation of TODs. The research findings demonstrated significant scope for the size of a TOD to expand to a much greater radius of activity from the public transport interchange, than the commonly quoted 400 to 600 meters, thus incorporating many more residents and potential patrons. The provision of Park & Rides, and associated support facilities like Kiss & Rides, have followed worldwide trends of high patronage demands from the middle and outer car dependent suburbs of our cities. The data collection and analysis gathered by the researcher demonstrated that in many cases Park & Rides should form part of a TOD to ensure ease of access to rail stations by all modes and patron types. The question, however, remains how best to plan the incorporation of a Park & Ride within a TOD and still maintain those features that attract and promote TODs as a living entity.

Benefits of collaborative ICT adoption for building project management

Purpose : Effective flow of data and communication at every stage of a construction project is essential for achieving required coordination and collaboration between the project participants, leading to successful management of the projects. In present scenario, when project participants are geographically separated, adoption of information communication technology (ICT) enables such effective communication. Thus, the purpose of this paper is to focus on ICT adoption for building project management.---------- Design/methodology/approach : It is difficult to quantitatively evaluate the benefits of ICT adoption in the multiple enterprise scenario of building project management. It requires qualitative analysis based on the perceptions of the construction professionals. The paper utilizes interpretive structural modeling (ISM) technique to assess importance of perceived benefits and their driving power and dependence on other benefits.---------- Findings : The developed ISM model shows that all the categories of benefits, i.e. benefits related to projects, team management, technology, and organization are inter-related and cannot be achieved in isolation. But, organization- and technology-related benefits have high-driving power and these are “strategic benefits” for the project team organizations. Thus, organizations are required to give more attention on strategically increasing these benefits from application of ICT. Originality/value – This analysis provides a road map to managers or project management organizations to decide that if they are planning ICT adoption for achieving certain benefits then which are the other driving benefits that should be achieved prior to that and also which are the dependent benefits that would be achieved by default.

Robust speech recognition using speech enhancement

Automatic Speech Recognition (ASR) has matured into a technology which is becoming more common in our everyday lives, and is emerging as a necessity to minimise driver distraction when operating in-car systems such as navigation and infotainment. In “noise-free” environments, word recognition performance of these systems has been shown to approach 100%, however this performance degrades rapidly as the level of background noise is increased. Speech enhancement is a popular method for making ASR systems more ro- bust. Single-channel spectral subtraction was originally designed to improve hu- man speech intelligibility and many attempts have been made to optimise this algorithm in terms of signal-based metrics such as maximised Signal-to-Noise Ratio (SNR) or minimised speech distortion. Such metrics are used to assess en- hancement performance for intelligibility not speech recognition, therefore mak- ing them sub-optimal ASR applications. This research investigates two methods for closely coupling subtractive-type enhancement algorithms with ASR: (a) a computationally-efficient Mel-filterbank noise subtraction technique based on likelihood-maximisation (LIMA), and (b) in- troducing phase spectrum information to enable spectral subtraction in the com- plex frequency domain. Likelihood-maximisation uses gradient-descent to optimise parameters of the enhancement algorithm to best fit the acoustic speech model given a word se- quence known a priori. Whilst this technique is shown to improve the ASR word accuracy performance, it is also identified to be particularly sensitive to non-noise mismatches between the training and testing data. Phase information has long been ignored in spectral subtraction as it is deemed to have little effect on human intelligibility. In this work it is shown that phase information is important in obtaining highly accurate estimates of clean speech magnitudes which are typically used in ASR feature extraction. Phase Estimation via Delay Projection is proposed based on the stationarity of sinusoidal signals, and demonstrates the potential to produce improvements in ASR word accuracy in a wide range of SNR. Throughout the dissertation, consideration is given to practical implemen- tation in vehicular environments which resulted in two novel contributions – a LIMA framework which takes advantage of the grounding procedure common to speech dialogue systems, and a resource-saving formulation of frequency-domain spectral subtraction for realisation in field-programmable gate array hardware. The techniques proposed in this dissertation were evaluated using the Aus- tralian English In-Car Speech Corpus which was collected as part of this work. This database is the first of its kind within Australia and captures real in-car speech of 50 native Australian speakers in seven driving conditions common to Australian environments.

