8,257 research outputs found

    Nanotechnology for the delivery of vaccines

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    Liposomes offer an ideal platform for the delivery of subunit vaccines, due to their versatility and flexibility, which allows for antigen as well as immunostimulatory lipids and TLR agonists to become associated with these bilayered vesicles. Liposomes have the ability to protect vaccine antigen, as well as enhance delivery to antigen presenting cells, whilst the importance of cationic surface charge for delivery of TB subunit vaccines and formation of an ‘antigen depot’ may play a key role in boosting cell-mediated immunity and Th1 immune responses. The rational design of vaccine adjuvants requires the thorough investigation into the physicochemical characteristics that dictate the function of a liposomal adjuvant. Within this thesis, physicochemical characteristics were investigated in order to show any effects on the biodistribution profiles and the ensuing immune responses of these formulations. Initially the role of liposome charge within the formulation was investigated and subsequently their efficacy as vaccine adjuvants in combination with their biodistribution was measured to allow the role of formulation in vaccine function to be considered. These results showed that cationic surface charge, in combination with high loading of H56 vaccine antigen through electrostatic binding, was crucial in the promotion of the ‘depot-effect’ at the injection site which increases the initiation of Th1 cell-mediated immune responses that are required to offer protection against tuberculosis. To further investigate this, different methods of liposome production were also investigated where antigen incorporation within the vesicles as well as surface adsorption were adopted. Using the dehydration-rehydration (DRV) method (where liposomes are freeze-dried in the presence of antigen to promote antigen encapsulation) and the double emulsion (DE) method, a range of liposomes entrapping antigen were formulated. Variation in the liposome preparation method can lead to antigen entrapment within the delivery system which has been shown to be greater for DRV-formulated liposomes compared to their DE-counterparts. This resulted in no significant effect on the vaccine biodistribution profile, as well as not significantly altering the efficacy of cationic liposomal adjuvants. To further enhance the efficacy of these systems, the addition of TLR agonists either at the vesicle surface as well as within the delivery system has been displayed through variation in the preparation method. Anionic liposomal adjuvants have been formulated, which displayed rapid drainage from the injection site to the draining lymph nodes and displayed a reduction in measured Th1 immune responses. However, variation in the preparation method can alter the immune response profile for anionic liposomal adjuvants with a bias in immune response to Th2 responses being noted. Through the use of high shear mixing and stepwise incorporation, the efficient loading of TLR agonist within liposomes has been shown. However, interestingly the conjugation between lipid and non-electrostatically bound TLR agonist, followed by insertion into the bilayer of DDA/TDB resulted in localised agonist retention at the injection site and further stimulation of the Th1 immune response at the SOI, spleen and draining lymphatics as well as enhanced antibody titres

    Surgical reconstruction of the acromioclavicular joint:Can we identify the optimal approach?

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    Abstract Injuries to the acromioclavicular (AC) joint are common, tending to occur secondary to traumatic injuries. Rockwood grade IV, V and VI injuries involve complete dislocation of the joint and require surgical reconstruction, with inconclusive literature on whether grade III injuries should be surgically or conservatively managed. There are over one hundred reported surgical techniques which reconstruct the AC joint, with little indication of which methods achieve the best results. Techniques can generally be considered as: anatomical reduction; CC ligament reconstruction; and anatomical reconstruction. Techniques which implant hardware to reduce the AC joint, such as the hook plate, are commonly implemented, but have been shown to alter the mechanics of the joint significantly, resulting in poor short-term and long-term outcomes. Methods which reconstruct both the acromioclavicular and coracoclavicular ligaments are comparatively new, and early reports suggest that they achieve biomechanical properties similar to the native joint. More focus should be placed on such techniques in the future to determine whether they offer a more suitable approach to improve patient outcomes following AC joint reconstruction

    Unpopular sovereignty?

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    Popular sovereignty was presented in modern constitutional discourse as a mode of collective action. It was supposedly manifest in the power to constitute, control and dismantle governments. Important strands of contemporary constitutional theory, notably legal constitutionalism and deliberative democracy, have taken leave of this tradition. They have severed the connection between sovereignty and action. What remains of popular sovereignty is fundamental rights and values, or dispersed networks of deliberation. This is based on the the idea that the place of power is ‘empty’ and legitimised on the principle of including ‘All-Affected-Interests’. The very concept of sovereignty thus becomes unpopular. This contribution aims to re-establish the link between popular sovereignty and action by examining sovereignty's emancipatory telos, its majoritarian mode of operation and its dependence on political citizenship

    Is Pupil Attainment Higher in Well-managed Schools?

