A study of magnetic non-linearity and finite length effects in solid iron subjected to a travelling MMF wave

This thesis describes an experimental and analytic study of the effects of magnetic non-linearity and finite length on the loss and field distribution in solid iron due to a travelling mmf wave. In the first half of the thesis, a two-dimensional solution is developed which accounts for the effects of both magnetic non-linearity and eddy-current reaction; this solution is extended, in the second half, to a three-dimensional model. In the two-dimensional solution, new equations for loss and flux/pole are given; these equations contain the primary excitation, the machine parameters and factors describing the shape of the normal B-H curve. The solution applies to machines of any air-gap length. The conditions for maximum loss are defined, and generalised torque/frequency curves are obtained. A relationship between the peripheral component of magnetic field on the surface of the iron and the primary excitation is given. The effects of magnetic non-linearity and finite length are combined analytically by introducing an equivalent constant permeability into a linear three-dimensional analysis. The equivalent constant permeability is defined from the non-linear solution for the two-dimensional magnetic field at the axial centre of the machine to avoid iterative solutions. In the linear three-dimensional analysis, the primary excitation in the passive end-regions of the machine is set equal to zero and the secondary end faces are developed onto the air-gap surface. The analyses, and the assumptions on which they are based, were verified on an experimental machine which consists of a three-phase rotor and alternative solid iron stators, one with copper end rings, and one without copper end rings j the main dimensions of the two stators are identical. Measurements of torque, flux /pole, surface current density and radial power flow were obtained for both stators over a range of frequencies and excitations. Comparison of the measurements on the two stators enabled the individual effects of finite length and saturation to be identified, and the definition of constant equivalent permeability to be verified. The penetration of the peripheral flux into the stator with copper end rings was measured and compared with theoretical penetration curves. Agreement between measured and theoretical results was generally good.

Polymer-phospholipid complexes for the solubilisation and delivery of drugs to the eye

Aim: Topical application of ophthalmic drugs is very inefficient; contact lenses used as drug delivery devices could minimize the drug loss and side effects. Styrene-maleic acid copolymers (PSMA) can form polymer-phospholipid complexes with dipalmitoyl phosphatidylcholine (DMPC) in the form of nanometric vesicles, which can easily solubilise hydrophobic drugs. They can be dispersed on very thin contact lens coatings to immobilize the drug on their surface. Methods: Two types of complexes stable at different pH values (5 and 7 respectively) where synthesized and loaded with drugs of different hydrophilicities during their formation process. The drug release was studied in vitro and compared to the free drug. Results: The mean sizes of the complexes obtained by light scattering were 50 nm and 450 nm respectively with low polydispersities. However, they were affected by the drugs load and release. An increase was observed in the duration of the release in the case of hydrophobic drugs, from days to weeks, avoiding initial “burst” and with a lesser amount of total drug released due to the interaction of the drug with the phospholipid core. The size and charge of the different drugs and the complexes nature also affected the release profile. Conclusions: Polymer-phospholipid complexes in the form of nanoparticles can be used to solubilise and release hydrophobic drugs in a controlled way. The drug load and release can be optimised to reach therapeutic values in the eye.

Hearing and vision:the age old problem

Opticians and audiologists tend to see the same people. Many factors that are associated with poorer vision, whether hereditary, pre-natal, or post-natal, are also associated with poorer hearing. The most common factor is simply old age. According to the Royal National Institute for Deaf People (RNID), more than half of all people aged over 60 have some degree of hearing loss and are gradually losing their hearing as part of the ageing process – a process known as presbycusis.

Tumour associated proteolysis and protein metabolism

The effect of cancer cachexia on protein metabolism has been studied in mice transplanted with the MAC16 adenocarcinoma. The progressive cachexia induced by the MAC16 tumour was characterised by a reduction in carcass nitrogen between 16-30% weight loss and a reciprocal increase in tumour nitrogen content. Carcass nitrogen loss was accompanied by a concomitant decrease in gastrocnemius muscle weight and nitrogen content and also by a decrease in liver nitrogen content. The loss of gastrocnemius muscle throughout the progression of cachexia was attributable to a 60% decrease in the rate of protein synthesis and a 240% increase in the rate of protein degradation. The loss of skeletal muscle protein that may be partially mediated by an increased rate of protein degradation has been correlated with a circulatory catabolic factor present only in cachectic tumour-bearing animals, that degrades host muscle in vitro. The proteolysis-inducing factor was found to be heat stable, not a serine protease and was inhibited by indomethacin and eicosapentaenoic acid (EPA) in a dose-related manner. The proteolytic factor induced prostaglandin E2 formation in the gastrocnemius muscle of non tumour-bearing animals and this effect was inhibited by indomethacin and EPA. In vivo studies show EPA (2.0g/kg-1 by gavage) to effectively reverse the decrease in body weight in animals bearing the MAC16 tumour with a concomitant reduction in tumour growth. Muscle from animals treated with EPA showed a decrease (60%) in protein degradation without an effect on protein synthesis. In vivo studies show branched chain amino acid treatment to be ineffective in moderating the cachectic effect of the MAC16 tumour. The action of the factor was largely mimicked by triarachidonin and trilinoleia. The increased serum levels of arachidonic acid in cachectic tumour-bearing animals may thus be responsible for increased protein degradation through prostanoid metabolism. The understanding of protein metabolism and catabolic factors in the cachectic animal may provide future avenues for the reversal of cachexia and the treatment of cancer.metabolism and catabolicmetabolism and cat

