ATM mediated phosphorylation of CHD4 contributes to genome maintenance

Background: In order to maintain cellular viability and genetic integrity cells must respond quickly following the induction of cytotoxic double strand DNA breaks (DSB). This response requires a number of processes including stabilisation of the DSB, signalling of the break and repair. It is becoming increasingly apparent that one key step in this process is chromatin remodelling. Results: Here we describe the chromodomain helicase DNA-binding protein (CHD4) as a target of ATM kinase. We show that ionising radiation (IR)-induced phosphorylation of CHD4 affects its intranuclear organization resulting in increased chromatin binding/retention. We also show assembly of phosphorylated CHD4 foci at sites of DNA damage, which might be required to fulfil its function in the regulation of DNA repair. Consistent with this, cells overexpressing a phospho-mutant version of CHD4 that cannot be phosphorylated by ATM fail to show enhanced chromatin retention after DSBs and display high rates of spontaneous damage. Conclusion: These results provide insight into how CHD4 phosphorylation might be required to remodel chromatin around DNA breaks allowing efficient DNA repair to occur.

Multiple human single-stranded DNA binding proteins function in genome maintenance : structural, biochemical and functional analysis

DNA exists predominantly in a duplex form that is preserved via specific base pairing. This base pairing affords a considerable degree of protection against chemical or physical damage and preserves coding potential. However, there are many situations, e.g. during DNA damage and programmed cellular processes such as DNA replication and transcription, in which the DNA duplex is separated into two singlestranded DNA (ssDNA) strands. This ssDNA is vulnerable to attack by nucleases, binding by inappropriate proteins and chemical attack. It is very important to control the generation of ssDNA and protect it when it forms, and for this reason all cellular organisms and many viruses encode a ssDNA binding protein (SSB). All known SSBs use an oligosaccharide/oligonucleotide binding (OB)-fold domain for DNA binding. SSBs have multiple roles in binding and sequestering ssDNA, detecting DNA damage, stimulating strand-exchange proteins and helicases, and mediation of protein–protein interactions. Recently two additional human SSBs have been identified that are more closely related to bacterial and archaeal SSBs. Prior to this it was believed that replication protein A, RPA, was the only human equivalent of bacterial SSB. RPA is thought to be required for most aspects of DNA metabolism including DNA replication, recombination and repair. This review will discuss in further detail the biological pathways in which human SSBs function.

Solar energy : utilization in building operations

In the face of increasing concern over global warming and climate change, interest in the utilizzation of solar energy for building operations is rapidly growing. In this entry, the importance of using renewable energy in building operations is first introduced. This is followed by a general overview on the energy from the sun and the methods to utilize solar energy. Possible applications of solar energy in building operations are then discussed, which include the use of solar energy in the forms of daylighting, hot water heating, space heating and cooling, and building-integrated photovoltaics.

