Inhibition of myeloperoxidase-mediated hypochlorous acid production by nitroxides

Tissue damage resulting from the extracellular production of HOCl (hypochlorous acid) by the MPO (myeloperoxidase)-hydrogen peroxide-chloride system of activated phagocytes is implicated as a key event in the progression of a number of human inflammatory diseases. Consequently, there is considerable interest in the development of therapeutically useful MPO inhibitors. Nitroxides are well established antioxidant compounds of low toxicity that can attenuate oxidative damage in animal models of inflammatory disease. They are believed to exert protective effects principally by acting as superoxide dismutase mimetics or radical scavengers. However, we show here that nitroxides can also potently inhibit MPO-mediated HOCl production, with the nitroxide 4-aminoTEMPO inhibiting HOCl production by MPO and by neutrophils with IC50 values of approx. 1 and 6 μM respectively. Structure–activity relationships were determined for a range of aliphatic and aromatic nitroxides, and inhibition of oxidative damage to two biologically-important protein targets (albumin and perlecan) are demonstrated. Inhibition was shown to involve one-electron oxidation of the nitroxides by the compound I form of MPO and accumulation of compound II. Haem destruction was also observed with some nitroxides. Inhibition of neutrophil HOCl production by nitroxides was antagonized by neutrophil-derived superoxide, with this attributed to superoxide-mediated reduction of compound II. This effect was marginal with 4-aminoTEMPO, probably due to the efficient superoxide dismutase-mimetic activity of this nitroxide. Overall, these data indicate that nitroxides have considerable promise as therapeutic agents for the inhibition of MPO-mediated damage in inflammatory diseases.

Scheduling trains as a blocking parallel-machine job shop scheduling problem

In this paper, the train scheduling problem is modelled as a blocking parallel-machine job shop scheduling (BPMJSS) problem. In the model, trains, single-track sections and multiple-track sections, respectively, are synonymous with jobs, single machines and parallel machines, and an operation is regarded as the movement/traversal of a train across a section. Due to the lack of buffer space, the real-life case should consider blocking or hold-while-wait constraints, which means that a track section cannot release and must hold the train until next section on the routing becomes available. Based on literature review and our analysis, it is very hard to find a feasible complete schedule directly for BPMJSS problems. Firstly, a parallel-machine job-shop-scheduling (PMJSS) problem is solved by an improved shifting bottleneck procedure (SBP) algorithm without considering blocking conditions. Inspired by the proposed SBP algorithm, feasibility satisfaction procedure (FSP) algorithm is developed to solve and analyse the BPMJSS problem, by an alternative graph model that is an extension of the classical disjunctive graph models. The proposed algorithms have been implemented and validated using real-world data from Queensland Rail. Sensitivity analysis has been applied by considering train length, upgrading track sections, increasing train speed and changing bottleneck sections. The outcomes show that the proposed methodology would be a very useful tool for the real-life train scheduling problems

A robust reactive scheduling model for intensive care units

The ICU is an integral part of any hospital and is under great load from patient arrivals as well as resource limitations. Scheduling of patients in the ICU is complicated by the two general types; elective surgery and emergency arrivals. This complicated situation is handled by creating a tentative initial schedule and then reacting to uncertain arrivals as they occur. For most hospitals there is little or no flexibility in the number of beds that are available for use now or in the future. We propose an integer programming model to handle a parallel machine reacting system for scheduled and unscheduled arrivals.

