PCTH: A novel orally active chelator for the treatment of iron overload disease

Our laboratories have prepared a novel class of iron (Fe) chelators of the 2-pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) class. This article will review the iron chelation efficacy of this series of chelators, both in cell culture and in animal models. Several PCIH analogs were shown to be effective at inducing iron mobilization and preventing iron uptake from the iron-transport protein, transferrin. Moreover, several of these ligands were effective at permeating the mitochondrion and inducing iron release. Studies in mice demonstrated that the PCIH analog, PCTH, was orally active and well tolerated by mice at doses ranging from 50 to 100 mg kg(-1) , twice daily (b.d.). A dose-dependent increase in fecal Fe-59 excretion was observed in the PCTH-treated group. This level of iron excretion was similar to that found for the orally effective chelators, pyridoxal isonicotinoyl hydrazone (PIH) and deferiprone (L1). The PCIH group of ligands clearly has the potential for the treatment of ss-thalassemia (thal) and Friedreich's Ataxia (FA).

Identification, mutagenesis, and transcriptional analysis of the methanesulfonate transport operon of methylosulfonomonas methylovora

Recently identified genes located downstream (3') of the msmEF (transport encoding) gene cluster, msmGH, and located 5' of the structural genes for methanesulfonate monooxygenase (MSAMO) are described from Methylosulfonomonas methylovora. Sequence analysis of the derived polypeptide sequences encoded by these genes revealed a high degree of identity to ABC-type transporters. MsmE showed similarity to a putative periplasmic substrate binding protein, MsmF resembled an integral membraneassociated protein, and MsmG was a putative ATP-binding enzyme. MsmH was thought to be the cognate permease component of the sulfonate transport system. The close association of these putative transport genes to the MSAMO structural genes msmABCD suggested a role for these genes in transport of methanesulfonic acid (MSA) into M. methylovora. msmEFGH and msmABCD constituted two operons for the coordinated expression of MSAMO and the MSA transporter systems. Reverse-transcription-PCR analysis of msmABCD and msmEFGH revealed differential expression of these genes during growth on MSA and methanol. The msmEFGH operon was constitutively expressed, whereas MSA induced expression of msmABCD. A mutant defective in msmE had considerably slower growth rates than the wild type, thus supporting the proposed role of MsmE in the transport of MSA into M. methylovora.

Interactions at the head-tape interface of a linear tape system

Many of the recent improvements in the capacity of data cartridge systems have been achieved through the use of narrower tracks, higher linear densities and continuous servo tracking with multi-channel heads. These changes have produced new tribological problems at the head/tape interface. It is crucial that the tribology of such systems is understood and this will continue since increasing storage capacities and faster transfer rates are constantly being sought. Chemical changes in the surface of single and dual layer MP tape have been correlated to signal performance. An accelerated tape tester, consisting of a custom made cycler ("loop tester"), was used to ascertain if results could be produced that were representative of a real tape drive system. A second set of experiments used a modified tape drive (Georgens cycler), which allowed the effects of the tape transport system on the tape surface to be studied. To isolate any effects on the tape surface due to the head/tape interface, read/write heads were not fitted to the cycler. Two further sets of experiments were conducted which included a head in the tape path. This allowed the effects of the head/tape interface on the physical and chemical properties of the head and tape surfaces to be investigated. It was during the final set of experiments that the effect on the head/tape interface, of an energised MR element, was investigated. The effect of operating each cycler at extreme relative humidity and temperature was investigated through the use of an environmental chamber. Extensive use was made of surface specific analytical techniques such as XPS, AFM, AES, and SEM to study the physical and chemical changes that occur at the head/tape interface. Results showed that cycling improved the signal performance of all the tapes tested. The data cartridge drive belt had an effect on the chemical properties of the tape surface on which it was in contact. Also binder degradation occurred for each tape and appeared to be greater at higher humidity. Lubricant was generally seen to migrate to the tape surface with cycling. Any surface changes likely to affect signal output occurred at the head surface rather than the tape.

