An investigation of dynamic human muscle function using a variable inertial loading system

This thesis has developed and utilised an inertial loading system to study human skeletal muscle power output. Specifically, the apparatus has been used to study the effects of different modes of exercise, muscle myosin isoform composition and the effects of ageing on the ability of the lower limb muscles to generate explosive power. A variable inertial loading system was designed and constructed which allowed for the sensitive detection of the rotational properties of a flywheel from which the contractile characteristics of muscle could be inferred. When housed in the Nottingham Power Rig (NPR) the peak power generated by young non-trained male subjects from a single lower limb thrust ranged from 608 - 965 Watts and was found to occur at inertial loads ranging from 0.09 - 0.22 kgm2. To investigate the low power outputs observed at the low inertial loads, where the contraction time was short, a pre release mechanism was incorporated into the flywheel assembly. Significant increases in power output of ~ 17% were achieved at the lowest inertial load (P = 0.02), if a prior build up of isometric torque was allowed prior to movement. This suggested that at the low inertial loads, without the pre release, insufficient time was allowed for the muscle to generate its maximum power output. The flywheel system was incorporated into a cycle ergometer to allow power - velocity characteristics to be examined during inertial sprint cycling. Peak power obtained in young subjects (n = 9) was significantly higher in the cycle exercise when compared with the NPR (1620 vs. 937 Watts). In contrast to the NPR where a parabolic relationship between power and inertial load was observed, during sprint cycling power plateaued above a 'critical' load. It was concluded that the repetitive acceleration of inertial loads, above this critical threshold, will always allow the expression of peak power during cycling as ultimately a velocity will be achieved which corresponds to that required for peak power generation. An analysis of the myosin heavy chain (MHC) isoform composition of the vastus lateralis muscle was performed in young and elderly male subjects (n = 14, mean age 29.4 and 73.8). The percentage MHC-II isoform composition was significantly lower in the older subjects as was the velocity at which peak power occurred (Vopt). Overall the Vopt during sprint cycling was found to be related to the percentage MHC-II composition of the vastus lateralis (R = 0 .82, P<0.001). Finally, muscle power was examined in Elite level master Olympic weightlifters (n = 54, aged 40 - 87 years) and aged matched controls. On average the weightlifters generated ~ 32% more peak power than their aged matched counterparts and required significantly higher inertial loads to express their peak power output. In spite of 'load optimisation', power declined at twice the rate of strength. The levels of power suggest a 20 year advantage for the weightlifters

Probing short-range magnetic order in a geometrically frustrated magnet by spin Seebeck effect

Competing magnetic interactions in geometrically frustrated magnets give rise to new forms of correlated matter, such as spin liquids and spin ices. Characterizing the magnetic structure of these states has been difficult due to the absence of long-range order. Here, we demonstrate that the spin Seebeck effect (SSE) is a sensitive probe of magnetic short-range order (SRO) in geometrically frustrated magnets. In low temperature (2 - 5 K) SSE measurements on a model frustrated magnet \mathrm{Gd_{3}Ga_{5}O_{12}}, we observe modulations in the spin current on top of a smooth background. By comparing to existing neutron diffraction data, we find that these modulations arise from field-induced magnetic ordering that is short-range in nature. The observed SRO is anisotropic with the direction of applied field, which is verified by theoretical calculation.Comment: 5 pages, 4 figure

The Microbial Community of a Terrestrial Anoxic Inter-Tidal Zone: A Model for Laboratory-Based Studies of Potentially Habitable Ancient Lacustrine Systems on Mars

