Carbodiimide-mediated synthesis of poly(L-lactide)-based networks

Poly(L-lactide-co-succinic anhydride) networks were synthesised via the carbodiimide-mediated coupling of poly(L-lactide) (PLLA) star polymers. When 4-(dimethylamino)pyridine (DMAP) alone was used as the catalyst gelation did not occur. However, when 4-(dimethylamino)pyridinium p-toluenesulfonate (DPTS), the salt of DMAP and p-toluenesulfonic acid (PTSA), was the catalyst, the networks obtained had gel fractions comparable to those which were reported for networks synthesised by conventional methods. Greater gel fractions and conversion of the prepolymer terminal hydroxyl groups were observed when the hydroxyl-terminated star prepolymers reacted with succinic anhydride in a one-pot procedure than when the hydroxyl-terminated star prepolymers reacted with presynthesised succinic-terminated star prepolymers. The thermal properties of the networks, glass transition temperature (Tg), melting temperature (Tm) and crystallinity (Xc) were all strongly influenced by the average molecular weights between the crosslinks ((M_c). The network with the smallest (M_c )(1400 g/mol) was amorphous and had a Tg of 59 °C while the network with the largest (M_c ) (7800 g/mol) was 15 % crystalline and had a Tg of 56 °C.

The contribution of different androgen receptor domains to receptor dimerization and signaling

The androgen receptor (AR) is a ligand-activated transcription factor of the nuclear receptor superfamily that plays a critical role in male physiology and pathology. Activated by binding of the native androgens testosterone and 5-dihydrotestosterone, the AR regulates transcription of genes involved in the development and maintenance of male phenotype and male reproductive function as well as other tissues such as bone and muscle. Deregulation of AR signaling can cause a diverse range of clinical conditions, including the X-linked androgen insensitivity syndrome, a form of motor neuron disease known as Kennedy’s disease, and male infertility. In addition, there is now compelling evidence that the AR is involved in all stages of prostate tumorigenesis including initiation, progression, and treatment resistance. To better understand the role of AR signaling in the pathogenesis of these conditions, it is important to have a comprehensive understanding of the key determinants of AR structure and function. Binding of androgens to the AR induces receptor dimerization, facilitating DNA binding and the recruitment of cofactors and transcriptional machinery to regulate expression of target genes. Various models of dimerization have been described for the AR, the most well characterized interaction being DNA-binding domain- mediated dimerization, which is essential for the AR to bind DNA and regulate transcription. Additional AR interactions with potential to contribute to receptor dimerization include the intermolecular interaction between the AR amino terminal domain and ligand-binding domain known as the N-terminal/C-terminal interaction, and ligand-binding domain dimerization. In this review, we discuss each form of dimerization utilized by the AR to achieve transcriptional competence and highlight that dimerization through multiple domains is necessary for optimal AR signaling.

Portfolio size effect in retirement accounts : what does it imply for lifecycle asset allocation funds?

Lifecycle funds offered by retirement plan providers allocate aggressively to risky asset classes when the employee participants are young, gradually switching to more conservative asset classes as they grow older and approach retirement. This approach focuses on maximizing growth of the accumulation fund in the initial years and preserving its value in the later years. The authors simulate terminal wealth outcomes based on conventional lifecycle asset allocation rules as well as on contrarian strategies that reverse the direction of asset switching. The evidence suggests that the growth in portfolio size over time significantly impacts the asset allocation decision. Due to the portfolio size effect that is observed by the authors, the terminal value of accumulation in retirement accounts is influenced more by the asset allocation strategy adopted in later years relative to that adopted in early years. By mechanistically switching to conservative assets in the later years of a plan, lifecycle strategies sacrifice significant growth opportunity and prove counterproductive to the participant's wealth accumulation objective. The authors' conclude that this sacrifice does not seem to be compensated adequately in terms of reducing the risk of potentially adverse outcomes.

