Mesoporous nanocrystalline zirconia with lamellar and MSU structure

Without introduction of any stabilizer, the mesoporous nanocrystalline zirconia with lamellar and MSU structure was obtained via solid state reaction coupled with surfactant templating method. The phase, surface area and pore structure of zirconia prepared with this novel method could be designed, tailored and controlled by varying synthesis parameters. The phase transformation was controlled by particle size. The mesostructure possesses nanocrystalline pore wall, which renders it more thermally stable than amorphous framework. The results suggest strongly that in solid state synthesis system mesostructure formation still follow the supramolecular self-assembly mechanism. The lamellar and reverse hexagonal structure could be transformed at different OH-/Zr molar ratios in order to sustain the low surface energy of the mesophases. The lamellar structure was preferred at higher OH-/Zr molar ratios but reverse hexagonal was at low ratios.

Towards the preparative and large-scale precision manafacture of virus-like particles

Virus-like particles (VLPs) are of interest in vaccination, gene therapy and drug delivery, but their potential has yet to be fully realized. This is because existing laboratory processes, when scaled, do not easily give a compositionally and architecturally consistent product. Research suggests that new process routes might ultimately be based on chemical processing by self-assembly, involving the precision manufacture of precursor capsomeres followed by in vitro VLP self-assembly and scale-up to required levels. A synergistic interaction of biomolecular design and bioprocess engineering (i.e. biomolecular engineering) is required if these alternative process routes and, thus, the promise of new VLP products, are to be realized.

The in-vitro bioactivity of mesoporous bioactive glasses

Ordered mesoporous bioactive glasses (MBGs) with different compositions were prepared by using nonionic block copolymer surfactants as structure-directing agents through an evaporation-induced self-assembly process. Their in-vitro bioactivities were studied in detail by electron microscopy, Fourier-transform infrared spectroscopy, and inductively coupled plasma (ICP) atomic emission spectroscopy. The ICP element analysis results were further calculated in terms of the total consumption of Ca and P, Delta[Ca]/Delta[P] ratios, and ionic activity product (IP) of hydroxyapatite. Through the above analysis, it is clear that MBGs show a different structure-bioactivity correlation compared to conventional sol-gel-derivcd BGs. The in vitro bioactivity of MBGs is dependent on the Si/Ca ratio in the network when the other material parameters such as the mesostructure and texture properties (pore size, pore volume) are controlled. MBG 80S15C with relatively lower calcium content exhibits the best in vitro bioactivity, in contrast to conventional sol-gel-derived BGs where usually higher calcium percentage BGs (e.g. 60S35C) show better bioactivity. Calcination temperature is another important factor that influences the in vitro bioactivity. According to our results, MBGs calcined at 973 K may possess the best in vitro bioactivity. The influences of the composition and calcination temperature upon bioactivity are explained in terms of the unique structures of MBGs. (c) 2006 Elsevier Ltd. All rights reserved.

Prophylactic HPV vaccines: Underlying mechanisms

Human papillomavirus virus-like particles (HPV VLP) can be generated by the synthesis and self-assembly in vitro of the major virus capsid protein L1. HPV L1 VLPs are morphologically and antigenically almost identical to native virions, and this technology has been exploited to produce HPV L1 VLP subunit vaccines. The vaccines elicit high titres of anti-L I VLP antibodies that persist at levels 10 times that of natural infections for at least 48 months. At present the assumption is that the protection achieved by these vaccines against incident HPV infection and HPV-associated ano-genital pathology is mediated via serum neutralising Immunoglobulin G (IgG). However, since there have been very few vaccine failures thus far, immune correlates of protection have not been established. The available evidence is that the immunodominant neutralising antibodies generated by L1 VLPs are type-specific and are not cross-neutralising, although highly homologous HPV pairs share minor cross-neutralisation epitopes. Important issues remaining to be addressed include the duration of protection and genotype replacement. (c) 2006 Elsevier Ltd. All rights reserved.

