Pro-inflammatory growth factors reduce secondary degeneration after traumatic spinal cord injury

The role of inflammatory response after spinal cord injury remains unclear. This thesis was a step forward in studying how promoting the inflammation, by delivery pro-inflammatory growth factors, affects the outcomes of spinal cord injury. A significant functional improvement was observed after treatment and these results suggest an interesting avenue for future clinical treatments and may provide a platform to improve the efficacy of other treatments.

The individual and interactive relationship between long chain omega-3 polyunsaturated fatty acids and physical activity as predictors of cognition in cognitively impaired and non-impaired older adults

Alterations in cognitive function are characteristic of the aging process in humans and other animals. However, the nature of these age related changes in cognition is complex and is likely to be influenced by interactions between genetic predispositions and environmental factors resulting in dynamic fluctuations within and between individuals. These inter and intra-individual fluctuations are evident in both so-called normal cognitive aging and at the onset of cognitive pathology. Mild Cognitive Impairment (MCI), thought to be a prodromal phase of dementia, represents perhaps the final opportunity to mitigate cognitive declines that may lead to terminal conditions such as dementia. The prognosis for people with MCI is mixed with the evidence suggesting that many will remain stable within 10-years of diagnosis, many will improve, and many will transition to dementia. If the characteristics of people who do not progress to dementia from MCI can be identified and replicated in others it may be possible to reduce or delay dementia onset, thus reducing a growing personal and public health burden. Furthermore, if MCI onset can be prevented or delayed, the burden of cognitive decline in aging populations worldwide may be reduced. A cognitive domain that is sensitive to the effects of advancing age, and declines in which have been shown to presage the onset of dementia in MCI patients, is executive function. Moreover, environmental factors such as diet and physical activity have been shown to affect performance on tests of executive function. For example, improvements in executive function have been demonstrated as a result of increased aerobic and anaerobic physical activity and, although the evidence is not as strong, findings from dietary interventions suggest certain nutrients may preserve or improve executive functions in old age. These encouraging findings have been demonstrated in older adults with MCI and their non-impaired peers. However, there are some gaps in the literature that need to be addressed. For example, little is known about the effect on cognition of an interaction between diet and physical activity. Both are important contributors to health and wellbeing, and a growing body of evidence attests to their importance in mental and cognitive health in aging individuals. Yet physical activity and diet are rarely considered together in the context of cognitive function. There is also little known about potential underlying biological mechanisms that might explain the physical activity/diet/cognition relationship. The first aim of this program of research was to examine the individual and interactive role of physical activity and diet, specifically long chain polyunsaturated fatty acid consumption(LCn3) as predictors of MCI status. The second aim is to examine executive function in MCI in the context of the individual and interactive effects of physical activity and LCn3.. A third aim was to explore the role of immune and endocrine system biomarkers as possible mediators in the relationship between LCn3, physical activity and cognition. Study 1a was a cross-sectional analysis of MCI status as a function of erythrocyte proportions of an interaction between physical activity and LCn3. The marine based LCn3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both received support in the literature as having cognitive benefits, although comparisons of the relative benefits of EPA or DHA, particularly in relation to the aetiology of MCI, are rare. Furthermore, a limited amount of research has examined the cognitive benefits of physical activity in terms of MCI onset. No studies have examined the potential interactive benefits of physical activity and either EPA or DHA. Eighty-four male and female adults aged 65 to 87 years, 50 with MCI and 34 without, participated in Study 1a. A logistic binary regression was conducted with MCI status as a dependent variable, and the individual and interactive relationships between physical activity and either EPA or DHA as predictors. Physical activity was measured using a questionnaire and specific physical activity categories were weighted according to the metabolic equivalents (METs) of each activity to create a physical activity intensity index (PAI). A significant relationship was identified between MCI outcome and the interaction between the PAI and EPA; participants with a higher PAI and higher erythrocyte proportions of EPA were more likely to be classified as non-MCI than their less active peers with less EPA. Study 1b was a randomised control trial using the participants from Study 1a who were identified with MCI. Given the importance of executive function