Experiments and observations on the behaviour and brain of the aging female mouse with special reference to dementia of the Alzheimer type

The objective of this research was to investigate the effects of normal aging and the additional effects of chronic exposure to two experimental diets, one enriched in aluminium, the other enriched in lecithin, on aspects of the behaviour and brain histology of the female mouse. The aluminium diet was administered in an attempt to develop a rodent model of Dementia of the Alzheimer Type (DAT). With normal aging, almost all assessed aspects of behaviour were found to be impaired. As regards cognition, selective impairments of single-trial passive avoidance and Morris place learning were observed. While all aspects of open-field behaviour were impaired, the degree of impairment was directly related to the degree of motoric complexity. Deficits were also observed on non-visual sensorimotor coordination tasks and in olfactory discrimination. Histologically, neuron loss, gliosis, vacuolation and congophilic angiopathy were observed in several of the brain regions/fibre tracts believed to contribute to the control of some of the assessed behaviours. The aluminium treatment had very selective effects on both behaviour and brain histology, inducing several features observed in DAT. Behaviourally, the treatment induced impaired spatial reference memory; reduced ambulation; disturbed olfactory function and induced the premature development of the senile pattern of swimming. Histologically, significant neuron loss and gliosis were observed in the hippocampus, entorhinal cortex, amygdala, medial septum, pyriform and pr-frontal cortex. In addition, the brain distribution of congophilic angiopathy was significantly increased by the treatment. The lecithin treatment had effects on both non-cognitive and cognitive aspects of behaviour. The effects of aging on open-field ambulation and rearing were partially ameliorated by the treatment. A similar effect was observed for single-trial passive avoidance performance. Age-dependent improvements in acquisition/retention were observed in 17-23 month mice and Morris place task performance was improved in 11 and 17 month mice. Histologically, a partial sparing of neurons in the cerebellum, hippocampus, entorhinal cortex and subiculum was observed.

Cracking capitalist realism: the new student movement and its post-capitalist politics

There is much talk of =the crisis‘ in higher education, often expressed in fatalistic narratives about the (im)possibility of critical resistance or alternatives to the deepening domination of neoliberal rationality and capitalist power throughout social life. But how precisely are we to make sense of this situation? In what ways is it experienced? And what knowledges and practices may help us to respond? These questions form the basis for a series of explorations of the history and character of this crisis, the particular historical conjuncture that we occupy today, and the different types of theoretical analysis and political response it seems to be engendering. Our talk will explore the tensions between readings of the situation as a paralyzing experience of domination, loss and impossibility, on the one hand, and radical transformation and the opening of future possibilities, on the other. We will finally consider what implications new forms of political theory being created in the new student movements have for reconceptualising praxis in higher education today, and perhaps for a wider imagination of post-capitalist politics.

Analysis of oxidized and chlorinated lipids by mass spectrometry and relevance to signalling

Oxidized and chlorinated phospholipids are generated under inflammatory conditions and are increasingly understood to play important roles in diseases involving oxidative stress. MS is a sensitive and informative technique for monitoring phospholipid oxidation that can provide structural information and simultaneously detect a wide variety of oxidation products, including chain-shortened and -chlorinated phospholipids. MSn technologies involve fragmentation of the compounds to yield diagnostic fragment ions and thus assist in identification. Advanced methods such as neutral loss and precursor ion scanning can facilitate the analysis of specific oxidation products in complex biological samples. This is essential for determining the contributions of different phospholipid oxidation products in disease. While many pro-inflammatory signalling effects of oxPLs (oxidized phospholipids) have been reported, it has more recently become clear that they can also have anti-inflammatory effects in conditions such as infection and endotoxaemia. In contrast with free radical-generated oxPLs, the signalling effects of chlorinated lipids are much less well understood, but they appear to demonstrate mainly pro-inflammatory effects. Specific analysis of oxidized and chlorinated lipids and the determination of their molecular effects are crucial to understanding their role in disease pathology.