Microscopic modelling of freeway operations

Freeways are divided roadways designed to facilitate the uninterrupted movement of motor vehicles. However, many freeways now experience demand flows in excess of capacity, leading to recurrent congestion. The Highway Capacity Manual (TRB, 1994) uses empirical macroscopic relationships between speed, flow and density to quantify freeway operations and performance. Capacity may be predicted as the maximum uncongested flow achievable. Although they are effective tools for design and analysis, macroscopic models lack an understanding of the nature of processes taking place in the system. Szwed and Smith (1972, 1974) and Makigami and Matsuo (1990) have shown that microscopic modelling is also applicable to freeway operations. Such models facilitate an understanding of the processes whilst providing for the assessment of performance, through measures of capacity and delay. However, these models are limited to only a few circumstances. The aim of this study was to produce more comprehensive and practical microscopic models. These models were required to accurately portray the mechanisms of freeway operations at the specific locations under consideration. The models needed to be able to be calibrated using data acquired at these locations. The output of the models needed to be able to be validated with data acquired at these sites. Therefore, the outputs should be truly descriptive of the performance of the facility. A theoretical basis needed to underlie the form of these models, rather than empiricism, which is the case for the macroscopic models currently used. And the models needed to be adaptable to variable operating conditions, so that they may be applied, where possible, to other similar systems and facilities. It was not possible to produce a stand-alone model which is applicable to all facilities and locations, in this single study, however the scene has been set for the application of the models to a much broader range of operating conditions. Opportunities for further development of the models were identified, and procedures provided for the calibration and validation of the models to a wide range of conditions. The models developed, do however, have limitations in their applicability. Only uncongested operations were studied and represented. Driver behaviour in Brisbane was applied to the models. Different mechanisms are likely in other locations due to variability in road rules and driving cultures. Not all manoeuvres evident were modelled. Some unusual manoeuvres were considered unwarranted to model. However the models developed contain the principal processes of freeway operations, merging and lane changing. Gap acceptance theory was applied to these critical operations to assess freeway performance. Gap acceptance theory was found to be applicable to merging, however the major stream, the kerb lane traffic, exercises only a limited priority over the minor stream, the on-ramp traffic. Theory was established to account for this activity. Kerb lane drivers were also found to change to the median lane where possible, to assist coincident mergers. The net limited priority model accounts for this by predicting a reduced major stream flow rate, which excludes lane changers. Cowan's M3 model as calibrated for both streams. On-ramp and total upstream flow are required as input. Relationships between proportion of headways greater than 1 s and flow differed for on-ramps where traffic leaves signalised intersections and unsignalised intersections. Constant departure onramp metering was also modelled. Minimum follow-on times of 1 to 1.2 s were calibrated. Critical gaps were shown to lie between the minimum follow-on time, and the sum of the minimum follow-on time and the 1 s minimum headway. Limited priority capacity and other boundary relationships were established by Troutbeck (1995). The minimum average minor stream delay and corresponding proportion of drivers delayed were quantified theoretically in this study. A simulation model was constructed to predict intermediate minor and major stream delays across all minor and major stream flows. Pseudo-empirical relationships were established to predict average delays. Major stream average delays are limited to 0.5 s, insignificant compared with minor stream delay, which reach infinity at capacity. Minor stream delays were shown to be less when unsignalised intersections are located upstream of on-ramps than signalised intersections, and less still when ramp metering is installed. Smaller delays correspond to improved merge area performance. A more tangible performance measure, the distribution of distances required to merge, was established by including design speeds. This distribution can be measured to validate the model. Merging probabilities can be predicted for given taper lengths, a most useful performance measure. This model was also shown to be applicable to lane changing. Tolerable limits to merging probabilities require calibration. From these, practical capacities can be estimated. Further calibration is required of traffic inputs, critical gap and minimum follow-on time, for both merging and lane changing. A general relationship to predict proportion of drivers delayed requires development. These models can then be used to complement existing macroscopic models to assess performance, and provide further insight into the nature of operations.

Modeling object identification and tracking errors on image-based safety assessment of earthmoving operations

Object identification and tracking have become critical for automated on-site construction safety assessment. The primary objective of this paper is to present the development of a testbed to analyze the impact of object identification and tracking errors caused by data collection devices and algorithms used for safety assessment. The testbed models workspaces for earthmoving operations and simulates safety-related violations, including speed limit violations, access violations to dangerous areas, and close proximity violations between heavy machinery. Three different cases were analyzed based on actual earthmoving operations conducted at a limestone quarry. Using the testbed, the impacts of device and algorithm errors were investigated for safety planning purposes.

In-depth analysis of the J.A.C.K. model

The Texas Transportation Commission (“the Commission”) is responsible for planning and making policies for the location, construction, and maintenance of a comprehensive system of highways and public roads in Texas. In order for the Commission to carry out its legislative mandate, the Texas Constitution requires that most revenue generated by motor vehicle registration fees and motor fuel taxes be used for constructing and maintaining public roadways and other designated purposes. The Texas Department of Transportation (TxDOT) assists the Commission in executing state transportation policy. It is the responsibility of the legislature to appropriate money for TxDOT’s operation and maintenance expenses. All money authorized to be appropriated for TxDOT’s operations must come from the State Highway Fund (also known as Fund 6, Fund 006, or Fund 0006). The Commission can then use the balance in the fund to fulfill its responsibilities. However, the value of the revenue received in Fund 6 is not keeping pace with growing demand for transportation infrastructure in Texas. Additionally, diversion of revenue to nontransportation uses now exceeds $600 million per year. As shown in Figure 1.1, revenues and expenditures of the State Highway Fund per vehicle mile traveled (VMT) in Texas have remained almost flat since 1993. In the meantime, construction cost inflation has gone up more than 100%, effectively halving the value of expenditure.