as a determinant of progression to more severe forms of cognitive impairment and dementia, Study 1b aimed to examine the individual and interactive effect of physical activity and supplementation with either EPA or DHA on executive function in a sample of older adults with MCI. Fifty male and female participants were randomly allocated to supplementation groups to receive 6-months of supplementation with EPA, or DHA, or linoleic acid (LA), a long chain polyunsaturated omega-6 fatty acid not known for its cognitive enhancing properties. Physical activity was measured using the PAI from Study 1a at baseline and follow-up. Executive function was measured using five tests thought to measure different executive function domains. Erythrocyte proportions of EPA and DHA were higher at follow-up; however, PAI was not significantly different. There was also a significant improvement in three of the five executive function tests at follow-up. However, regression analyses revealed that none of the variance in executive function at follow-up was predicted by EPA, DHA, PAI, the EPA by PAI interaction, or the DHA by PAI interaction. The absence of an effect may be due to a small sample resulting in limited power to find an effect, the lack of change in physical activity over time in terms of volume and/or intensity, or a combination of both reduced power and no change in physical activity. Study 2a was a cross-sectional study using cognitively unimpaired older adults to examine the individual and interactive effects of LCn3 and PAI on executive function. Several possible explanations for the absence of an effect were identified. From this consideration of alternative explanations it was hypothesised that post-onset interventions with LCn3 either alone or in interation with self-reported physical activity may not be beneficial in MCI. Thus executive function responses to the individual and interactive effects of physical activity and LCn3 were examined in a sample of older male and female adults without cognitive impairment (n = 50). A further aim of study 2a was to operationalise executive function using principal components analysis (PCA) of several executive function tests. This approach was used firstly as a data reduction technique to overcome the task impurity problem, and secondly to examine the executive function structure of the sample for evidence of de-differentiation. Two executive function components were identified as a result of the PCA (EF 1 and EF 2). However, EPA, DHA, the PAI, or the EPA by PAI or DHA by PAI interactions did not account for any variance in the executive function components in subsequent hierarchical multiple regressions. Study 2b was an exploratory correlational study designed to explore the possibility that immune and endocrine system biomarkers may act as mediators of the relationship between LCn3, PAI, the interaction between LCn3 and PAI, and executive functions. Insulin-like growth factor-1 (IGF-1), an endocrine system growth hormone, and interleukin-6 (IL-6) an immune system cytokine involved in the acute inflammatory response, have both been shown to affect cognition including executive functions. Moreover, IGF-1 and IL-6 have been shown to be antithetical in so far as chronically increased IL-6 has been associated with reduced IGF-1 levels, a relationship that has been linked to age related morbidity. Further, physical activity and LCn3 have been shown to modulate levels of both IGF-1 and IL-6. Thus, it is possible that the cognitive enhancing effects of LCn3, physical activity or their interaction are mediated by changes in the balance between IL-6 and IGF-1. Partial and non-parametric correlations were conducted in a subsample of participants from Study 2a (n = 13) to explore these relationships. Correlations of interest did not reach significance; however, the coefficients were quite large for several relationships suggesting studies with larger samples may be warranted. In summary, the current program of research found some evidence supporting an interaction between EPA, not DHA, and higher energy expenditure via physical activity in differentiating between older adults with and without MCI. However, a RCT examining executive function in older adults with MCI found no support for increasing EPA or DHA while maintaining current levels of energy expenditure. Furthermore, a cross-sectional study examining executive function in older adults without MCI found no support for better executive function performance as a function of increased EPA or DHA consumption, greater energy expenditure via physical activity or an interaction between physical activity and either EPA or DHA. Finally, an examination of endocrine and immune system biomarkers revealed promising relationships in terms of executive function in non-MCI older adults particularly with respect to LCn3 and physical activity. Taken together, these findings demonstrate a potential benefit of increasing physical activity and LCn3 consumption, particularly EPA, in mitigating the risk of developing MCI. In contrast, no support was found for a benefit to executive function as a result of increased physical activity, LCn3 consumption or an interaction between physical activity and LCn3, in participants with and without MCI. These results are discussed with reference to previous findings in the literature including possible limitations and opportunities for future research.

