Development of lipid-core-peptide (LCP) based vaccines for the prevention of the group A streptococcal (GAS) infection

Traditional vaccines consisting of whole attenuated micro-organisms. or microbial components administered with adjuvant, have been demonstrated as one of the most cost-effective and successful public health interventions. Their use in large scale immunisation programs has lead to the eradication of smallpox, reduced morbidity and mortality from many once common diseases, and reduced strain on health services. However, problems associated with these vaccines including risk of infection. adverse effects, and the requirement for refrigerated transport and storage have led to the investigation of alternative vaccine technologies. Peptide vaccines, consisting of either whole proteins or individual peptide epitopes, have attracted much interest, as they may be synthesised to high purity and induce highly specific immune responses. However, problems including difficulties stimulating long lasting immunity. and population MHC diversity necessitating multiepitopic vaccines and/or HLA tissue typing of patients complicate their development. Furthermore, toxic adjuvants are necessary to render them immunogenic. and as such non-toxic human-compatible adjuvants need to be developed. Lipidation has been demonstrated as a human compatible adjuvant for peptide vaccines. The lipid-core-peptide (LCP) system. incorporating lipid adjuvant, carrier, and peptide epitopes, exhibits promise as a lipid-based peptide vaccine adjuvant. The studies reviewed herein investigate the use of the LCP system for developing vaccines to protect against group A streptococcal (GAS) infection. The studies demonstrate that LCP-based GAS vaccines are capable of inducing high-titres of antigen specific IgG antibodies. Furthermore. mice immunised with an LCP-based GAS vaccine were protected against challenge with 8830 strain GAS.

Crystalline lanthanum hydroxycarbonates with controlled phases and varied morphologies prepared on non-crystalline substrates

Lanthanum hydroxycarbonate crystals with controlled phases and varied morphologies were prepared on the surface of a non-crystalline substrate, glass. The phases and morphologies of the crystals were controlled conveniently by varying the reaction temperature and the quantity of starting materials. Orthorhombic crystals were obtained at 160 degreesC, distributed individually on the substrate and had a flaky rhombic shape. Hexagonal crystals were obtained at 180 degreesC. The crystals had a rhomboidal shape, were uniform and continuous enough to form a solid film on the substrate. The substrates were corroded under the hydrothermal conditions and offered a coarse surface for the crystal growth. The hexagonal lanthanum hydroxycarbonate was discovered to show significant second harmonic generation, which would be of interest for developing novel optical materials. (C) 2004 Elsevier Inc. All rights reserved.

Quantifying aphasic people's social lives in the context of non-aphasic peers

Background: Developing the knowledge base on the impact of aphasia on people's social lives has become increasingly important in recent times to further our understanding of the broad consequences of communication disability and thus provide appropriate services. Past research clearly indicates that relationships and social activities with family members and others undergo change with the onset of aphasia in an individual, however more evidence of a quantitative nature would be beneficial. Aims: The current research furthers our knowledge by quantifying chronically aphasic older people's regular social contacts and social activities, and places them in context by comparing them with healthy older people of similar age and education. Methods & Procedures: A total of 30 aphasic participants aged 57 to 88 years, and 71 non-aphasic controls aged 62 to 98 years were interviewed by a speech and language therapist using self-report measures of Social Network Analysis (Antonucci & Akiyama, 1987) and Social Activities Checklist (Cruice, 2001, in Worrall & Hickson, 2003). Demographic information was also collected. Descriptive statistics are presented and independent samples t tests were used to examine differences between the groups. Outcomes & Results: Participants with primarily mild to moderate aphasic impairment reported a considerable range of social contacts (5-51) and social activities (8-18). Many significant differences were evident between the two groups' social contacts and activities. On average, aphasic participants had nine fewer social contacts (mainly friend'' relationships) and three fewer social activities (mainly leisure'' activities) than their non-aphasic peers. The majority of controls were satisfied with their social activities, whereas the majority of aphasic participants were not and wanted to be doing more. There were some general similarities between the groups, in terms of range of social contacts, overall pattern of social relationships, and core social activities. Conclusions: Older people with chronic aphasia had significantly fewer social contacts and social activities than their peers. People with aphasia expressed a desire to increase the social activity of their lives. Given the importance of leisure activity and relationships with friends as well as family for positive well-being, speech and language therapists may direct their rehabilitation efforts towards two areas: (1) conversational partner programmes training friends to maintain these relationships; and (2) encouraging and supporting aphasic clients in leisure activities of their choice.

