Prediction of cis/trans isomerization in proteins using PSI-BLAST profiles and secondary structure information

Background The majority of peptide bonds in proteins are found to occur in the trans conformation. However, for proline residues, a considerable fraction of Prolyl peptide bonds adopt the cis form. Proline cis/trans isomerization is known to play a critical role in protein folding, splicing, cell signaling and transmembrane active transport. Accurate prediction of proline cis/trans isomerization in proteins would have many important applications towards the understanding of protein structure and function. Results In this paper, we propose a new approach to predict the proline cis/trans isomerization in proteins using support vector machine (SVM). The preliminary results indicated that using Radial Basis Function (RBF) kernels could lead to better prediction performance than that of polynomial and linear kernel functions. We used single sequence information of different local window sizes, amino acid compositions of different local sequences, multiple sequence alignment obtained from PSI-BLAST and the secondary structure information predicted by PSIPRED. We explored these different sequence encoding schemes in order to investigate their effects on the prediction performance. The training and testing of this approach was performed on a newly enlarged dataset of 2424 non-homologous proteins determined by X-Ray diffraction method using 5-fold cross-validation. Selecting the window size 11 provided the best performance for determining the proline cis/trans isomerization based on the single amino acid sequence. It was found that using multiple sequence alignments in the form of PSI-BLAST profiles could significantly improve the prediction performance, the prediction accuracy increased from 62.8% with single sequence to 69.8% and Matthews Correlation Coefficient (MCC) improved from 0.26 with single local sequence to 0.40. Furthermore, if coupled with the predicted secondary structure information by PSIPRED, our method yielded a prediction accuracy of 71.5% and MCC of 0.43, 9% and 0.17 higher than the accuracy achieved based on the singe sequence information, respectively. Conclusion A new method has been developed to predict the proline cis/trans isomerization in proteins based on support vector machine, which used the single amino acid sequence with different local window sizes, the amino acid compositions of local sequence flanking centered proline residues, the position-specific scoring matrices (PSSMs) extracted by PSI-BLAST and the predicted secondary structures generated by PSIPRED. The successful application of SVM approach in this study reinforced that SVM is a powerful tool in predicting proline cis/trans isomerization in proteins and biological sequence analysis.

The relative importance of factors influencing bicycling crash risk

Government promotion of active transport has renewed interest in cycling safety. Research has shown that bicyclists are up to 20 times more likely to be involved in serious injury crashes than drivers. On-road cycling injuries are under-reported in police data, and many non-serious injuries are not recorded in any official database. This study aims to explore the relationships between rider characteristics and environmental factors that influence per kilometre risk of bicycle-related crash and non-crash injuries.

Raising awareness of traffic pollution: the potential benefits and problems of using a warning smell

Exposure to traffic pollution is increasing worldwide as people move to cities, and as more vehicles join the roads, creating longer journeys and more traffic jams. Most traffic pollutants are odourless and invisible, which hides exposure from the public. If traffic pollution had a distinctive smell it would enable people to avoid exposure, and increase the political will for difficult policy changes. A smell may also instigate longer-term changes, such as switching to active transport for school pick-ups. A smell could be added using a fuel additive or a temporary device attached to vehicle exhausts.