Mathematical modelling of tumour growth and interaction with host tissue and the immune system

In this thesis, three mathematical models describing the growth of solid tumour incorporating the host tissue and the immune system response are developed and investigated. The initial model describes the dynamics of the growing tumour and immune response before being extended in the second model by introducing a time-varying dendritic cell-based treatment strategy. Finally, in the third model, we present a mathematical model of a growing tumour using a hybrid cellular automata. These models can provide information to pre-experimental work to assist in designing more effective and efficient laboratory experiments related to tumour growth and interactions with the immune system and immunotherapy.

Deposition of hydrocarbon molecules on diamond (001) surfaces : atomic scale modeling

The impact induced chemisorption of hydrocarbon molecules (CH3 and CH2) on H-terminated diamond (001)-(2x1) surface was investigated by molecular dynamics simulation using the many-body Brenner potential. The deposition dynamics of the CH3 radical at impact energies of 0.1-50 eV per molecule was studied and the energy threshold for chemisorption was calculated. The impact-induced decomposition of hydrogen atoms and the dimer opening mechanism on the surface was investigated. Furthermore, the probability for dimer opening event induced by chemisorption of CH, was simulated by randomly varying the impact position as well as the orientation of the molecule relative to the surface. Finally, the energetic hydrocarbons were modeled, slowing down one after the other to simulate the initial fabrication of diamond-like carbon (DLC) films. The structure characteristic in synthesized films with different hydrogen flux was studied. Our results indicate that CH3, CH2 and H are highly reactive and important species in diamond growth. Especially, the fraction of C-atoms in the film having sp(3) hybridization will be enhanced in the presence of H atoms, which is in good agreement with experimental observations. (C) 2002 Elsevier Science B.V. All rights reserved.

The role of human capital in economic growth revisited

Benhabib and Spiegel (1994) examine the role of human capital in the development process empirically using a theory-driven specification rather than the standard production function approach. While they find evidence of a positive impact of human capital on income growth, their result is not robust to the inclusion of inequality as an additional covariate. Using an alternate dataset and different measures of inequality, we find robust support for the hypothesis that human capital matters even when we account for the adverse effect of income inequality on growth.

Physical performance profile of sub-elite juvenile Gaelic Games players and the prevalence of a Relative Age Effect (RAE)