Conformational analysis of the natural iron chelator myo-inositol 1,2,3-trisphosphate using a pyrene-based fluorescent mimic

myo-Inositol phosphates possessing the 1,2,3-trisphosphate motif share the remarkable ability to completely inhibit iron-catalysed hydroxyl radical formation. The simplest derivative, myo-inositol 1,2,3-trisphosphate [Ins(1,2,3)P3], has been proposed as an intracellular iron chelator involved in iron transport. The binding conformation of Ins(1,2,3)P3 is considered to be important to complex Fe3+ in a 'safe' manner. Here, a pyrene-based fluorescent probe, 4,6-bispyrenoyl-myo-inositol 1,2,3,5-tetrakisphosphate [4,6-bispyrenoyl Ins(1,2,3,5)P4], has been synthesised and used to monitor the conformation of the 1,2,3-trisphosphate motif using excimer fluorescence emission. Ring-flip of the cyclohexane chair to the penta-axial conformation occurs upon association with Fe3+, evident from excimer fluorescence induced by π-π stacking of the pyrene reporter groups, accompanied by excimer formation by excitation at 351 nm. This effect is unique amongst biologically relevant metal cations, except for Ca 2+ cations exceeding a 1:1 molar ratio. In addition, the thermodynamic constants for the interaction of the fluorescent probe with Fe3+ have been determined. The complexes formed between Fe 3+ and 4,6-bispyrenoyl Ins(1,2,3,5)P4 display similar stability to those formed with Ins(1,2,3)P3, indicating that the fluorescent probe acts as a good model for the 1,2,3-trisphosphate motif. This is further supported by the antioxidant properties of 4,6-bispyrenoyl Ins(1,2,3,5)P4, which closely resemble those obtained for Ins(1,2,3)P3. The data presented confirms that Fe3+ binds tightly to the unstable penta-axial conformation of myo-inositol phosphates possessing the 1,2,3-trisphosphate motif. © 2010 The Royal Society of Chemistry.

Smart and sustainable public transport systems through improving level and quality of service

Buses are considered a slow, low comfort and low reliability transport system, thus its negative and por image. In the framework of the 3iBS project (2012), several examples of innovative and/or effective solutions regarding the Level of Service (LoS) were analysed aiming to provide operators, practitioners and policy makers with a set of Good Practice Guidelines to strengthen the competitiveness of the bus in the urban environment. The identification of the key indicators regarding vehicles, infrastructure and operation was possible through the analysis of a set of case studies -among which Barcelona (Spain), Cagliari (Italy), London (United Kingdom), Paris and Nantes (France). A cross comparison between the case studies was carried out for contrasting the level of achievement of the different criteria considered. The information provided on Regulatory, Financial and Technical issues allows the identification of a number of specific factors influencing the implementation of a high quality transport scheme, and set the basis for the elaboration of a set of Guidelines for the implementation of an intelligent, innovative and integrated bus system, including the main barriers to be tackled.

Associations of public transport accessibility with walking, obesity, metabolic syndrome and diabetes

Objective: To examine associations of public transport system accessibility with walking, obesity, metabolic syndrome and diabetes/impaired glucose regulation. Methods: Associations of public transport accessibility with self-reported walking for transport or recreation and measured biomarkers of chronic disease risk were estimated in 5241 adult residents of 42 randomly selected areas in Australia in 2004/05, drawn from the second wave of a population-based cohort study (AusDiab). Public transport accessibility was objectively measured using an adaptation of the Public Transport Accessibility Levels (PTAL) methodology, comprising both GIS derived spatial and temporal accessibility measures. Logistic regression models were adjusted for individual and environmental level covariates and clustering within areas. Results: Above median public transport accessibility was positively associated with a walking time of more than the median 90 min per week (OR=1.28, 95%CI 1.03, 1.60) and walking above the recommended 150 min per week (OR=1.35, 95%CI 1.11, 1.63). There were no associations of public transport accessibility with obesity (OR=1.05, 95%CI 0.85, 1.30), the metabolic syndrome (OR=1.09, 95%CI 0.91, 1.31) nor diabetes/impaired glucose regulation (OR=1.11, 95%CI 0.94, 1.30). Findings were similar for a subgroup reporting no vigorous recreational physical activity. Conclusions: In this Australian sample, public transport accessibility was positively associated with walking at recommended levels, including for people who are not otherwise vigorously active. Significance: Walking is crucial for increasing physical activity levels and population health, as well as maximising public transport system efficiency. Building evidence on public transport accessibility and walking will enable governments to exploit this important synergy.

