N,N'-Carbonyldiimidazole-mediated functionalization of superparamagnetic nanoparticles as vaccine carrier

Particulates with specific sizes and characteristics can induce potent immune responses by promoting antigen uptake of appropriate immuno-stimulatory cell types. Magnetite (Fe3O4) nanoparticles have shown many potential bioapplications due to their biocompatibility and special characteristics. Here, superparamagnetic Fe3O4 nanoparticles (SPIONs) with high magnetization value (70emug-1) were stabilized with trisodium citrate and successfully conjugated with a model antigen (ovalbumin, OVA) via N,N'-carbonyldiimidazole (CDI) mediated reaction, to achieve a maximum conjugation capacity at approximately 13μgμm-2. It was shown that different mechanisms governed the interactions between the OVA molecules and magnetite nanoparticles at different pH conditions. We evaluated as-synthesized SPION against commercially available magnetite nanoparticles. The cytotoxicity of these nanoparticles was investigated using mammalian cells. The reported CDI-mediated reaction can be considered as a potential approach in conjugating biomolecules onto magnetite or other biodegradable nanoparticles for vaccine delivery.

Mathematical models of calcium and tight junctions in normal and reconstructed epidermis

This project investigated the calcium distributions of the skin, and the growth patterns of skin substitutes grown in the laboratory, using mathematical models. The research found that the calcium distribution in the upper layer of the skin is controlled by three different mechanisms, not one as previously thought. The research also suggests that tight junctions, which are adhesions between neighbouring skin cells, cannot be solely responsible for the differences in the growth patterns of skin substitutes and normal skin.

Numerical investigation of case hardening of plant tissue during dying and its influence on the cellular level shrinkage

Dried plant food materials are one of the major contributors to the global food industry. Widening the fundamental understanding on different mechanisms of food material alterations during drying assists the development of novel dried food products and processing techniques. In this regard, case hardening is an important phenomenon, commonly observed during the drying processes of plant food materials, which significantly influences the product quality and process performance. In this work, a recent meshfree-based numerical model of the authors is further improved and used to simulate the influence of case hardening on shrinkage characteristics of plant tissues during drying. In order to model fluid and wall mechanisms in each cell, Smoothed Particle Hydrodynamics (SPH) and the Discrete Element Method (DEM) are used. The model is fundamentally more capable of simulating large deformation of multiphase materials, when compared with conventional grid-based modelling techniques such as Finite Element Methods (FEM) or Finite Difference Methods (FDM). Case hardening is implemented by maintaining distinct moisture levels in the different cell layers of a given tissue. In order to compare and investigate different factors influencing tissue deformations under case hardening, four different plant tissue varieties (apple, potato, carrot and grape) are studied. The simulation results indicate that the inner cells of any given tissue undergo limited shrinkage and cell wall wrinkling compared to the case hardened outer cell layers of the tissues. When comparing unique deformation characteristics of the different tissues, irrespective of the normalised moisture content, the cell size, cell fluid turgor pressure and cell wall characteristics influence the tissue response to case hardening.

Exercise, Nutrition, and Bone Health

Optimal bone metabolism is the result of hormonal, nutritional, and mechanical harmony, and a deficit in one area is usually impossible to overcome by improvements in others. Exercise during growth influences bone modeling locally at the regions being loaded, whereas calcium is thought to act systemically to influence bone remodeling. Despite acting through different mechanisms, a growing body of research suggests that exercise and calcium may not operate independently. Low dietary calcium intake or reduced bioavailability may minimize the adaptive response to exercise-induced bone loading. Conversely, adequate levels of calcium intake can maximize the positive effect of physical activity on bone health during the growth period of children and adolescents. Research also suggests that adequate levels of calcium intake can maximize bone density at the regions being loaded during exercise. Achieving optimal bone health and minimizing one’s risk of osteoporotic fracture later in life depend on a lifelong approach. This approach relies on the establishment of an optimum level of bone during the growth years, with a subsequent goal to maintain and slow the rate of age-related bone loss thereafter. Exercise, adequate nutrition, and optimal hormone levels are the components that influence the bone outcome. Making healthy nutritional choices, engaging in weight-bearing physical activity, and ensuring optimal hormone levels during growth provides a window of opportunity to build optimal bone mass, to reduce the risk of fracture later in life. Concurrent management of fracture risk with a physical activity prescription, adequate nutrition, and pharmacotherapy for osteoporosis when required offers the best approach to optimal bone health throughout adulthood.