Industrial playwriting : forms, strategies, and methods for creative production

This study, in its exploration of the attached play scripts and their method of development, evaluates the forms, strategies, and methods of an organised model of formalised playwriting. Through the examination, reflection and reaction to a perceived crisis in playwriting in the Australian theatre sector, the notion of Industrial Playwriting is arrived at: a practice whereby plays are designed and constructed, and where the process of writing becomes central to the efficient creation of new work and the improvement of the writer’s skill and knowledge base. Using a practice-led methodology and action research the study examines a system of play construction appropriate to and addressing the challenges of the contemporary Australian theatre sector. Specifically, using the action research methodology known as design-based research a conceptual framework was constructed to form the basis of the notion of Industrial Playwriting. From this two plays were constructed using a case study method and the process recorded and used to create a practical, step-by-step system of Industrial Playwriting. In the creative practice of manufacturing a single authored play, and then a group-devised play, Industrial Playwriting was tested and found to also offer a valid alternative approach to playwriting in the training of new and even emerging playwrights. Finally, it offered insight into how Industrial Playwriting could be used to greatly facilitate theatre companies’ ongoing need to have access to new writers and new Australian works, and how it might form the basis of a cost effective writer development model. This study of the methods of formalised writing as a means to confront some of the challenges of the Australian theatre sector, the practice of playwriting and the history associated with it, makes an original and important contribution to contemporary playwriting practice.

Object-centric process models and the design of flexible processes

Mainstream business process modelling techniques promote a design paradigm wherein the activities to be performed within a case, together with their usual execution order, form the backbone of a process model, on top of which other aspects are anchored. This paradigm, while eective in standardised and production-oriented domains, shows some limitations when confronted with processes where case-by-case variations and exceptions are the norm. In this thesis we develop the idea that the eective design of exible process models calls for an alternative modelling paradigm, one in which process models are modularised along key business objects, rather than along activity decompositions. The research follows a design science method, starting from the formulation of a research problem expressed in terms of requirements, and culminating in a set of artifacts that have been devised to satisfy these requirements. The main contributions of the thesis are: (i) a meta-model for object-centric process modelling incorporating constructs for capturing exible processes; (ii) a transformation from this meta-model to an existing activity-centric process modelling language, namely YAWL, showing the relation between object-centric and activity-centric process modelling approaches; and (iii) a Coloured Petri Net that captures the semantics of the proposed meta-model. The meta-model has been evaluated using a framework consisting of a set of work ow patterns. Moreover, the meta-model has been embodied in a modelling tool that has been used to capture two industrial scenarios.

Metaheuristic approaches to the hybrid flow shop scheduling problem with a cost-related criterion

In the paper, the flow-shop scheduling problem with parallel machines at each stage (machine center) is studied. For each job its release and due date as well as a processing time for its each operation are given. The scheduling criterion consists of three parts: the total weighted earliness, the total weighted tardiness and the total weighted waiting time. The criterion takes into account the costs of storing semi-manufactured products in the course of production and ready-made products as well as penalties for not meeting the deadlines stated in the conditions of the contract with customer. To solve the problem, three constructive algorithms and three metaheuristics (based one Tabu Search and Simulated Annealing techniques) are developed and experimentally analyzed. All the proposed algorithms operate on the notion of so-called operation processing order, i.e. the order of operations on each machine. We show that the problem of schedule construction on the base of a given operation processing order can be reduced to the linear programming task. We also propose some approximation algorithm for schedule construction and show the conditions of its optimality.

Alternative film production

Typically a film producer expects the director and actors to 'do their job' within a scheduled timeframe. Rather than expecting the creative principals to just deliver, a production model can be tailored to help this creative team produce successful outcomes. This research paper contrasts alternative production models with a traditional (or standard) production and presents possibilities for producers to emphasise the collaborative potential for their production.

Virtual Environment Visualisation of Executable Business Process Models

Business Process Modelling is a fast growing field in business and information technology, which uses visual grammars to model and execute the processes within an organisation. However, many analysts present such models in a 2D static and iconic manner that is difficult to understand by many stakeholders. Difficulties in understanding such grammars can impede the improvement of processes within an enterprise due to communication problems. In this chapter we present a novel framework for intuitively visualising animated business process models in interactive Virtual Environments. We also show that virtual environment visualisations can be performed with present 2D business process modelling technology, thus providing a low barrier to entry for business process practitioners. Two case studies are presented from film production and healthcare domains that illustrate the ease with which these visualisations can be created. This approach can be generalised to other executable workflow systems, for any application domain being modelled.

