Characterization and optimization of bilosomes for oral vaccine delivery

Oral vaccines offer significant benefits due to the ease of administration, better patient compliance and non-invasive, needle-free administration. However, this route is marred by the harsh gastro intestinal environment which is detrimental to many vaccine formats. To address this, a range of delivery systems have been considered including bilosomes; these are bilayer vesicles constructed from non-ionic surfactants combined with the inclusion of bile salts which can stabilize the vesicles in the gastro intestinal tract by preventing membrane destabilization. The aim of this study was to investigate the effect of formulation parameters on bilosome carriers using Design of Experiments to select an appropriate formulation to assess in vivo. Bilosomes were constructed from monopalmitoylglycerol, cholesterol, dicetyl phosphate and sodium deoxycholate at different blends ratios. The optimized bilosome formulation was identified and the potential of this formulation as an oral vaccine delivery system were assessed in biodistribution and vaccine efficacy studies. Results showed that the larger bilosomes vesicles (~6 µm versus 2 µm in diameter) increased uptake within the Peyer's patches and were able to reduce median temperature differential change and promote a reduction in viral cell load in an influenza challenge study. © 2013 Informa UK, Ltd.

The normal optic nerve variations in an optometric population:Possible ocular and systemic influences

Early detection of glaucoma relies on a detailed knowledge of how the normal optic nerve (ONH) varies within the population. The purpose of this study focused on two main areas; 1. To explore the optic nerve head appearance in the normal optometric population and compare the south Asian (principally Pakistani) with the European white population, correcting for possible ocular and non-ocular influences in a multiple regression model. The main findings were: • The optic discs of the South Asian (SA) and White European (WE) populations were not statistically different in size. The SA group possessed discs with increased cupping and thinner neuro-retinal rims (NRR) compared with the WE group. The SA group also demonstrated a more vertically oval shape than the WE population. These differences were significant at the p<0.01 level. • The upper limits of inter-eye asymmetry were: ≤0.2 for cup to disc area ratio, and 3mmHg for intra-ocular pressure (IOP) for both ethnic groups and this did not increase with age. IOP asymmetry did not vary with gender, ethnicity or a family history of glaucoma and was independent of ONH asymmetry. ONH and IOP asymmetry are therefore independent risk factors when screening for glaucoma for both ethnic groups. 2. To investigate the validity of the ISNT rule: inferior> superior> nasal> temporal NRR thickness in the optometric population. The main findings were: • As disc size increased the disc become rounder and less vertically oval in shape. Vertically oval discs had thicker superior and inferior NRRs and thinner nasal and temporal NRRs compared with rounder disc shapes due to cup shape being independent of disc shape. Vertically oval discs were therefore more likely to obey the ISNT rule than larger rounder discs. • The ISNT rule has a low adherence in our sample of normal eyes (5.7%). However, by removing the nasal sector to become the IST rule, 74.5% of normal eyes obeyed. SA eyes and female gender were more likely to obey the ISNT rule due to increased disc ovality. The IST rule is independent of disc shape and therefore more suitable for assessing discs from both ethnic backgrounds. Obeying the ISNT rule or IST rule was not related to disc or cup size.

Broadly tunable high-power random fibre laser

As shown recently, a long telecommunication fibre may be treated as a natural one-dimensional random system, where lasing is possible due to a combination of random distributed feedback via Rayleigh scattering by natural refractive index inhomogeneities and distributed amplification through the Raman effect. Here we present a new type of a random fibre laser with a narrow (∼1 nm) spectrum tunable over a broad wavelength range (1535-1570 nm) with a uniquely flat (∼0.1 dB) and high (>2 W) output power and prominent (>40 %) differential efficiency, which outperforms traditional fibre lasers of the same category, e.g. a conventional Raman laser with a linear cavity formed in the same fibre by adding point reflectors. Analytical model is proposed that explains quantitatively the higher efficiency and the flatter tuning curve of the random fiber laser compared to conventional one. The other important features of the random fibre laser like "modeless" spectrum of specific shape and corresponding intensity fluctuations as well as the techniques of controlling its output characteristics are discussed. Outstanding characteristics defined by new underlying physics and the simplicity of the scheme implemented in standard telecom fibre make the demonstrated tunable random fibre laser a very attractive light source both for fundamental science and practical applications such as optical communication, sensing and secure transmission. © 2012 Copyright Society of Photo-Optical Instrumentation Engineers (SPIE).

Energy-based damage and fracture framework for viscoelastic asphalt concrete

A framework based on the continuum damage mechanics and thermodynamics of irreversible processes using internal state variables is used to characterize the distributed damage in viscoelastic asphalt materials in the form of micro-crack initiation and accumulation. At low temperatures and high deformation rates, micro-cracking is considered as the source of nonlinearity and thus the cause of deviation from linear viscoelastic response. Using a non-associated damage evolution law, the proposed model shows the ability to describe the temperature-dependent processes of micro-crack initiation, evolution and macro-crack formation with good comparison to the material response in the Superpave indirect tensile (IDT) strength test.