Bicycling injuries and perceived risk

Introduction Government promotion of active transport has renewed interest in cycling safety. Research has shown that bicyclists are up to 20 times more likely to be involved in serious injury crashes than drivers. On-road cycling injuries are under-reported in police data, and many non-serious injuries are not recorded in any official database. This study aims to explore the relationships between rider characteristics and environmental factors that influence per kilometre risk of bicycle-related crash and non-crash injuries. Method A survey of 2,532 Queensland adults who had ridden at least once in the past year was conducted from October 2009 to March 2010, with most responses received online (99.3%). Riders were asked where they rode (footpath, bike path, road etc.), average travel speed, purpose of riding, type of bike ridden, how far and how often they rode in. Measures of rider experience, skill, safety perceptions, safety behaviours, crash involvement and demographic characteristics were also collected. RESULTS Increasing exposure and having more expensive bicycles were shown to reduce the risk per km of crash and non-crash injury rates, and to reduce perceived risk. Never wearing bright coloured clothing related to increased crash risk, use of fluorescent and reflective clothing had no effect on crash risk. Riding in low-speed environments, never using a front light, and riding in low-speed environments were associated with reduced non-crash injury risk. Perceived risk was influenced by exposure, use of conspicuity aids and helmets, riding for utilitarian reasons, and group-riding behaviours. DISCUSSION Perceived risk does not appear to influence injury rates and injury rates do not appear to influence the perceived risk of cycling. Riders who perceive cycling to be risky tend not to be commuters, do not engage in group riding and always wear helmets. Not all measures of conspicuity were associated with risk, with rear lights found to have no relationship to injury. The risks of experiencing a crash or non-crash injury were similar, therefore injury prevention strategies should expand their scope to include other factors such as the importance of bicycle set-up.

A new approach for trip generation estimation for use in traffic impact assessments

Findings from an online survey conducted by Queensland University of Technology (QUT) shows that Australia is suffering from a lack of data reflecting trip generation for use in Traffic Impact Assessments (TIAs). Current independent variables for trip generation estimation are not able to create robust outcomes as well. It is also challenging to account for the impact of the new development on public and active transport as well as the effect of trip chaining behaviour in Australian TIA studies. With this background in mind, research is being implemented by QUT to find a new approach developing a combined model of trip generation and mode choice with consideration of trip chaining effects. It is expected that the model will provide transferable outcomes as it is developed based on socio-demographic parameters. Child Care Centres within the Brisbane area have been nominated for model development. At the time, the project is in the data collection phase. Findings from the pilot survey associated with capturing trip chaining and mode choice information reveal that applying questionnaire is able to capture required information in an acceptable level. The result also reveals that several centres within an area should be surveyed in order to provide sufficient data for trip chaining and modal split analysis.

The integrated land use and transportation indexing model : assessing the sustainability of the Gold Coast, Australia

Urban sustainability and sustainable urban development concepts have been identified as the ultimate goal of many contemporary planning endeavours and have become central concepts on which the urban development policies are formulated. In the confinement of these concepts, land use and transport integration has been highlighted as one of the most important policy objectives considering the interrelationship between them and available intervention means of planning. While its interpretation varies, in Australia, it has been embraced as integration of land use and transport planning/policies and been an integral part of regional and local plans. Accordingly, a number of principles have been defined to guide its implementation, to name a few, planning for compact and connected urban development, encouraging active transport modes, creation of mixed-use activity centres and public transport precincts, provision of high quality public transport services, and enhancing character and amenity of urban areas. However, there is lack of an evaluation framework to measure the extent of achievement of implementation of these principles. In pursuit of filling this gap, this study aims to devise an evaluation framework to measure the performance of urban settings according to the integration principles in South East Queensland, Australia context and to demarcate problematic areas which can be intervened by planning tools...

A comparison of perceived crash risk among cyclists and drivers in Brisbane

The Queensland Government has implemented strategies promoting a shift from individual car use to active transport, a transition which requires drivers to adapt to sharing the road with increased numbers of people cycling through transport network. For this to occur safely, changes in both road infrastructure and road user expectations and behaviors will be needed. Creating separate cycle infrastructure does not remove the need for cyclists to commence, cross or finish travel on shared roads. Currently intersections are one of the predominant shared road spaces where crashes result in cyclists being injured or killed. This research investigates how Brisbane cyclists and drivers perceive risk when interacting with other road users at intersections. The current study replicates a French study conducted by co-authors Chaurand and Delhomme in 2011 and extends it to assess gender effects which have been reported in other Australian cycling research. An online survey was administered to experienced cyclists and drivers. Participants rated the level of risk they felt when imagining a number of different road situations. Based on the earlier French study it is expected that perceived crash risk will be influenced both by the participant’s mode of travel and the type of interacting vehicle and perceived risk will be greater when the interaction is with a car than a bicycle. It is predicted that risk perception will decrease as the level of experience increases and that male participants will have a higher perception of skill and lower perception of risk than females. The findings of this Queensland study will provide a valuable insight into perceived risk and the traffic behaviours of drivers and cyclists when interacting with other road users and results will be available for presentation at the Congress.

