8 research outputs found
Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume
The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18
7 10 124 ) or temporal stage (p = 3.96
7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine
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Continued Testing of the Cannon Caliber Electromagnetic Gun System (CCEMG)
The cannon caliber electromagnetic gun system is based upon a compulsator driven 30 mm rapid fire railgun system. The objective of the program was to develop a compact, lightweight test bed capable of launching three, five round salvoes of 185 g integrated launch packages to 1.85 km/s at a firing rate of 5 Hz. Per contractual requirements, the pulse power system is also size compatible with the amphibious assault vehicle. The pulse power system was developed around a fourth generation air-core, 4-pole rotating armature, self-excited, compulsator design. Although the contract for this effort has expired, the system continues to be used in part to demonstrate compulsator driven railgun technology. This system has performed seven single shots using identical control settings for each shot, which is the first such experience using a compulsator driven railgun system. This paper describes the experimental set-up for the demonstrations and compares the generator, converter, gun switch, and launcher performances for each shotCenter for Electromechanic
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Testing of the Cannon Caliber Rapid Fire Railgun
A rapid fire launcher has been designed, built, and tested in single-shot mode for the Cannon Caliber Electromagnetic Gun (CCEMG) System. The 2.25-m long railgun has a rectangular cross-section (30 mm round bore equivalent) and has a series, two-turn augmented rail configuration. The gun is designed for rapid fire operation; three, five round salvos of 185 g integrated launch packages (ILPs) accelerated to 1,850 m/s with a minimum time between salvos of 2.5 s. Launch packages will be autoloaded at a repetition rate of 5 Hz via a hydraulic mechanism capable of up to 3,000 lb insertion forces. The railgun support structure and flexible buswork permit the railgun to recoil approximately 2 cm to mitigate the electromagnetic repulsion loads. Multiple 830 kA pulses provided from the CCEMG compulsator power supply require the gun to be liquid cooled for thermal management. Diagnostics for the single-shot tests include B-dots, flux rulers, voltage, and current measuring sensors. Other launcher diagnostics include rail conductor temperatures, coolant temperatures, and railgun preload mechanism (flatjacks) dynamic pressures. This paper presents the test results and general gun performance observations for single-shot, compulsator powered experimentsCenter for Electromechanic
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Laboratory Testing of the Pulse Power System for the Cannon Caliber Electromagnetic Gun System (CCEMG)
The team of (prime contractor) United Defense LP (UDLP) and The University of Texas at Austin Center for Electromechanics (UT-CEM) has completed a significant portion of the testing phase of a trailer mounted compulsator driven 35 mm (round bore equivalent) rapid fire railgun system. The objective of the program is to develop a compact, lightweight pulse power test bed capable of launching 3, 5 round salvos of 185-g integrated launch packages to 1.85 km/s at a firing rate of 5 Hz. Per contractual requirements, the pulse power system is also size compatible with the Amphibious Assault Vehicle (AAV). The pulse power system is developed around a second generation air-core, 4-pole rotating armature, self-excited, compulsator design. The 40 MJ at 12,000 rpm composite rotor stores all 15 shots inertially and is capable of 2.5 GW performance into the 2.21 m long series augmented railgun. This paper describes the CCEMG pulse power supply configuration and highlights important features of the commissioning test plan. The paper then presents test results from mechanical runs, stand alone compulsator (CPA) rectifier tests, short circuit tests, and single shot live fire tests. Finally, CPA performance is compared with predictions for the single shot tests presentedCenter for Electromechanic
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Predicted versus Actual Performance of a Model Scale Compulsator System
Performance testing of the model-scale CPA was completed at the University of Texas Center for Electromechanics. A major part of the project was the development of design and simulation codes that would accurately represent the performance of pulsed alternators. This paper discusses the components of the system and its operational sequence. Details of the performance simulation model are presented along with test data. The test result is compared to the predicted dataCenter for Electromechanic