Exploring gut microbiome – host interactions in the extremes of health and disease

Introduction: Multi ‘omics analyses, including metabonomic and metagenomic profiling techniques, have enabled new insights into systems biology over the past decade. Using two extremes of a continuum between health and disease – elite athletes and obese patients undergoing bariatric surgery – the work in this thesis aims to apply metabolic phenotyping to further understand the impact of exercise, diet and obesity on human metabolism. Furthermore, through combinatorial analysis of metabonomic and gut microbiome data sets, host – gut microbiome co-metabolism and its influence on health is explored in these two extreme populations. Methods: Biofluids were collected from three cohorts: i) elite athletes and age and sex matched controls, ii) healthy individuals before and after a high protein diet, exercise regime or both, and iii) obese subjects pre and post bariatric surgery. Multiple analytical platforms were utilised for metabolic profiling including 1H-NMR spectroscopy, UPLC-MS and GC-MS. Gut microbiome analysis was performed using next generation metagenomic sequencing. After pre-processing the metabonomic and metagenomic data; univariate, unsupervised and supervised multivariate analyses were performed as well as gut microbiome-metabolite association studies. Results: Distinct metabolic and microbial phenotypes existed between both athletes and controls and between obese patients before and after bariatric surgery. Discriminatory metabolites higher in athletes include metabolites associated with muscle turnover, vitamins and recovery supplements, a high protein diet and those derived from gut microbes. Interestingly, increased bacterial diversity seen in athletes correlated with a specific subset of metabolites. Similarly, bariatric surgery resulted in large changes to circulating metabolites. A number of these metabolites were linked to changes in the gut microbiome, including bile acids, short-chain fatty acids and amino acids. Conclusion: This thesis extends existing knowledge of the gut microbiome’s influence on human health through small molecule signalling. Mechanistic studies are now needed to establish causal links between gut microbes, changes to circulating metabolites and disease status.Open Acces

Variable area nozzle including a plurality of convexly vanes with a crowned contour, in a vane to vane sealing arrangement and with nonuniform lengths

A variable area nozzle comprising a concentric support and a plurality of convexly contoured self sealing vanes is disclosed and claimed. The vanes are circumferentially and rotatably mounted to the concentric support forming a nozzle infinitely positionable between a first position corresponding to a minimum area nozzle and a second position corresponding to a maximum area nozzle. A closer, which is preferably a shape memory alloy (SMA), urges the nozzle toward the first position corresponding to a minimum area nozzle. Periodically spaced openers act between adjacent vanes to urge the nozzle to a second position corresponding to a maximum area nozzle

Torsional Magnetorheological Device

A magnetorheological device comprising a housing having a divider within the housing is disclosed and claimed. A rotary impeller having two paddles is rotatably mounted within the housing. The rotary impeller sealingly engages the divider and the paddles in combination with the divider forms a first chamber and a second chamber. Magnetorheological fluid resides in the chambers and a passageway interconnects the first and second chambers. A coil surrounds a portion of the passageway such that when energized the magnetorheological fluid solidifies plugging the passageway. As the impeller rotates, it pushes the incompressible fluid against the divider in the housing and the plug in the passageway and retards and/or stops the motion of the impeller

Increased Corrosion Resistance of Zinc Magnesium Aluminum Galvanised Coating through Germanium Additions

The corrosion performance of a Zinc Magnesium Aluminium alloy was shown to improve through the addition of a quaternary element, Germanium. Improved corrosion resistance can be attributed to microstructural changes in the alloy due to Ge addition while in the molten state. The proportion of the most active MgZn2 phase which has been shown to initiate the corrosion reaction in a ZMA alloy was reduced thorough the formation of Mg2Ge crystals. The formation of crystal structures within the alloy also increased the heterogeneous nucleation of the primary zinc phase. The Scanning Vibrating Electrode Technique (SVET) was used to measure the rate of corrosion, anode life and zinc loss of the alloy samples. The results showed a zinc loss of around 50% when compared to standard ZMA alloy without Ge addition

Effect of Thermomechanical Processing on the Microstructure, Properties, and Work Behavior of a Ti50.5 Ni29.5 Pt20 High-Temperature Shape Memory Alloy

