Single-stranded DNA-binding protein hSSB1 is critical for genomic stability

Single-strand DNA (ssDNA)-binding proteins (SSBs) are ubiquitous and essential for a wide variety of DNA metabolic processes, including DNA replication, recombination, DNA damage detection and repair1. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating nucleases, helicases and strand-exchange proteins, activating transcription and mediating protein–protein interactions. In eukaryotes, the major SSB, replication protein A (RPA), is a heterotrimer1. Here we describe a second human SSB (hSSB1), with a domain organization closer to the archaeal SSB than to RPA. Ataxia telangiectasia mutated (ATM) kinase phosphorylates hSSB1 in response to DNA double-strand breaks (DSBs). This phosphorylation event is required for DNA damage-induced stabilization of hSSB1. Upon induction of DNA damage, hSSB1 accumulates in the nucleus and forms distinct foci independent of cell-cycle phase. These foci co-localize with other known repair proteins. In contrast to RPA, hSSB1 does not localize to replication foci in S-phase cells and hSSB1 deficiency does not influence S-phase progression. Depletion of hSSB1 abrogates the cellular response to DSBs, including activation of ATM and phosphorylation of ATM targets after ionizing radiation. Cells deficient in hSSB1 exhibit increased radiosensitivity, defective checkpoint activation and enhanced genomic instability coupled with a diminished capacity for DNA repair. These findings establish that hSSB1 influences diverse endpoints in the cellular DNA damage response.

Modelling bus lost time : an additional parameter influencing bus dwell time and station platform capacity at a BRT station platform

The common approach to estimate bus dwell time at a BRT station is to apply the traditional dwell time methodology derived for suburban bus stops. In spite of being sensitive to boarding and alighting passenger numbers and to some extent towards fare collection media, these traditional dwell time models do not account for the platform crowding. Moreover, they fall short in accounting for the effects of passenger/s walking along a relatively longer BRT platform. Using the experience from Brisbane busway (BRT) stations, a new variable, Bus Lost Time (LT), is introduced in traditional dwell time model. The bus lost time variable captures the impact of passenger walking and platform crowding on bus dwell time. These are two characteristics which differentiate a BRT station from a bus stop. This paper reports the development of a methodology to estimate bus lost time experienced by buses at a BRT platform. Results were compared with the Transit Capacity and Quality of Servce Manual (TCQSM) approach of dwell time and station capacity estimation. When the bus lost time was used in dwell time calculations it was found that the BRT station platform capacity reduced by 10.1%.

Capability for infrastructure asset capacity management

Infrastructure capacity management is the process of ensuring optimal provision of infrastructure assets to support business operations. Effectiveness in this process will enable infrastructure asset owners and its stakeholders to receive full value on their investment. Management research has shown that an organisation can only achieve business value when it has the right capabilities. This paradigm can also be applied to infrastructure capacity management. With competing needs for limited organisation resources, the challenge for infrastructure organisations is to identify and invest their limited resources to develop the right capabilities in the management of their infrastructure capacity. Using a multiple case study approach, the challenges faced in the management of infrastructure asset capacity and the approaches that can be adopted to overcome these challenges were explored. Conceptualising the approaches adopted by the case participants, the findings suggest that infrastructure organisations must strengthen their stakeholder connectivity capability in order to effectively manage the capacity of their infrastructure assets.

Report on capacity-building workshops for road safety in Indonesia

In addition to the established problem of road safety in developing countries such as Indonesia, the agencies responsible for road safety often lack personnel with professional training in road safety. In Indonesia this is compounded by a need for more effective collaboration between agencies. In 2009, CARRS-Q was commissioned under the Indonesia Transport Safety Assistance Package to provide professional training in road safety for middle level officers in Jakarta, the province of Jawa Barat, and the cities of Bandung, Bogor and Sukabumi, aimed at developing action plans and fostering collaboration between agencies. This was achieved through a workshop, which followed up by a second workshop with the same participants. The course was very well received, action plans were successfully prepared during the first workshop, and most had progressed well by the time of the second workshop. Good cooperation between agencies was also evident. There would be considerable benefits in extending modified workshops more widely in Indonesia.