Next Generation ‘Filmmaking’: New Markets, New Methods and New Business Models

Digital production and distribution technologies may create new opportunities for filmmaking in Australia. A culture of new approaches to filmmaking is emerging driven by ‘next generation filmmakers’ who are willing to consider new business models: from online web series to short films produced for mobile phones. At the same time cultural representation itself is transforming within an interactive, social media driven environment. Yet there is very little research into next generation filmmaking. The aim of this paper is to scope and discuss three key aspects of next generation filmmaking, namely: digital trends in film distribution and marketing; processes and strategies of ‘next generation’ filmmakers; and case studies of viable next generation business models and filmmaking practices. We conclude with a brief examination of the implications for media and cultural policy which suggests the future possibility of a rapprochement between creative industries discourse and cultural policy.

Modelling photochemical production of fine particulates in a toluene/NOx/water vapour system

This work investigates the computer modelling of the photochemical formation of smog products such as ozone and aerosol, in a system containing toluene, NOx and water vapour. In particular, the problem of modelling this process in the Commonwealth Scientific and Industrial Research Organization (CSIRO) smog chambers, which utilize outdoor exposure, is addressed. The primary requirement for such modelling is a knowledge of the photolytic rate coefficients. Photolytic rate coefficients of species other than N02 are often related to JNo2 (rate coefficient for the photolysis ofN02) by a simple factor, but for outdoor chambers, this method is prone to error as the diurnal profiles may not be similar in shape. Three methods for the calculation of diurnal JNo2 are investigated. The most suitable method for incorporation into a general model, is found to be one which determines the photolytic rate coefficients for N02, as well as several other species, from actinic flux, absorption cross section and quantum yields. A computer model was developed, based on this method, to calculate in-chamber photolysis rate coefficients for the CSIRO smog chambers, in which ex-chamber rate coefficients are adjusted by accounting for variation in light intensity by transmittance through the Teflon walls, albedo from the chamber floor and radiation attenuation due to clouds. The photochemical formation of secondary aerosol is investigated in a series of toluene-NOx experiments, which were performed in the CSIRO smog chambers. Three stages of aerosol formation, in plots of total particulate volume versus time, are identified: a delay period in which no significant mass of aerosol is formed, a regime of rapid aerosol formation (regime 1) and a second regime of slowed aerosol formation (regime 2). Two models are presented which were developed from the experimental data. One model is empirically based on observations of discrete stages of aerosol formation and readily allows aerosol growth profiles to be calculated. The second model is based on an adaptation of published toluene photooxidation mechanisms and provides some chemical information about the oxidation products. Both models compare favorably against the experimental data. The gross effects of precursor concentrations (toluene, NOx and H20) and ambient conditions (temperature, photolysis rate) on the formation of secondary aerosol are also investigated, primarily using the mechanism model. An increase in [NOx]o results in increased delay time, rate of aerosol formation in regime 1 and volume of aerosol formed in regime 1. This is due to increased formation of dinitrocresol and furanone products. An increase in toluene results in a decrease in the delay time and an increase in the rate of aerosol formation in regime 1, due to enhanced reactivity from the toluene products, such as the radicals from the photolysis of benzaldehyde. Water vapor has very little effect on the formation of aerosol volume, except that rates are slightly increased due to more OH radicals from reaction with 0(1D) from ozone photolysis. Increased temperature results in increased volume of aerosol formed in regime 1 (increased dinitrocresol formation), while increased photolysis rate results in increased rate of aerosol formation in regime 1. Both the rate and volume of aerosol formed in regime 2 are increased by increased temperature or photolysis rate. Both models indicate that the yield of secondary particulates from hydrocarbons (mass concentration aerosol formed/mass concentration hydrocarbon precursor) is proportional to the ratio [NOx]0/[hydrocarbon]0