Neural activity associated with semantic versus phonological anomia treatments in aphasia

Naming impairments in aphasia are typically targeted using semantic and/or phonologically based tasks. However, it is not known whether these treatments have different neural mechanisms. Eight participants with aphasia received twelve treatment sessions using an alternating treatment design, with fMRI scans pre- and post-treatment. Half the sessions employed Phonological Components Analysis (PCA), and half the sessions employed Semantic Feature Analysis (SFA). Pre-treatment activity in the left caudate correlated with greater immediate treatment success for items treated with SFA, whereas recruitment of the left supramarginal gyrus and right precuneus post-treatment correlated with greater immediate treatment success for items treated with PCA. The results support previous studies that have found greater treatment outcome to be associated with activity in predominantly left hemisphere regions, and suggest that different mechanisms may be engaged dependent on the type of treatment employed.

Transition to an unsteady flow induced by a fin on the sidewall of a differentially heated air-filled square cavity and heat transfer

The transition from a steady to an unsteady flow induced by an adiabatic fin on the sidewall of a differentially heated air-filled cavity is numerically investigated. Numerical simulations have been performed over the range of Rayleigh numbers from Ra = 105–109. The temporal development and spatial structures of natural convection flows in the cavity with a fin are described. It has been demonstrated that the fin may induce the transition to an unsteady flow and the critical Rayleigh number for the occurrence of the transition is between 3.72 × 106 and 3.73 × 106. Furthermore, the peak frequencies of the oscillations triggered by different mechanisms are obtained through spectral analysis. It has been found that the flow rate through the cavity with a fin is larger than that without a fin under the unsteady flow, indicating that the fin may improve the unsteady flow in the cavity.

Mathematical models of calcium and tight junctions in normal and reconstructed epidermis

This project investigated the calcium distributions of the skin, and the growth patterns of skin substitutes grown in the laboratory, using mathematical models. The research found that the calcium distribution in the upper layer of the skin is controlled by three different mechanisms, not one as previously thought. The research also suggests that tight junctions, which are adhesions between neighbouring skin cells, cannot be solely responsible for the differences in the growth patterns of skin substitutes and normal skin.

Is the sum more than the corporate entrepreneurship parts? the different effects of social capital on innovation, venturing, and renewal processes

