Spatial patterns of β-amyloid (Aβ) deposits in familial and sporadic Alzheimer's disease

The spatial patterns of the diffuse, primitive, and classic β-amyloid (Aβ) deposits were compared in cortical regions in early-onset familial Alzheimer's disease (EO-FAD) linked to mutations of the amyloid precursor protein APP) or presenilin 1 (PSEN1) genes, late-onset familial AD (LO-FAD), and sporadic AD (SAD). The objective was to determine whether genetic factors influenced the spatial patterns of the Aβ deposits. Aβ deposits were distributed either in clusters which were regularly distributed parallel to the pia mater or in larger, non-regularly distributed clusters. There were no significant differences in spatial pattern of the diffuse deposits between patient groups but mean cluster size of the diffuse deposits was larger in FAD compared with SAD. Primitive Aβ deposits were more frequently distributed in regular clusters and less frequently distributed in large clusters in FAD compared with SAD. Classic Aβ deposits were more frequently distributed in regularly spaced clusters and less frequently distributed in large clusters in LO-FAD compared with EO-FAD. There were no significant differences in the spatial patterns or cluster sizes of Aβ deposits in cases classified according to apolipoprotein E (APOE) genotype. These results suggest (1) greater deposition of Aβ in the form of clusters of diffuse deposits in FAD, (2) a greater proportion of diffuse deposits may be converted to primitive deposits in SAD, (3) classic deposits are more widely distributed in EO-FAD, and (4) the presence of APOE allele ε4 has little effect on the spatial patterns of Aβ deposits.

Burning questions, but no burning answers: collocation and idiomaticity

The attention of linguists has increasingly shifted from grammar to lexis. Collocation has emerged as a key feature of lexis. Research using large language corpora has not only helped to identify the significant collocates of individual words but also to confirm the importance of collocation in the language system. John Sinclair has suggested that language operates on two principles: open choice and idiom. If so, then collocation would appear to be the minimal level of idiomaticity. One problem with collocation is that words that habitually co-occur form less distinct, often discontinuous, idiomatic units, whereas grammar generally works with more precisely delineated and contiguous structural units. This paper uses examples from corpus evidence to look at various aspects of collocation.

Spatial distribution of diffuse, primitive, and classic amyloid-beta deposits and blood vessels in the upper laminae of the frontal cortex in Alzheimer disease

The spatial distribution of the diffuse, primitive, and classic amyloid-beta deposits was studied in the upper laminae of the superior frontal gyrus in cases of sporadic Alzheimer disease (AD). Amyloid-beta-stained tissue was counterstained with collagen IV to determine whether the spatial distribution of the amyloid-beta deposits along the cortex was related to blood vessels. In all patients, amyloid-beta deposits and blood vessels were aggregated into distinct clusters and in many patients, the clusters were distributed with a regular periodicity along the cortex. The clusters of diffuse and primitive deposits did not coincide with the clusters of blood vessels in most patients. However, the clusters of classic amyloid-beta deposits coincided with those of the large diameter (>10 microm) blood vessels in all patients and with clusters of small-diameter (< 10 microm) blood vessels in four patients. The data suggest that, of the amyloid-beta subtypes, the clusters of classic amyloid-beta deposits appear to be the most closely related to blood vessels and especially to the larger-diameter, vertically penetrating arterioles in the upper cortical laminae.

The spatial patterns of Lewy bodies, senile plaques, and neurofibrillary tangles in dementia with Lewy bodies

The spatial patterns of Lewy bodies (LB), senile plaques (SP), and neurofibrillary tangles (NFT) were studied in ubiquitin-stained sections of the temporal lobe in cases of dementia with Lewy bodies (DLB), which varied in the degree of associated Alzheimer's disease (AD) pathology. In all patients, LB, SP, and NFT developed in clusters and in a significant proportion of brain areas, the clusters exhibited a regular periodicity parallel to the tissue boundary. In the lateral occipitotemporal gyrus (LOT) and parahippocampal gyrus (PHG), the clusters of LB were larger than those of the SP and NFT but in the hippocampus, clusters of the three lesions were of similar size. Mean cluster size of the LB, SP, and NFT was similar in cases of DLB with and without significant associated AD pathology. LB density was positively correlated with SP and NFT density in 42 and 17% of brain areas analyzed, respectively, while SP and NFT densities were positively correlated in 7% of brain areas. The data suggest that LB in DLB exhibit similar spatial patterns to SP and NFT in AD and that SP and NFT exhibit similar spatial patterns in DLB and AD. In addition, in some instances, clusters of LB appeared to be more closely related spatially to the clusters of SP than to NFT.