Reformulation of a thermostable broadly protective recombinant vaccine against human papilloma virus

The causal relationship between Human Papilloma Virus (HPV) infection and cervical cancer has motivated the development, and further improvement, of prophylactic vaccines against this virus. 70% of cervical cancers, 80% of which in low-resources countries, are associated to HPV16 and HPV18 infection, with 13 additional HPV types, classified as high-risk, responsible for the remaining 30% of tumors. Current vaccines, Cervarix® (GlaxoSmithKline) and Gardasil®(Merk), are based on virus-like particles (VLP) obtained by self-assembly of the major capsid protein L1. Despite their undisputable immunogenicity and safety, the fact that protection afforded by these vaccines is largely limited to the cognate serotypes included in the vaccine (HPV 16 and 18, plus five additional viral types incorporated into a newly licensed nonavalent vaccine) along with high production costs and reduced thermal stability, are pushing the development of 2nd generation HPV vaccines based on minor capsid protein L2. The increase in protection broadness afforded by the use of L2 cross-neutralizing epitopes, plus a marked reduction of production costs due to bacterial expression of the antigens and a considerable increase in thermal stability could strongly enhance vaccine distribution and usage in low-resource countries. Previous studies from our group identified three tandem repeats of the L2 aa. 20-38 peptide as a strongly immunogenic epitope if exposed on the scaffold protein thioredoxin (Trx). The aim of this thesis work is the improvement of the Trx-L2 vaccine formulation with regard to cross-protection and thermostability, in order to identify an antigen suitable for a phase I clinical trial. By testing Trx from different microorganisms, we selected P. furiosus thioredoxin (PfTrx) as the optimal scaffold because of its sustained peptide epitope constraining capacity and striking thermal stability (24 hours at 100°C). Alternative production systems, such as secretory Trx-L2 expression in the yeast P. pastoris, have also been set-up and evaluated as possible means to further increase production yields, with a concomitant reduction of production costs. Limitations in immune-responsiveness caused by MHC class II polymorphisms –as observed, for example, in different mouse strains- have been overcome by introducing promiscuous T-helper (Th) epitopes, e.g., PADRE (Pan DR Epitope), at both ends of PfTrx. This allowed us to obtain fairly strong immune responses even in mice (C57BL/6) normally unresponsive to the basic Trx-L2 vaccine. Cross-protection was not increased, however. I thus designed, produced and tested a novel multi-epitope formulation consisting of 8 and 11 L2(20-38) epitopes derived from different HPV types, tandemly joined into a single thioredoxin molecule (“concatemers”). To try to further increase immunogenicity, I also fused our 8X and 11X PfTrx-L2 concatemers to the N-terminus of an engineered complement-binding protein (C4bp), capable to spontaneously assemble into ordered hepatmeric structures, previously validated as a molecular adjuvant. Fusion to C4bp indeed improved antigen presentation, with a fairly significant increase in both immunogenicity and cross-protection. Another important issue I addressed, is the reduction of vaccine doses/treatment, which can be achieved by increasing immunogenicity, while also allowing for a delayed release of the antigen. I obtained preliminary, yet quite encouraging results in this direction with the use of a novel, solid-phase vaccine formulation, consisting of the basic PfTrx-L2 vaccine and its C4bp fusion derivative adsorbed to mesoporus silica-rods (MSR).

Exploitation of fibre characteristics in temperature sensing and radio-over-fibre applications

The development of sensing devices is one of the instrumentation fields that has grown rapidly in the last decade. Corresponding to the swift advance in the development of microelectronic sensors, optical fibre sensors are widely investigated because of their advantageous properties over the electronics sensors such as their wavelength multiplexing capability and high sensitivity to temperature, pressure, strain, vibration and acoustic emission. Moreover, optical fibre sensors are more attractive than the electronics sensors as they can perform distributed sensing, in terms of covering a reasonably large area using a single piece of fibre. Apart from being a responsive element in the sensing field, optical fibre possesses good assets in generating, distributing, processing and transmitting signals in the future broadband information network. These assets include wide bandwidth, high capacity and low loss that grant mobility and flexibility for wireless access systems. Among these core technologies, the fibre optic signal processing and transmission of optical and radio frequency signals have been the subjects of study in this thesis. Based on the intrinsic properties of single-mode optical fibre, this thesis aims to exploit the fibre characteristics such as thermal sensitivity, birefringence, dispersion and nonlinearity, in the applications of temperature sensing and radio-over-fibre systems. By exploiting the fibre thermal sensitivity, a fully distributed temperature sensing system consisting of an apodised chirped fibre Bragg grating has been implemented. The proposed system has proven to be efficient in characterising grating and providing the information of temperature variation, location and width of the heat source applied in the area under test.To exploit the fibre birefringence, a fibre delay line filter using a single high-birefringence optical fibre structure has been presented. The proposed filter can be reconfigured and programmed by adjusting the input azimuth of launched light, as well as the strength and direction of the applied coupling, to meet the requirements of signal processing for different purposes in microwave photonic and optical filtering applications. To exploit the fibre dispersion and nonlinearity, experimental investigations have been carried out to study their joint effect in high power double-sideband and single-sideband modulated links with the presence of fibre loss. The experimental results have been theoretically verified based on the in-house implementation of the split-step Fourier method applied to the generalised nonlinear Schrödinger equation. Further simulation study on the inter-modulation distortion in two-tone signal transmission has also been presented so as to show the effect of nonlinearity of one channel on the other. In addition to the experimental work, numerical simulations have also been carried out in all the proposed systems, to ensure that all the aspects concerned are comprehensively investigated.

