Integrated Omics for the global mapping of biomolecules in LDL

Circulating low density lipoproteins (LDL) are thought to play a crucial role in the onset and development of atherosclerosis, though the detailed molecular mechanisms responsible for their biological effects remain controversial. The complexity of biomolecules (lipids, glycans and protein) and structural features (isoforms and chemical modifications) found in LDL particles hampers the complete understanding of the mechanism underlying its atherogenicity. For this reason the screening of LDL for features discriminative of a particular pathology in search of biomarkers is of high importance. Three major biomolecule classes (lipids, protein and glycans) in LDL particles were screened using mass spectrometry coupled to liquid chromatography. Dual-polarity screening resulted in good lipidome coverage, identifying over 300 lipid species from 12 lipid sub-classes. Multivariate analysis was used to investigate potential discriminators in the individual lipid sub-classes for different study groups (age, gender, pathology). Additionally, the high protein sequence coverage of ApoB-100 routinely achieved (≥70%) assisted in the search for protein modifications correlating to aging and pathology. The large size and complexity of the datasets required the use of chemometric methods (Partial Least Square-Discriminant Analysis, PLS-DA) for their analysis and for the identification of ions that discriminate between study groups. The peptide profile from enzymatically digested ApoB-100 can be correlated with the high structural complexity of lipids associated with ApoB-100 using exploratory data analysis. In addition, using targeted scanning modes, glycosylation sites within neutral and acidic sugar residues in ApoB-100 are also being explored. Together or individually, knowledge of the profiles and modifications of the major biomolecules in LDL particles will contribute towards an in-depth understanding, will help to map the structural features that contribute to the atherogenicity of LDL, and may allow identification of reliable, pathology-specific biomarkers. This research was supported by a Marie Curie Intra-European Fellowship within the 7th European Community Framework Program (IEF 255076). Work of A. Rudnitskaya was supported by Portuguese Science and Technology Foundation, through the European Social Fund (ESF) and "Programa Operacional Potencial Humano - POPH".

Migration and mobility of new Polish migrants in England:narratives of lived experience

This thesis sets out to understand the act of migrating in a period of growing movement of people. It captures the subjective experience of individual migrants, as narrated in the migration stories of 32 “new” Polish migrants in the West Midlands region of England. Since the enlargement of the European Union in 2004, over half a million Poles have arrived and registered to work in the UK, constituting one of the largest migration movements in contemporary Britain and Europe. This influx of predominantly young migrants opened up public and academic debates regarding the social relations between the Polish migrants and the host society, their duration of stay, and the impact on the economy and social services. While a substantial amount of research has now been undertaken on this migration, this thesis highlights some of the significant features of migration to Britain and Europe today, namely its dynamic, fluid, complex and varied character. Through four themes of lived experience of migration, migration and mobility, gender, and return migration, this thesis uncovers and explores the phenomenon of post-2004 EU migration from the perspective of migrants themselves. Migrant stories in this thesis are linked with experiences and meanings of migration, but also migrants’ emotions, perceptions, views and opinions. By exploring individual journeys of migration and deliberating over the determinants and consequences of migration, this thesis asks how the processes of migration and mobility come into play in the everyday lives of migrant people, and how this impacts on questions of identity, home, belonging, gender, as well as return.

Scaling the Advantages of Intra-channel Nonlinearity Compensation in Future Flexible Optical Networks

We report that, contrary to common perception, intra-channel nonlinearity compensation offers significant improvements of up to 4dB, in nonlinear tolerance (Q-factor), in a flexible traffic scenario, and further improvements with increasing local link dispersion, for an optical transport network employing flexible 28Gbaud PM-mQAM transponders.

Post-national citizenship without post-national identity? A case study of UK immigration policy and intra-EU migration

A key dividing line in the literature on post-national citizenship concerns the role of collective identity. While some hold that a post-national form of identity is desirable in developing citizenship in contexts such as the European Union (EU), others question the defensibility of a collective identity at this supra-national level. The aim of this article is to intervene in this debate, drawing on qualitative research to consider the extent to which post-national citizenship should be accompanied by a form of post-national identity. The article takes the UK as a case study, and explores tensions between the immigration policies and rhetoric of the Coalition Government since 2010 and the post-national citizenship rights of EU citizens migrating into British local communities. It draws on independently collected qualitative data from the county of Herefordshire, UK, to argue that the persistent reinforcement of national identity reproduces national lines of difference which further problematise the full realisation of European citizenship. At a theoretical level, this highlights the need for the development of post-national citizenship rights to be accompanied by a paradigmatic shift in the way that collective identity is constituted in post-national contexts.