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    Linking the Workplace Employment Relations Surveys 2004 and 2011 to administrative data on pupil attainment in England we examine whether secondary and primary schools who deploy more intensive human resource management (HRM) practices have higher pupil attainment. We find intensive use of HRM practices is positively and significantly correlated with higher labour productivity and quality of provision, and with better financial performance, most notably in primary schools, but it is not associated with higher pupil attainment as indicated by assessment scores at Key Stage 2, Key Stage 4 and value-added measures based on assessments at these points

    Globally and Locally Minimal Weight Spanning Tree Networks

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    The competition between local and global driving forces is significant in a wide variety of naturally occurring branched networks. We have investigated the impact of a global minimization criterion versus a local one on the structure of spanning trees. To do so, we consider two spanning tree structures - the generalized minimal spanning tree (GMST) defined by Dror et al. [1] and an analogous structure based on the invasion percolation network, which we term the generalized invasive spanning tree or GIST. In general, these two structures represent extremes of global and local optimality, respectively. Structural characteristics are compared between the GMST and GIST for a fixed lattice. In addition, we demonstrate a method for creating a series of structures which enable one to span the range between these two extremes. Two structural characterizations, the occupied edge density (i.e., the fraction of edges in the graph that are included in the tree) and the tortuosity of the arcs in the trees, are shown to correlate well with the degree to which an intermediate structure resembles the GMST or GIST. Both characterizations are straightforward to determine from an image and are potentially useful tools in the analysis of the formation of network structures.Comment: 23 pages, 5 figures, 2 tables, typographical error correcte

    Do cladistic and morphometric data capture common patterns of morphological disparity?

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    The distinctly non-random diversity of organismal form manifests itself in discrete clusters of taxa that share a common body plan. As a result, analyses of disparity require a scalable comparative framework. The difficulties of applying geometric morphometrics to disparity analyses of groups with vastly divergent body plans are overcome partly by the use of cladistic characters. Character-based disparity analyses have become increasingly popular, but it is not clear how they are affected by character coding strategies or revisions of primary homology statements. Indeed, whether cladistic and morphometric data capture similar patterns of morphological variation remains a moot point. To address this issue, we employ both cladistic and geometric morphometric data in an exploratory study of disparity focussing on caecilian amphibians. Our results show no impact on relative intertaxon distances when different coding strategies for cladistic characters were used or when revised concepts of homology were considered. In all instances, we found no statistically significant difference between pairwise Euclidean and Procrustes distances, although the strength of the correlation among distance matrices varied. This suggests that cladistic and geometric morphometric data appear to summarize morphological variation in comparable ways. Our results support the use of cladistic data for characterizing organismal disparity

    Constraining the nature of High Frequency Peakers. I. The spectral variability

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    We investigate the spectral characteristics of 51 candidate High Frequency Peakers (HFPs), from the ``bright'' HFP sample, in order to determine the nature of each object, and to obtain a smaller sample of genuine young radio sources. Simultaneous multi-frequency VLA observations carried out at various epochs have been used to detect flux density and spectral shape variability in order to pinpoint contaminant objects, since young radio sources are not expected to be significantly variable on such a short time-scale. From the analysis of the spectral variability we find 13 contaminant objects, 11 quasars, 1 BL Lac, and 1 unidentified object, which we have rejected from the sample of candidate young radio sources. The 6 years elapsed between the first and latest observing run are not enough to detect any substantial evolution of the overall spectrum of genuine, non variable, young radio sources. If we also consider the pc-scale information, we find that the total radio spectrum we observe is the result of the superposition of the spectra of different regions (lobes, hot-spots, core, jets), instead of a single homogeneous radio component. This indicates that the radio source structure plays a relevant role in determining the spectral shape also in the rather common case in which the morphology appears unresolved even on high-resolution scales.Comment: 14 pages, 3 figures; accepted for pubblication in A&

    Diffractive energy spreading and its semiclassical limit

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    We consider driven systems where the driving induces jumps in energy space: (1) particles pulsed by a step potential; (2) particles in a box with a moving wall; (3) particles in a ring driven by an electro-motive-force. In all these cases the route towards quantum-classical correspondence is highly non-trivial. Some insight is gained by observing that the dynamics in energy space, where nn is the level index, is essentially the same as that of Bloch electrons in a tight binding model, where nn is the site index. The mean level spacing is like a constant electric field and the driving induces long range hopping 1/(n-m).Comment: 19 pages, 11 figs, published version with some improved figure

    Counting strategies and semantic analysis as applied to class inclusion

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    This study examined strategic and semantic aspects of the answers given by preschool children to class inclusion problems. The Piagetian logical model for class inclusion was contrasted with an alternative, problem processing model in three experiments. A major component of the alternative model is an enumeration strategy which is advantageous for learning reliable counting skills. The counting strategy was found to explain the inclusion errors of young children better than did the logic of the task. It was also found that young children understand the semantics of inclusion but are unable to coordinate their semantic knowledge with their counting strategy. Methodologically, one of the experiments suggested a fruitful extension of task analysis (Simon, 1969) to experimental design.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/21868/1/0000272.pd
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