Soft hydrogels from nanotubes of poly(ethylene oxide)−tetraphenylalanine conjugates prepared by click chemistry

A new poly(ethylene oxide)-tetraphenylalanine polymer-peptide conjugate has been prepared via a “click” reaction between an alkyne-modified peptide and an azide-terminated PEO oligomer. Self-assembled nanotubes are formed after dialysis of a THF solution of this polymer-peptide conjugate against water. The structure of these nanotubes has been probed by circular dichroism, IR, TEM, and SAXS. From these data, it is apparent that self-assembly involves the formation of antiparallel ß-sheets and p-p-stacking. Nanotubes are formed at concentrations between 2 and 10 mg mL-1. Entanglement between adjacent nanotubes occurs at higher concentrations, resulting in the formation of soft hydrogels. Gel strength increases at higher polymer-peptide conjugate concentration, as expected.

Psychological therapies for chronic pelvic pain:systematic review of randomized controlled trials

Chronic pelvic pain (CPP), a common cause of disability in women, is a condition best viewed in the biopsychosocial framework. Psychological interventions are frequently considered alongside medical and surgical treatments. Our objective was to evaluate the effectiveness of psychological therapies for the treatment of CPP. Electronic literature searches were conducted in Medline, Embase, PsycInfo and DARE databases from database inception to April 2010. Reference lists of selected articles were searched for further articles. The studies selected were randomized controlled trials of psychological therapies in patients with CPP compared with no treatment, standard gynecological treatment or another form of psychological therapy. Two reviewers independently selected articles without language restrictions and extracted data covering study characteristics, study quality and results. Reduction in pain, measured using visual analog scales or other measurements, was the main outcome measure. Of the 107 citations identified, four studies satisfied the inclusion criteria. Compared with no psychological intervention, therapy produced a standardized mean pain score of -3.27 [95% confidence interval (CI) -4.52 to -2.02] and 1.11 (95% CI -0.05 to 2.27) at 3 months and -3.95 (95% CI -5.35 to -2.55) and 0.54 (95% CI -0.78 to 1.86) at 6 months and greater, based on a visual analog scale score of 0-10. The current evidence does not allow us to conclude whether psychological interventions have an effect on self-reported pain scores in women with CPP.

Amino acid, peptide and drug transport across monolayers of human intestinal (CAC0-2) cells in vitro

The properties of Caco-2 monolayers were compared on aluminium oxide and nitrocellulose permeable-supports. On nitrocellulose, Caco-2 cells displayed a higher rate of taurocholic acid transport than those cultured on aluminium oxide inserts. In addition, Caco-2 cells grown on these two inserts were not comparable with respect to cell morphology, cell numbers and transepithelial electrical resistance. The low adsorption potential of the aluminium oxide inserts, particularly for high molecular weight or lipophilic ligands, offers a distinct advantage over nitrocellulose inserts for drug transport studies. The carrier-mediated uptake and transport of the imino acid (L-proline) and the acidic amino acids (L-aspartate and L-glutamate) have been studied. At pH7.4, L-proline uptake is mediated via an A-system carrier. Elevated uptake and transport under acidic conditions occurs by activation of a distinct carrier population. Acidic amino acid transport is mediated via a X-AG system. The flux of baclofen, CGP40116 andCGP40117 across Caco-2 monolayers was described by passive transport. The transport of three peptides, thyrotrophin-releasing hormone, SQ29852 and cyclosporin were investigated. Thyrotrophin-releasing hormone transport acrossCaco-2 monolayers was characterised by a minor saturable (carrier-mediated,approximately 25%) pathway, superimposed onto a major non-saturable (diffusional)pathway. SQ29852 uptake into Caco-2 monolayers is described by a major saturable mechanism (Km = 0.91 mM) superimposed onto a minor passive component.However, the initial-rate of SQ29852 transport is consistent with a passive transepithelial transport mechanism. These data highlight the possibility that itsbasolateral efflux is severely retarded such that the passive paracellular transportdictates the overall transepithelial transport characteristics. In addition, modelsuitable for investigating the transepithelial transport of cyclosporin A has been developed. A modification of the conventional Caco-2 model has been developed which has a calcium-free Ap donor-solution and a Bl receiver-solution containing the minimumcalcium concentration required to maintain monolayer integrity (100 μM). The influence of calcium and magnesium on the absorption of [14C]pamidronate was evaluated by comparing its transport across the conventional and minimum calciumCaco-2 models. Ap calcium and magnesium ions retard the Ap-to-Bl flux of pamidronate across Caco-2 monolayers. The effect of self-emulsifying oleic acid-Tween 80 formulations on Caco-2monolayer integrity has been investigated. Oleic acid-Tween 80 (1 0:1) formulations produced a dose-dependent disruption of Caco-2 monolayer integrity. This disruption was related to the oleic acid content of the formulation.