Gaelic Games are the indigenous sports played in Ireland, the most popular being Gaelic football and hurling. The games are contact sports and the physical demands are thought to be similar to those of Australian Rules football, rugby union, rugby league, field hockey, and lacrosse (Delahunt et al., 2011). The difference in chronological age between children in a single age group is known as relative age and its consequences as the RAE, whereby younger players are disadvantaged (Del Campo et al., 2010). The purpose of this study was to describe the physical and performance profile of sub-elite juvenile Gaelic Games players and to establish if a RAE is present in this cohort and any influence physiological moderator variables may have on this. Following receipt of ethical approval (EHSREC11-45), six sub-elite county development squads (Under-14/15/16 age groups, male, n=115) volunteered to partake in the study. Anthropometric data including skin folds and girths were collected. A number of field tests of physical performance including 5 and 20m speed, vertical and broad jump distance, and an estimate of VO2max were carried out. Descriptive data are presented as Mean SD. Juvenile sub-elite Gaelic Games players aged 14.53 0.82 y were 172.87 7.63 cm tall, had a mass of 64.74 11.06 kg, a BMI of 21.57 2.82 kg.m-2 and 9.22 4.78 % body fat. Flexibility, measured by sit and reach was 33.62 6.86 cm and lower limb power measured by vertical and broad jump were 42.19 5.73 and 191.16 25.26 cm, respectively. Participant time to complete 5m, 20m and an agility test (T-Test) was 1.12 0.07, 3.31 0.30 and 9.31 0.55 s respectively. Participant’s estimated VO2max was 48.23 5.05 ml.kg.min-1. Chi-Square analysis of birth month by quartile (Q1 = January-March) revealed that a RAE was present in this cohort, whereby an over-representation of players born in Q1 compared with Q2, Q3 and Q4 was evident (2 = 14.078, df = 3, p = 0.003). Kruskal-Wallis analysis of the data revealed no significant difference in any of the performance parameters based on quartile of birth (Alpha level = 0.05).This study provides a physical performance profile of juvenile sub-elite Gaelic Games players, comparable with those of other sports such as soccer and rugby. This novel data can inform us of the physical requirements of the sport. The evidence of a RAE is similar to that observed in other contact sports such as soccer and rugby league (Carling et al, 2009; Till et al, 2010). Although a RAE exists in this cohort, this cannot be explained by any physical/physiological moderator variables. Carling C et al. (2009). Scandinavian Journal of Medicine and Science in Sport 19, 3-9. Delahunt E et al. (2011). Journal of Athletic Training 46, 241-5. Del Campo DG et al. (2010). Journal of Sport Science and Medicine 9, 190-198. Delorme N et al. (2010). European Journal of Sport Science 10, 91-96. Till K et al. (2010). Scandinavian Journal of Medicine and Science in Sports 20, 320-329.

Effects of soluble dietary cellulose on specific growth rate, survival and digestive enzyme activities in three freshwater crayfish (Cherax) species

The current study evaluated the effect of soluble dietary cellulose on growth, survival and digestive enzyme activity in three endemic, Australian freshwater crayfish species (redclaw: Cherax quadricarinatus, marron: C. tenuimanus, yabby: C. destructor). Separate individual feeding trials were conducted for late-stage juveniles from each species in an automated recirculating freshwater, culture system. Animals were fed either a test diet (TD) that contained 20% soluble cellulose or a reference diet (RD) substituted with the same amount of corn starch, over a 12 week period. Redclaw fed with RD showed significantly higher (p<0.05) specific growth rates (SGR) compared with animals fed the TD, while SGR of marron and yabby fed the two diets were not significantly different. Expressed cellulase activity levels in redclaw were not significantly different between diets. Marron and yabby showed significantly higher cellulase activity when fed the RD (p<0.05). Amylase and protease activity in all three species were significantly higher in the animals fed with RD (p<0.05). These results indicate that test animals of all three species appear to utilize starch more efficiently than soluble dietary cellulose in their diet. The inclusion of 20% soluble cellulose in diets did not appear, however, to have a significant negative effect on growth rates.

Repeated intrauterine exposures to inflammatory stimuli attenuated transforming growth factor-β signaling in the ovine fetal lung

Background: Bronchopulmonary dysplasia (BPD) is one of the most common complications after preterm birth and is associated with intrauterine exposure to bacteria. Transforming growth factor-β (TGFβ) is implicated in the development of BPD. Objectives: We hypothesized that different and/or multiple bacterial signals could elicit divergent TGFβ signaling responses in the developing lung. Methods: Time-mated pregnant Merino ewes received an intra-amniotic injection of lipopolysaccharide (LPS) and/or Ureaplasma parvum serovar 3 (UP) at 117 days' and/or 121/122 days' gestational age (GA). Controls received an equivalent injection of saline and or media. Lambs were euthanized at 124 days' GA (term = 150 days' GA). TGFβ1, TGFβ2, TGFβ3, TGFβ receptor (R)1 and TGFβR2 protein levels, Smad2 phosphorylation and elastin deposition were evaluated in lung tissue. Results: Total TGFβ1 and TGFβ2 decreased by 24 and 51% after combined UP+LPS exposure, whereas total TGFβ1 increased by 31% after 7 days' LPS exposure but not after double exposures. Alveolar expression of TGFβR2 decreased 75% after UP, but remained unaltered after double exposures. Decreased focal elastin deposition after single LPS exposure was prevented by double exposures. Conclusions: TGFβ signaling components and elastin responded differently to intrauterine LPS and UP exposure. Multiple bacterial exposures attenuated TGFβ signaling and normalized elastin deposition.