Extending constructability concept to include operation and maintenance issues

The concept of constructability uses integration art of individual functions through a valuable and timely construction inputs into planning and design development stages. It results in significant savings in cost and time needed to finalize infrastructure projects. However, available constructability principles, developed by CII Australia (1993), do not cover Operation and Maintenance (O&M) phases of projects, whilst major cost and time in multifaceted infrastructure projects are spent in post-occupancy stages. This paper discusses the need to extend the constructability concept by examining current O&M issues in the provision of multifaceted building projects. It highlights available O&M problems and shortcomings of building projects, as well as their causes and reasons in different categories. This initial categorization is an efficient start point for testing probable present O&M issues in various cases of complex infrastructure building projects. This preliminary categorization serve as a benchmark to develop an extended constructability model that considers the whole project life cycle phases rather than a specific phase. It anticipates that the development of an extended constructability model can reduce significant number of reworks, mistakes, extra costs and time wasted during delivery stages of multifaceted building projects.

Asset life prediction and maintenance decision-making using a non-linear non-Gaussian state space model

Estimating and predicting degradation processes of engineering assets is crucial for reducing the cost and insuring the productivity of enterprises. Assisted by modern condition monitoring (CM) technologies, most asset degradation processes can be revealed by various degradation indicators extracted from CM data. Maintenance strategies developed using these degradation indicators (i.e. condition-based maintenance) are more cost-effective, because unnecessary maintenance activities are avoided when an asset is still in a decent health state. A practical difficulty in condition-based maintenance (CBM) is that degradation indicators extracted from CM data can only partially reveal asset health states in most situations. Underestimating this uncertainty in relationships between degradation indicators and health states can cause excessive false alarms or failures without pre-alarms. The state space model provides an efficient approach to describe a degradation process using these indicators that can only partially reveal health states. However, existing state space models that describe asset degradation processes largely depend on assumptions such as, discrete time, discrete state, linearity, and Gaussianity. The discrete time assumption requires that failures and inspections only happen at fixed intervals. The discrete state assumption entails discretising continuous degradation indicators, which requires expert knowledge and often introduces additional errors. The linear and Gaussian assumptions are not consistent with nonlinear and irreversible degradation processes in most engineering assets. This research proposes a Gamma-based state space model that does not have discrete time, discrete state, linear and Gaussian assumptions to model partially observable degradation processes. Monte Carlo-based algorithms are developed to estimate model parameters and asset remaining useful lives. In addition, this research also develops a continuous state partially observable semi-Markov decision process (POSMDP) to model a degradation process that follows the Gamma-based state space model and is under various maintenance strategies. Optimal maintenance strategies are obtained by solving the POSMDP. Simulation studies through the MATLAB are performed; case studies using the data from an accelerated life test of a gearbox and a liquefied natural gas industry are also conducted. The results show that the proposed Monte Carlo-based EM algorithm can estimate model parameters accurately. The results also show that the proposed Gamma-based state space model have better fitness result than linear and Gaussian state space models when used to process monotonically increasing degradation data in the accelerated life test of a gear box. Furthermore, both simulation studies and case studies show that the prediction algorithm based on the Gamma-based state space model can identify the mean value and confidence interval of asset remaining useful lives accurately. In addition, the simulation study shows that the proposed maintenance strategy optimisation method based on the POSMDP is more flexible than that assumes a predetermined strategy structure and uses the renewal theory. Moreover, the simulation study also shows that the proposed maintenance optimisation method can obtain more cost-effective strategies than a recently published maintenance strategy optimisation method by optimising the next maintenance activity and the waiting time till the next maintenance activity simultaneously.

