Spatial relationships between diffuse prion protein deposits and neuronal perikarya in variant Creutzfeldt-Jakob disease

Two morphological types of prion protein (PrPsc) deposit occur in the cerebral cortex of cases of variant Creutzfeldt-Jakob disease (vCJD), viz., diffuse and florid deposits. The objective of this study was to determine whether diffuse-type PrPsc deposits in areas of the cerebral cortex in six cases of the variant form of CJD (vCJD) were spatially correlated with neurons and whether diffuse deposit size was related to the number of adjacent neurons contributing PrPsc. In cortical gyri, density of surviving neurons was 5.38-12.15 per 50 × 200 µm sample field, neurons being distributed randomly, regularly or were clustered relative to the pia mater. Density of neurons embedded within diffuse deposits, however, was three to eight times their overall density in the section. In addition, diffuse deposit area was positively correlated with the number of embedded neurons. The frequency distribution of diffuse deposits with 0, 1, 2, 3, …, n, embedded neurons did not deviate from a Poisson distribution. These results suggest: (1) diffuse deposits in vCJD develop in situ as a result of the formation of PrPsc in relation to clusters of neurons, (2) size of a diffuse deposit is determined by the number of adjacent neurons which develop PrPsc, and (3) the probability that PrPsc is formed in relation to one neuron is independent of that of its neighbour.

West Midlands English:Birmingham and the Black Country

This volume focuses on the closely allied yet differing linguistic varieties of Birmingham and its immediate neighbour to the west, the industrial heartland of the Black Country. Both of these areas rose to economic prominence and success during the Industrial Revolution, and both have suffered economically and socially as a result of post-war industrial decline. The industrial heritage of both areas has meant that tight knit and socially homogeneous individual areas in each region have demonstrated in many respects little linguistic change over time, and have continued to exhibit linguistic features, especially morphological constructions, peculiar to these areas or now restricted to these areas. At the same time, immigration from other areas of the British Isles over time, from Commonwealth countries and later from EU member states, together with increased social mobility, have meant that newly developing structures and more widespread UK linguistic phenomena have spread into these varieties. This volume provides a clear description of the structure of the linguistic varieties spoken in the two areas. Following the structure of the Dialects of English volumes, it provides: •A comprehensive overview of the phonological, grammatical and lexical structure of both varieties, as well as similarities between the two varieties and distinguishing features •Thorough discussion of the historical and social factors behind the development of the varieties and the stigma attached to these varieties •Discussion of the unusual situation of the Black Country as an area undefined in geographical and administrative terms, existing only in the imagination •Examples of the variety from native speakers of differing ethnicities, ages and genders •An annotated bibliography for further consultation

Within-site variation in lichen growth rates and its implications for direct lichenometry

Variation in lichen growth rates poses a significant challenge for the application of direct lichenometry, i.e. the construction of lichen dating curves from direct measurement of growth rates. To examine the magnitude and possible causes of within-site growth variation, radial growth rates (RaGRs) of thalli of the fast-growing foliose lichen Melanelia fuliginosa ssp. fuliginosa (Fr. ex Duby) Essl. and the slow-growing crustose lichen Rhizocarpon geographicum (L.) DC. were studied on two S-facing slate rock surfaces in north Wales, UK using digital photography and an image analysis system (Image-J). RaGRs of M. fuliginosa ssp. fuliginosa varied from 0.44 to 2.63 mmyr-1 and R. geographicum from 0.10 to 1.50 mmyr-1.5. Analysis of variance suggested no significant variation in RaGRs with vertical or horizontal location on the rock, thallus diameter, aspect, slope, light intensity, rock porosity, rock surface texture, distance to nearest lichen neighbour or distance to vegetation on the rock surface. The frequency distribution of RaGR did not deviate from a normal distribution. It was concluded that despite considerable growth rate variation in both species studied, growth curves could be constructed with sufficient precision to be useful for direct lichenometry. © 2014 Swedish Society for Anthropology and Geography.

Structure of glassy GeO2

The full set of partial structure factors for glassy germania, or GeO2, were accurately measured by using the method of isotopic substitution in neutron diffraction in order to elucidate the nature of the pair correlations for this archetypal strong glass former. The results show that the basic tetrahedral Ge(O-1/2)(4) building blocks share corners with a mean inter-tetrahedral Ge-O-Ge bond angle of 132(2)degrees. The topological and chemical ordering in the resultant network displays two characteristic length scales at distances greater than the nearest neighbour. One of these describes the intermediate range order, and manifests itself by the appearance of a first sharp diffraction peak in the measured diffraction patterns at a scattering vector k(FSDP) approximate to 1.53 angstrom(-1), while the other describes so-called extended range order, and is associated with the principal peak at k(PP) = 2.66( 1) angstrom(-1). We find that there is an interplay between the relative importance of the ordering on these length scales for tetrahedral network forming glasses that is dominated by the extended range ordering with increasing glass fragility. The measured partial structure factors for glassy GeO2 are used to reproduce the total structure factor measured by using high energy x-ray diffraction and the experimental results are also compared to those obtained by using classical and first principles molecular dynamics simulations.