Comparison of Motorists’ and Cyclists’ perception of bicycle safety

Increasing the modal share of public transit systems has become paramount in aiding the reduction on the excessive reliance of personal motor vehicles. More so the need to increase the share of active modes of transport such as the use of bicycles, therefore there is an ever increasing need to use bicycles both on shared pedestrian paths and on-road cycling. The risk to cyclist, or consequently the perception of the risk from both cyclists and motorists alike, is an important factor to increase the use of this transport mode. This paper investigates perception of bicycle safety by conducting a survey and analysing the survey data to understand how participants with different backgrounds perceive the risks of cycling for transport. Contributing factors to people’s perception of bicycle safety were identified and compared across different road user groups, based upon which recommendations were made on how to improve bicycle safety.

Advance transit oriented development typology : case study in Brisbane, Australia

Internationally, transit oriented development (TOD) is characterised by moderate to high density development with diverse land use patterns and well connected street networks centred around high frequency transit stops (bus and rail). Although different TOD typologies have been developed in different contexts, they are based on subjective evaluation criteria derived from the context in which they are built and typically lack a validation measure. Arguably there exist sets of TOD characteristics that perform better in certain contexts, and being able to optimise TOD effectiveness would facilitate planning and supporting policy development. This research utilises data from census collection districts (CCDs) in Brisbane with different sets of TOD attributes measured across six objectively quantified built environmental indicators: net employment density, net residential density, land use diversity, intersection density, cul-de-sac density, and public transport accessibility. Using these measures, a Two Step Cluster Analysis was conducted to identify natural groupings of the CCDs with similar profiles, resulting in four unique TOD clusters: (a) residential TODs, (b) activity centre TODs, (c) potential TODs, and; (d) TOD non-suitability. The typologies are validated by estimating a multinomial logistic regression model in order to understand the mode choice behaviour of 10,013 individuals living in these areas. Results indicate that in comparison to people living in areas classified as residential TODs, people who reside in non-TOD clusters were significantly less likely to use public transport (PT) (1.4 times), and active transport (4 times) compared to the car. People living in areas classified as potential TODs were 1.3 times less likely to use PT, and 2.5 times less likely to use active transport compared to using the car. Only a little difference in mode choice behaviour was evident between people living in areas classified as residential TODs and activity centre TODs. The results suggest that: (a) two types of TODs may be suitable for classification and effect mode choice in Brisbane; (b) TOD typology should be developed based on their TOD profile and performance matrices; (c) both bus stop and train station based TODs are suitable for development in Brisbane.

Ran is a potential therapeutic target for cancer cells with molecular changes associated with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways

Purpose Cancer cells have been shown to be more susceptible to Ran knockdown than normal cells. We now investigate whether Ran is a potential therapeutic target of cancers with frequently found mutations that lead to higher Ras/MEK/ERK [mitogen-activated protein/extracellular signal-regulated kinase (ERK; MEK)] and phosphoinositide 3-kinase (PI3K)/Akt/mTORC1 activities. Experimental Design Apoptosis was measured by flow cytometry [propidium iodide (PI) and Annexin V staining] and MTT assay in cancer cells grown under different conditions after knockdown of Ran. The correlations between Ran expression and patient survival were examined in breast and lung cancers. Results Cancer cells with their PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways inhibited are less susceptible to Ran silencing-induced apoptosis. K-Ras-mutated, c-Met-amplified, and Pten-deleted cancer cells are also more susceptible to Ran silencing-induced apoptosis than their wild-type counterparts and this effect is reduced by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers. This association is dramatically enhanced in cancers with increased c-Met or osteopontin expression, or with oncogenic mutations of K-Ras or PIK3CA, all of which are mutations that potentially correlate with activation of the PI3K/Akt/mTORC1 and/or Ras/MEK/ERK pathways. Silencing Ran also results in dysregulation of nucleocytoplasmic transport of transcription factors and downregulation of Mcl-1 expression, at the transcriptional level, which are reversed by inhibitors of the PI3K/Akt/mTORC1 and MEK/ERK pathways. Conclusion Ran is a potential therapeutic target for treatment of cancers with mutations/changes of expression in protooncogenes that lead to activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. ©2011 AACR.