A bondgraph approach to formation control using relative state measurements

In this paper we apply port-Hamiltonian theory with the bondgraph modelling approach to the problem of formation control using partial measurements of relative positions. We present a control design that drives a group of vehicles to a desired formation without requiring inter-vehicle communications or global position and velocity measurements to be available. Our generic approach is applicable to any form of relative measurement between vehicles, but we specifically consider the important cases of relative bearings and relative distances. In the case of bearings, our theory closely relates to the field of image-based visual servo (IBVS) control. We present simulation results to support the developed theory.

Life-history constraints in grassland plant species : a growth-defence trade-off is the norm

Plant growth can be limited by resource acquisition and defence against consumers, leading to contrasting trade-off possibilities. The competition-defence hypothesis posits a trade-off between competitive ability and defence against enemies (e.g. herbivores and pathogens). The growth-defence hypothesis suggests that strong competitors for nutrients are also defended against enemies, at a cost to growth rate. We tested these hypotheses using observations of 706 plant populations of over 500 species before and following identical fertilisation and fencing treatments at 39 grassland sites worldwide. Strong positive covariance in species responses to both treatments provided support for a growth-defence trade-off: populations that increased with the removal of nutrient limitation (poor competitors) also increased following removal of consumers. This result held globally across 4 years within plant life-history groups and within the majority of individual sites. Thus, a growth-defence trade-off appears to be the norm, and mechanisms maintaining grassland biodiversity may operate within this constraint.

Essays on technology adoption under uncertainty, globalization and economic growth

This thesis examines how the initial institutional and technological aspects of the economy and the reforms that alter these aspects influence long run growth and development. These issues are addressed in the framework of stochastic endogenous growth models and an empirical framework. The thesis is able to explain why developing nations exhibit diverse growth and inequality patterns. Consequently, the thesis raises a number of policy implications regarding how these nations can improve their economic outcomes.

A combined environmental scanning electron microscopy and Raman microscopy study of methanol oxidation on silver(I) oxide

The techniques of environmental scanning electron microscopy (ESEM) and Raman microscopy have been used to respectively elucidate the morphological changes and nature of the adsorbed species on silver(I) oxide powder, during methanol oxidation conditions. Heating Ag2O in either water vapour or oxygen resulted firstly in the decomposition of silver(I) oxide to polycrystalline silver at 578 K followed by sintering of the particles at higher temperature. Raman spectroscopy revealed the presence of subsurface oxygen and hydroxyl species in addition to surface hydroxyl groups after interaction with water vapour. Similar species were identified following exposure to oxygen in an ambient atmosphere. This behaviour indicated that the polycrystalline silver formed from Ag2O decomposition was substantially more reactive than silver produced by electrochemical methods. The interaction of water at elevated temperatures subsequent to heating silver(I) oxide in oxygen resulted in a significantly enhanced concentration of subsurface hydroxyl species. The reaction of methanol with Ag2O at high temperatures was interesting in that an inhibition in silver grain growth was noted. Substantial structural modification of the silver(I) oxide material was induced by catalytic etching in a methanol/air mixture. In particular, "pin-hole" formation was observed to occur at temperatures in excess of 773 K, and it was also recorded that these "pin- holes" coalesced to form large-scale defects under typical industrial reaction conditions. Raman spectroscopy revealed that the working surface consisted mainly of subsurface oxygen and surface Ag=O species. The relative lack of sub-surface hydroxyl species suggested that it was the desorption of such moieties which was the cause of the "pin-hole" formation.