Perceived Accessibility of Public Transport as a Potential Indicator of Social Inclusion

Perceived accessibility has been acknowledged as an important aspect of transport policy since the 70s. Nevertheless, very few empirical studies have been conducted in this field. When aiming to improve social inclusion, by making sus-tainable transport modes accessible to all, it is important to understand the factors driving perceived accessibility. Un-like conventional accessibility measures, perceived accessibility focuses on the perceived possibilities and ease of en-gaging in preferred activities using different transport modes. We define perceived accessibility in terms of how easy it is to live a satisfactory life with the help of the transport system, which is not necessarily the same thing as the objec-tive standard of the system. According to previous research, perceived accessibility varies with the subjectively-rated quality of the mode of transport. Thus, improvements in quality (e.g. trip planning, comfort, or safety) increase the per-ceived accessibility and make life easier to live using the chosen mode of transport. This study (n=750) focuses on the perceived accessibility of public transport, captured using the Perceived Accessibility Scale PAC (Lättman, Olsson, & Fri-man, 2015). More specifically, this study aims to determine how level of quality affects the perceived accessibility in public transport. A Conditional Process Model shows that, in addition to quality, feeling safe and frequency of travel are important predictors of perceived accessibility. Furthermore, elderly and those in their thirties report a lower level of perceived accessibility to their day-to-day activities using public transport. The basic premise of this study is that sub-jective experiences may be as important as objective indicators when planning and designing for socially inclusive transport systems.

Effects of fare collection policy on operating characteristics of a Brisbane busway station

Transit agencies across the world are increasingly shifting their fare collection mechanisms towards fully automated systems like the smart card. One of the objectives in implementing such a system is to reduce the boarding time per passenger and hence reduce the overall dwell time for the buses at the bus stops/bus rapid transit (BRT) stations. TransLink, the transit authority responsible for public transport management in South East Queensland, has introduced ‘GoCard’ technology using the Cubic platform for fare collection on its public transport system. In addition to this, three inner city BRT stations on South East Busway spine are operating as pre-paid platforms during evening peak time. This paper evaluates the effects of these multiple policy measures on operation of study busway station. The comparison between pre and post policy scenarios suggests that though boarding time per passenger has decreased, while the alighting time per passenger has increased slightly. However, there is a substantial reduction in operating efficiency was observed at the station.

AITPM Email Newsletter Volume 0903, March 2009: Presidents Message

President’s Report Hello fellow AITPM members, First I would like on behalf of all AITPM members to send our condolences to all who have been affected by February’s tragic bushfires in regional Victoria, and deliver our best wishes to all of those involved in the rebuilding efforts. Over time I expect that the Victorian Government’s Royal Commission will analyse the circumstances and put forward a range of measures which will improve fire safety in vulnerable areas. As transport professionals it will be important for us to consider the findings and look to undertaking any recommendations that relate to the work we do. Not only in Victoria, but nationwide. In particular, the importance of logistics was highlighted following the fire events. Donors across Australia were this time requested to donate money rather than goods, presumably due in part to problems associated with the transport system coping with additional uncoordinated freight load, whilst being needed to support emergency management vehicle and managed freight movements. Notwithstanding, it was wonderful to see otherwise difficult to obtain goods, such as animal feed, being donated from far afield and transported in kind by trucking operators. As stated in last month’s Newsletter, AITPM made a direct cash donation to the Red Cross Bushfire Appeal immediately following the events, and a further donation to the Queensland Premier’s Disaster Relief Fund to support recovery after the North Queensland floods, which claimed seven lives. Again, we will need to monitor how the rebuilding effort unfolds particularly in regional Victoria and centres including Ingham in North Queensland, but I would urge all AITPM members who are in a position to support the restoration of the affected communities to play a part, particularly over time once the initial shock subsides and the steady job of rebuilding is underway. Onto lighter matters, AITPM’s flagship event, the 2009 AITPM National Conference, Traffic Beyond Tomorrow, being held in Adelaide from 5 to 7 August, is fast approaching. www.aitpm.com has all of the details about how to register, sponsor a booth, and so forth. We are looking forward to catching up with our conference “regulars” and meeting with new folks to AITPM, and Australian traffic and transport planning and management. Adelaide is one of my favourite places to visit and I’m looking forward to riding the light rail line extension through town and checking out progress on the road system development. Best regards all, Jon Bunker

