Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

Australian baby boomers switched to more environment friendly modes of transport during the global financial crisis

The global financial crisis (GFC) in 2008 rocked local, regional, and state economies throughout the world. Several intermediate outcomes of the GFC have been well documented in the literature including loss of jobs and reduced income. Relatively little research has, however, examined the impacts of the GFC on individual level travel behaviour change. To address this shortcoming, HABITAT panel data were employed to estimate a multinomial logit model to examine mode switching behaviour between 2007 (pre-GFC) and 2009 (post-GFC) of a baby boomers cohort in Brisbane, Australia—a city within a developed country that has been on many metrics the least affected by the GFC. In addition, a Poisson regression model was estimated to model the number of trips made by individuals in 2007, 2008, and 2009. The South East Queensland Travel Survey datasets were used to develop this model. Four linear regression models were estimated to assess the effects of the GFC on time allocated to travel during a day: one for each of the three travel modes including public transport, active transport, less environmentally friendly transport; and an overall travel time model irrespective of mode. The results reveal that individuals were more likely to switch to public transport who lost their job or whose income reduced between 2007 and 2009. Individuals also made significantly fewer trips in 2008 and 2009 compared to 2007. Individuals spent significantly less time using less environmentally friendly transport but more time using public transport in 2009. Baby boomers switched to more environmentally friendly travel modes during the GFC.

Cycling for transport and recreation : associations with socio-economic position, environmental perceptions, and psychological disposition

OBJECTIVE Interest is growing in promoting utility cycling (i.e., for transport) as a means of incorporating daily physical activity (PA) into people’s lives, but little is known about correlates of utility cycling. Our primary aim was to examine cross-sectional relationships between socio-economic characteristics, neighborhood environment perceptions and psychological disposition with utility cycling (with or without additional recreational cycling). A secondary aim was to compare these relationships with those for recreation-only cycling. METHOD Baseline survey data (2007) from 10,233 participants in HABITAT, a multilevel longitudinal study of PA, sedentary behavior, and health in Brisbane adults aged 40-65 years, were analysed using multinomial regression modelling. RESULTS Greater income, habitual PA, and positive beliefs about PA were associated with utility and recreation-only cycling (p<0.05). Always having vehicle access and not in the labor force were associated with recreation-only cycling (p<0.05). Some or no vehicle access, part-time employment, and perceived environmental factors (little crime, few cul-de-sacs, nearby transport and recreational destinations) were associated with utility cycling (p<0.05). CONCLUSION Our findings suggest differences in associations between socio-economic, neighborhood perceptions and psychological factors and utility and recreation-only cycling in Brisbane residents aged 40-65 years. Tailored approaches appear to be required to promote utility and recreational cycling.

Exact series solutions of reactive transport models with general initial conditions

Exact solutions of partial differential equation models describing the transport and decay of single and coupled multispecies problems can provide insight into the fate and transport of solutes in saturated aquifers. Most previous analytical solutions are based on integral transform techniques, meaning that the initial condition is restricted in the sense that the choice of initial condition has an important impact on whether or not the inverse transform can be calculated exactly. In this work we describe and implement a technique that produces exact solutions for single and multispecies reactive transport problems with more general, smooth initial conditions. We achieve this by using a different method to invert a Laplace transform which produces a power series solution. To demonstrate the utility of this technique, we apply it to two example problems with initial conditions that cannot be solved exactly using traditional transform techniques.

A spatial-indexing model for measuring neighbourhood-level land-use and transport integration

Significant attention has been given in urban policy literature to the integration of land-use and transport planning and policies—with a view to curbing sprawling urban form and diminishing externalities associated with car-dependent travel patterns. By taking land-use and transport interaction into account, this debate mainly focuses on how a successful integration can contribute to societal well-being, providing efficient and balanced economic growth while accomplishing the goal of developing sustainable urban environments and communities. The integration is also a focal theme of contemporary urban development models, such as smart growth, liveable neighbourhoods, and new urbanism. Even though available planning policy options for ameliorating urban form and transport-related externalities have matured—owing to growing research and practice worldwide—there remains a lack of suitable evaluation models to reflect on the current status of urban form and travel problems or on the success of implemented integration policies. In this study we explore the applicability of indicator-based spatial indexing to assess land-use and transport integration at the neighbourhood level. For this, a spatial index is developed by a number of indicators compiled from international studies and trialled in Gold Coast, Queensland, Australia. The results of this modelling study reveal that it is possible to propose an effective metric to determine the success level of city plans considering their sustainability performance via composite indicator methodology. The model proved useful in demarcating areas where planning intervention is applicable, and in identifying the most suitable locations for future urban development and plan amendments. Lastly, we integrate variance-based sensitivity analysis with the spatial indexing method, and discuss the applicability of the model in other urban contexts.