Essays on durable goods consumption and firm innovation

This dissertation comprises three individual chapters. Chapter Two examines how free riding across neighbors influenced the diffusion of color television sets in rural China. Chapter Three tests for asymmetric information between a firm’s management and other investors concerning its patent output. Chapter Four discusses how knowledge stocks influence a patenting firm’s later diversification. Chapter Two documents the existence of a type of network effects—free riding across neighbors—in the consumption of color television sets in rural China, which reduces the propensity of non-owners to purchase. I construct a model of the timing of the purchase of a durable good in the presence of free riding, and test its key implications using household survey data in rural China. Chapter Three tests for asymmetric information between a firm’s management and other investors about its patent output by examining insider trading patterns and stock price changes in R&D intensive firms. It demonstrates that management has considerable information about its patent output beyond what is known to investors. It also shows that the predictive power of insider trading patterns on patent output comes from purchases rather than sales. Chapter Four discusses two sequential channels through which knowledge stocks may influence a firm’s later diversification. One is that firms with more knowledge are more likely to enter a new industry. The other is that firms’ businesses have a better chance of surviving, conditional on being formed. By examining U.S. public patenting firms in manufacturing sectors for 1984-1996, I find that knowledge stocks predict the likelihood of new industry entry when controlling for firm size. However, this predictive power is weakened when diversification effects are included. On the other hand, a survival study of newly established segments shows that initial knowledge stocks have significant positive effects on segment survival, whereas diversification effects are insignificant.

Personal autonomy in discharge planning decision -making in mentally alert hospitalized elderly individuals: The social workers' perspective

This study was conducted to understand (a) hospital social workers' perspectives about patients' personal autonomy and self-determination, (b) their experiences, and (c) their beliefs and behaviors. The study used the maximum variation sampling strategy to select hospitals and hospital social work respondents. Individual interviews were conducted with 31 medical/surgical and mental health hospital social workers who worked in 13 hospitals. The data suggest the following four points. First, the hospital setting as an outside influence as it relates to illness and safety, and its four categories, mentally alert patients, family members, health care professionals, and social work respondents, seems to enhance or diminish patients' autonomy in discharge planning decision making. Second, respondents report they believe patients must be safe both inside and outside the hospital. In theory, respondents support autonomy and self-determination, respect patients' wishes, and believe patients are the decision makers. However, in practice, respondents respect autonomy and self-determination to a point. Third, a model, The Patient's Decision in Discharge Planning: A Continuum, is presented where a safe discharge plan is at one end of a continuum, while an unsafe discharge plan is at the other end. Respondents respect personal autonomy and the patient's self-determination to a point. This point is likely to be located in a gray area where the patient's decision crosses from one end of the continuum to the other. When patients decide on an unsafe discharge plan, workers' interventions range from autonomy to paternalism. And fourth, the hospital setting as an outside influence may not offer the best opportunity for patients to make decisions (a) because of beliefs family members and health care professionals hold about the value of patient self-determination, and (b) because patients may not feel free to make decisions in an environment where they are surrounded by family members, health care professionals, and social work respondents who have power and who think they know best. Workers need to continue to educate elderly patients about their right to self-determination in the hospital setting. ^

Approximation de la distribution de la distance entre deux courbes empiriques

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Fabrication of sub-10 nm lamellar structures by solvent vapour annealing of block copolymers

Fabrication of nanoscale patterns through the bottom-up approach of self-assembly of phase-separated block copolymers (BCP) holds promise for nanoelectronics applications. For lithographic applications, it is useful to vary the morphology of BCPs by monitoring various parameters to make “from lab to fab” a reality. Here I report on the solvent annealing studies of lamellae forming polystyrene-blockpoly( 4-vinylpyridine) (PS-b-P4VP). The high Flory-Huggins parameter (χ = 0.34) of PS-b-P4VP makes it an ideal BCP system for self-assembly and template fabrication in comparison to other BCPs. Different molecular weights of symmetric PS-b-P4VP BCPs forming lamellae patterns were used to produce nanostructured thin films by spin-coating from mixture of toluene and tetrahydrofuran(THF). In particular, the morphology change from micellar structures to well-defined microphase separated arrangements is observed. Solvent annealing provides a better alternative to thermal treatment which often requires long annealing periods. The choice of solvent (single and dual solvent exposure) and the solvent annealing conditions have significant effects on the morphology of films and it was found that a block neutral solvent was required to realize vertically aligned PS and P4VP lamellae. Here, we have followed the formation of microdomain structures with time development at different temperatures by atomic force microscopy (AFM). The highly mobilized chains phase separate quickly due to high Flory-Huggins (χ) parameter. Ultra-small feature size (~10 nm pitch size) nanopatterns were fabricated by using low molecular weight PSb- P4VP (PS and P4VP blocks of 3.3 and 3.1 kg mol-1 respectively). However, due to the low etch contrast between the blocks, pattern transfer of the BCP mask is very challenging. To overcome the etch contrast problem, a novel and simple in-situ hard mask technology is used to fabricate the high aspect ratio silicon nanowires. The lamellar structures formed after self-assembly of phase separated PS-b-P4VP BCPs were used to fabricate iron oxide nanowires which acted as hard mask material to facilitate the pattern transfer into silicon and forming silicon nanostructures. The semiconductor and optical industries have shown significant interest in two dimensional (2D) molybdenum disulphide (MoS2) as a potential device material due to its low band gap and high mobility. However, current methods for its synthesis are not ‘fab’ friendly and require harsh environments and processes. Here, I also report a novel method to prepare MoS2 layered structures via self-assembly of a PS-b-P4VP block copolymer system. The formation of the layered MoS2 was confirmed by XPS, Raman spectroscopy and high resolution transmission electron microscopy.