Document retrieval based on a cognitive model of dialogue

Owing to the rise in the volume of literature, problems arise in the retrieval of required information. Various retrieval strategies have been proposed, but most of that are not flexible enough for their users. Specifically, most of these systems assume that users know exactly what they are looking for before approaching the system, and that users are able to precisely express their information needs according to l aid- down specifications. There has, however, been described a retrieval program THOMAS which aims at satisfying incompletely- defined user needs through a man- machine dialogue which does not require any rigid queries. Unlike most systems, Thomas attempts to satisfy the user's needs from a model which it builds of the user's area of interest. This model is a subset of the program's "world model" - a database in the form of a network where the nodes represent concepts since various concepts have various degrees of similarities and associations, this thesis contends that instead of models which assume equal levels of similarities between concepts, the links between the concepts should have values assigned to them to indicate the degree of similarity between the concepts. Furthermore, the world model of the system should be structured such that concepts which are related to one another be clustered together, so that a user- interaction would involve only the relevant clusters rather than the entire database such clusters being determined by the system, not the user. This thesis also attempts to link the design work with the current notion in psychology centred on the use of the computer to simulate human cognitive processes. In this case, an attempt has been made to model a dialogue between two people - the information seeker and the information expert. The system, called Thomas-II, has been implemented and found to require less effort from the user than Thomas.

Social capital and tacit knowledge sharing in organisational projects in Malaysian ICT companies

An increasing number of organisational researchers have turned to social capital theory in an attempt to better understand the impetus for knowledge sharing at the individual and organisational level. This thesis extends that research by investigating the impact of social capital on knowledge sharing at the group-level in the organisational project context. The objective of the thesis is to investigate the importance of social capital in fostering tacit knowledge sharing among the team members of a project. The analytical focus is on the Nahapiet and Ghoshal framework of social capital but also includes elements of other scholars' work. In brief, social capital is defined as an asset that is embedded in the network of relationships possessed by an individual or social unit. It is argued that the main dimensions of social capital that are of relevance to knowledge sharing are structural, cognitive, and relational because these, among other things, foster the exchange and combination of knowledge and resources among the team members. Empirically, the study is based on the grounded theory method. Data were collected from five projects in large, medium, and small ICT companies in Malaysia. Underpinned by the constant comparative method, data were derived from 55 interviews, and observations. The data were analysed using open, axial, and selective coding. The analysis also involved counting frequency occurrence from the coding generated by grounded theory to find the important items and categories under social capital dimensions and knowledge sharing, and for further explaining sub-groups within the data. The analysis shows that the most important dimension for tacit knowledge sharing is structural capital. Most importantly, the findings also suggest that structural capital is a prerequisite of cognitive capital and relational capital at the group-level in an organisational project. It also found that in a project context, relational capital is hard to realise because it requires time and frequent interactions among the team members. The findings from quantitative analysis show that frequent meetings and interactions, relationship, positions, shared visions, shared objectives, and collaboration are among the factors that foster the sharing of tacit knowledge among the team members. In conclusion, the present study adds to the existing literature on social capital in two main ways. Firstly, it distinguishes the dimensions of social capital and identifies that structural capital is the most important dimension in social capital and it is a prerequisite of cognitive and relational capital in a project context. Secondly, it identifies the causal sequence in the dimension of social capital suggesting avenues for further theoretical and empirical work in this emerging area of inquiry.