A Cyber-Physical System Simulator for risk-free transport studies

The article introduces a novel platform for conducting controlled and risk-free driving and traveling behavior studies, called Cyber-Physical System Simulator (CPSS). The key features of CPSS are: (1) simulation of multiuser immersive driving in a threedimensional (3D) virtual environment; (2) integration of traffic and communication simulators with human driving based on dedicated middleware; and (3) accessibility of multiuser driving simulator on popular software and hardware platforms. This combination of features allows us to easily collect large-scale data on interesting phenomena regarding the interaction between multiple user drivers, which is not possible with current single-user driving simulators. The core original contribution of this article is threefold: (1) we introduce a multiuser driving simulator based on DiVE, our original massively multiuser networked 3D virtual environment; (2) we introduce OpenV2X, a middleware for simulating vehicle-to-vehicle and vehicle to infrastructure communication; and (3) we present two experiments based on our CPSS platform. The first experiment investigates the “rubbernecking” phenomenon, where a platoon of four user drivers experiences an accident in the oncoming direction of traffic. Second, we report on a pilot study about the effectiveness of a Cooperative Intelligent Transport Systems advisory system.

A design approach to the study of people's experiences with technologies in the context of public transport

Relevant to the study of people’s attitudes towards public transport use is the consideration to the role of technology as part of the travel experience. Technologies aim to enhance daily tasks but tend to change the way people interact with products and can be perceived as difficult to use. This is critical in the context of “public use” where products and services are to be used by the population at large: adults, children, elderly, people with disabilities, and tourists. From different perspectives, the topic of users and the use of technologies have been studied in the social sciences and human computer interaction fields; however, earlier approaches fail to address the ways in which experiential knowledge informs people’s interactions with products and technologies, and how such information could guide the design of future technologies. This paper describes a pilot study, part of a larger ongoing exploratory research that investigates people’s experiences with infrastructure, systems, and technologies in the context of public transport. The methodological approach included focus groups, field observations, and retrospective verbal reports. At this stage, the study found that four context led factors were the primary source of reference informing participants’ actions and interactions; they are: (i) context >> experience, (ii) context >> interface, (iii) context >> knowledge, (iv) context >> emotion.

Public transport travel time variability definitions and monitoring

Public Transport Travel Time Variability (PTTV) is essential for understanding the deteriorations in the reliability of travel time, optimizing transit schedules and route choices. This paper establishes the key definitions of PTTV in which firstly include all buses, and secondly include only a single service from a bus route. The paper then analyzes the day-to-day distribution of public transport travel time by using Transit Signal Priority data. A comprehensive approach, using both parametric bootstrapping Kolmogorov-Smirnov test and Bayesian Information Creation technique is developed, recommends Lognormal distribution as the best descriptor of bus travel time on urban corridors. The probability density function of Lognormal distribution is finally used for calculating probability indicators of PTTV. The findings of this study are useful for both traffic managers and statisticians for planning and analyzing the transit systems.

Development of an inter-vehicle communications & positioning platform for transport safety applications

This project is a breakthrough in developing new scientific approaches for the design, development and evaluation of inter-vehicle communications, networking and positioning systems as part of Cooperative Intelligent Transportation Systems ensuring the safety of both roads and rail networks. This research focused on the elicitation, specification, analysis and validation of requirements for Vehicle-to-Vehicle communications and networking, and Vehicle-to-Vehicle positioning, which are accomplished with the research platform developed for this study. A number of mathematical models for communications, networking and positioning were developed from which simulations and field experiments were conducted to evaluate the overall performance of the platform. The outcomes of this research significantly contribute to improving the performance of the communications and positioning components of Cooperative Intelligent Transportation Systems.

In-vehicle railway level crossing warning systems : can intelligent transport systems deliver?

Intelligent Transport System (ITS) technology is seen as a cost-effective way to increase the conspicuity of approaching trains and the effectiveness of train warnings at level crossings by providing an in-vehicle warning of an approaching train. The technology is often seen as a potential low-cost alternative to upgrading passive level crossings with traditional active warning systems (flashing lights and boom barriers). ITS platforms provide sensor, localization and dedicated short-range communication (DSRC) technologies to support cooperative applications such as collision avoidance for road vehicles. In recent years, in-vehicle warning systems based on ITS technology have been trialed at numerous locations around Australia, at level crossing sites with active and passive controls. While significant research has been conducted on the benefits of the technology in nominal operating modes, little research has focused on the effects of the failure modes, the human factors implications of unreliable warnings and the technology adoption process from the railway industry’s perspective. Many ITS technology suppliers originate from the road industry and often have limited awareness of the safety assurance requirements, operational requirements and legal obligations of railway operators. This paper aims to raise awareness of these issues and start a discussion on how such technology could be adopted. This paper will describe several ITS implementation cenarios and discuss failure modes, human factors considerations and the impact these scenarios are likely to have in terms of safety, railway safety assurance requirements and the practicability of meeting these requirements. The paper will identify the key obstacles impeding the adoption of ITS systems for the different implementation scenarios and a possible path forward towards the adoption of ITS technology.