Anyone for non-scalarity?

This paper examines the status of scalarity in the analysis of the meaning of the English determiner any. The latter’s position as a prime exemplar of the category of polarity-sensitive items has led it to be generally assumed to have scalar meaning. Scalar effects are absent however from a number of common uses of this word. This suggests that any does not involve scales as part of its core meaning, but produces them as a derived interpretative property. The role of three factors in the derivation of the expressive effect of scalarity is explored: grammatical number, stress and the presence of gradable concepts in the NP. The general conclusions point to the importance of developing a causal semantic analysis in which the contributions of each of the various meaningful components of an utterance to the overall message expressed are carefully distinguished.

Synthesis and characterization of dual-functionalized core-shell fluorescent microspheres for bioconjugation and cellular delivery

The efficient transport of micron-sized beads into cells, via a non-endocytosis mediated mechanism, has only recently been described. As such there is considerable scope for optimization and exploitation of this procedure to enable imaging and sensing applications to be realized. Herein, we report the design, synthesis and characterization of fluorescent microsphere-based cellular delivery agents that can also carry biological cargoes. These core-shell polymer microspheres possess two distinct chemical environments; the core is hydrophobic and can be labeled with fluorescent dye, to permit visual tracking of the microsphere during and after cellular delivery, whilst the outer shell renders the external surfaces of the microspheres hydrophilic, thus facilitating both bioconjugation and cellular compatibility. Cross-linked core particles were prepared in a dispersion polymerization reaction employing styrene, divinylbenzene and a thiol-functionalized co-monomer. These core particles were then shelled in a seeded emulsion polymerization reaction, employing styrene, divinylbenzene and methacrylic acid, to generate orthogonally functionalized core-shell microspheres which were internally labeled via the core thiol moieties through reaction with a thiol reactive dye (DY630-maleimide). Following internal labeling, bioconjugation of green fluorescent protein (GFP) to their carboxyl-functionalized surfaces was successfully accomplished using standard coupling protocols. The resultant dual-labeled microspheres were visualized by both of the fully resolvable fluorescence emissions of their cores (DY630) and shells (GFP). In vitro cellular uptake of these microspheres by HeLa cells was demonstrated conventionally by fluorescence-based flow cytometry, whilst MTT assays demonstrated that 92% of HeLa cells remained viable after uptake. Due to their size and surface functionalities, these far-red-labeled microspheres are ideal candidates for in vitro, cellular delivery of proteins, as described in the accompanying paper.

Femtosecond inscription of superimposed, non-overlapping fibre Bragg gratings

A method for direct inscription of fibre Bragg gratings laterally separated by inscription in separate segments of the fibre core is demonstrated for the first time.

Knowledge transfer in website design:exploring the processes and benefits of design collaboration for non-creative Micros

