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Direct thrust force control of primary permanent magnet linear motor based on improved extended state observer and model-free adaptive predictive control
Get PDFA model-free adaptive predictive control algorithm based on an improved extended state observer (IESO) is proposed to solve the problem that the primary permanent magnet linear motor is susceptible to time-varying parameters and unknown disturbances. Firstly, a model-free adaptive control algorithm based on compact format is designed to achieve high control precision of the system and reduce thrust fluctuation, only through the input/output data of the system. Because the traditional model-free adaptive control is too sensitive to the internal parameters of the controller, a combination of model-free adaptive control and predictive control is further developed. By predicting the data for a future time in advance, the sensitivity to the internal parameters of the controller is reduced and the control performance is further improved. Since the load change and other nonlinear disturbances in practical applications have a great impact on the control effect of the system, an improved extended state observer is further used to compensate for the impact of nonlinear disturbances on the control system. In addition, the stability of the closed-loop system is analyzed. Comparable simulation results clearly demonstrate the good tracking performance and strong robustness of the proposed control
Development of antisense oligonucleotides with therapeutic potential for treating amyotrophic lateral sclerosis
No full textAmyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterised by degenerative changes to both upper and lower motor neurons. Current treatment options for ALS are based on symptom management and respiratory support, with the only approved medications prolonging survival for just a few months. Over 60 clinical trials for drugs to treat ALS have ended in disappointment in the last decades, the majority of which were for small molecule-based treatments.
Antisense oligonucleotides (AONs) are short nucleic acid analogues that can be designed to directly and specifically target the pathological hallmarks of disease at the RNA level. AONs can work via several mechanisms including strategies that rely on the endogenous RNase H enzymes to degrade target transcripts or strategies that involve the steric block of splicing factors or cellular machinery. Developments in AON based medicine in recent years has led to several new AON therapies receiving approvals to treat various conditions. The work outlined in this thesis has involved the development and assessment of AONs with therapeutic potential for treating ALS. AONs with the phosphorodiamidate morpholino oligomer (PMO) chemistry were preferred in this work due to their strong safety profile and clinical approvals for Duchenne muscular dystrophy. AONs that rely on RNase H require chemical modifications such as the phosphorothioate backbone (PS) modification to increase their stability and cellular uptake. PMOs are nucleic acid analogous that are inherently stable but are not compatible with RNase H activity, instead requiring a steric blocking strategy.
ALS is a heterogenous disease, however a common feature is the cytoplasmic aggregation of proteins. The transactive response DNA-binding protein 43 (TDP-43) encoded by the TARDBP gene was identified in 2006 as a primary protein component of intracellular inclusions in most ALS cases, occurring in more than 90% of patients. As TDP-43 is autoregulated, its cytoplasmic mislocalisation in ALS leads to its upregulation. In this work, AONs with the PMO chemistry that utilise a splice-switching strategy were developed that can reduce the expression of TDP-43. It has recently been discovered that mislocalisation of TDP-43 leads to the downregulation of Stathmin-2, an important neuronal protein involved in axonal development and repair. AONs that can prevent the down-regulation of Stathmin-2 in response to TDP-43 nuclear depletion in human cells were also successfully developed. These AONs alone or in combination could have therapeutic potential to treat the majority of sporadic ALS patients. iii A subset of ALS patients, including some with early-onset ALS, have pathogenic variants in the FUS gene which leads to FUS protein mislocalisation and aggregation. There is also mounting evidence that FUS may play a role in the pathogenesis of sporadic ALS. Another focus of this study was the development of AONs that can modify expression of FUS. Two strategies were explored, including a splice switching strategy, to reduce total FUS expression. A steric blocking PMO AON was developed that can reduce FUS expression in human cells. As FUS-ALS is usually inherited in an autosomal dominant manner, a second strategy aimed to selectively knock down expression of only one FUS allele. This therapeutic strategy would allow expression of the normal allele in FUS-ALS patients, reducing potential complications due to insufficiency of the protein. Several AON design parameters and chemistries were explored with AONs using the newer thiophosphoramidate morpholino oligomer chemistry showing promise in achieving this aim.