Phenotypic and genotypic analysis of intestinal spirochacies

Pulsed field gel electrophoresis of 82 intestinal spirochaete isolates showed specific differentiation of Serpulina pilosicoli and Serpulina hyodysenteriae although considerable heterogeneity was observed, especially amongst S. pilosicoli isolates. In several cases genotypically similar isolates originated from different animals suggesting that cross-species transmission may have occurred. The Caco-2 and Caco-21HT29 cell models have been proposed as potentially realistic models of intestinal infection. Quantitation of adhesion to the cells showed isolate 3 82/91 (from a bacteraemia) to adhere at significantly greater numbers than any other isolate tested. This isolate produced a PFGE profile which differed from other S. pilosicoli isolates and so would be of interest for further study. Comparison of bacteraemic and other S. pilosicoli isolates suggested that bacteraemic isolates were not more specifically adapted for adhesion to, or invasion of the epithelial cell layer than other S. pilosicoli isolates. Genotypically similar isolates from differing animal origins adhered to the Caco-2 model at similar levels. Generation of a random genomic library of S. pilosicoli and screening with species specific monoclonal antibody has enabled the identification of a gene sequence encoding a protein which showed significant homology with an ancestral form of the enzyme pyruvate oxidoreductase. Immunoscreening with polyclonal serum identified the sequences of two gene clusters and a probable arylsulphatase. One gene cluster represented a ribosomal gene cluster which has a similar molecular arrangement to Borrelia burgdorjeri, Treponema pallidum and Thermatoga maritima. The other gene cluster contained an ABC transporter protein, sorbitol dehydrogenase and phosphomannose isomerase. An ELISA type assay was used to demonstrate that isolates of S. pilosicoli could adhere to components of the extracellular matrix such as collagen (type 1), fibronectin, laminin, and porcine gastric mucin.

Status and professional association councils. Available in 4 volumes.

This thesis examines the predictive value of a conceptual distinction between status-seeking associations and status-maintaining associations for enhancing understanding of ten selected professional associations and of the attitudes, values, behaviour and policies of their governing organs. Thirty four specific hypotheses have been tested by such research methods as questionnaires administered to individuals and associations, participant observation and an examination of association minutes and publications. Certain hypotheses have been found to be valid for particular matched pairs and/or groups of associations. The findings of the study suggest that the present conceptualisation of profession, the individual professional, professionalism, professionalisation, professional status and that relating to the role of the professions in society needs to be refined and modified in varying degrees in application to accounting associations, business graduate associations and management associations. The concept of the `ideal type' profession is shown to be of limited value in understanding certain aspects of the activities of business graduate and management associations. The findings of the study suggest that in future the professional associations examined may attach less importance to their qualifying role and lay more stress upon their representational role. The professional association faces a managerial challenge to adjust and adapt to a range of `external' pressures and `internal' demands from members and may increasingly need to be regarded as an organisation that possesses certain combinations or sets of characteristics rather than as a type of organisation that possesses a particular or relatively exclusive set. With a blurring of the distinction between the professional and state sector vocational education, and a growing customer/market orientation associated with the changing nature of work, membership of a professional association may, in future, come to be associated rather more with securing access to a relevant range of services and less with qualification for a particular career.

Synchronization processes in nonlinear systems and their relation to cortical oscillatory dynamics

