title: Hierarchical interface-based supervisory control using the conflict preorder

authors: Malik, Robi

subjects: discrete event systems

abstract: Hierarchical Interface-Based Supervisory Control decomposes a large discrete event system into subsystems linked to each other by interfaces, facilitating the design of complex systems and the re-use of components. By ensuring that each subsystem satisfies its interface consistency conditions locally, it can be ensured that the complete system is controllable and nonblocking. The interface consistency conditions proposed in this paper are based on the conflict preorder, providing increased flexibility over previous approaches. The framework requires only a small number of interface consistency conditions, and allows for the design of multi-level hierarchies that are provably controllable and nonblocking.

text: Hierarchical interface-based supervisory control using the conflict preorder Hierarchical Interface-Based Supervisory Control decomposes a large discrete event system into subsystems linked to each other by interfaces, facilitating the design of complex systems and the re-use of components. By ensuring that each subsystem satisfies its interface consistency conditions locally, it can be ensured that the complete system is controllable and nonblocking. The interface consistency conditions proposed in this paper are based on the conflict preorder, providing increased flexibility over previous approaches. The framework requires only a small number of interface consistency conditions, and allows for the design of multi-level hierarchies that are provably controllable and nonblocking.

year: 2012

title: Decoupling enzyme catalysis from thermal denaturation

authors: Easter, Ashley Davys

subjects: equilibrium model

abstract: The equilibrium model (EM) (Daniel et al., 2001) postulates two forms of a folded enzyme, one catalytically active (Eact) and the other inactive (Einact), which interconvert via a fast thermal equilibrium (Keq) (Figure A). This model for enzyme catalysis accounts for experimentally observed time and temperature profiles of enzyme/substrate systems more accurately than the classically derived, single folded-species, model (Figure B). In both models, the denatured species (X) is formed via the kinact process, which is temperature and time-dependent.
(FIgure A) (Figure B) Comparison between the equilibrium model and classical model for enzyme catalysis. For both, the vertical axis is catalytic rate (M s-1), the left-right axis is increasing temperature (K) and the back-front axis is assay duration (s).
The physical basis for the Eact/Einact equilibrium is unknown. To study the equilibrium, the temperature midpoint of the Eact/Einact transition (Teq) has to be separated from the thermostability of the enzyme (Tm) to allow the Einact species to exist in measurable concentrations without exhibiting denaturation.
Mutations were made in a well-studied and NMR-accessible ribonuclease, barnase, to alter the thermostability and/or the Teq of the enzyme activity. The stability properties of each mutant were measured and the activity against two substrates assayed. New models were derived and fitted against wild-type barnase, and an ideal data set, to give insight into alternative irreversible and reversible denaturation pathways. Simulations of these models were developed to benchmark potential dynamics work and explain the movements of species within each model's framework.
Assay data fits to the EM and alternative models show a preference for irreversible denaturation pathways via the Einact species. A mathematically simplified model was also found that accounts for data and could provide an alternative method for determining EM parameters. Although fits of barnase to the EM were statistically good, the denaturation properties could not be reconciled with the literature or experimentally determined values for stability and unfolding. Simulations illustrating how the Eact, Einact and denatured (X) species interact also corroborate this finding.
Despite this discrepancy (in fitted parameters to the EM), it is hypothesised that the Teq and Tm of a disulphide-bridged mutant of barnase have been successfully decoupled. This mutant has been 15N- labelled for future NMR dynamics measurements. New approaches to the EM model are proposed where the separate determination of enzyme thermodynamic properties (e.g., rate and free energy of denaturation) would allow other EM parameters to be fitted independently to each data set.