This thesis explores the interaction between Micros (<10 employees) from non-creative sectors and website designers ("Creatives") that occurred when creating a website of a higher order than a basic template site. The research used Straussian Grounded Theory Method with a longitudinal design, in order to identify what knowledge transferred to the Micros during the collaboration, how it transferred, what factors affected the transfer and outcomes of the transfer including behavioural additionality. To identify whether the research could be extended beyond this, five other design areas were also examined, as well as five Small to Medium Enterprises (SMEs) engaged in website and branding projects. The findings were that, at the start of the design process, many Micros could not articulate their customer knowledge, and had poor marketing and visual language skills, knowledge core to web design, enabling targeted communication to customers through images. Despite these gaps, most Micros still tried to lead the process. To overcome this disjoint, the majority of the designers used a knowledge transfer strategy termed in this thesis as ‘Bi-Modal Knowledge Transfer’, where the Creative was aware of the transfer but the Micro was unaware, both for drawing out customer knowledge from the Micro and for transferring visual language skills to the Micro. Two models were developed to represent this process. Two models were also created to map changes in the knowledge landscapes of customer knowledge and visual language – the Knowledge Placement Model and the Visual Language Scale. The Knowledge Placement model was used to map the placement of customer knowledge within the consciousness, extending the known Automatic-Unconscious -Conscious model, adding two more locations – Peripheral Consciousness and Occasional Consciousness. Peripheral Consciousness is where potential knowledge is held, but not used. Occasional Consciousness is where potential knowledge is held but used only for specific tasks. The Visual Language Scale was created to measure visual language ability from visually responsive, where the participant only responds personally to visual symbols, to visually multi-lingual, where the participant can use visual symbols to communicate with multiple thought-worlds. With successful Bi-Modal Knowledge Transfer, the outcome included not only an effective website but also changes in the knowledge landscape for the Micros and ongoing behavioural changes, especially in marketing. These effects were not seen in the other design projects, and only in two of the SME projects. The key factors for this difference between SMEs and Micros appeared to be an expectation of knowledge by the Creatives and failure by the SMEs to transfer knowledge within the company.

Cost-reduction using non-uniform traffic in optical networks

Next-generation networks are likely to be non-uniform in all their aspects, including number of lightpaths carried per link, number of wavelengths per link, number of fibres per link, asymmetry of the links, and traffic flows. Routing and wavelength allocation models generally assume that the optical network is uniform and that the number of wavelengths per link is a constant. In practice however, some nodes and links carry heavy traffic and additional wavelengths are needed in those links. We study a wavelength-routed optical network based on the UK JANET topology where traffic demands between nodes are assumed to be non-uniform. We investigate how network capacity can be increased by locating congested links and suggesting cost-effective upgrades. Different traffic demands patterns, hop distances, number of wavelengths per link, and routing algorithms are considered. Numerical results show that a 95% increase in network capacity is possible by overlaying fibre on just 5% of existing links. We conclude that non-uniform traffic allocation can be beneficial to localize traffic in nodes and links deep in the network core and provisioning of additional resources there can efficiently and cost-effectively increase network capacity. © 2013 IEEE.

UV inscribed long period gratings with femtosecond ablated axial fibre slots for polarization control

We present data on the development a new type of optical fibre polariser and the characterisation of its wavelength properties. The device is fashioned using a two step process. Firstly, a standard UV long period grating (LPG) with a period of 330μm is inscribed into hydrogenated SMF-28, followed by femtosecond laser ablation of a groove parallel to the fibre axis. The UV inscribed LPGs have inherently low birefringence. However, the removal of the cladding layer parallel to the location of the LPG within the fibre core (as a result the ablation) modifies the cladding modes that couple with the LPG. Furthermore, the groove breaks the fibre symmetry introducing a non-uniform stress profile across the fibre cross section leading to significant birefringence. We show that increasing the depth of the groove increases the birefringence, and this behaviour coupled with the ability to control the wavelength location of the LPGs attenuations peaks results in a polariser able to operate at almost any wavelength and birefringence. The maximum birefringence reported here as polarisation mode splitting was approximately 39±0.1nm with a polarisation loss of 10dB. © 2011 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Convex and exact games with non-transferable utility

We generalize exactness to games with non-transferable utility (NTU). A game is exact if for each coalition there is a core allocation on the boundary of its payoff set. Convex games with transferable utility are well-known to be exact. We consider ve generalizations of convexity in the NTU setting. We show that each of ordinal, coalition merge, individual merge and marginal convexity can be uni¯ed under NTU exactness. We provide an example of a cardinally convex game which is not NTU exact. Finally, we relate the classes of Π-balanced, totally Π-balanced, NTU exact, totally NTU exact, ordinally convex, cardinally convex, coalition merge convex, individual merge convex and marginal convex games to one another.