AITPM Email Newsletter Volume 0911, November 2009 : President's Message

President’s Report Hello fellow AITPM members, It is interesting to follow the news at present, where transport costs are getting a significant airing. Treasury Secretary Dr Ken Henry has enunciated something Australians may have considered extremely radical just a few years back, but in the present time appears to quite a few to be a realistic alternative. That being a rethink of the way we are charged for using our vehicles. It appears that serious consideration is being given to congestion charging, perhaps in place at least to some extent, of fuel excise. As a transport professional I am pleased that the debate has elevated to the national level, and would look forward that AITPM might contribute appropriately to it. As a motorist though, I naturally have my concerns about being hit in the hip pocket. Not that I actually drive during congested periods very much. I am fortunate to live five minutes either side of two well serviced bus corridors, one of which will eventually become a busway, and work in the central business district, which is hub from all spokes in Brisbane. As such, bus and foot are my preferred commute modes. Ah but I should not gloat, as my smart card fare is about to increase by 20 percent in the New Year! And if the newspapers are to be believed, further substantial increments are proposed over the coming few years. This is reported to recoup some more of the costs of actually providing the quality public transport system that we enjoy in our region. So I expect it will be very interesting to see how transport economics will play out in reality in the coming few years, and how governments cater to Australians who either cannot afford substantial increases in transport costs or have no viable alternatives to those facilities whose costs will increase. The 2010 AITPM National Conference, “What’s New?”, still has the opportunity for authors to submit an abstract for consideration so please consider how you might contribute to the event. Best regards to all, Jon Bunker

Transportation disadvantage determination framework : space-time organisation measure in determining transportation disadvantage

Transportation disadvantage has been recognised to be the key source of social exclusion. Therefore an appropriate process is required to investigate and seek to resolve this problem. Currently, determination of Transportation Disadvantage is postulate based on income, poverty and mobility level. Transportation disadvantage may best regard be based on accessibility perspectives as they represent inability of the individual to access desired activities. This paper attempts to justify a process in determining transportation disadvantage by incorporating accessibility and social transporation conflict as the essence of a framework. The framework embeds space time organisation within the dimension of accessibility to identify a rigorous definition of transportation disadvantage. In developing the framework, the definition, dimension, component and measure of accessibility were scrutinised. The findings suggest the definition and dimension are the significant approach of research to evaluate travel experience of the disadvantaged. Concurrently, location accessibility measures will be incorprated to strenghten the determination of accessibility level. Literature review in social exclusion and mobility-related exclusion identified the dimension and source of transportation disadvantage. It was revealed that the appropriate approach to justify trasnportation disadvantaged is to incorporate space-time organisation within the studied components. The suggested framework is an inter-related process consisting of component of accessibility; individual, networking (transport system) and activities (destination). The integration and correlation among the components shall determine the level of transportation disadvantage. Prior findings are used to retrieve the spatial distribution of transportation disadvantaged and appropriate policies are developed to resolve the problems.