Vehicle-to-vehicle real-time relative positioning using 5.9 GHz DSRC media

Vehicular accidents are one of the deadliest safety hazards and accordingly an immense concern of individuals and governments. Although, a wide range of active autonomous safety systems, such as advanced driving assistance and lane keeping support, are introduced to facilitate safer driving experience, these stand-alone systems have limited capabilities in providing safety. Therefore, cooperative vehicular systems were proposed to fulfill more safety requirements. Most cooperative vehicle-to-vehicle safety applications require relative positioning accuracy of decimeter level with an update rate of at least 10 Hz. These requirements cannot be met via direct navigation or differential positioning techniques. This paper studies a cooperative vehicle platform that aims to facilitate real-time relative positioning (RRP) among adjacent vehicles. The developed system is capable of exchanging both GPS position solutions and raw observations using RTCM-104 format over vehicular dedicated short range communication (DSRC) links. Real-time kinematic (RTK) positioning technique is integrated into the system to enable RRP to be served as an embedded real-time warning system. The 5.9 GHz DSRC technology is adopted as the communication channel among road-side units (RSUs) and on-board units (OBUs) to distribute GPS corrections data received from a nearby reference station via the Internet using cellular technologies, by means of RSUs, as well as to exchange the vehicular real-time GPS raw observation data. Ultimately, each receiving vehicle calculates relative positions of its neighbors to attain a RRP map. A series of real-world data collection experiments was conducted to explore the synergies of both DSRC and positioning systems. The results demonstrate a significant enhancement in precision and availability of relative positioning at mobile vehicles.

Genes and growth performance in crustacean species : a review of relevant genomic studies in crustaceans and other taxa

Global aquaculture has expanded rapidly to address the increasing demand for aquatic protein needs and an uncertain future for wild fisheries. To date, however, most farmed aquatic stocks are essentially wild and little is known about their genomes or the genes that affect important economic traits in culture. Biologists have recognized that recent technological advances including next generation sequencing (NGS) have opened up the possibility of generating genome wide sequence data sets rapidly from non-model organisms at a reasonable cost. In an era when virtually any study organism can 'go genomic', understanding gene function and genetic effects on expressed quantitative trait locus phenotypes will be fundamental to future knowledge development. Many factors can influence the individual growth rate in target species but of particular importance in agriculture and aquaculture will be the identification and characterization of the specific gene loci that contribute important phenotypic variation to growth because the information can be applied to speed up genetic improvement programmes and to increase productivity via marker-assisted selection (MAS). While currently there is only limited genomic information available for any crustacean species, a number of putative candidate genes have been identified or implicated in growth and muscle development in some species. In an effort to stimulate increased research on the identification of growth-related genes in crustacean species, here we review the available information on: (i) associations between genes and growth reported in crustaceans, (ii) growth-related genes involved with moulting, (iii) muscle development and degradation genes involved in moulting, and; (iv) correlations between DNA sequences that have confirmed growth trait effects in farmed animal species used in terrestrial agriculture and related sequences in crustacean species. The information in concert can provide a foundation for increasing the rate at which knowledge about key genes affecting growth traits in crustacean species is gained.

Relative abundance of full-length and truncated FOXP1 isoforms is associated with differential NFκB activity in Follicular Lymphoma

FOXP1 is a transcriptional repressor that has been proposed to repress the expression of some NFκB-responsive genes. Furthermore, truncated forms of FOXP1 have been associated with a subtype of Diffuse Large B-cell Lymphoma characterised by constitutive NFκB activity, indicating that they may inhibit this repression. We have shown that FL tumors have increased relative abundance of truncated FOXP1 isoforms and this is associated with increased expression of NFκB-associated genes. Our results provide strong evidence that relative FOXP1 isoform abundance is associated with NFκB activity in FL, and could potentially be used as a marker for this gene signature.