The structure of the rare-earth phosphate glass(Sm2O3)0.205(P2O5)0.795 studied by anomalous dispersion neutron diffraction

The role of the Sm3+ ions in the structure of vitreous Sm2O3•4P2O5 has been investigated using the neutron diffraction anomalous dispersion technique, which employs the wavelength dependence of the real and imaginary parts of the neutron scattering length close to an absorption resonance. The data described here represent the first successful complete neutron anomalous dispersion study on an amorphous material. This experimental methodology permits one to determine exclusively the closest Sm• •• Sm separation. Knowledge of the R•••R (R = rare-earth) pairwise correlation is key to understanding the optical and magnetic properties of rare-earth phosphate glasses. The anomalous difference correlation function, ΔT''(r), shows a dominant feature pertaining to a Sm•••Sm separation, centred at 4.8 Å. The substantial width and marked asymmetry of this peak indicates that the minimum approach of Sm3+ ions could be as close as 4 Å. Information on other pairwise correlations is also revealed via analysis of T (r) and ΔT (r) correlation functions: Sm3+ ions display an average co-ordination number, n Sm(O), of 7, with a mean Sm–O bond length of 2.375(5) Å whilst the PO4 tetrahedra have a mean P–O bond length of 1.538(2) Å. Second- and third-neighbour correlations are also identified. These results corroborate previous findings. Such consistency lends support to the application of the anomalous dispersion technique to determine separations.

Disseminating a warning message to evacuate:a simulation study of the behaviour of neighbours

Large-scale evacuations are a recurring theme on news channels, whether in response to major natural or manmade disasters. The role of warning dissemination is a key part in the success of such large-scale evacuations and its inadequacy in certain cases has been a 'primary contribution to deaths and injuries' (Hayden et al.; 2007). Along with technology-driven 'official warning channels' (e.g. sirens, mass media), the role of unofficial channel (e.g. neighbours, personal contacts, volunteer wardens) has proven to be significant in warning the public of the need to evacuate. Although post-evacuation studies identify the behaviours of evacuees as disseminators of the warning message, there has not been a detailed study that quantifies the effects of such behaviour on the warning message dissemination. This paper develops an Agent-Based Simulation (ABS) model of multiple agents (evacuee households) in a hypothetical community to investigate the impact of behaviour as an unofficial channel on the overall warning dissemination. Parameters studied include the percentage of people who warn their neighbours, the efficiency of different official warning channels, and delay time to warn neighbours. Even with a low proportion of people willing to warn their neighbour, the results showed considerable impact on the overall warning dissemination. © 2012 Elsevier B.V. All rights reserved.

Informal dissemination scenarios and the effectiveness of evacuation warning dissemination of households:a simulation study

Timely warning of the public during large scale emergencies is essential to ensure safety and save lives. This ongoing study proposes an agent-based simulation model to simulate the warning message dissemination among the public considering both official channels and unofficial channels The proposed model was developed in NetLogo software for a hypothetical area, and requires input parameters such as effectiveness of each official source (%), estimated time to begin informing others, estimated time to inform others and estimated percentage of people (who do not relay the message). This paper demonstrates a means of factoring the behaviour of the public as informants into estimating the effectiveness of warningdissemination during large scale emergencies. The model provides a tool for the practitioner to test the potential impact of the informal channels on the overall warning time and sensitivity of the modelling parameters. The tool would help the practitioners to persuade evacuees to disseminate the warning message informing others similar to the ’Run to thy neighbour campaign conducted by the Red cross.