Mining patterns and factors contributing to crash severity on road curves

Road curves are an important feature of road infrastructure and many serious crashes occur on road curves. In Queensland, the number of fatalities is twice as many on curves as that on straight roads. Therefore, there is a need to reduce drivers’ exposure to crash risk on road curves. Road crashes in Australia and in the Organisation for Economic Co-operation and Development(OECD) have plateaued in the last five years (2004 to 2008) and the road safety community is desperately seeking innovative interventions to reduce the number of crashes. However, designing an innovative and effective intervention may prove to be difficult as it relies on providing theoretical foundation, coherence, understanding, and structure to both the design and validation of the efficiency of the new intervention. Researchers from multiple disciplines have developed various models to determine the contributing factors for crashes on road curves with a view towards reducing the crash rate. However, most of the existing methods are based on statistical analysis of contributing factors described in government crash reports. In order to further explore the contributing factors related to crashes on road curves, this thesis designs a novel method to analyse and validate these contributing factors. The use of crash claim reports from an insurance company is proposed for analysis using data mining techniques. To the best of our knowledge, this is the first attempt to use data mining techniques to analyse crashes on road curves. Text mining technique is employed as the reports consist of thousands of textual descriptions and hence, text mining is able to identify the contributing factors. Besides identifying the contributing factors, limited studies to date have investigated the relationships between these factors, especially for crashes on road curves. Thus, this study proposed the use of the rough set analysis technique to determine these relationships. The results from this analysis are used to assess the effect of these contributing factors on crash severity. The findings obtained through the use of data mining techniques presented in this thesis, have been found to be consistent with existing identified contributing factors. Furthermore, this thesis has identified new contributing factors towards crashes and the relationships between them. A significant pattern related with crash severity is the time of the day where severe road crashes occur more frequently in the evening or night time. Tree collision is another common pattern where crashes that occur in the morning and involves hitting a tree are likely to have a higher crash severity. Another factor that influences crash severity is the age of the driver. Most age groups face a high crash severity except for drivers between 60 and 100 years old, who have the lowest crash severity. The significant relationship identified between contributing factors consists of the time of the crash, the manufactured year of the vehicle, the age of the driver and hitting a tree. Having identified new contributing factors and relationships, a validation process is carried out using a traffic simulator in order to determine their accuracy. The validation process indicates that the results are accurate. This demonstrates that data mining techniques are a powerful tool in road safety research, and can be usefully applied within the Intelligent Transport System (ITS) domain. The research presented in this thesis provides an insight into the complexity of crashes on road curves. The findings of this research have important implications for both practitioners and academics. For road safety practitioners, the results from this research illustrate practical benefits for the design of interventions for road curves that will potentially help in decreasing related injuries and fatalities. For academics, this research opens up a new research methodology to assess crash severity, related to road crashes on curves.

Water sensitive urban design : landscape planning and design to improve water quality in Shijiazhaung and Yueyang

Water quality issues are heavily dependent on land development and management decisions within river and lake catchments or watersheds. Economic benefits of urbanisation may be short‐ lived without cleaner environmental outcomes. However, whole‐of‐catchment thinking is not, as yet, as frequent a consideration in urban planning and development in China as it is in many other countries. Water is predominantly seen as a resource to be ‘owned’ by different jurisdictions and allocated to numerous users, both within a catchment and between catchments. An alternative to this approach is to think of water in the same way as other commodities that must be kept moving through a complex transport system. Water must ultimately arrive at particular destinations in the biosphere, although it travels across a broad landscape and may be held up temporarily at certain places along the way. While water extraction can be heavily controlled, water pollution is far more difficult to regulate. Both have significant impacts on water availability and flows both now and in the future. As Chinese cities strive to improve economic conditions for their citizens, new centres are being rebuilt and environmental valued

Discrete choice modelling of combined mode and departure time

Typical daily decision-making process of individuals regarding use of transport system involves mainly three types of decisions: mode choice, departure time choice and route choice. This paper focuses on the mode and departure time choice processes and studies different model specifications for a combined mode and departure time choice model. The paper compares different sets of explanatory variables as well as different model structures to capture the correlation among alternatives and taste variations among the commuters. The main hypothesis tested in this paper is that departure time alternatives are also correlated by the amount of delay. Correlation among different alternatives is confirmed by analyzing different nesting structures as well as error component formulations. Random coefficient logit models confirm the presence of the random taste heterogeneity across commuters. Mixed nested logit models are estimated to jointly account for the random taste heterogeneity and the correlation among different alternatives. Results indicate that accounting for the random taste heterogeneity as well as inter-alternative correlation improves the model performance.

Prospective bus rapid transit scenarios for pilot corridor in Dhaka

Dhaka doesn’t have a mature transport system. Lacking in institutional arrangements, policy and planning, and law enforcement, the transport system operates has developed ad hoc and is situationally problematic. Absence of proper coordination between modes, poor public transport system, inadequate pedestrian facilities, and environmental degradation justify full consideration of Bus Rapid Transit (BRT) in Dhaka. BRT centres on sustainable transport principles. BRT is a system, which is capable to mitigate Dhaka’s transport problem if properly planned. In Strategic transport plan of Dhaka three BRT transport corridor has been proposed and BRT pre-feasibility study came up with one pilot corridor for early implementation of BRT. This paper first reviews international best practices then explores various BRT system packages and evaluates the suitability of these BRT packages by analyzing current bus service condition and physical and geometric configuration along the BRT pilot corridor. It concludes by proposing some BRT scenarios, which can be considered for further evaluation with respect to speed, delay, travel time and environmental pollution.