CD73 and CD29 concurrently mediate the mechanically induced decrease of migratory capacity of mesenchymal stromal cells

The assumption that mesenchymal stromal cell (MSC)-based therapies are capable of augmenting physiological regeneration processes has fostered intensive basic and clinical research activities. However, to achieve sustained therapeutic success in vivo, not only the biological, but also the mechanical microenvironment of MSCs during these regeneration processes needs to be taken into account. This is especially important for e.g., bone fracture repair, since MSCs present at the fracture site undergo significant biomechanical stimulation. This study has therefore investigated cellular characteristics and the functional behaviour of MSCs in response to mechanical loading. Our results demonstrated a reduced expression of MSC surface markers CD73 (ecto-5’-nucleotidase) and CD29 (integrin β1) after loading. On the functional level, loading led to a reduced migration of MSCs. Both effects persisted for a week after the removal of the loading stimulus. Specifi c inhibition of CD73/CD29 demonstrated their substrate dependent involvement in MSC migration after loading. These results were supported by scanning electron microscopy images and phalloidin staining of actin fi laments displaying less cell spreading, lamellipodia formation and actin accumulations. Moreover, focal adhesion kinase and Src-family kinases were identified as candidate downstream targets of CD73/CD29 that might contribute to the mechanically induced decrease in MSC migration. These results suggest that MSC migration is controlled by CD73 CD29, which in turn are regulated by mechanical stimulation of cells. We therefore speculate that MSCs migrate into the fracture site, become mechanically entrapped, and thereby accumulate to fulfil their regenerative functions.

Replication of the Frank-Starling response in a Mock Circulation loop

Mock circulation loops (MCLs) are used to evaluate cardiovascular devices prior to in-vivo trials; however they lack the vital autoregulatory responses that occur in humans. This study aimed to develop and implement a left and right ventricular Frank-Starling response in a MCL. A proportional controller based on ventricular end diastolic volume was used to control the driving pressure of the MCL’s pneumatically operated ventricles. Ventricular pressure-volume loops and end systolic pressure-volume relationships were produced for a variety of healthy and pathological conditions and compared with human data to validate the simulated Frank-Starling response. The non-linear Frank-Starling response produced in this study successfully altered left and right ventricular contractility with changing preload and was validated with previously reported data. This improvement to an already detailed MCL has resulted in a test rig capable of further refining cardiovascular devices and reducing the number of in-vivo trials.

Seismic capacity of building constructed in slip formed load bearing wall panels

Constructing buildings using slip formed load bearing wall panels is becoming increasingly popular in Sri Lanka due to several advantages; low cost, environmental friendliness and rapid construction technique. These wall panels are already successfully implemented in many low rise buildings. However, the seismic capacities of these buildings have not been properly studied. Few seismic activities reported in Sri Lanka have not caused severe structural damage, but predictions can not be made as to whether this will continue to be the case in the future. This highlights the need to study the seismic capacity of buildings constructed in slip formed load bearing wall panels. This paper presents a study of the seismic capacity of the existing medium rise building.

Busway platform bus capacity analysis

Bus Rapid Transit (BRT), because of its operational flexibility and simplicity, is rapidly gaining popularity with urban designers and transit planners. Earlier BRTs were bus shared lane or bus only lane, which share the roadway with general and other forms of traffic. In recent time, more sophisticated designs of BRT have emerged, such as busway, which has separate carriageway for buses and provides very high physical separation of buses from general traffic. Line capacities of a busway are predominately dependent on bus capacity of its stations. Despite new developments in BRT designs, the methodology of capacity analysis is still based on traditional principles of kerbside bus stop on bus only lane operations. Consequently, the tradition methodology lacks accounting for various dimensions of busway station operation, such as passenger crowd, passenger walking and bus lost time along the long busway station platform. This research has developed a purpose made bus capacity analysis methodology for busway station analysis. Extensive observations of kerbside bus stops and busway stations in Brisbane, Australia were made and differences in their operation were studied. A large scale data collection was conducted using the video recording technique at the Mater Hill Busway Station on the South East Busway in Brisbane. This research identified new parameters concerning busway station operation, and through intricate analysis identified the elements and processes which influence the bus dwell time at a busway station platform. A new variable, Bus lost time, was defined and its quantitative descriptions were established. Based on these finding and analysis, a busway station platform bus capacity methodology was developed, comprising of new models for busway station lost time, busway station dwell time, busway station loading area bus capacity, and busway station platform bus capacity. The new methodology not only accounts for passenger boarding and alighting, but also covers platform crowd and bus lost time in station platform bus capacity estimation. The applicability of this methodology was shown through demonstrative examples. Additionally, these examples illustrated the significance of the bus lost time variable in determining station capacities.