This thesis was focused on theoretical models of synchronization to cortical dynamics as measured by magnetoencephalography (MEG). Dynamical systems theory was used in both identifying relevant variables for brain coordination and also in devising methods for their quantification. We presented a method for studying interactions of linear and chaotic neuronal sources using MEG beamforming techniques. We showed that such sources can be accurately reconstructed in terms of their location, temporal dynamics and possible interactions. Synchronization in low-dimensional nonlinear systems was studied to explore specific correlates of functional integration and segregation. In the case of interacting dissimilar systems, relevant coordination phenomena involved generalized and phase synchronization, which were often intermittent. Spatially-extended systems were then studied. For locally-coupled dissimilar systems, as in the case of cortical columns, clustering behaviour occurred. Synchronized clusters emerged at different frequencies and their boundaries were marked through oscillation death. The macroscopic mean field revealed sharp spectral peaks at the frequencies of the clusters and broader spectral drops at their boundaries. These results question existing models of Event Related Synchronization and Desynchronization. We re-examined the concept of the steady-state evoked response following an AM stimulus. We showed that very little variability in the AM following response could be accounted by system noise. We presented a methodology for detecting local and global nonlinear interactions from MEG data in order to account for residual variability. We found crosshemispheric nonlinear interactions of ongoing cortical rhythms concurrent with the stimulus and interactions of these rhythms with the following AM responses. Finally, we hypothesized that holistic spatial stimuli would be accompanied by the emergence of clusters in primary visual cortex resulting in frequency-specific MEG oscillations. Indeed, we found different frequency distributions in induced gamma oscillations for different spatial stimuli, which was suggestive of temporal coding of these spatial stimuli. Further, we addressed the bursting character of these oscillations, which was suggestive of intermittent nonlinear dynamics. However, we did not observe the characteristic-3/2 power-law scaling in the distribution of interburst intervals. Further, this distribution was only seldom significantly different to the one obtained in surrogate data, where nonlinear structure was destroyed. In conclusion, the work presented in this thesis suggests that advances in dynamical systems theory in conjunction with developments in magnetoencephalography may facilitate a mapping between levels of description int he brain. this may potentially represent a major advancement in neuroscience.

A survey of urban open space using colour infra-red aerial photographs

There has been a dramatic change in the U.K. government policy regarding the establishment of new towns. The emphasis is now on the redevelopment of existing cities rather than on building new ones. This has created an urgent need to carry out detailed surveys and inventories of many aspects of urban land use in metropolitan areas: this study concentrates on just one aspect - urban open space. In the first stage a comparison was made between 1:10,000 scale black and white and 1:10,000 scale colour infra-red aerial photographs, to compare the type and amount of open space information which could be obtained from these two sources. The advantages of using colour infra-red photography were clearly demonstrated in this comparison. The second stage was the use of colour infra-red photography as the sole source of data to survey and map the urban open space of a sample area in Merseyside Metropolitan County. This sample area comprised eleven 1/4km2 squares, on each of which a 20m x 20m grid cell was placed to record, directly from the photography, 625 sets of data. Each set of data recorded the type and amount of open space, its surface cover, maintenance status and management. The data recorded were fed into a computer and a suite of programs was developed to provide output in both computer map and statistical form, for each of the eleven -1/4km2 -sample areas. The third stage involved a comparison of open space data with socio-economic status. Merseyside County Planning Authority had previously conducted a socio-economic survey of the county, and this information was used to identify ' the socio-economic status of the population in the eleven ilkm2 areas of this project. This comparison revealed many interesting and useful relationships between the provision of urban open space and socio-economic status.

Building cliques and alliances as practices to 'make things happen' in complex networks

The Roma population has become a policy issue highly debated in the European Union (EU). The EU acknowledges that this ethnic minority faces extreme poverty and complex social and economic problems. 52% of the Roma population live in extreme poverty, 75% in poverty (Soros Foundation, 2007, p. 8), with a life expectancy at birth of about ten years less than the majority population. As a result, Romania has received a great deal of policy attention and EU funding, being eligible for 19.7 billion Euros from the EU for 2007-2013. Yet progress is slow; it is debated whether Romania's government and companies were capable to use these funds (EurActiv.ro, 2012). Analysing three case studies, this research looks at policy implementation in relation to the role of Roma networks in different geographical regions of Romania. It gives insights about how to get things done in complex settings and it explains responses to the Roma problem as a „wicked‟ policy issue. This longitudinal research was conducted between 2008 and 2011, comprising 86 semi-structured interviews, 15 observations, and documentary sources and using a purposive sample focused on institutions responsible for implementing social policies for Roma: Public Health Departments, School Inspectorates, City Halls, Prefectures, and NGOs. Respondents included: governmental workers, academics, Roma school mediators, Roma health mediators, Roma experts, Roma Councillors, NGOs workers, and Roma service users. By triangulating the data collected with various methods and applied to various categories of respondents, a comprehensive and precise representation of Roma network practices was created. The provisions of the 2001 „Governmental Strategy to Improve the Situation of the Roma Population‟ facilitated forming a Roma network by introducing special jobs in local and central administration. In different counties, resources, people, their skills, and practices varied. As opposed to the communist period, a new Roma elite emerged: social entrepreneurs set the pace of change by creating either closed cliques or open alliances and by using more or less transparent practices. This research deploys the concept of social/institutional entrepreneurs to analyse how key actors influence clique and alliance formation and functioning. Significantly, by contrasting three case studies, it shows that both closed cliques and open alliances help to achieve public policy network objectives, but that closed cliques can also lead to failure to improve the health and education of Roma people in a certain region.