Antecedents of importer relationship performance in Latin America

Emerging market importers are increasingly engaging in relationships with foreign suppliers. Nevertheless, characteristics of the institutional and cultural environments of countries may affect relationship behaviour. Furthermore research on relationship marketing primarily focuses on the marketing activities of exporters from developed countries and much less attention is paid to the import side of the exchange process. Thus, the objective of this study is to empirically examine importer relationship performance in a Latin America context. This article proposes and tests a conceptual model that includes the antecedents and outcomes of trust and commitment with a survey of Chilean importers. The model uses confirmatory factor analysis (CFA) to develop the construct measures and structural equation modelling (SEMS) to test the model. The findings of this study contribute to a better understanding of the driving forces of trust and commitments and their influence on importing firms' performance in an emerging market context.

Investigation of mechanisms governing emission of odorants

The literature identifies several models that describe inter-phase mass transfer, key to the emission process. While the emission process is complex and these models may be more or less successful at predicting mass transfer rates, they identify three key variables for a system involving a liquid and an air phase in contact with it: • A concentration (or partial pressure) gradient driving force; • The fluid dynamic characteristics within the liquid and air phases, and • The chemical properties of the individual components within the system. In three applied research projects conducted prior to this study, samples collected with two well-known sampling devices resulted in very different odour emission rates. It was not possible to adequately explain the differences observed. It appeared likely, however, that the sample collection device might have artefact effects on the emission of odorants, i.e. the sampling device appeared to have altered the mass transfer process. This raised the obvious question: Where two different emission rates are reported for a single source (differing only in the selection of sampling device), and a credible explanation for the difference in emission rate cannot be provided, which emission rate is correct? This research project aimed to identify the factors that determine odour emission rates, the impact that the characteristics of a sampling device may exert on the key mass transfer variables, and ultimately, the impact of the sampling device on the emission rate itself. To meet these objectives, a series of targeted reviews, and laboratory and field investigations, were conducted. Two widely-used, representative devices were chosen to investigate the influence of various parameters on the emission process. These investigations provided insight into the odour emission process generally, and the influence of the sampling device specifically.

Evolutionary algorithms for sustainable building design

This approach to sustainable design explores the possibility of creating an architectural design process which can iteratively produce optimised and sustainable design solutions. Driven by an evolution process based on genetic algorithms, the system allows the designer to “design the building design generator” rather than to “designs the building”. The design concept is abstracted into a digital design schema, which allows transfer of the human creative vision into the rational language of a computer. The schema is then elaborated into the use of genetic algorithms to evolve innovative, performative and sustainable design solutions. The prioritisation of the project’s constraints and the subsequent design solutions synthesised during design generation are expected to resolve most of the major conflicts in the evaluation and optimisation phases. Mosques are used as the example building typology to ground the research activity. The spatial organisations of various mosque typologies are graphically represented by adjacency constraints between spaces. Each configuration is represented by a planar graph which is then translated into a non-orthogonal dual graph and fed into the genetic algorithm system with fixed constraints and expected performance criteria set to govern evolution. The resultant Hierarchical Evolutionary Algorithmic Design System is developed by linking the evaluation process with environmental assessment tools to rank the candidate designs. The proposed system generates the concept, the seed, and the schema, and has environmental performance as one of the main criteria in driving optimisation.

Who and Why? Demographic and psychographic differences between consumers who have altered their shopping behaviour during a recession and those who have not

Research suggests that people differ in terms of changing their shopping behaviour during a recession. This paper reports on a preliminary descriptive study assessing what influences those consumers who have altered their shopping behaviour during such times. Driving the alteration of shopping behaviour were both demographic (age, gender, education, and nationality) and psychographic variables (attitudes, and head vs. heart decision making). Overall, the findings show that there are statistically significant differences between the two groups’ that marketers can address in their marketing strategies during the recession.