The role of zinc in the anti-tumour and anti-cachectic activity of D-myo-inositol 1,2,6-triphosphate

Background: D-myo-inositol-1,2,6-triphosphate (a-trinositol, AT) is a polyanionic molecule capable of chelating divalent metal ions with anti-tumour and anti-cachectic activity in a murine model. Methods: To investigate the role of zinc in this process, mice bearing cachexia-inducing MAC16 tumour were treated with AT, with or without concomitant administration of ZnSO4. Results: At a dose of 40mgkg-1, AT effectively attenuated both weight loss and growth of the MAC16 tumour, and both effects were attenuated by co-administration of Zn2+. The concentration of zinc in gastrocnemius muscle increased with increasing weight loss, whereas administration of AT decreased the levels of zinc in plasma, skeletal muscle and tumour, which were restored back to control values after administration of ZnSO4. Conclusion: These results suggest that zinc is important in both tumour growth and cachexia in this animal model.

Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes

BACKGROUND: Patients with advanced cancer suffer from cachexia, which is characterised by a marked weight loss, and is invariably associated with the presence of tumoral and humoral factors which are mainly responsible for the depletion of fat stores and muscular tissue. METHODS: In this work, we used cytotoxicity and enzymatic assays and morphological analysis to examine the effects of a proteolysis-inducing factor (PIF)-like molecule purified from ascitic fluid of Walker tumour-bearing rats (WF), which has been suggested to be responsible for muscle atrophy, on cultured C2C12 muscle cells. RESULTS: WF decreased the viability of C2C12 myotubes, especially at concentrations of 20-25 mug.mL-1. There was an increase in the content of the pro-oxidant malondialdehyde, and a decrease in antioxidant enzyme activity. Myotubes protein synthesis decreased and protein degradation increased together with an enhanced in the chymotrypsin-like enzyme activity, a measure of functional proteasome activity, after treatment with WF. Morphological alterations such as cell retraction and the presence of numerous cells in suspension were observed, particularly at high WF concentrations. CONCLUSION: These results indicate that WF has similar effects to those of proteolysis-inducing factor, but is less potent than the latter. Further studies are required to determine the precise role of WF in this experimental model. © 2008 Yano et al; licensee BioMed Central Ltd.

Visual field and structural correlates of progression in age-related macular degeneration

Presentation Purpose:To examine the correlation of central visual field loss and progression of structural changes in the macular area in age-related macular degeneration (AMD). Methods:Central 10° standard and short-wavelength automated perimetry (SWAP) visual fields were acquired in 39 eyes of 24 patients with AMD using a Humphrey Field Analyzer. Stereoscopic fundus photographs were graded1 by two independent observers and the stage of disease determined2. Custom software mapped perimetric data onto fundus images in order to relate structural changes to functional loss. Results:Mean deviation (MD) in standard perimetry changed from 0.04 dB at stage 1 to -12.39 dB at stage 4 (r2=0.48, p<0.001). The group mean SWAP MD was -5.26 dB at stage 1 and increased to -17.08 dB at stage 4 (r2=0.53, p<0.001). Pattern standard deviation (PSD) also increased with advancing stage in standard perimetry; 1.32 dB to 8.67 dB at stage 1 and 4, respectively (r2=0.54, p<0.001). In SWAP, PSD increased from 2.86 dB to 5.63 dB at stage 1 and stage 4 (r2=0.43, p<0.001). Defect frequency was greater in SWAP than standard perimetry. Early stage defects occurred with the greatest frequency at eccentricities of 3.2° and 5.1° in standard perimetry and at 4.2° in SWAP. Late stage defects were most frequent at 1° eccentricity in standard perimetry and at 1° and 9° in SWAP. MD declined with increasing affected retinal area over the central 3000µm; by 0.20 dB (r2=0.67, p<0.001) and 0.18 dB (r2=0.49, p<0.001) per % increase in defect area for standard perimetry and SWAP respectively. 41% of defects were associated with structural changes on the retina in standard perimetry and 43% in SWAP. Conclusions:Sensitivity decreased with advancing stage of AMD, with a greater effect demonstrated in SWAP compared to standard perimetry. The central field became less uniform as stage increased. SWAP defects occurred at similar locations but were deeper and wider than corresponding defects in standard perimetry. Central loss in SWAP is a sensitive marker of functional progression in AMD.1. Bird et al. (1995) Surv Ophthalmol 39:367-3742. van Leeuwen et al. (2003) Arch Ophthalmol 121:519-526