Evidence indicates that Gale crater on Mars harboured a fluvio-lacustrine environment that was subjected to physio-chemical variations such as changes in redox conditions and evaporation with salinity changes, over time. Microbial communities from terrestrial environmental analogues sites are important for studying such potential habitability environments on early Mars, especially in laboratory-based simulation experiments. Traditionally, such studies have predominantly focused on microorganisms from extreme terrestrial environments. These are applicable to a range of Martian environments; however, they lack relevance to the lacustrine systems. In this study, we characterise an anoxic inter-tidal zone as a terrestrial analogue for the Gale crater lake system according to its chemical and physical properties, and its microbiological community. The sub-surface inter-tidal environment of the River Dee estuary, United Kingdom (53°21'015.40" N, 3°10'024.95" W) was selected and compared with available data from Early Hesperian-time Gale crater, and temperature, redox, and pH were similar. Compared to subsurface ‘groundwater’-type fluids invoked for the Gale subsurface, salinity was higher at the River Dee site, which are more comparable to increases in salinity that likely occurred as the Gale crater lake evolved. Similarities in clay abundance indicated similar access to, specifically, the bio-essential elements Mg, Fe and K. The River Dee microbial community consisted of taxa that were known to have members that could utilise chemolithoautotrophic and chemoorganoheterotrophic metabolism and such a mixed metabolic capability would potentially have been feasible on Mars. Microorganisms isolated from the site were able to grow under environment conditions that, based on mineralogical data, were similar to that of the Gale crater’s aqueous environment at Yellowknife Bay. Thus, the results from this study suggest that the microbial community from an anoxic inter-tidal zone is a plausible terrestrial analogue for studying habitability of fluvio-lacustrine systems on early Mars, using laboratory-based simulation experiments

Antiferromagnetic spin Seebeck Effect

We report on the observation of the spin Seebeck effect in antiferromagnetic MnF$_2$. A device scale on-chip heater is deposited on a bilayer of Pt (4 nm)/MnF$_2$ (110) (30 nm) grown by molecular beam epitaxy on a MgF$_2$ (110) substrate. Using Pt as a spin detector layer it is possible to measure thermally generated spin current from MnF$_2$ through the inverse spin Hall effect. The low temperature (2 - 80 K) and high magnetic field (up to 140 kOe) regime is explored. A clear spin flop transition corresponding to the sudden rotation of antiferromagnetic spins out of the easy axis is observed in the spin Seebeck signal when large magnetic fields (>9 T) are applied parallel the easy axis of the MnF$_2$ thin film. When magnetic field is applied perpendicular to the easy axis, the spin flop transition is absent, as expected

Machine Learning-Based Method for Personalized and Cost-Effective Detection of Alzheimer's Disease

Diagnosis of Alzheimer's disease (AD) is often difficult, especially early in the disease process at the stage of mild cognitive impairment (MCI). Yet, it is at this stage that treatment is most likely to be effective, so there would be great advantages in improving the diagnosis process. We describe and test a machine learning approach for personalized and cost-effective diagnosis of AD. It uses locally weighted learning to tailor a classifier model to each patient and computes the sequence of biomarkers most informative or cost-effective to diagnose patients. Using ADNI data, we classified AD versus controls and MCI patients who progressed to AD within a year, against those who did not. The approach performed similarly to considering all data at once, while significantly reducing the number (and cost) of the biomarkers needed to achieve a confident diagnosis for each patient. Thus, it may contribute to a personalized and effective detection of AD, and may prove useful in clinical settings.</p

Risk of cardiovascular disease and total mortality in adults with type 1 diabetes: Scottish registry linkage study

&lt;p&gt;Background: Randomized controlled trials have shown the importance of tight glucose control in type 1 diabetes (T1DM), but few recent studies have evaluated the risk of cardiovascular disease (CVD) and all-cause mortality among adults with T1DM. We evaluated these risks in adults with T1DM compared with the non-diabetic population in a nationwide study from Scotland and examined control of CVD risk factors in those with T1DM.&lt;/p&gt; &lt;p&gt;Methods and Findings: The Scottish Care Information-Diabetes Collaboration database was used to identify all people registered with T1DM and aged ≥20 years in 2005–2007 and to provide risk factor data. Major CVD events and deaths were obtained from the national hospital admissions database and death register. The age-adjusted incidence rate ratio (IRR) for CVD and mortality in T1DM (n = 21,789) versus the non-diabetic population (3.96 million) was estimated using Poisson regression. The age-adjusted IRR for first CVD event associated with T1DM versus the non-diabetic population was higher in women (3.0: 95% CI 2.4–3.8, p&#60;0.001) than men (2.3: 2.0–2.7, p&#60;0.001) while the IRR for all-cause mortality associated with T1DM was comparable at 2.6 (2.2–3.0, p&#60;0.001) in men and 2.7 (2.2–3.4, p&#60;0.001) in women. Between 2005–2007, among individuals with T1DM, 34 of 123 deaths among 10,173 who were &#60;40 years and 37 of 907 deaths among 12,739 who were ≥40 years had an underlying cause of death of coma or diabetic ketoacidosis. Among individuals 60–69 years, approximately three extra deaths per 100 per year occurred among men with T1DM (28.51/1,000 person years at risk), and two per 100 per year for women (17.99/1,000 person years at risk). 28% of those with T1DM were current smokers, 13% achieved target HbA1c of &#60;7% and 37% had very poor (≥9%) glycaemic control. Among those aged ≥40, 37% had blood pressures above even conservative targets (≥140/90 mmHg) and 39% of those ≥40 years were not on a statin. Although many of these risk factors were comparable to those previously reported in other developed countries, CVD and mortality rates may not be generalizable to other countries. Limitations included lack of information on the specific insulin therapy used.&lt;/p&gt; &lt;p&gt;Conclusions: Although the relative risks for CVD and total mortality associated with T1DM in this population have declined relative to earlier studies, T1DM continues to be associated with higher CVD and death rates than the non-diabetic population. Risk factor management should be improved to further reduce risk but better treatment approaches for achieving good glycaemic control are badly needed.&lt;/p&gt