text: Decoupling enzyme catalysis from thermal denaturation The equilibrium model (EM) (Daniel et al., 2001) postulates two forms of a folded enzyme, one catalytically active (Eact) and the other inactive (Einact), which interconvert via a fast thermal equilibrium (Keq) (Figure A). This model for enzyme catalysis accounts for experimentally observed time and temperature profiles of enzyme/substrate systems more accurately than the classically derived, single folded-species, model (Figure B). In both models, the denatured species (X) is formed via the kinact process, which is temperature and time-dependent.
(FIgure A) (Figure B) Comparison between the equilibrium model and classical model for enzyme catalysis. For both, the vertical axis is catalytic rate (M s-1), the left-right axis is increasing temperature (K) and the back-front axis is assay duration (s).
The physical basis for the Eact/Einact equilibrium is unknown. To study the equilibrium, the temperature midpoint of the Eact/Einact transition (Teq) has to be separated from the thermostability of the enzyme (Tm) to allow the Einact species to exist in measurable concentrations without exhibiting denaturation.
Mutations were made in a well-studied and NMR-accessible ribonuclease, barnase, to alter the thermostability and/or the Teq of the enzyme activity. The stability properties of each mutant were measured and the activity against two substrates assayed. New models were derived and fitted against wild-type barnase, and an ideal data set, to give insight into alternative irreversible and reversible denaturation pathways. Simulations of these models were developed to benchmark potential dynamics work and explain the movements of species within each model's framework.
Assay data fits to the EM and alternative models show a preference for irreversible denaturation pathways via the Einact species. A mathematically simplified model was also found that accounts for data and could provide an alternative method for determining EM parameters. Although fits of barnase to the EM were statistically good, the denaturation properties could not be reconciled with the literature or experimentally determined values for stability and unfolding. Simulations illustrating how the Eact, Einact and denatured (X) species interact also corroborate this finding.
Despite this discrepancy (in fitted parameters to the EM), it is hypothesised that the Teq and Tm of a disulphide-bridged mutant of barnase have been successfully decoupled. This mutant has been 15N- labelled for future NMR dynamics measurements. New approaches to the EM model are proposed where the separate determination of enzyme thermodynamic properties (e.g., rate and free energy of denaturation) would allow other EM parameters to be fitted independently to each data set.

year: 2010

title: Te Aka Roa o Te Oranga, the far reaching vines of wellness: The development of a framework to evaluate alcohol and drug treatment for Māori

authors: Robertson, Paul

subjects: Maori

abstract: The impact of alcohol and other drug
problems for Māori is well documented.
Substance use has been implicated in a
range of physical and mental health
problems, and a variety of negative social
statistics such as high rates of imprisonment. To date there has been
little systematic documentation of treatment
practices, and limited operationalisation of
Māori health frameworks. The evaluation
of the outcomes of alcohol and other drug
treatments is an area in which there is a
paucity of documentation, in terms of
methods and frameworks for evaluation,
and actual data. Te Aka Roa O Te Oranga (TAROTO)
was developed from a range of projects
undertaken by the National Addiction
Centre. The TARATO evaluation framework
embraces a holistic perspective: developed
to examine the interaction between the
client, whānau, practitioner, and
service/organisation. The aim of the
framework is to clarify the complex
relationships and interactions between
stakeholders within the context of
treatment. It will also help to elucidate the
strengths and weaknesses of individual
services. Within this framework, a range of
indicators and outcomes of “successful
treatment” will be explored. The current project is the first phase of
a broader project that will make a
significant contribution to improvements in
Māori health via further developing
effective treatments of alcohol and other
drug related problems.

text: Te Aka Roa o Te Oranga, the far reaching vines of wellness: The development of a framework to evaluate alcohol and drug treatment for Māori The impact of alcohol and other drug
problems for Māori is well documented.
Substance use has been implicated in a
range of physical and mental health
problems, and a variety of negative social
statistics such as high rates of imprisonment. To date there has been
little systematic documentation of treatment
practices, and limited operationalisation of
Māori health frameworks. The evaluation
of the outcomes of alcohol and other drug
treatments is an area in which there is a
paucity of documentation, in terms of
methods and frameworks for evaluation,
and actual data. Te Aka Roa O Te Oranga (TAROTO)
was developed from a range of projects
undertaken by the National Addiction
Centre. The TARATO evaluation framework
embraces a holistic perspective: developed
to examine the interaction between the
client, whānau, practitioner, and
service/organisation. The aim of the
framework is to clarify the complex
relationships and interactions between
stakeholders within the context of
treatment. It will also help to elucidate the
strengths and weaknesses of individual
services. Within this framework, a range of
indicators and outcomes of “successful
treatment” will be explored. The current project is the first phase of
a broader project that will make a
significant contribution to improvements in
Māori health via further developing
effective treatments of alcohol and other
drug related problems.

year: 2003