The kernel is in the least core for permutation games

Permutation games are totally balanced transferable utility cooperative games arising from certain sequencing and re-assignment optimization problems. It is known that for permutation games the bargaining set and the core coincide, consequently, the kernel is a subset of the core. We prove that for permutation games the kernel is contained in the least core, even if the latter is a lower dimensional subset of the core. By means of a 5-player permutation game we demonstrate that, in sense of the lexicographic center procedure leading to the nucleolus, this inclusion result can not be strengthened. Our 5-player permutation game is also an example (of minimum size) for a game with a non-convex kernel.

(Table S1) Brominated flame retardant concentrations in an ice core from Holtedahlfonna, Svalbard

Brominated flame retardants (BFRs) have been found in Arctic wildlife, lake sediment, and air. To identify the atmospheric BFR deposition history on Svalbard, Norway, we analyzed 19 BFRs, including hexabromocyclododecane (HBCD), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), decabromodiphenyl ethane (DBDPE), pentabromoethylbenzene (PBEB),and 15 polybrominated diphenyl ether congeners (PBDE) in the upper 34 m of an ice core (representing 1953-2005) from Holtedahlfonna, the western-most ice sheet on Svalbard. All of the non-PBDE compounds were detected in nearly continuous profiles in the core. Seven PBDEs were not observed above background (28,47,66,100,99,154,153), while 4 were found in 1 or 2 of 6 segments (17,85,138,183). BDEs-49,71,190,209 had nearly continuous profiles but only BDE-209 in large amounts. The greatest inputs were HBCD and BDE-209, 910, and 320 pg/cm**2/yr from 1995-2005. DBDPE, BTBPE, and PBEB show nearly continuous input growth in recent core segments, but all were <6 pg/cm**2/yr. Long-range atmospheric processes may have moved these particle-bound BFRs to the site, probably during the Arctic haze season. Average air mass trajectories over 10 years show >75% of atmospheric flow to Holtedahlfonna coming from Eurasia during haze periods (March and April).

(Table 3) Mediterranean core-top d18O values for various planktonic foraminiferal species

A box model is presented to simulate changes in Mediterranean long-term average salinity and d18O over the past 20,000 years. Simulations are validated by comparison with observations. Sensitivity tests illustrate robustness with respect to the main assumptions and uncertainties. The results show that relative humidity over the Mediterranean remained relatively constant around 70%, apparently narrowly constrained to the lower end of the range observed globally over sea surfaces by the basin's land-locked character. Isotopic depletion in run off, relative to the present, is identified as the main potential cause of depletions in the Mediterranean d18O record. Also, slight increases in relative humidity (of the order of 5%) might have caused very pronounced isotopic depletions, such as that in sapropel S5 of the penultimate interglacial maximum. The model shows distinctly non proportional responses of d18O and salinity to environmental change, which argues against the use of isotope residuals in Mediterranean paleosalinity reconstructions.

Sulfate and methane concentrations measured in pore water of sediment core GeoB13809-1 and GeoB13849-1

Several previous studies have shown that submarine mass-movements can profoundly impact the shape of pore water profiles. Therefore, pore water geochemistry and diffusion models were proposed as tools for identifying and dating recent (max. several thousands of years old) mass-transport deposits (MTDs). In particular, sulfate profiles evidentially indicate transient pore water conditions generated by submarine landslides. After mass-movements that result in the deposition of sediment packages with distinct pore water signatures, the sulfate profiles can be kink-shaped and evolve into the concave and linear shape with time due to molecular diffusion. Here we present data from the RV METEOR cruise M78/3 along the continental margin off Uruguay and Argentina. Sulfate profiles of 15 gravity cores are compared with the respective acoustic facies recorded by a sediment echosounder system. Our results show that in this very dynamic depositional setting, non-steady state profiles occur often, but are not exclusively associated with mass-movements. Three sites that show acoustic indications for recent MTDs are presented in detail. Where recent MTDs are identified, a geochemical transport/reaction model is used to estimate the time that has elapsed since the perturbation of the pore water system and, thus, the timing of the MTD emplacement. We conclude that geochemical analyses are a powerful complementary tool in the identification of recent MTDs and provide a simple and accurate way of dating such deposits.