RNA-Mediated Neurodegeneration Caused by the Fragile X Premutation rCGG Repeats in Drosophila

AbstractFragile X syndrome carriers have FMR1 alleles, called premutations, with an intermediate number of 5′ untranslated CGG repeats between patients (>200 repeats) and normal individuals (<60 repeats). A novel neurodegenerative disease has recently been appreciated in some premutation carriers. As no neurodegeneration is seen in fragile X patients, who do not express FMR1, we hypothesize that lengthened rCGG repeats of the premutation transcript may lead to neurodegeneration. Here, using Drosophila melanogaster, we show that 90 rCGG repeats alone are sufficient to cause neurodegeneration. This phenotype is neuron specific and rCGG repeat dosage sensitive. Although devoid of mutant protein, this neurodegeneration exhibits neuronal inclusion bodies that are Hsp70 and ubiquitin positive. Overexpression of Hsp70 could suppress the neurodegeneration. These results demonstrate that neurodegenerative phenotype associated with fragile X premutation is indeed caused by the lengthened rCGG repeats and provide the first in vivo experimental demonstration of RNA-mediated neurodegeneration

2-Aminoacetophenone as a potential breath biomarker for Pseudomonas aeruginosa in the cystic fibrosis lung

<p>Abstract</p> <p>Background</p> <p><it>Pseudomonas aeruginosa </it>infections are associated with progressive life threatening decline of lung function in cystic fibrosis sufferers. Growth of <it>Ps. aeruginosa </it>releases a "grape-like" odour that has been identified as the microbial volatile organic compound 2-aminoacetophenone (2-AA).</p> <p>Methods</p> <p>We investigated 2-AA for its specificity to <it>Ps. aeruginosa </it>and its suitability as a potential breath biomarker of colonisation or infection by Solid Phase Micro Extraction and Gas Chromatography-Mass Spectrometry (GC/MS).</p> <p>Results</p> <p>Cultures of 20 clinical strains of <it>Ps. aeruginosa </it>but not other respiratory pathogens had high concentrations of 2-AA in the head space of <it>in vitro </it>cultures when analysed by GC/MS. 2-AA was stable for 6 hours in deactivated glass sampling bulbs but was not stable in Tedlar^®bags. Optimisation of GC/MS allowed detection levels of 2-AA to low pico mol/mol range in breath. The 2-AA was detected in a significantly higher proportion of subjects colonised with <it>Ps. aeruginosa </it>15/16 (93.7%) than both the healthy controls 5/17 (29%) (p < 0.0002) and CF patients not colonised with <it>Ps. aeruginosa </it>4/13(30.7%) (p < 0.001). The sensitivity and specificity of the 2-AA breath test compared to isolation of <it>Ps. aeruginosa </it>in sputum and/or BALF was 93.8% (95% CI, 67-99) and 69.2% (95% CI, 38-89) respectively. The peak integration values for 2-AA analysis in the breath samples were significantly higher in <it>Ps. aeruginosa </it>colonised subjects (median 242, range 0-1243) than the healthy controls (median 0, range 0-161; p < 0.001) and CF subjects not colonised with <it>Ps. aeruginosa </it>(median 0, range 0-287; p < 0.003)</p> <p>Conclusions</p> <p>Our results report 2-AA as a promising breath biomarker for the detection of <it>Ps. aeruginosa </it>infections in the cystic fibrosis lung.</p