The appropriateness of default investment options in defined contribution plans : Australian evidence

For participants in defined contribution (DC) plans who refrain from exercising investment choice, plan contributions are invested following the default investment option of their respective plans. Since default investment options of different plans vary widely in terms of their benchmark asset allocation, the most important determinant of investment performance, participants enrolled in these options face significantly different wealth outcomes at retirement. This paper simulates the terminal wealth outcomes under different static asset allocation strategies to evaluate their relative appeal as default investment choice in DC plans. We find that strategies with low or moderate allocation to stocks are consistently outperformed in terms of upside potential of exceeding the participant’s wealth accumulation target at retirement as well as downside risk of falling below that target outcome by aggressive strategies whose allocation to stocks approach 100%. The risk of extremely adverse wealth outcomes for plan participants also does not appear to be very sensitive to asset allocation. Our evidence suggests the appropriateness of strategies heavily tilted towards stocks to be nominated as default investment options in DC plans unless plan providers emphasize predictability of wealth outcomes over adequacy of retirement wealth.

Effect of simulated space environments on piezoelectric vinylidene flouride-based polymers

Piezoelectric polymers based on polyvinylidene flouride (PVDF) are of interest as adaptive materials for large aperture space-based telescopes. In this study, two piezoelectric polymers, PVDF and P(VDF-TrFE), were exposed to conditions simulating the thermal, radiative and atomic oxygen conditions of low Earth orbit. The degradation pathways were governed by a combination of chemical and physical degradation processes with the molecular changes primarily induced via radiative damage, and physical damage from temperature and atomic oxygen exposure, as evident from depoling, loss of orientation and surface erosion. The piezoelectric responsiveness of each polymer was strongly dependent on exposure temperature. Radiation and atomic oxygen exposure caused physical and chemical degradation, which would ultimately cause terminal damage of thin films, but did not adversely affect the piezoelectric properties.