Assessing population limits : a carrying capacity approach to planning

While purporting to enhance Australia’s sustainability, the federal government’s Population Strategy rejects the assessment of the limiting factors to future population growth, thus avoiding urgent threshold issues such as resource depletion and environmental destruction. A more forward-thinking and whole-system perspective would assess and incorporate critical biophysical limits into governance processes with suitable prioritisation. It would encourage communities to examine their individual and collective responsibilities in the context of these limits in order to most equitably optimise outcomes; and it would employ both a resource-based examination of minimum population requirements, and an impact-based assessment of maximum thresholds. This carrying capacity approach to planning could help guide society towards a more sustainable future.

Utilizing industry-led innovation capacity to enhance supply chain performance : an empirical study

A fundamental principle of the resource-based (RBV) of the firm is that the basis for a competitive advantage lies primarily in the application of bundles of valuable strategic capabilities and resources at a firm’s or supply chain’s disposal. These capabilities enact research activities and outputs produced by industry funded R&D bodies. Such industry lead innovations are seen as strategic industry resources, because effective utilization of industry innovation capacity by sectors such as the Australian beef industry are critical, if productivity levels are to increase. Academics and practitioners often maintain that dynamic supply chains and innovation capacity are the mechanisms most likely to deliver performance improvements in national industries.. Yet many industries are still failing to capitalise on these strategic resources. In this research, we draw on the resource-based view (RBV) and embryonic research into strategic supply chain capabilities. We investigate how two strategic supply chain capabilities (supply chain performance differential capability and supply chain dynamic capability) influence industry-led innovation capacity utilization and provide superior performance enhancements to the supply chain. In addition, we examine the influence of size of the supply chain operative as a control variable. Results indicate that both small and large supply chain operatives in this industry believe these strategic capabilities influence and function as second-order latent variables of this strategic supply chain resource. Additionally respondents acknowledge size does impacts both the amount of influence these strategic capabilities have and the level of performance enhancement expected by supply chain operatives from utilizing industry-led innovation capacity. Results however also indicate contradiction in this industry and in relation to existing literature when it comes to utilizing such e-resources.

Greener and leaner : unleashing capacity of railroad concrete ties via limit states concept

New knowledge has raised a concern about the cost-ineffective design methods and the true performance of railroad prestressed concrete ties. Because of previous knowledge deficiencies, railway civil and track engineers have been aware of the conservative design methods for structural components in any railway track that rely on allowable stresses and material strength reductions. In particular, railway sleeper (or railroad tie) is an important component of railway tracks and is commonly made of prestressed concrete. The existing code for designing such components makes use of the permissible stress design concept, whereas the fiber stresses over cross sections at initial and final stages are limited by some empirical values. It is believed that the concrete ties complying with the permissible stress concept possess unduly untapped fracture toughness, based on a number of proven experiments and field data. Collaborative research run by the Australian Cooperative Research Centre for Railway Engineering and Technologies (Rail CRC) was initiated to ascertain the reserved capacity of Australian railway prestressed concrete ties that were designed using the existing design code. The findings have led to the development of a new limit-states design concept. This paper highlights the conventional and the new limit-states design philosophies and their implication to both the railway community and the public. © 2011 American Society of Civil Engineers.