Principal Topic Although corporate entrepreneurship is of vital importance for long-term firm survival and growth (Zahra and Covin, 1995), researchers still struggle with understanding how to manage corporate entrepreneurship activities. Corporate entrepreneurship consists of three parts: innovation, venturing, and renewal processes (Guth and Ginsberg, 1990). Innovation refers to the development of new products, venturing to the creation of new businesses, and renewal to redefining existing businesses (Sharma, and Chrisman, 1999; Verbeke et al., 2007). Although there are many studies focusing on one of these aspects (cf. Burgelman, 1985; Huff et al., 1992), it is very difficult to compare the outcomes of these studies due to differences in contexts, measures, and methodologies. This is a significant lack in our understanding of CE, as firms engage in all three aspects of CE, making it important to compare managerial and organizational antecedents of innovation, venturing and renewal processes. Because factors that may enhance venturing activities may simultaneously inhibit renewal activities. The limited studies that did empirically compare the individual dimensions (cf. Zahra, 1996; Zahra et al., 2000; Yiu and Lau, 2008; Yiu et al., 2007) generally failed to provide a systematic explanation for potential different effects of organizational antecedents on innovation, venturing, and renewal. With this study we aim to investigate the different effects of structural separation and social capital on corporate entrepreneurship activities. The access to existing and the development of new knowledge has been deemed of critical importance in CE-activities (Floyd and Wooldridge, 1999; Covin and Miles, 2007; Katila and Ahuja, 2002). Developing new knowledge can be facilitated by structurally separating corporate entrepreneurial units from mainstream units (cf. Burgelman, 1983; Hill and Rothaermel, 2003; O'Reilly and Tushman, 2004). Existing knowledge and resources are available through networks of social relationships, defined as social capital (Nahapiet and Ghoshal, 1998; Yiu and Lau, 2008). Although social capital has primarily been studied at the organizational level, it might be equally important at top management level (Belliveau et al., 1996). However, little is known about the joint effects of structural separation and integrative mechanisms to provide access to social capital on corporate entrepreneurship. Could these integrative mechanisms for example connect the separated units to facilitate both knowledge creation and sharing? Do these effects differ for innovation, venturing, and renewal processes? Are the effects different for organizational versus top management team integration mechanisms? Corporate entrepreneurship activities have for example been suggested to take place at different levels. Whereas innovation is suggested to be a more bottom-up process, strategic renewal is a more top-down process (Floyd and Lane, 2000; Volberda et al., 2001). Corporate venturing is also a more bottom-up process, but due to the greater required resource commitments relative to innovation, it ventures need to be approved by top management (Burgelman, 1983). As such we will explore the following key research question in this paper: How do social capital and structural separation on organizational and TMT level differentially influence innovation, venturing, and renewal processes? Methodology/Key Propositions We investigated our hypotheses on a final sample of 240 companies in a variety of industries in the Netherlands. All our measures were validated in previous studies. We targeted a second respondent in each firm to reduce problems with single-rater data (James et al., 1984). We separated the measurement of the independent and the dependent variables in two surveys to create a one-year time lag and reduce potential common method bias (Podsakoff et al., 2003). Results and Implications Consistent with our hypotheses, our results show that configurations of structural separation and integrative mechanisms have different effects on the three aspects of corporate entrepreneurship. Innovation was affected by organizational level mechanisms, renewal by integrative mechanisms on top management team level and venturing by mechanisms on both levels. Surprisingly, our results indicated that integrative mechanisms on top management team level had negative effects on corporate entrepreneurship activities. We believe this paper makes two significant contributions. First, we provide more insight in what the effects of ambidextrous organizational forms (i.e. combinations of differentiation and integration mechanisms) are on venturing, innovation and renewal processes. Our findings show that more valuable insights can be gained by comparing the individual parts of corporate entrepreneurship instead of focusing on the whole. Second, we deliver insights in how management can create a facilitative organizational context for these corporate entrepreneurship activities.

Investigation of molecular mechanisms regulating biomineralization of pearl oyster Pinctada maxima