Impact of senescence and disease on the structural and functional performance of the visual pathway

The diagnosis and monitoring of ocular disease presents considerable clinical difficulties for two main reasons i) the substantial physiological variation of anatomical structure of the visual pathway and ii) constraints due to technical limitations of diagnostic hardware. These are further confounded by difficulties in detecting early loss or change in visual function due to the masking of disease effects, for example, due to a high degree of redundancy in terms of nerve fibre number along the visual pathway. This thesis addresses these issues across three areas of study: 1. Factors influencing retinal thickness measures and their clinical interpretation As the retina is the principal anatomical site for damage associated with visual loss, objective measures of retinal thickness and retinal nerve fibre layer thickness are key to the detection of pathology. In this thesis the ability of optical coherence tomography (OCT) to provide repeatable and reproducible measures of retinal structure at the macula and optic nerve head is investigated. In addition, the normal physiological variations in retinal thickness and retinal nerve fibre layer thickness are explored. Principal findings were: • Macular retinal thickness and optic nerve head measurements are repeatable and reproducible for normal subjects and diseased eyes • Macular and retinal nerve fibre layer thickness around the optic nerve correlate negatively with axial length, suggesting that larger eyes have thinner retinae, potentially making them more susceptible to damage or disease • Foveola retinal thickness increases with age while retinal nerve fibre layer thickness around the optic nerve head decreases with age. Such findings should be considered during examination of the eye with suspect pathology or in long-term disease monitoring 2. Impact of glucose control on retinal anatomy and function in diabetes Diabetes is a major health concern in the UK and worldwide and diabetic retinopathy is a major cause of blindness in the working population. Objective, quantitative measurements of retinal thickness. particularly at the macula provide essential information regarding disease progression and the efficacy of treatment. Functional vision loss in diabetic patients is commonly observed in clinical and experimental studies and is thought to be affected by blood glucose levels. In the first study of its kind, the short term impact of fluctuations in blood glucose levels on retinal structure and function over a 12 hour period in patients with diabetes are investigated. Principal findings were: • Acute fluctuations in blood glucose levels are greater in diabetic patients than normal subjects • The fluctuations in blood glucose levels impact contrast sensitivity scores. SWAP visual fields, intraocular pressure and diastolic pressure. This effect is similar for type 1 and type 2 diabetic patients despite the differences in their physiological status. • Long-term metabolic control in the diabetic patient is a useful predictor in the fluctuation of contrast sensitivity scores. • Large fluctuations in blood glucose levels and/or visual function and structure may be indicative of an increased risk of development or progression of retinopathy 3. Structural and functional damage of the visual pathway in glaucomatous optic neuropathy The glaucomatous eye undergoes a number of well documented pathological changes including retinal nerve fibre loss and optic nerve head damage which is correlated with loss of functional vision. In experimental glaucoma there is evidence that glaucomatous damage extends from retinal ganglion cells in the eye, along the visual pathway, to vision centres in the brain. This thesis explores the effects of glaucoma on retinal nerve fibre layer thickness, ocular anterior anatomy and cortical structure, and its correlates with visual function in humans. Principal findings were: • In the retina, glaucomatous retinal nerve fibre layer loss is less marked with increasing distance from the optic nerve head, suggesting that RNFL examination at a greater distance than traditionally employed may provide invaluable early indicators of glaucomatous damage • Neuroretinal rim area and retrobulbar optic nerve diameter are strong indicators of visual field loss • Grey matter density decreases at a rate of 3.85% per decade. There was no clear evidence of a disease effect • Cortical activation as measured by fMRI was a strong indicator of functional damage in patients with significant neuroretinal rim loss despite relatively modest visual field defects These investigations have shown that the effects of senescence are evident in both the anterior and posterior visual pathway. A variety of anatomical and functional diagnostic protocols for the investigation of damage to the visual pathway in ocular disease are required to maximise understanding of the disease processes and thereby optimising patient care.

Fibre laser using a microchannel based loss tuning element for refractive index sensing

We have proposed and demonstrated a fibre laser system using a microchannel as a cavity loss tuning element for surrounding medium refractive index (SRI) sensing. A ~6µm width microchannel was created by femtosecond (fs) laser inscription assisted chemical etching in the cavity fibre, which offers a direct access to the external liquids. When the SRI changes, the microchannel behaves as a loss tuning element, hence modulating the laser cavity loss and output power. The results indicate that the presented laser sensing system has a linear response to the SRI with a sensitivity in the order of 10-5. Using higher pump power and more sensitive photodetector, the SRI sensitivity could be further enhanced.