Studies of the radiation chemistry and grafting of a fluoropolymer

The radiation chemistry and the grafting of a fluoropolymer, poly(tetrafluoroethylene-coperfluoropropyl vinyl ether) (PFA), was investigated with the aim of developing a highly stable grafted support for use in solid phase organic chemistry (SPOC). A radiation-induced grafting method was used whereby the PFA was exposed to ionizing radiation to form free radicals capable of initiating graft copolymerization of styrene. To fully investigate this process, both the radiation chemistry of PFA and the grafting of styrene to PFA were examined. Radiation alone was found to have a detrimental effect on PFA when irradiated at 303 K. This was evident from the loss in the mechanical properties due to chain scission reactions. This meant that when radiation was used for the grafting reactions, the total radiation dose needed to be kept as low as possible. The radicals produced when PFA was exposed to radiation were examined using electron spin resonance spectroscopy. Both main-chain (–CF2–C.F–CF2-) and end-chain (–CF2–C.F2) radicals were identified. The stability of the majority of the main-chain radicals when the polymer was heated above the glass transition temperature suggested that they were present mainly in the crystalline regions of the polymer, while the end-chain radicals were predominately located in the amorphous regions. The radical yield at 77 K was lower than the radical yield at 303 K suggesting that cage recombination at low temperatures inhibited free radicals from stabilizing. High-speed MAS 19F NMR was used to identify the non-volatile products after irradiation of PFA over a wide temperature range. The major products observed over the irradiation temperature 303 to 633 K included new saturated chain ends, short fluoromethyl side chains in both the amorphous and crystalline regions, and long branch points. The proportion of the radiolytic products shifted from mainly chain scission products at low irradiation temperatures to extensive branching at higher irradiation temperatures. Calculations of G values revealed that net crosslinking only occurred when PFA was irradiated in the melt. Minor products after irradiation at elevated temperatures included internal and terminal double bonds and CF3 groups adjacent to double bonds. The volatile products after irradiation at 303 K included tetrafluoromethane (CF4) and oxygen-containing species from loss of the perfluoropropyl ether side chains of PFA as identified by mass spectrometry and FTIR spectroscopy. The chemical changes induced by radiation exposure were accompanied by changes in the thermal properties of the polymer. Changes in the crystallinity and thermal stability of PFA after irradiation were examined using DSC and TGA techniques. The equilibrium melting temperature of untreated PFA was 599 K as determined using a method of extrapolation of the melting temperatures of imperfectly formed crystals. After low temperature irradiation, radiation- induced crystallization was prevalent due to scission of strained tie molecules, loss of perfluoropropyl ether side chains, and lowering of the molecular weight which promoted chain alignment and hence higher crystallinity. After irradiation at high temperatures, the presence of short and long branches hindered crystallization, lowering the overall crystallinity. The thermal stability of the PFA decreased with increasing radiation dose and temperature due to the introduction of defect groups. Styrene was graft copolymerized to PFA using -radiation as the initiation source with the aim of preparing a graft copolymer suitable as a support for SPOC. Various grafting conditions were studied, such as the total dose, dose rate, solvent effects and addition of nitroxides to create “living” graft chains. The effect of dose rate was examined when grafting styrene vapour to PFA using the simultaneous grafting method. The initial rate of grafting was found to be independent of the dose rate which implied that the reaction was diffusion controlled. When the styrene was dissolved in various solvents for the grafting reaction, the graft yield was strongly dependent of the type and concentration of the solvent used. The greatest graft yield was observed when the solvent swelled the grafted layers and the substrate. Microprobe Raman spectroscopy was used to map the penetration of the graft into the substrate. The grafted layer was found to contain both poly(styrene) (PS) and PFA and became thicker with increasing radiation dose and graft yield which showed that grafting began at the surface and progressively penetrated the substrate as the grafted layer was swollen. The molecular weight of the grafted PS was estimated by measuring the molecular weight of the non-covalently bonded homopolymer formed in the grafted layers using SEC. The molecular weight of the occluded homopolymer was an order of magnitude greater than the free homopolymer formed in the surrounding solution suggesting that the high viscosity in the grafted regions led to long PS grafts. When a nitroxide mediated free radical polymerization was used, grafting occurred within the substrate and not on the surface due to diffusion of styrene into the substrate at the high temperatures needed for the reaction to proceed. Loading tests were used to measure the capacity of the PS graft to be functionialized with aminomethyl groups then further derivatized. These loading tests showed that samples grafted in a solution of styrene and methanol had superior loading capacity over samples graft using other solvents due to the shallow penetration and hence better accessibility of the graft when methanol was used as a solvent.

Terminally-ill people living alone without a caregiver: an Australian national scoping study of palliative care needs

Home-based palliative care services are facing increasing challenges in servicing the needs of clients who live alone and without a primary caregiver. The findings from the analysis of 721 services’ records from three Australian states, and feedback from health professionals in interviews and postal surveys, demonstrated that there were aspects of being on one’s own with a terminal illness and living at home that require a specialised approach and support. This study explored the issues of palliative care patients living alone, from a service provider perspective, and provided evidence-based information to assist with service planning. The study made recommendations to the Australian Department of Health and Ageing about services considered important in developing support structures for this growing population.

Culture independent analysis of greyback canegrub-associated microflora and microbial community comparison using subtractive hybridisation