Biomineralization is a process encompassing all mineral containing tissues produced within an organism. The most dynamic example of this process is the formation of the mollusk shell, comprising a variety of crystal phases and microstructures. The organic component incorporated within the shell is said to dictate this remarkable architecture. Subsequently, for the past decade considerable research have been undertaken to identify and characterize the protein components involved in biomineralization. Despite these efforts the general understanding of the process remains ambiguous. This study employs a novel molecular approach to further the elucidation of the shell biomineralization. A microarray platform has been custom generated (PmaxArray 1.0) from the pearl oyster Pinctada maxima. PmaxArray 1.0 consists of 4992 expressed sequence tags (ESTs) originating from the mantle, an organ involved in shell formation. This microarray has been used as the primary tool for three separate investigations in an effort to associate transcriptional gene expression from P. maxima to the process of shell biomineralization. The first investigation analyzes the spatial expression of ESTs throughout the mantle organ. The mantle was dissected into five discrete regions and each analyzed for gene expression with PmaxArray 1.0. Over 2000 ESTs were differentially expressed among the tissue sections, identifying five major expression regions. Three of these regions have been proposed to have shell formation functions belonging to nacre, prismatic calcite and periostracum. The spatial gene expression map was confirmed by in situ hybridization, localizing a subset of ESTs from each expression region to the same mantle area. Comparative sequence analysis of ESTs expressed in the proposed shell formation regions with the BLAST tool, revealed a number of the transcripts were novel while others showed significant sequence similarities to previously characterized shell formation genes. The second investigation correlates temporal EST expression during P. maxima larval ontogeny with transitions in shell mineralization during the same period. A timeline documenting the morphologicat microstructural and mineralogical shell characteristics of P. maxima throughout larval ontogeny has been established. Three different shell types were noted based on the physical characters and termed, prodissoconch I, prodissoconch 11 and dissoconch. PmaxArray 1.0 analyzed ESTs expression of animals throughout the larval development of P. maxima, noting up-regulation of 359 ESTs in association with the shell transitions from prodissoconch 1 to prodissoconch 11 to dissoconch. Comparative sequence analysis of these ESTs indicates a number of the transcripts are novel as well as showing significant sequence similarities between ESTs and known shell matrix associated genes and proteins. These ESTs are discussed in relation to the shell characters associated with their temporal expression. The third investigation uses PmaxArray 1.0 to analyze gene expression in the mantle tissue of P. maxima specimens exposed to sub-lethal concentrations of a shell-deforming toxin, tributyltin (TBT). The shell specific effects of TBT are used in this investigation to interpret differential expression of ESTs with respect to shell formation functions. A lethal and sublethal TBT concentration range was established for P. maxima, noting a concentration of 50 ng L- 1 TBT as sub-lethal over a 21 day period. Mantle tissue from P. maxima animals treated with 50 ng L- 1 TBT was assessed for differential EST expression with untreated control animals. A total of 102 ESTs were identified as differentially expressed in association with TBT exposure, comparative sequence identities included an up-regulation of immunity and detoxification related genes and down-regulation of several shell matrix genes. A number of transcripts encoding novel peptides were additionally identified. The potential actions of these genes are discussed with reference to TBT toxicity and shell biomineralization. This thesis has used a microarray platform to analyze gene expression in spatial, temporal and toxicity investigations, revealing the involvement of numerous gene transcripts in specific shell formation functions. Investigation of thousands of transcripts simultaneously has provided a holistic interpretation of the organic components regulating shell biomineralization.

Wear mechanisms and scale effects in two-body abrasion

The ‘particle size effect’ and its manifestation in abrasion still attracts considerable debate as to its origins and the ranking of its likely causes. Experiments have been conducted to study the important contribution that the formation of wear debris can have on the progression of wear. The experiments consist of unlubricated (dry) pin-on-disk tests with silicon carbide coated paper of varying particle size, with different pin material, diameter and loads. It has been observed that the influence of debris formation on wear rate is more pronounced for fine abrasives and soft-wearing materials. Consequently, it is proposed that the particle size effect can be explained in terms of geometrical scaling and the evolution of third-body effects with diminishing particle diameter.

Theoretical investigation of mechanisms of formation and interaction of nanoparticles