Investigating the link between transit oriented development and sustainable travel behavior in Brisbane : a case-control study

The purpose of this research is to empirically test the prevailing view that transit oriented development enhances the use of more sustainable modes of transport using Brisbane, Australia as a case. Transit oriented development has been adopted as a new policy tool to reduce car-based travel worldwide. Despite being a billion dollar investment, the impacts of transit oriented development on promoting sustainable travel behavior is not conclusive. The research uses a case-control approach to empirically investigate this relationship based on travel behavior data collected from 88 individuals living in two contrasting neighborhoods in Brisbane: Kelvin Grove Urban Village – a transit oriented development, and Annerley – a traditional suburb (non-transit oriented development). A comparative investigation of travel behavior was subsequently conducted using distance travelled by modes and purposes between the neighborhoods. Results show that the availability of opportunity and services located within the transit oriented development reduces the car use by 5% and increases the use of active transport by 4%. The findings in this research support the implementation of TOD policies in Brisbane.

Understanding causal relationships between the built and social environment, health and associated behaviours and risk factors

Introduction: Built environment interventions designed to reduce non-communicable diseases and health inequity, complement urban planning agendas focused on creating more ‘liveable’, compact, pedestrian-friendly, less automobile dependent and more socially inclusive cities.However, what constitutes a ‘liveable’ community is not well defined. Moreover, there appears to be a gap between the concept and delivery of ‘liveable’ communities. The recently funded NHMRC Centre of Research Excellence (CRE) in Healthy Liveable Communities established in early 2014, has defined ‘liveability’ from a social determinants of health perspective. Using purpose-designed multilevel longitudinal data sets, it addresses five themes that address key evidence-base gaps for building healthy and liveable communities. The CRE in Healthy Liveable Communities seeks to generate and exchange new knowledge about: 1) measurement of policy-relevant built environment features associated with leading non-communicable disease risk factors (physical activity, obesity) and health outcomes (cardiovascular disease, diabetes) and mental health; 2) causal relationships and thresholds for built environment interventions using data from longitudinal studies and natural experiments; 3) thresholds for built environment interventions; 4) economic benefits of built environment interventions designed to influence health and wellbeing outcomes; and 5) factors, tools, and interventions that facilitate the translation of research into policy and practice. This evidence is critical to inform future policy and practice in health, land use, and transport planning. Moreover, to ensure policy-relevance and facilitate research translation, the CRE in Healthy Liveable Communities builds upon ongoing, and has established new, multi-sector collaborations with national and state policy-makers and practitioners. The symposium will commence with a brief introduction to embed the research within an Australian health and urban planning context, as well as providing an overall outline of the CRE in Healthy Liveable Communities, its structure and team. Next, an overview of the five research themes will be presented. Following these presentations, the Discussant will consider the implications of the research and opportunities for translation and knowledge exchange. Theme 2 will establish whether and to what extent the neighbourhood environment (built and social) is causally related to physical and mental health and associated behaviours and risk factors. In particular, research conducted as part of this theme will use data from large-scale, longitudinal-multilevel studies (HABITAT, RESIDE, AusDiab) to examine relationships that meet causality criteria via statistical methods such as longitudinal mixed-effect and fixed-effect models, multilevel and structural equation models; analyse data on residential preferences to investigate confounding due to neighbourhood self-selection and to use measurement and analysis tools such as propensity score matching and ‘within-person’ change modelling to address confounding; analyse data about individual-level factors that might confound, mediate or modify relationships between the neighbourhood environment and health and well-being (e.g., psychosocial factors, knowledge, perceptions, attitudes, functional status), and; analyse data on both objective neighbourhood characteristics and residents’ perceptions of these objective features to more accurately assess the relative contribution of objective and perceptual factors to outcomes such as health and well-being, physical activity, active transport, obesity, and sedentary behaviour. At the completion of the Theme 2, we will have demonstrated and applied statistical methods appropriate for determining causality and generated evidence about causal relationships between the neighbourhood environment, health, and related outcomes. This will provide planners and policy makers with a more robust (valid and reliable) basis on which to design healthy communities.