Representational modes of thinking employed by children aged thirteen and fourteen, and their relationship to performance in standardised tests of ability, measures of creativity and personality

This thesis proposes that despite many experimental studies of thinking, and the development of models of thinking, such as Bruner's (1966) enactive, iconic and symbolic developmental modes, the imagery and inner verbal strategies used by children need further investigation to establish a coherent, theoretical basis from which to create experimental curricula for direct improvement of those strategies. Five hundred and twenty-three first, second and third year comprehensive school children were tested on 'recall' imagery, using a modified Betts Imagery Test; and a test of dual-coding processes (Paivio, 1971, p.179), by the P/W Visual/Verbal Questionnaire, measuring 'applied imagery' and inner verbalising. Three lines of investigation were pursued: 1. An investigation a. of hypothetical representational strategy differences between boys and girls; and b. the extent to which strategies change with increasing age. 2. The second and third year children's use of representational processes, were taken separately and compared with performance measures of perception, field independence, creativity, self-sufficiency and self-concept. 3. The second and third year children were categorised into four dual-coding strategy groups: a. High Visual/High Verbal b. Low Visual/High Verbal c. High Visual/Low Verbal d. Low Visual/Low Verbal These groups were compared on the same performance measures. The main result indicates that: 1. A hierarchy of dual-coding strategy use can be identified that is significantly related (.01, Binomial Test) to success or failure in the performance measures: the High Visual/High Verbal group registering the highest scores, the Low Visual/High Verbal and High Visual/Low Verbal groups registering intermediate scores, and the Low Visual/Low Verbal group registering the lowest scores on the performance measures. Subsidiary results indicate that: 2. Boys' use of visual strategies declines, and of verbal strategies increases, with age; girls' recall imagery strategy increases with age. Educational implications from the main result are discussed, the establishment of experimental curricula proposed, and further research suggested.

Having a word with yourself:neural correlates of self-criticism and self-reassurance

Self-criticism is strongly correlated with a range of psychopathologies, such as depression, eating disorders and anxiety. In contrast, self-reassurance is inversely associated with such psychopathologies. Despite the importance of self-judgements and evaluations, little is known about the neurophysiology of these internal processes. The current study therefore used a novel fMRI task to investigate the neuronal correlates of self-criticism and self-reassurance. Participants were presented statements describing two types of scenario, with the instruction to either imagine being self-critical or self-reassuring in that situation. One scenario type focused on a personal setback, mistake or failure, which would elicit negative emotions, whilst the second was of a matched neutral event. Self-criticism was associated with activity in lateral prefrontal cortex (PFC) regions and dorsal anterior cingulate (dAC), therefore linking self-critical thinking to error processing and resolution, and also behavioural inhibition. Self-reassurance was associated with left temporal pole and insula activation, suggesting that efforts to be self-reassuring engage similar regions to expressing compassion and empathy towards others. Additionally, we found a dorsal/ventral PFC divide between an individual's tendency to be self-critical or self-reassuring. Using multiple regression analyses, dorsolateral PFC activity was positively correlated with high levels of self-criticism (assessed via self-report measure), suggesting greater error processing and behavioural inhibition in such individuals. Ventrolateral PFC activity was positively correlated with high self-reassurance. Our findings may have implications for the neural basis of a range of mood disorders that are characterised by a preoccupation with personal mistakes and failures, and a self-critical response to such events.