The work presented in this thesis has provided evidence that splice-switching AON based therapeutics that can reduce expression of TDP-43 while preventing the down-regulation of Stathmin-2 is feasible. Like-wise both splice-switching and RNase H utilising allele selective, FUS targeted AONs have been developed that have therapeutic potential in treating FUS-ALS. With further development, there is hope that this work may contribute to the availability of disease altering antisense based therapeutics for ALS patients
Characteristics and outcomes of culture-negative prosthetic joint infections from the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort study
Get PDFIntroduction: Culture-negative (CN) prosthetic joint infections (PJIs) account for approximately 10 % of all PJIs and present significant challenges for clinicians. We aimed to explore the significance of CN PJIs within a large prospective cohort study, comparing their characteristics and outcomes with culture-positive (CP) cases. Methods: The Prosthetic joint Infection in Australia and New Zealand Observational (PIANO) study is a prospective, multicentre observational cohort study that was conducted at 27 hospitals between 2014 and 2017. We compared baseline characteristics and outcomes of all patients with CN PJI from the PIANO cohort with those of CP cases. We report on PJI diagnostic criteria in the CN cohort and apply internationally recognized PJI diagnostic guidelines to determine optimal CN PJI detection methods. Results: Of the 650 patients with 24-month outcome data available, 55 (8.5 %) were CN and 595 were CP. Compared with the CP cohort, CN patients were more likely to be female (32 (58.2 %) vs. 245 (41.2 %); p = 0.016), involve the shoulder joint (5 (9.1 %) vs. 16 (2.7 %); p = 0.026), and have a lower mean C-reactive protein (142 mg L−1 vs. 187 mg L−1; p = 0.016). Overall, outcomes were superior in CN patients, with culture negativity an independent predictor of treatment success at 24 months (adjusted odds ratio, aOR, of 3.78 and 95 %CI of 1.65–8.67). Suboptimal diagnostic sampling was common in both cohorts, with CN PJI case detection enhanced using the Infectious Diseases Society of America PJI diagnostic guidelines. Conclusions: Current PJI diagnostic guidelines vary substantially in their ability to detect CN PJI, with comprehensive diagnostic sampling necessary to achieve diagnostic certainty. Definitive surgical management strategies should be determined by careful assessment of infection type, rather than by culture status alone
The Second International Indian Ocean Expedition (IIOE-2): Revisiting 110°E
No full textThis Special Issue is an outcome of ship's time aboard the RV Investigator to revisit 110°E. We gratefully acknowledge the Australian Marine National Facility and the assistance of the captain, crew, technical team, scientific participants and numerous funders in bringing voyage IN2019_V03 to fruition. The IIOE-2 Special Issues in Deep-Sea Research II have been advanced through SIBER (Sustained Indian Ocean Biogeochemistry and Ecosystem Research), a regional programme of IMBeR (Integrate
Smart breeding driven by big data, artificial intelligence, and integrated genomic-enviromic prediction
Get PDFThe first paradigm of plant breeding involves direct selection-based phenotypic observation, followed by predictive breeding using statistical models for quantitative traits constructed based on genetic experimental design and, more recently, by incorporation of molecular marker genotypes. However, plant performance or phenotype (P) is determined by the combined effects of genotype (G), envirotype (E), and genotype by environment interaction (GEI). Phenotypes can be predicted more precisely by training a model using data collected from multiple sources, including spatiotemporal omics (genomics, phenomics, and enviromics across time and space). Integration of 3D information profiles (G-P-E), each with multidimensionality, provides predictive breeding with both tremendous opportunities and great challenges. Here, we first review innovative technologies for predictive breeding. We then evaluate multidimensional information profiles that can be integrated with a predictive breeding strategy, particularly envirotypic data, which have largely been neglected in data collection and are nearly untouched in model construction. We propose a smart breeding scheme, integrated genomic-enviromic prediction (iGEP), as an extension of genomic prediction, using integrated multiomics information, big data technology, and artificial intelligence (mainly focused on machine and deep learning). We discuss how to implement iGEP, including spatiotemporal models, environmental indices, factorial and spatiotemporal structure of plant breeding data, and cross-species prediction. A strategy is then proposed for prediction-based crop redesign at both the macro (individual, population, and species) and micro (gene, metabolism, and network) scales. Finally, we provide perspectives on translating smart breeding into genetic gain through integrative breeding platforms and open-source breeding initiatives. We call for coordinated efforts in smart breeding through iGEP, institutional partnerships, and innovative technological support
Land use and dingo baiting are correlated with the density of kangaroos in rangeland systems