Intermittent fasting:a dietary intervention for prevention of diabetes and cardiovascular disease?

Intermittent fasting, in which individuals fast on consecutive or alternate days, has been reported to facilitate weight loss and improve cardiovascular risk. This review evaluates the various approaches to intermittent fasting and examines the advantages and limitations for use of this approach in the treatment of obesity and type 2 diabetes. © The Author(s) 2013.

Editorial : which weight loss diet?

Full editorial: A recent study evaluating the long-term (2 yr) weight reducing efficacy of different types of diets – high or low in carbohydrates (CHOs), protein or fat - confirmed that it is calorie deficit not dietary composition that determines the loss and maintenance of body weight.1 Is there any advantage in following a specific weight loss diet? Short-term use of nutritionally complete commercially available (very) low calorie diets has benefited people with diabetes when  supported by education programmes.2 Initial weight loss has been encouraging with some fad diets eg the Atkins and the South Beach diets, but these diets are difficult to maintain and there are safety issues regarding their short- and long-term use – especially in people with diabetes.3 The types of macronutrients consumed can have a considerable impact on glycaemic control and energy metabolism. Although a low CHO diet additionally enhances initial weight loss by reducing cellular water content, if fat is not proportionally reduced the diet may not benefit the lipid profile for vascular disease risk. High fat and high protein diets – which are simultaneously low in CHOs – increase vulnerability to hypoglycaemia in people taking insulin secretagogues or on insulin therapy, and may promote excess fat metabolism and ketogenesis, particularly in people vulnerable to lack of insulin. Very low protein diets are not recommended as lean body mass tends to be reduced in diabetes. Altering the macronutrient balance has implications for the micronutrient mix: deficiencies are higher if more foods are excluded and conversely specific micronutrient excess can occur with some fad diets. The altered nutrient mix affects intestinal fauna and flora, and gut motility and glycaemic control are influenced by the quantity and type of fibre consumed. Support programmes help individuals achieve long term weight loss and there is mounting evidence that community schemes which educate and promote lifestyle changes may stem the rising tide of obesity and consequent type 2 diabetes.4 Consuming smaller portions of a balanced diet (and adjusting antidiabetic medications accordingly) will create an energy deficit to promote healthy weight loss. Increased movement/exercise will enhance this energy deficit. Knowledge (eg 1g fat has 2.25 times more energy than 1g CHO) allows sensible food choices and compensation for inclusion of small volumes of  ‘naughty but nice’ foods. Ultimately weight control requires self control. References 1. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859–73. 2. Bennett P. Obesity, diabetes and VLCD. Br J Diabetes Vasc Dis 2004;4:328–30. 3. Baldwin EJ. Fad diets in diabetes. Br J Diabetes Vasc DIs 2004;4:333–7. 4. Romon M, Lommoz A, Tafflet M et al. Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes. Public Health Nutr 2008; Dec 28, 1–8 [Epub ahead of print].

The prevalence and phenotype of activated microglia/macrophages within the spinal cord of the hyperostotic mouse (twy/twy) changes in response to chronic progressive spinalcord compression:implications for human cervical compressive myelopathy

Background:Cervical compressive myelopathy, e.g. due to spondylosis or ossification of the posterior longitudinal ligament is a common cause of spinal cord dysfunction. Although human pathological studies have reported neuronal loss and demyelination in the chronically compressed spinal cord, little is known about the mechanisms involved. In particular, the neuroinflammatory processes that are thought to underlie the condition are poorly understood. The present study assessed the localized prevalence of activated M1 and M2 microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal cord compression, as a model of human disease.Methods:Inflammatory cells and cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric analysis. Computed tomography and standard histology confirmed a progressive spinal cord compression through the spontaneously development of an impinging calcified mass.Results:The prevalence of CD11b-positive cells, in the compressed spinal cord increased over time with a concurrent decrease in neurons. The CD11b-positive cell population was initially formed of arginase-1- and CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and CD16/32-positive M1 microglia/macrophages. There was a transient increase in levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and macrophage antigen (Mac) -2 progressively increased.Conclusions:Spinal cord compression was associated with a temporal M2 microglia/macrophage response, which may act as a possible repair or neuroprotective mechanism. However, the persistence of the neural insult also associated with persistent expression of Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, which may lead to neuronal loss and demyelination despite the presence of neurotrophic factors. This understanding of the aetiopathology of chronic spinal cord compression is of importance in the development of new treatment targets in human disease. © 2013 Hirai et al.