In situ studies of phase separation and crystallization directed by Marangoni instabilities during spin-coating

Results of a pioneering study are presented in which for the first time, crystallization, phase separation and Marangoni instabilities occurring during the spin-coating of polymer blends are directly visualized, in real-space and real-time. The results provide exciting new insights into the process of self-assembly, taking place during spin-coating, paving the way for the rational design of processing conditions, to allow desired morphologies to be obtained. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Executive function and emotional focus in autobiographical memory specificity in older adults

The current study examined the role of executive function in retrieval of specific autobiographical memories in older adults with regard to control of emotion during retrieval. Older and younger adults retrieved memories of specific events in response to emotionally positive, negative and neutral word cues. Contributions of inhibitory and updating elements of executive function to variance in autobiographical specificity were assessed to determine processes involved in the commonly found age-related reduction in specificity. A negative relationship between age and specificity was only found in retrieval to neutral cues. Alternative explanations of this age preservation of specificity of emotional recall are explored, within the context of control of emotion in the self-memory system and preserved emotional processing and positivity effect in older adults. The pattern of relationships suggests updating, rather than inhibition as the source of age-related reduction in specificity, but that emotional processing (particularly of positively valenced memories) is not influenced by age-related variance in executive control. The tendency of older adults to focus on positive material may thus act as a buffer against detrimental effects of reduced executive function capacity on autobiographical retrieval, representing a possible target for interventions to improve specificity of autobiographical memory retrieval in older adults.

Investigating polymer-peptide conjugates and electrospinning for the production of advanced materials

This thesis describes the production of advanced materials comprising a wide array of polymer-based building blocks. These materials include bio-hybrid polymer-peptide conjugates, based on phenylalanine and poly(ethylene oxide), and polymers with intrinsic microporosity (PIMs). Polymer-peptides conjugates were previously synthesised using click chemistry. Due to the inherent disadvantages of the reported synthesis, a new, simpler, inexpensive protocol was sought. Three synthetic methods based on amidation chemistry were investigated for both oligopeptide and polymerpeptide coupling. The resulting conjugates produced were then assessed by various analytical techniques, and the new synthesis was compared with the established protocol. An investigation was also carried out focussing on polymer-peptide coupling via ester chemistry, involving deprotection of the carboxyl terminus of the peptide. Polymer-peptide conjugates were also assessed for their propensity to self-assemble into thixotropic gels in an array of solvent mixtures. Determination of the rules governing this particular self-assembly (gelation) was required. Initial work suggested that at least four phenylalanine peptide units were necessary for self-assembly, due to favourable hydrogen bond interactions. Quantitative analysis was carried out using three analytical techniques (namely rheology, FTIR, and confocal microscopy) to probe the microstructure of the material and provided further information on the conditions for self-assembly. Several polymers were electrospun in order to produce nanofibres. These included novel materials such as PIMs and the aforementioned bio-hybrid conjugates. An investigation of the parameters governing successful fibre production was carried out for PIMs, polymer-peptide conjugates, and for nanoparticle cages coupled to a polymer scaffold. SEM analysis was carried out on all material produced during these electrospinning experiments.

Ash control methods to limit biomass inorganic content and its effect on fast pyrolysis bio-oil stability

This research investigates specific ash control methods to limit inorganic content within biomass prior to fast pyrolysis and effect of specific ash components on fast pyrolysis processing, mass balance yields and bio-oil quality and stability. Inorganic content in miscanthus was naturally reduced over the winter period from June (7.36 wt. %) to February (2.80 wt. %) due to a combination of senescence and natural leaching from rain water. September harvest produced similar mass balance yields, bio-oil quality and stability compared to February harvest (conventional harvest), but nitrogen content in above ground crop was to high (208 kg ha.-1) to maintain sustainable crop production. Deionised water, 1.00% HCl and 0.10% Triton X-100 washes were used to reduce inorganic content of miscanthus. Miscanthus washed with 0.10% Triton X-100 resulted in the highest total liquid yield (76.21 wt. %) and lowest char and reaction water yields (9.77 wt. % and 8.25 wt. % respectively). Concentrations of Triton X-100 were varied to study further effects on mass balance yields and bio-oil stability. All concentrations of Triton X-100 increased total liquid yield and decreased char and reaction water yields compared to untreated miscanthus. In terms of bio-oil stability 1.00% Triton X-100 produced the most stable bio-oil with lowest viscosity index (2.43) and lowest water content index (1.01). Beech wood was impregnated with potassium and phosphorus resulting in lower liquid yields and increased char and gas yields due to their catalytic effect on fast pyrolysis product distribution. Increased potassium and phosphorus concentrations produced less stable bio-oils with viscosity and water content indexes increasing. Fast pyrolysis processing of phosphorus impregnated beech wood was problematic as the reactor bed material agglomerated into large clumps due to char formation within the reactor, affecting fluidisation and heat transfer.