Modelling and solving train scheduling problems under capacity constraints

Many large coal mining operations in Australia rely heavily on the rail network to transport coal from mines to coal terminals at ports for shipment. Over the last few years, due to the fast growing demand, the coal rail network is becoming one of the worst industrial bottlenecks in Australia. As a result, this provides great incentives for pursuing better optimisation and control strategies for the operation of the whole rail transportation system under network and terminal capacity constraints. This PhD research aims to achieve a significant efficiency improvement in a coal rail network on the basis of the development of standard modelling approaches and generic solution techniques. Generally, the train scheduling problem can be modelled as a Blocking Parallel- Machine Job-Shop Scheduling (BPMJSS) problem. In a BPMJSS model for train scheduling, trains and sections respectively are synonymous with jobs and machines and an operation is regarded as the movement/traversal of a train across a section. To begin, an improved shifting bottleneck procedure algorithm combined with metaheuristics has been developed to efficiently solve the Parallel-Machine Job- Shop Scheduling (PMJSS) problems without the blocking conditions. Due to the lack of buffer space, the real-life train scheduling should consider blocking or hold-while-wait constraints, which means that a track section cannot release and must hold a train until the next section on the routing becomes available. As a consequence, the problem has been considered as BPMJSS with the blocking conditions. To develop efficient solution techniques for BPMJSS, extensive studies on the nonclassical scheduling problems regarding the various buffer conditions (i.e. blocking, no-wait, limited-buffer, unlimited-buffer and combined-buffer) have been done. In this procedure, an alternative graph as an extension of the classical disjunctive graph is developed and specially designed for the non-classical scheduling problems such as the blocking flow-shop scheduling (BFSS), no-wait flow-shop scheduling (NWFSS), and blocking job-shop scheduling (BJSS) problems. By exploring the blocking characteristics based on the alternative graph, a new algorithm called the topological-sequence algorithm is developed for solving the non-classical scheduling problems. To indicate the preeminence of the proposed algorithm, we compare it with two known algorithms (i.e. Recursive Procedure and Directed Graph) in the literature. Moreover, we define a new type of non-classical scheduling problem, called combined-buffer flow-shop scheduling (CBFSS), which covers four extreme cases: the classical FSS (FSS) with infinite buffer, the blocking FSS (BFSS) with no buffer, the no-wait FSS (NWFSS) and the limited-buffer FSS (LBFSS). After exploring the structural properties of CBFSS, we propose an innovative constructive algorithm named the LK algorithm to construct the feasible CBFSS schedule. Detailed numerical illustrations for the various cases are presented and analysed. By adjusting only the attributes in the data input, the proposed LK algorithm is generic and enables the construction of the feasible schedules for many types of non-classical scheduling problems with different buffer constraints. Inspired by the shifting bottleneck procedure algorithm for PMJSS and characteristic analysis based on the alternative graph for non-classical scheduling problems, a new constructive algorithm called the Feasibility Satisfaction Procedure (FSP) is proposed to obtain the feasible BPMJSS solution. A real-world train scheduling case is used for illustrating and comparing the PMJSS and BPMJSS models. Some real-life applications including considering the train length, upgrading the track sections, accelerating a tardy train and changing the bottleneck sections are discussed. Furthermore, the BPMJSS model is generalised to be a No-Wait Blocking Parallel- Machine Job-Shop Scheduling (NWBPMJSS) problem for scheduling the trains with priorities, in which prioritised trains such as express passenger trains are considered simultaneously with non-prioritised trains such as freight trains. In this case, no-wait conditions, which are more restrictive constraints than blocking constraints, arise when considering the prioritised trains that should traverse continuously without any interruption or any unplanned pauses because of the high cost of waiting during travel. In comparison, non-prioritised trains are allowed to enter the next section immediately if possible or to remain in a section until the next section on the routing becomes available. Based on the FSP algorithm, a more generic algorithm called the SE algorithm is developed to solve a class of train scheduling problems in terms of different conditions in train scheduling environments. To construct the feasible train schedule, the proposed SE algorithm consists of many individual modules including the feasibility-satisfaction procedure, time-determination procedure, tune-up procedure and conflict-resolve procedure algorithms. To find a good train schedule, a two-stage hybrid heuristic algorithm called the SE-BIH algorithm is developed by combining the constructive heuristic (i.e. the SE algorithm) and the local-search heuristic (i.e. the Best-Insertion- Heuristic algorithm). To optimise the train schedule, a three-stage algorithm called the SE-BIH-TS algorithm is developed by combining the tabu search (TS) metaheuristic with the SE-BIH algorithm. Finally, a case study is performed for a complex real-world coal rail network under network and terminal capacity constraints. The computational results validate that the proposed methodology would be very promising because it can be applied as a fundamental tool for modelling and solving many real-world scheduling problems.