A grouping model for distributed pipeline assets maintenance decision

Distributed pipeline assets systems are crucial to society. The deterioration of these assets and the optimal allocation of limited budget for their maintenance correspond to crucial challenges for water utility managers. Decision makers should be assisted with optimal solutions to select the best maintenance plan concerning available resources and management strategies. Much research effort has been dedicated to the development of optimal strategies for maintenance of water pipes. Most of the maintenance strategies are intended for scheduling individual water pipe. Consideration of optimal group scheduling replacement jobs for groups of pipes or other linear assets has so far not received much attention in literature. It is a common practice that replacement planners select two or three pipes manually with ambiguous criteria to group into one replacement job. This is obviously not the best solution for job grouping and may not be cost effective, especially when total cost can be up to multiple million dollars. In this paper, an optimal group scheduling scheme with three decision criteria for distributed pipeline assets maintenance decision is proposed. A Maintenance Grouping Optimization (MGO) model with multiple criteria is developed. An immediate challenge of such modeling is to deal with scalability of vast combinatorial solution space. To address this issue, a modified genetic algorithm is developed together with a Judgment Matrix. This Judgment Matrix is corresponding to various combinations of pipe replacement schedules. An industrial case study based on a section of a real water distribution network was conducted to test the new model. The results of the case study show that new schedule generated a significant cost reduction compared with the schedule without grouping pipes.

Design of a preliminary error impact analysis model for spatial safety assessment of earthmoving operations

Regardless of technology benefits, safety planners still face difficulties explaining errors related to the use of different technologies and evaluating how the errors impact the performance of safety decision making. This paper presents a preliminary error impact analysis testbed to model object identification and tracking errors caused by image-based devices and algorithms and to analyze the impact of the errors for spatial safety assessment of earthmoving and surface mining activities. More specifically, this research designed a testbed to model workspaces for earthmoving operations, to simulate safety-related violations, and to apply different object identification and tracking errors on the data collected and processed for spatial safety assessment. Three different cases were analyzed based on actual earthmoving operations conducted at a limestone quarry. Using the testbed, the impacts of the errors were investigated for the safety planning purpose.

Maintenance strategy optimization using a continuous-state partially observable semi-Markov decision process

Due to the limitation of current condition monitoring technologies, the estimates of asset health states may contain some uncertainties. A maintenance strategy ignoring this uncertainty of asset health state can cause additional costs or downtime. The partially observable Markov decision process (POMDP) is a commonly used approach to derive optimal maintenance strategies when asset health inspections are imperfect. However, existing applications of the POMDP to maintenance decision-making largely adopt the discrete time and state assumptions. The discrete-time assumption requires the health state transitions and maintenance activities only happen at discrete epochs, which cannot model the failure time accurately and is not cost-effective. The discrete health state assumption, on the other hand, may not be elaborate enough to improve the effectiveness of maintenance. To address these limitations, this paper proposes a continuous state partially observable semi-Markov decision process (POSMDP). An algorithm that combines the Monte Carlo-based density projection method and the policy iteration is developed to solve the POSMDP. Different types of maintenance activities (i.e., inspections, replacement, and imperfect maintenance) are considered in this paper. The next maintenance action and the corresponding waiting durations are optimized jointly to minimize the long-run expected cost per unit time and availability. The result of simulation studies shows that the proposed maintenance optimization approach is more cost-effective than maintenance strategies derived by another two approximate methods, when regular inspection intervals are adopted. The simulation study also shows that the maintenance cost can be further reduced by developing maintenance strategies with state-dependent maintenance intervals using the POSMDP. In addition, during the simulation studies the proposed POSMDP shows the ability to adopt a cost-effective strategy structure when multiple types of maintenance activities are involved.

Forced landing technologies for unmanned aerial vehicles : towards safer operations

While using unmanned systems in combat is not new, what will be new in the foreseeable future is how such systems are used and integrated in the civilian space. The potential use of Unmanned Aerial Vehicles in civil and commercial applications is becoming a fact, and is receiving considerable attention by industry and the research community. The majority of Unmanned Aerial Vehicles performing civilian tasks are restricted to flying only in segregated space, and not within the National Airspace. The areas that UAVs are restricted to flying in are typically not above populated areas, which in turn are the areas most useful for civilian applications. The reasoning behind the current restrictions is mainly due to the fact that current UAV technologies are not able to demonstrate an Equivalent Level of Safety to manned aircraft, particularly in the case of an engine failure which would require an emergency or forced landing. This chapter will preset and guide the reader through a number of developments that would facilitate the integration of UAVs into the National Airspace. Algorithms for UAV Sense-and-Avoid and Force Landings are recognized as two major enabling technologies that will allow the integration of UAVs in the civilian airspace. The following sections will describe some of the techniques that are currently being tested at the Australian Research Centre for Aerospace Automation (ARCAA), which places emphasis on the detection of candidate landing sites using computer vision, the planning of the descent path trajectory for the UAV, and the decision making process behind the selection of the final landing site.