Topological versus chemical ordering in network glasses at intermediate and extended length scales

Atomic ordering in network glasses on length scales longer than nearest-neighbour length scales has long been a source of controversy(1-6). Detailed experimental information is therefore necessary to understand both the network properties and the fundamentals of glass formation. Here we address the problem by investigating topological and chemical ordering in structurally disordered AX2 systems by applying the method of isotopic substitution in neutron diffraction to glassy ZnCl2. This system may be regarded as a prototypical ionic network forming glass, provided that ion polarization effects are taken into account(7), and has thus been the focus of much attention(8-14). By experiment, we show that both the topological and chemical ordering are described by two length scales at distances greater than nearest-neighbour length scales. One of these is associated with the intermediate range, as manifested by the appearance in the measured diffraction patterns of a first sharp diffraction peak at 1.09( 3) angstrom(-1); the other is associated with an extended range, which shows ordering in the glass out to 62( 4) angstrom. We also find that these general features are characteristic of glassy GeSe2, a prototypical covalently bonded network material(15,16). The results therefore offer structural insight into those length scales that determine many important aspects of supercooled liquid and glass phenomenology(11).

Visualisation of bioinformatics datasets

Analysing the molecular polymorphism and interactions of DNA, RNA and proteins is of fundamental importance in biology. Predicting functions of polymorphic molecules is important in order to design more effective medicines. Analysing major histocompatibility complex (MHC) polymorphism is important for mate choice, epitope-based vaccine design and transplantation rejection etc. Most of the existing exploratory approaches cannot analyse these datasets because of the large number of molecules with a high number of descriptors per molecule. This thesis develops novel methods for data projection in order to explore high dimensional biological dataset by visualising them in a low-dimensional space. With increasing dimensionality, some existing data visualisation methods such as generative topographic mapping (GTM) become computationally intractable. We propose variants of these methods, where we use log-transformations at certain steps of expectation maximisation (EM) based parameter learning process, to make them tractable for high-dimensional datasets. We demonstrate these proposed variants both for synthetic and electrostatic potential dataset of MHC class-I. We also propose to extend a latent trait model (LTM), suitable for visualising high dimensional discrete data, to simultaneously estimate feature saliency as an integrated part of the parameter learning process of a visualisation model. This LTM variant not only gives better visualisation by modifying the project map based on feature relevance, but also helps users to assess the significance of each feature. Another problem which is not addressed much in the literature is the visualisation of mixed-type data. We propose to combine GTM and LTM in a principled way where appropriate noise models are used for each type of data in order to visualise mixed-type data in a single plot. We call this model a generalised GTM (GGTM). We also propose to extend GGTM model to estimate feature saliencies while training a visualisation model and this is called GGTM with feature saliency (GGTM-FS). We demonstrate effectiveness of these proposed models both for synthetic and real datasets. We evaluate visualisation quality using quality metrics such as distance distortion measure and rank based measures: trustworthiness, continuity, mean relative rank errors with respect to data space and latent space. In cases where the labels are known we also use quality metrics of KL divergence and nearest neighbour classifications error in order to determine the separation between classes. We demonstrate the efficacy of these proposed models both for synthetic and real biological datasets with a main focus on the MHC class-I dataset.

Medical emergency alarm dissemination in urban environments

During medical emergencies, the ability to communicate the state and position of injured individuals is essential. In critical situations or crowd aggregations, this may result difficult or even impossible due to the inaccuracy of verbal communication, the lack of precise localization for the medical events, and/or the failure/congestion of infrastructure-based communication networks. In such a scenario, a temporary (ad hoc) wireless network for disseminating medical alarms to the closest hospital, or medical field personnel, can be usefully employed to overcome the mentioned limitations. This is particularly true if the ad hoc network relies on the mobile phones that people normally carry, since they are automatically distributed where the communication needs are. Nevertheless, the feasibility and possible implications of such a network for medical alarm dissemination need to be analysed. To this aim, this paper presents a study on the feasibility of medical alarm dissemination through mobile phones in an urban environment, based on realistic people mobility. The results showed the dependence between the medical alarm delivery rates and both people and hospitals density. With reference to the considered urban scenario, the time needed to delivery medical alarms to the neighbour hospital with high reliability is in the order of minutes, thus revealing the practicability of the reported network for medical alarm dissemination. © 2013 Elsevier Ltd. All rights reserved.

Improved data visualisation through multiple dissimilarity modelling

Popular dimension reduction and visualisation algorithms rely on the assumption that input dissimilarities are typically Euclidean, for instance Metric Multidimensional Scaling, t-distributed Stochastic Neighbour Embedding and the Gaussian Process Latent Variable Model. It is well known that this assumption does not hold for most datasets and often high-dimensional data sits upon a manifold of unknown global geometry. We present a method for improving the manifold charting process, coupled with Elastic MDS, such that we no longer assume that the manifold is Euclidean, or of any particular structure. We draw on the benefits of different dissimilarity measures allowing for the relative responsibilities, under a linear combination, to drive the visualisation process.