Get PDFRangelands worldwide have been subject to broadscale modification, such as widespread predator control, introduction of permanent livestock water and altered vegetation to improve grazing. In Australia, these landscape changes have resulted in kangaroos (i.e. large macropods) populations increasing over the past 200 years. Kangaroos are a key contributor to total grazing pressure and in conjunction with livestock and feral herbivores have been linked to land degradation. We used 22 years of aerial survey data to investigate whether the density of 3 macropod species in the southern rangelands of Western Australia was associated with: (i) land use, including type of livestock, total livestock, density of feral goats, type of land tenure, and kangaroo commercial harvest effort; (ii) predator management, including permitted dingo control effort, estimated dingo abundance, and presence of the State Barrier Fence (a dingo exclusion fence); and (iii) environmental variables: ruggedness, rainfall, fractional cover, and total standing dry matter. Red kangaroos (Osphranter rufus) were most abundant in flat, open vegetation, on pastoral land, where area permitted for dingo control was high, and numbers were positively associated with antecedent rainfall with a 12-month delay. Western grey kangaroos (Macropus fuliginosus) were most abundant on flat, agricultural land, but less abundant in areas with high permitted dingo control. Euros (Osphranter robustus) were most abundant in rugged pastoral land with open vegetation, where permitted dingo control was high. While environmental variables are key drivers of landscape productivity and kangaroo populations, anthropogenic factors such as land use and permitted dingo control are strongly associated with kangaroo abundance
Presence of microplastics alone and co-existence with hydrochar unexpectedly mitigate ammonia volatilization from rice paddy soil and affect structure of soil microbiome
No full textMicroplastics (MPs), as an emerging pollutant, may cause deleterious changes to the nitrogen cycle in terrestrial ecosystems. However, single impact of MPs and synergistic effects of MPs with hydrochar on ammonia (NH3) volatilization and soil microbiome in paddy fields has been largely unexplored. In this study, polyethylene (PE), polyacrylonitrile (PAN) and straw-derived hydrochar (HBC) were selected for observations in an entire rice cycle growth period. Results showed that under the condition of 0.5% (w/w) MPs concentration, presence of MPs alone and co-existence of MPs and HBC (MPs + HBC) unexpectedly mitigated cumulative NH3 volatilization from paddy soil compared with the control with no MPs or HBC addition. MPs + HBC increased NH3 volatilization by 37.8–46.2% compared with MPs alone, indicating that co-existence of MPs and HBC weaken the mitigation effect of MPs on NH3 volatilization. Additionally, results of nitrogen cycle related microorganisms closely related to NH3 volatilization demonstrated that MPs + HBC altered the bacterial community structure and species diversity. These findings provide an important opportunity to advance our understanding of the impacts of MPs in agricultural environment and soils, and provide a sound theoretical basis for rationalizing the application of HBC in soil with MPs
Influence of tDCS over right inferior frontal gyrus and pre-supplementary motor area on perceptual decision-making and response inhibition: A healthy ageing perspective
No full textA wide body of literature suggests that transcranial direct current stimulation (tDCS) administered over the prefrontal cortex can improve executive function – including decision-making and inhibitory control – in healthy young adults. However, the effects of tDCS in older adults are largely unknown. Here, using a double-blind, sham-controlled approach, changes in a combined perceptual decision-making and inhibitory control task were assessed before and after the application of tDCS (1 mA, 20 minute) targeting the right inferior frontal gyrus (rIFG) or pre-supplementary motor area (preSMA) in 42 young (18–34 years) and 41 older (60–80 years) healthy adults. Compared to sham stimulation, anodal tDCS over the preSMA improved decision-making speed for both age groups. Furthermore, the inhibitory control performance of older and younger adults was improved by preSMA and rIFG stimulation, respectively. This study provides evidence that tDCS can improve both perceptual decision-making and inhibitory control in healthy older adults, with the causal role of the preSMA and rIFG regions in cognitive control appearing to vary as a function of healthy ageing
First record of the stump-tailed lizard tick, Amblyomma albolimbatum (Ixodida, Ixodidae) parasitising a human
No full textTicks are haematophagous arthropods that parasitise a wide range of vertebrate hosts. In Australia, there are currently 74 tick species described; 22 tick species have been reported parasitising humans. The stump-tailed lizard tick, Amblyomma albolimbatum, feeds on reptiles, most commonly lizards and snakes; however, we report the first case of A. albolimbatum parasitising a human. The nymphal tick was removed while conducting fieldwork on western tiger snakes (Notechis scutatus occidentalis) in an urban city environment near Perth, Western Australia. The tick was identified using morphological descriptions, which was further supported by the abundance of all parasitic stages of A. albolimbatum on the tiger snakes sampled. The number of tick species recorded from humans in Australia is now revised to 23 species. With the increasing incidence of tick-borne illnesses in Australia, this study highlights the need to report cases of new or atypical hosts, particularly humans, and especially when the ticks have been associated with zoonotic pathogens
Running demands and activity profile of men’s rugby sevens: A tournament scenario
No full textThis study profiled the changes in running performances and collisions within a Rugby sevens tournament. Sixteen male players were equipped with global positioning system units while competing at the 2015 and 2016 Asia Rugby Sevens series held in Colombo and Hong Kong, respectively. Both tournaments consisted of 4 matches each, and were played over 2 days (i.e., 2 matches/day). Total distance (TD) covered increased in match 3 compared with matches 1 (19 ± 19%; p < 0.001) and 2 (16 ± 11%; p = 0.001), whilst a decrease in TD in match 4 compared with match 3 (8 ± 9%; p = 0.019) was observed. Distances covered within 6.1–12 km·h-1 and 12.1–14 km·h-1 speed bands were generally higher in matches 3 and/or 4 when compared with match 1 and/or 2 (p < 0.05). Frequency of entries into 14.1–18 km·h-1 speed zone was decreased in match 4 compared with match 3 (45 ± 41%; p = 0.009), whilst incidences of heavy, very heavy and severe collisions were generally higher in matches 3 or 4 compared with matches 1 or 2 (p < 0.05). In conclusion, while some decrements in the final match were evident, running performance were generally maintained throughout despite the competitive and congested nature of Rugby Sevens tournaments