TiNiPt shape memory alloys are particularly promising for use as solid state actuators in environments up to 300 C, due to a reasonable balance of properties, including acceptable work output. However, one of the challenges to commercializing a viable high-temperature shape memory alloy (HTSMA) is to establish the appropriate primary and secondary processing techniques for fabrication of the material in a required product form such as rod and wire. Consequently, a Ti(50.5)Ni(29.5)Pt20 alloy was processed using several techniques including single-pass high-temperature extrusion, multiple-pass high-temperature extrusion, and cold drawing to produce bar stock, thin rod, and fine wire, respectively. The effects of heat treatment on the hardness, grain size, room temperature tensile properties, and transformation temperatures of hot- and cold-worked material were examined. Basic tensile properties as a function of temperature and the strain-temperature response of the alloy under constant load, for the determination of work output, were also investigated for various forms of the Ti(50.5)Ni(29.5)Pt20 alloy, including fine wire

Development of a HTSMA-Actuated Surge Control Rod for High-Temperature Turbomachinery Applications

In recent years, a demand for compact, lightweight, solid-state actuation systems has emerged, driven in part by the needs of the aeronautics industry. However, most actuation systems used in turbomachinery require not only elevated temperature but high-force capability. As a result, shape memory alloy (SMA) based systems have worked their way to the forefront of a short list of viable options to meet such a technological challenge. Most of the effort centered on shape memory systems to date has involved binary NiTi alloys but the working temperatures required in many aeronautics applications dictate significantly higher transformation temperatures than the binary systems can provide. Hence, a high temperature shape memory alloy (HTSMA) based on NiTiPdPt, having a transformation temperature near 300 C, was developed. Various thermo-mechanical processing schemes were utilized to further improve the dimensional stability of the alloy and it was later extruded/drawn into wire form to be more compatible with envisioned applications. Mechanical testing on the finished wire form showed reasonable work output capability with excellent dimensional stability. Subsequently, the wire form of the alloy was incorporated into a benchtop system, which was shown to provide the necessary stroke requirements of approx.0.125 inches for the targeted surge-control application. Cycle times for the actuator were limited to ~4 seconds due to control and cooling constraints but this cycle time was determined to be adequate for the surge control application targeted as the primary requirement was initial actuation of a surge control rod, which could be completed in approximately one second

Review of Full-Scale Docking Seal Testing Capabilities

NASA is developing a new docking system to support future space exploration missions to low-Earth orbit, the Moon, and Mars. This mechanism, called the Low Impact Docking System (LIDS), is designed to connect pressurized space vehicles and structures including the Crew Exploration Vehicle, International Space Station, and lunar lander. NASA Glenn Research Center (GRC) is playing a key role in developing the main interface seal for this new docking system. These seals will be approximately 147 cm (58 in.) in diameter. To evaluate the performance of the seals under simulated operating conditions, NASA GRC is developing two new test rigs: a non-actuated version that will be used to measure seal leak rates and an actuated test rig that will be able to measure both seal leak rates and loads. Both test rigs will be able to evaluate the seals under seal-on-seal or seal-on-plate configurations at temperatures from -50 to 50 C (-58 to 122 F) under operational and pre-flight checkout pressure gradients in both aligned and misaligned conditions

Full-Scale System for Quantifying Leakage of Docking System Seals for Space Applications

NASA is developing a new docking and berthing system to support future space exploration missions to low-Earth orbit, the Moon, and Mars. This mechanism, called the Low Impact Docking System, is designed to connect pressurized space vehicles and structures. NASA Glenn Research Center is playing a key role in developing advanced technology for the main interface seal for this new docking system. The baseline system is designed to have a fully androgynous mating interface, thereby requiring a seal-on-seal configuration when two systems mate. These seals will be approximately 147 cm (58 in.) in diameter. NASA Glenn has designed and fabricated a new test fixture which will be used to evaluate the leakage of candidate full-scale seals under simulated thermal, vacuum, and engagement conditions. This includes testing under seal-on-seal or seal-on-plate configurations, temperatures from -50 to 50 C (-58 to 122 F), operational and pre-flight checkout pressure gradients, and vehicle misalignment (plus or minus 0.381 cm (0.150 in.)) and gapping (up to 0.10 cm (0.040 in.)) conditions. This paper describes the main design features of the test rig and techniques used to overcome some of the design challenges