Controlled electronic transport in single-walled carbon nanotube networks : selecting electron hopping and chemical doping mechanisms

The electronic transport in both intrinsic and acid-treated single-walled carbon nanotube networks containing more than 90% semiconducting nanotubes is investigated using temperature-dependent resistance measurements. The semiconducting behavior observed in the intrinsic network is attributed to the three-dimensional electron hopping mechanism. In contrast, the chemical doping mechanism in the acid-treated network is found to be responsible for the revealed metal-like linear resistivity dependence in a broad temperature range. This effective method to control the electrical conductivity of single-walled carbon nanotube networks is promising for future nanoscale electronics, thermometry, and bolometry. © 2010 American Institute of Physics.

Electron transport across magnetic field in low-temperature plasmas : an alternative approach for obtaining evidence of Bohm mechanism

A comparative study involving both experimental and numerical investigations was made to resolve a long-standing problem of understanding electron conductivity mechanism across magnetic field in low-temperature plasmas. We have calculated the plasma parameters from experimentally obtained electric field distribution, and then made a 'back' comparison with the distributions of electron energy and plasma density obtained in the experiment. This approach significantly reduces an influence of the assumption about particular phenomenology of the electron conductivity in plasma. The results of the experiment and calculations made by this technique have showed that the classical conductivity is not capable of providing realistic total current and electron energy, whereas the phenomenological anomalous Bohm mobility has demonstrated a very good agreement with the experiment. These results provide an evidence in favor of the Bohm conductivity, thus making it possible to clarify this pressing long-living question about the main driving mechanism responsible for the electron transport in low-temperature plasmas.

Urban Informatics and Public Transport

The holistic urban experience we perceive when immersed in an urban context is at the heart of urban informatics. This experience encompasses all urban elements such as architecture, people, and culture. Urban informatics explores the possibilities and opportunities created by new technologies and information for enhancing the urban experience. Public transport is an essential urban experience. Everyday, urban dwellers takes public transport to commute and move between different parts of the city. Public transport serves people from all over the city and moves them through different places in the city, using different means of transportation. The nature of public transport—involving people, places, and technologies, makes it a fitting context for urban informatics interventions. There are three main aspects of the public transport experience that can readily benefit from urban informatics interventions the: pragmatic aspect, hedonistic aspect, and social aspect. From the pragmatic perspective, these interventions can help people to be more efficient and effective in taking public transport. Hedonistic-related interventions aim to bring enjoyment and fun to our mundane commute. Finally, urban informatics can strengthen the sense of community in a socially-passive context like public transport environments through adopting socially focused interventions.

Minimum cost of transport in human running is not ubiquitous

Purpose This study explores recent claims that humans exhibit a minimum cost of transport (CoTmin) for running which occurs at an intermediate speed, and assesses individual physiological, gait and training characteristics. Methods Twelve healthy participants with varying levels of fitness and running experience ran on a treadmill at six self-selected speeds in a discontinuous protocol over three sessions. Running speed (km[middle dot]hr-1), V[spacing dot above]O2 (mL[middle dot]kg-1[middle dot]km-1), CoT (kcal[middle dot]km-1), heart rate (beats[middle dot]min-1) and cadence (steps[middle dot]min-1) were continuously measured. V[spacing dot above]O2 max was measured on a fourth testing session. The occurrence of a CoTmin was investigated and its presence or absence examined with respect to fitness, gait and training characteristics. Results Five participants showed a clear CoTmin at an intermediate speed and a statistically significant (p < 0.05) quadratic CoT-speed function, while the other participants did not show such evidence. Participants were then categorized and compared with respect to the strength of evidence for a CoTmin (ClearCoTmin and NoCoTmin). The ClearCoTmin group displayed significantly higher correlation between speed and cadence; more endurance training and exercise sessions per week; than the NoCoTmin group; and a marginally non-significant but higher aerobic capacity. Some runners still showed a CoTmin at an intermediate speed even after subtraction of resting energy expenditure. Conclusion The findings confirm the existence of an optimal speed for human running, in some but not all participants. Those exhibiting a COTmin undertook a higher volume of running, ran with a cadence that was more consistently modulated with speed, and tended to be aerobically fitter. The ability to minimise the energetic cost of transport appears not to be ubiquitous feature of human running but may emerge in some individuals with extensive running experience.