In this thesis an investigation into theoretical models for formation and interaction of nanoparticles is presented. The work presented includes a literature review of current models followed by a series of five chapters of original research. This thesis has been submitted in partial fulfilment of the requirements for the degree of doctor of philosophy by publication and therefore each of the five chapters consist of a peer-reviewed journal article. The thesis is then concluded with a discussion of what has been achieved during the PhD candidature, the potential applications for this research and ways in which the research could be extended in the future. In this thesis we explore stochastic models pertaining to the interaction and evolution mechanisms of nanoparticles. In particular, we explore in depth the stochastic evaporation of molecules due to thermal activation and its ultimate effect on nanoparticles sizes and concentrations. Secondly, we analyse the thermal vibrations of nanoparticles suspended in a fluid and subject to standing oscillating drag forces (as would occur in a standing sound wave) and finally on lattice surfaces in the presence of high heat gradients. We have described in this thesis a number of new models for the description of multicompartment networks joined by a multiple, stochastically evaporating, links. The primary motivation for this work is in the description of thermal fragmentation in which multiple molecules holding parts of a carbonaceous nanoparticle may evaporate. Ultimately, these models predict the rate at which the network or aggregate fragments into smaller networks/aggregates and with what aggregate size distribution. The models are highly analytic and describe the fragmentation of a link holding multiple bonds using Markov processes that best describe different physical situations and these processes have been analysed using a number of mathematical methods. The fragmentation of the network/aggregate is then predicted using combinatorial arguments. Whilst there is some scepticism in the scientific community pertaining to the proposed mechanism of thermal fragmentation,we have presented compelling evidence in this thesis supporting the currently proposed mechanism and shown that our models can accurately match experimental results. This was achieved using a realistic simulation of the fragmentation of the fractal carbonaceous aggregate structure using our models. Furthermore, in this thesis a method of manipulation using acoustic standing waves is investigated. In our investigation we analysed the effect of frequency and particle size on the ability for the particle to be manipulated by means of a standing acoustic wave. In our results, we report the existence of a critical frequency for a particular particle size. This frequency is inversely proportional to the Stokes time of the particle in the fluid. We also find that for large frequencies the subtle Brownian motion of even larger particles plays a significant role in the efficacy of the manipulation. This is due to the decreasing size of the boundary layer between acoustic nodes. Our model utilises a multiple time scale approach to calculating the long term effects of the standing acoustic field on the particles that are interacting with the sound. These effects are then combined with the effects of Brownian motion in order to obtain a complete mathematical description of the particle dynamics in such acoustic fields. Finally, in this thesis, we develop a numerical routine for the description of "thermal tweezers". Currently, the technique of thermal tweezers is predominantly theoretical however there has been a handful of successful experiments which demonstrate the effect it practise. Thermal tweezers is the name given to the way in which particles can be easily manipulated on a lattice surface by careful selection of a heat distribution over the surface. Typically, the theoretical simulations of the effect can be rather time consuming with supercomputer facilities processing data over days or even weeks. Our alternative numerical method for the simulation of particle distributions pertaining to the thermal tweezers effect use the Fokker-Planck equation to derive a quick numerical method for the calculation of the effective diffusion constant as a result of the lattice and the temperature. We then use this diffusion constant and solve the diffusion equation numerically using the finite volume method. This saves the algorithm from calculating many individual particle trajectories since it is describes the flow of the probability distribution of particles in a continuous manner. The alternative method that is outlined in this thesis can produce a larger quantity of accurate results on a household PC in a matter of hours which is much better than was previously achieveable.

Investigation of mechanisms governing emission of odorants

The literature identifies several models that describe inter-phase mass transfer, key to the emission process. While the emission process is complex and these models may be more or less successful at predicting mass transfer rates, they identify three key variables for a system involving a liquid and an air phase in contact with it: • A concentration (or partial pressure) gradient driving force; • The fluid dynamic characteristics within the liquid and air phases, and • The chemical properties of the individual components within the system. In three applied research projects conducted prior to this study, samples collected with two well-known sampling devices resulted in very different odour emission rates. It was not possible to adequately explain the differences observed. It appeared likely, however, that the sample collection device might have artefact effects on the emission of odorants, i.e. the sampling device appeared to have altered the mass transfer process. This raised the obvious question: Where two different emission rates are reported for a single source (differing only in the selection of sampling device), and a credible explanation for the difference in emission rate cannot be provided, which emission rate is correct? This research project aimed to identify the factors that determine odour emission rates, the impact that the characteristics of a sampling device may exert on the key mass transfer variables, and ultimately, the impact of the sampling device on the emission rate itself. To meet these objectives, a series of targeted reviews, and laboratory and field investigations, were conducted. Two widely-used, representative devices were chosen to investigate the influence of various parameters on the emission process. These investigations provided insight into the odour emission process generally, and the influence of the sampling device specifically.