Greyback canegrubs cost the Australian sugarcane industry around $13 million per annum in damage and control. A novel and cost effective biocontrol bacterium could play an important role in the integrated pest management program currently in place to reduce damage and control associated costs. During the course of this project, terminal restriction fragment length polymorphism (TRFLP), 16-S rDNA cloning, suppressive subtractive hybridisation (SSH) and entomopathogen-specific PCR screening were used to investigate the little studied canegrub-associated microflora in an attempt to discover novel pathogens from putatively-diseased specimens. Microflora associated with these soil-dwelling insects was found to be both highly diverse and divergent between individual specimens. Dominant members detected in live specimens were predominantly from taxa of known insect symbionts while dominant sequences amplified from dead grubs were homologous to putativelysaprophytic bacteria and bacteria able to grow during refrigeration. A number of entomopathogenic bacteria were identified such as Photorhabdus luminescens and Pseudomonas fluorescens. Dead canegrubs prior to decomposition need to be analysed if these bacteria are to be isolated. Novel strategies to enrich putative pathogen-associated sequences (SSH and PCR screening) were shown to be promising approaches for pathogen discovery and the investigation of canegrubsassociated microflora. However, due to inter- and intra-grub-associated community diversity, dead grub decomposition and PCR-specific methodological limitations (PCR bias, primer specificity, BLAST database restrictions, 16-S gene copy number and heterogeneity), recommendations have been made to improve the efficiency of such techniques. Improved specimen collection procedures and utilisation of emerging high-throughput sequencing technologies may be required to examine these complex communities in more detail. This is the first study to perform a whole-grub analysis and comparison of greyback canegrub-associated microbial communities. This work also describes the development of a novel V3-PCR based SSH technique. This was the first SSH technique to use V3-PCR products as a starting material and specifically compare bacterial species present in a complex community.

Investigation of 'off-line‘ relaxation phenomena in oil filled transformers

Power transformers are one of the most important and costly equipment in power generation, transmission and distribution systems. Current average age of transformers in Australia is around 25 years and there is a strong economical tendency to use them up to 50 years or more. As the transformers operate, they get degraded due to different loading and environmental operating stressed conditions. In today‘s competitive energy market with the penetration of distributed energy sources, the transformers are stressed more with minimum required maintenance. The modern asset management program tries to increase the usage life time of power transformers with prognostic techniques using condition indicators. In the case of oil filled transformers, condition monitoring methods based on dissolved gas analysis, polarization studies, partial discharge studies, frequency response analysis studies to check the mechanical integrity, IR heat monitoring and other vibration monitoring techniques are in use. In the current research program, studies have been initiated to identify the degradation of insulating materials by the electrical relaxation technique known as dielectrometry. Aging leads to main degradation products like moisture and other oxidized products due to fluctuating thermal and electrical loading. By applying repetitive low frequency high voltage sine wave perturbations in the range of 100 to 200 V peak across available terminals of power transformer, the conductive and polarization parameters of insulation aging are identified. An in-house novel digital instrument is developed to record the low leakage response of repetitive polarization currents in three terminals configuration. The technique is tested with known three transformers of rating 5 kVA or more. The effects of stressing polarization voltage level, polarizing wave shapes and various terminal configurations provide characteristic aging relaxation information. By using different analyses, sensitive parameters of aging are identified and it is presented in this thesis.

Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species

Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates.

Theory and development of GPS integrity monitoring system

This thesis discusses various aspects of the integrity monitoring of GPS applied to civil aircraft navigation in different phases of flight. These flight phases include en route, terminal, non-precision approach and precision approach. The thesis includes four major topics: probability problem of GPS navigation service, risk analysis of aircraft precision approach and landing, theoretical analysis of Receiver Autonomous Integrity Monitoring (RAIM) techniques and RAIM availability, and GPS integrity monitoring at a ground reference station. Particular attention is paid to the mathematical aspects of the GPS integrity monitoring system. The research has been built upon the stringent integrity requirements defined by civil aviation community, and concentrates on the capability and performance investigation of practical integrity monitoring systems with rigorous mathematical and statistical concepts and approaches. Major contributions of this research are: • Rigorous integrity and continuity risk analysis for aircraft precision approach. Based on the joint probability density function of the affecting components, the integrity and continuity risks of aircraft precision approach with DGPS were computed. This advanced the conventional method of allocating the risk probability. • A theoretical study of RAIM test power. This is the first time a theoretical study on RAIM test power based on the probability statistical theory has been presented, resulting in a new set of RAIM criteria. • Development of a GPS integrity monitoring and DGPS quality control system based on GPS reference station. A prototype of GPS integrity monitoring and DGPS correction prediction system has been developed and tested, based on the A USN A V GPS base station on the roof of QUT ITE Building.

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.