Scheduling coordination through negotiation between train service providers in an open railway access market

A schedule coordination problem involving two train services provided by different operators is modeled as an optimization of revenue intake. The coordination is achieved through the adjustment of commencement times of the train services by negotiation. The problem is subject to constraints regarding to passenger demands and idle costs of rolling-stocks from both operators. This paper models the operators as software agents having the flexibility to incorporate one of the two (and potentially more) proposed negotiation strategies. Empirical results show that agents employing different combination of strategies have significant impact on the quality of solution and negotiation time.

A prioritised fuzzy constraint satisfaction approach to model agent negotiation for railway scheduling

With the recent regulatory reforms in a number of countries, railways resources are no longer managed by a single party but are distributed among different stakeholders. To facilitate the operation of train services, a train service provider (SP) has to negotiate with the infrastructure provider (IP) for a train schedule and the associated track access charge. This paper models the SP and IP as software agents and the negotiation as a prioritized fuzzy constraint satisfaction (PFCS) problem. Computer simulations have been conducted to demonstrate the effects on the train schedule when the SP has different optimization criteria. The results show that by assigning different priorities on the fuzzy constraints, agents can represent SPs with different operational objectives.

Hierarchical Bayesian models for estimating the extent of plant pest invasions

Plant biosecurity requires statistical tools to interpret field surveillance data in order to manage pest incursions that threaten crop production and trade. Ultimately, management decisions need to be based on the probability that an area is infested or free of a pest. Current informal approaches to delimiting pest extent rely upon expert ecological interpretation of presence / absence data over space and time. Hierarchical Bayesian models provide a cohesive statistical framework that can formally integrate the available information on both pest ecology and data. The overarching method involves constructing an observation model for the surveillance data, conditional on the hidden extent of the pest and uncertain detection sensitivity. The extent of the pest is then modelled as a dynamic invasion process that includes uncertainty in ecological parameters. Modelling approaches to assimilate this information are explored through case studies on spiralling whitefly, Aleurodicus dispersus and red banded mango caterpillar, Deanolis sublimbalis. Markov chain Monte Carlo simulation is used to estimate the probable extent of pests, given the observation and process model conditioned by surveillance data. Statistical methods, based on time-to-event models, are developed to apply hierarchical Bayesian models to early detection programs and to demonstrate area freedom from pests. The value of early detection surveillance programs is demonstrated through an application to interpret surveillance data for exotic plant pests with uncertain spread rates. The model suggests that typical early detection programs provide a moderate reduction in the probability of an area being infested but a dramatic reduction in the expected area of incursions at a given time. Estimates of spiralling whitefly extent are examined at local, district and state-wide scales. The local model estimates the rate of natural spread and the influence of host architecture, host suitability and inspector efficiency. These parameter estimates can support the development of robust surveillance programs. Hierarchical Bayesian models for the human-mediated spread of spiralling whitefly are developed for the colonisation of discrete cells connected by a modified gravity model. By estimating dispersal parameters, the model can be used to predict the extent of the pest over time. An extended model predicts the climate restricted distribution of the pest in Queensland. These novel human-mediated movement models are well suited to demonstrating area freedom at coarse spatio-temporal scales. At finer scales, and in the presence of ecological complexity, exploratory models are developed to investigate the capacity for surveillance information to estimate the extent of red banded mango caterpillar. It is apparent that excessive uncertainty about observation and ecological parameters can impose limits on inference at the scales required for effective management of response programs. The thesis contributes novel statistical approaches to estimating the extent of pests and develops applications to assist decision-making across a range of plant biosecurity surveillance activities. Hierarchical Bayesian modelling is demonstrated as both a useful analytical tool for estimating pest extent and a natural investigative paradigm for developing and focussing biosecurity programs.