NT2 derived neuronal and astrocytic network signalling

A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns) expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As) exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

Common variance in amplitude envelope perception tasks and their impact on phoneme duration perception and reading and spelling in Finnish children with reading disabilities

Our goal was to investigate auditory and speech perception abilities of children with and without reading disability (RD) and associations between auditory, speech perception, reading, and spelling skills. Participants were 9-year-old, Finnish-speaking children with RD (N = 30) and typically reading children (N = 30). Results showed significant group differences between the groups in phoneme duration discrimination but not in perception of amplitude modulation and rise time. Correlations among rise time discrimination, phoneme duration, and spelling accuracy were found for children with RD. Those children with poor rise time discrimination were also poor in phoneme duration discrimination and in spelling. Results suggest that auditory processing abilities could, at least in some children, affect speech perception skills, which in turn would lead to phonological processing deficits and dyslexia.

Spectatorship and the war on terror:creating consensus through global audiences

This paper considers the staging of violence, atrocities, and sexuality in the conduct of the war on terror. The piece discusses the manner in which the terms of the war on terror appear to shut down possible debate and examines the rhetorical and representational strategies that cause this. The paper argues that the war on terror includes a cultural project that seeks to create a consenting global audience. This cultural project appears more diffuse and less immediately instrumental than the military and diplomatic activities of this global battle. The piece argues that it is through the circulation of open secrets and accounts of torture and abuse that a global audience is constructed as both witness and participant in the practices and objectives of the war and that this positioning is designed to corral audience understanding into the suggested narratives of the proponents of the war. Este documento considera el escenario de la violencia, las atrocidades y la sexualidad en la conducta de la guerra contra el terror. El artículo plantea la manera en que los términos de la guerra contra el terror parecen suspender un posible debate y examina las estrategias retóricas y representativas que causaron esto. El documento plantea que la guerra contra el terror incluye un proyecto cultural que busca crear una audiencia global de común acuerdo. Este proyecto cultural parece más difuso y menos útil en el momento, que las actividades militares y diplomáticas de esta batalla global. El artículo sostiene que es mediante la circulación de secretos abiertos y de informes sobre la tortura y el abuso, que se forma una audiencia global tanto testigos como participantes de las prácticas y los objetivos de la guerra y que esa posición está designada a encerrar el conocimiento de la audiencia dentro de los relatos sugeridos por los proponentes de guerra.

Industrial policy, FDI and employment:still a 'missing a strategy'

This paper contrasts the effects of trade, inward FDI and technological development upon the demand for skilled and unskilled workers in the UK. By focussing on industry level data panel data on smaller firms, the paper also contrasts these effects with those generated by large scale domestic investment. The analysis is placed within the broader context of shifts in British industrial policy, which has seen significant shifts from sectoral to horizontal measures and towards stressing the importance of SMEs, clusters and new technology, all delivered at the regional scale. This, however, is contrasted with continued elements of British and EU regional policy which have emphasised the attraction of inward investment in order to alleviate regional unemployment. The results suggest that such policies are not naturally compatible; that while both trade and FDI benefit skilled workers, they have adverse effects on the demand for unskilled labour in the UK. At the very least this suggests the need for a range of policies to tackle various targets (including in this case unemployment and social inclusion) and the need to integrate these into a coherent industrial strategy at various levels of governance, whether regional and/or national. This has important implications for the form of any ‘new’ industrial policy.