Soft toric contact lens prescribing in different countries

There have been significant improvements in toric soft contact lens design over the past decade. Data from our international contact lens prescribing survey were mined to assess recent trends in toric soft contact lens fitting. This survey was conducted by sending up to 1000 survey forms to contact lens fitters in Australia, Canada, Japan, the Netherlands, Norway, the UK and the USA each year between 2000 and 2009. Practitioners were asked to record data relating to the first 10 contact lens fits or refits performed after receiving the forms and to return them to us for analysis. The data revealed a gradual increase in the extent of toric soft lens fitting this century. Excluding Japan – which had a consistently low rate of soft toric lens fitting over the survey period – soft toric lenses now represent over 35% of all soft lenses prescribed; it can be assumed that, on average (and again excluding Japan), all cases of astigmatism 0.75 D or less remains uncorrected among contact lens wearers. Toric lenses are fitted more to those who are older, full-time wearers and reusable lens wearers, and less to those wearing silicone hydrogel and extended wear lenses.

Functional fixation : experimental evidence on the presentation of financial information through different digital formats

This study examines whether, in the presentation of financial information, digital formats address the concern over users’ functional fixation. The accounting literature indicates that the presentation of financial information either within the financial statements or in the notes to the financial statements often creates functional fixation where users of financial statements fail to adjust for differences in accounting policy. This leads users to judge what would otherwise be identical financial situations as being different due to the different accounting policies and methods adopted. It has been suggested that the use of digital formats in presenting financial reports may overcome functional fixation. Using an experimental design involving accountants in public practice, the results indicate that the use of digital formats to present financial reports does not fully overcome the issue of functional fixation in the processing of financial information. Although the participants were able to identify and extract relevant information, irrespective of whether or not the information was presented within the financial statements or in the notes to the accounts, the evidence indicates that functional fixation remained when the participants made final decisions based on available information. This suggests that functional fixation may not be caused by access to or extraction of information but by the level of perceived significance based on where the information is reported in the financial statements. In general, the results indicate that current technology may not be able to fully reduce functional fixation in the evaluation of financial information prepared in accordance with different accounting policies and methods.

The effect of various temperature indicators on different mortality categories in a subtropical city of Brisbane, Australia.

BACKGROUND: The relationship between temperature and mortality has been explored for decades and many temperature indicators have been applied separately. However, few data are available to show how the effects of different temperature indicators on different mortality categories, particularly in a typical subtropical climate. OBJECTIVE: To assess the associations between various temperature indicators and different mortality categories in Brisbane, Australia during 1996-2004. METHODS: We applied two methods to assess the threshold and temperature indicator for each age and death groups: mean temperature and the threshold assessed from all cause mortality was used for all mortality categories; the specific temperature indicator and the threshold for each mortality category were identified separately according to the minimisation of AIC. We conducted polynomial distributed lag non-linear model to identify effect estimates in mortality with one degree of temperature increase (or decrease) above (or below) the threshold on current days and lagged effects using both methods. RESULTS: Akaike's Information Criterion was minimized when mean temperature was used for all non-external deaths and deaths from 75 to 84 years; when minimum temperature was used for deaths from 0 to 64 years, 65-74 years, ≥ 85 years, and from the respiratory diseases; when maximum temperature was used for deaths from cardiovascular diseases. The effect estimates using certain temperature indicators were similar as mean temperature both for current day and lag effects. CONCLUSION: Different age groups and death categories were sensitive to different temperature indicators. However, the effect estimates from certain temperature indicators did not significantly differ from those of mean temperature.