Scaling the Advantages of Intra-channel Nonlinearity Compensation in Future Flexible Optical Networks

We report that, contrary to common perception, intra-channel nonlinearity compensation offers significant improvements of up to 4dB, in nonlinear tolerance (Q-factor), in a flexible traffic scenario, and further improvements with increasing local link dispersion, for an optical transport network employing flexible 28Gbaud PM-mQAM transponders.

Mobility changes in older age: neuropsychological, neurophysiological and cognitive predictors of successful adaptation in a real world scenario

The aims of this thesis were to investigate the neuropsychological, neurophysiological, and cognitive contributors to mobility changes with increasing age. In a series of studies with adults aged 45-88 years, unsafe pedestrian behaviour and falls were investigated in relation to i) cognitive functions (including response time variability, executive function, and visual attention tests), ii) mobility assessments (including gait and balance and using motion capture cameras), iii) motor initiation and pedestrian road crossing behavior (using a simulated pedestrian road scene), iv) neuronal and functional brain changes (using a computer based crossing task with magnetoencephalography), and v) quality of life questionnaires (including fear of falling and restricted range of travel). Older adults are more likely to be fatally injured at the far-side of the road compared to the near-side of the road, however, the underlying mobility and cognitive processes related to lane-specific (i.e. near-side or far-side) pedestrian crossing errors in older adults is currently unknown. The first study explored cognitive, motor initiation, and mobility predictors of unsafe pedestrian crossing behaviours. The purpose of the first study (Chapter 2) was to determine whether collisions at the near-side and far-side would be differentially predicted by mobility indices (such as walking speed and postural sway), motor initiation, and cognitive function (including spatial planning, visual attention, and within participant variability) with increasing age. The results suggest that near-side unsafe pedestrian crossing errors are related to processing speed, whereas far-side errors are related to spatial planning difficulties. Both near-side and far-side crossing errors were related to walking speed and motor initiation measures (specifically motor initiation variability). The salient mobility predictors of unsafe pedestrian crossings determined in the above study were examined in Chapter 3 in conjunction with the presence of a history of falls. The purpose of this study was to determine the extent to which walking speed (indicated as a salient predictor of unsafe crossings and start-up delay in Chapter 2), and previous falls can be predicted and explained by age-related changes in mobility and cognitive function changes (specifically within participant variability and spatial ability). 53.2% of walking speed variance was found to be predicted by self-rated mobility score, sit-to-stand time, motor initiation, and within participant variability. Although a significant model was not found to predict fall history variance, postural sway and attentional set shifting ability was found to be strongly related to the occurrence of falls within the last year. Next in Chapter 4, unsafe pedestrian crossing behaviour and pedestrian predictors (both mobility and cognitive measures) from Chapter 2 were explored in terms of increasing hemispheric laterality of attentional functions and inter-hemispheric oscillatory beta power changes associated with increasing age. Elevated beta (15-35 Hz) power in the motor cortex prior to movement, and reduced beta power post-movement has been linked to age-related changes in mobility. In addition, increasing recruitment of both hemispheres has been shown to occur and be beneficial to perform similarly to younger adults in cognitive tasks (Cabeza, Anderson, Locantore, & McIntosh, 2002). It has been hypothesised that changes in hemispheric neural beta power may explain the presence of more pedestrian errors at the farside of the road in older adults. The purpose of the study was to determine whether changes in age-related cortical oscillatory beta power and hemispheric laterality are linked to unsafe pedestrian behaviour in older adults. Results indicated that pedestrian errors at the near-side are linked to hemispheric bilateralisation, and neural overcompensation post-movement, 4 whereas far-side unsafe errors are linked to not employing neural compensation methods (hemispheric bilateralisation). Finally, in Chapter 5, fear of falling, life space mobility, and quality of life in old age were examined to determine their relationships with cognition, mobility (including fall history and pedestrian behaviour), and motor initiation. In addition to death and injury, mobility decline (such as pedestrian errors in Chapter 2, and falls in Chapter 3) and cognition can negatively affect quality of life and result in activity avoidance. Further, number of falls in Chapter 3 was not significantly linked to mobility and cognition alone, and may be further explained by a fear of falling. The objective of the above study (Study 2, Chapter 3) was to determine the role of mobility and cognition on fear of falling and life space mobility, and the impact on quality of life measures. Results indicated that missing safe pedestrian crossing gaps (potentially indicating crossing anxiety) and mobility decline were consistent predictors of fear of falling, reduced life space mobility, and quality of life variance. Social community (total number of close family and friends) was also linked to life space mobility and quality of life. Lower cognitive functions (particularly processing speed and reaction time) were found to predict variance in fear of falling and quality of life in old age. Overall, the findings indicated that mobility decline (particularly walking speed or walking difficulty), processing speed, and intra-individual variability in attention (including motor initiation variability) are salient predictors of participant safety (mainly pedestrian crossing errors) and wellbeing with increasing age. More research is required to produce a significant model to explain the number of falls.