Do dissonants in transit oriented development adjust commuting travel behaviour?

Residential dissonance signifies a mismatch between an individual’s preferred and actual proximal land use patterns in residential neighbourhoods, whereas residential consonance signifies agreement between actual and preferred proximal land uses. Residential dissonance is a relatively unexplored theme in the literature, yet it acts as a barrier to the development of sustainable transport and land use policy. This research identifies mode choice behaviour of four groups living in transit oriented development (TOD) and non-TOD areas in Brisbane, Australia using panel data from 2675 commuters: TOD consonants, TOD dissonants, non-TOD consonants, and non-TOD dissonants. The research investigates a hypothetical understanding that dissonants adjust their travel attitudes and perceptions according to their surrounding land uses over time. The adjustment process was examined by comparing the commuting mode choice behaviour of dissonants between 2009 and 2011. Six binary logistic regression models were estimated, one for each of the three modes considered (e.g. public transport, active transport, and car) and one for each of the 2009 and 2011 waves. Results indicate that TOD dissonants and non-TOD consonants were less likely to use the public transport and active transport; and more likely to use the car compared with TOD consonants. Non-TOD dissonants use public transport and active transport equally to TOD consonants. The results suggest that commuting mode choice behaviour is largely determined by travel attitudes than built environment factors; however, the latter influence public transport and car use propensity. This research also supports the view that dissonants adjust their attitudes to surrounding land uses, but very slowly. Both place (e.g. TOD development) and people-based (e.g. motivational) policies are needed for an effective travel behavioural shift.

Commuting mode choice in transit oriented development: Disentangling the effects of competitive neighbourhoods, travel attitudes, and self-selection

This research identifies the commuting mode choice behaviour of 3537 adults living in different types of transit oriented development (TOD) in Brisbane by disentangling the effects of their “evil twin” transit adjacent developments (TADs), and by also controlling for residential self-selection, travel attitudes and preferences, and socio-demographic effects. A TwoStep cluster analysis was conducted to identify the natural groupings of respondents’ living environment based on six built environment indicators. The analysis resulted in five types of neighbourhoods: urban TODs, activity centre TODs, potential TODs, TADs, and traditional suburbs. HABITAT survey data were used to derive the commute mode choice behaviour of people living in these neighbourhoods. In addition, statements reflecting both respondents’ travel attitudes and living preferences were also collected as part of the survey. Factor analyses were conducted based on these statements and these derived factors were then used to control for residential self-selection. Four binary logistic regression models were estimated, one for each of the travel modes used (e.g. public transport, active transport, less sustainable transport such as the car/taxi, and other), to differentiate between the commuting behaviour of people living in the five types of neighbourhoods. The findings verify that urban TODs enhance the use of public transport and reduce car usage. No significant difference was found in the commuting behaviour between respondents living in traditional suburbs and TADs. The results confirm the hypothesis that TADs are the “evil twin” of TODs. The data indicates that TADs and the mode choices of residents in these neighbourhoods is a missed transport policy opportunity. Further policy efforts are required for a successive transition of TADs into TODs in order to realise the full benefits of these. TOD policy should also be integrated with context specific TOD design principles.

Mechanism of glycine uptake by the silk glands of the silkworm Bombyx mori L

The transport of glycine in vitro into the silk glands of the silkworm has been studied. Glycine accumulates inside the tissue to a concentration higher than that present outside, indicating an active transport mechanism. The kinetics of uptake show a biphasic curve and two apparent Km values for accumulation, 0.33 mM and 5.00 mM. The effect of inhibitors on the energy metabolism of glycine transport is inconclusive. Exchange studies indicate the existence of two pools inside the gland, one that is easily removed by exchange and osmotic shock, and the other which is not. The results obtained conform with the carrier model of Britten and McClure concerning the amino-acid pool in E. coli.