Approximation de la distribution de la distance entre deux courbes empiriques

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy

OBJECTIVES: Radiotherapy is planned to achieve the optimal physical dose distribution to the target tumour volume whilst minimising dose to the surrounding normal tissue. Recent in vitro experimental evidence has demonstrated an important role for intercellular communication in radiobiological responses following non-uniform exposures. This study aimed to model the impact of these effects in the context of techniques involving highly modulated radiation fields or spatially fractionated treatments such as GRID therapy.

METHODS: Using the small animal radiotherapy research platform (SARRP) as a key enabling technology to deliver precision imaged-guided radiotherapy, it is possible to achieve spatially modulated dose distributions that model typical clinical scenarios. In this work, we planned uniform and spatially fractionated dose distributions using multiple isocentres with beam sizes of 0.5 - 5 mm to obtain 50% volume coverage in a subcutaneous murine tumour model, and applied a model of cellular response that incorporates intercellular communication to assess the potential impact of signalling effects with different ranges.

RESULTS: Models of GRID treatment plans which incorporate intercellular signalling showed increased cell killing within the low dose region. This results in an increase in the Equivalent Uniform Dose (EUD) for GRID exposures compared to standard models, with some GRID exposures being predicted to be more effective than uniform delivery of the same physical dose.

CONCLUSIONS: This study demonstrates the potential impact of radiation induced signalling on tumour cell response for spatially fractionated therapies and identifies key experiments to validate this model and quantify these effects in vivo.

ADVANCES IN KNOWLEDGE: This study highlights the unique opportunities now possible using advanced preclinical techniques to develop a foundation for biophysical optimisation in radiotherapy treatment planning.

Spectral analysis of four 'hypervariable' AGN: a micro-needle in the haystack?

We analyze four extreme AGN transients to explore the possibility that they are caused by rare, high-amplitude microlensing events. These previously unknown type-I AGN are located in the redshift range 0.6-1.1 and show changes of > 1.5 magnitudes in the g-band on a timescale of ~years. Multi-epoch optical spectroscopy, from the William Herschel Telescope, shows clear differential variability in the broad line fluxes with respect to the continuum changes and also evolution in the line profiles. In two cases a simple point-source, point-lens microlensing model provides an excellent match to the long-term variability seen in these objects. For both models the parameter constraints are consistent with the microlensing being due to an intervening stellar mass object but as yet there is no confirmation of the presence of an intervening galaxy. The models predict a peak amplification of 10.3/13.5 and an Einstein timescale of 7.5/10.8 years respectively. In one case the data also allow constraints on the size of the CIII] emitting region, with some simplifying assumptions, to to be ~1.0-6.5 light-days and a lower limit on the size of the MgII emitting region to be > 9 light-days (half-light radii). This CIII] radius is perhaps surprisingly small. In the remaining two objects there is spectroscopic evidence for an intervening absorber but the extra structure seen in the lightcurves requires a more complex lensing scenario to adequately explain.

Avaliação do potencial cancerigénico de microcistinas (cianotoxinas)

Tese de doutoramento em Farmácia (Toxicologia), apresentada à Faculdade de Farmácia da Universidade de Lisboa, 2009.

Towards participatory political theology: democratic consolidation in Southeastern Europe and the role of Eastern Christianity in the process

This thesis defends the position that the Eastern Orthodoxy has the potential to develop, on the basis of its core concepts and doctrines, a new political theology that is participatory, personalist and universalist. This participatory political theology, as I name it, endorses modern democracy and the values of civic engagement. It enhances the process of democracy-building and consolidation in the SEE countries through cultivating the ethos of participation and concern with the common good among and the recognition of the dignity and freedom of the person. This political-theological model is developed while analyzing critically the traditional models of church-state relations (the symphonia model corresponding to the medieval empire and the Christian nation model corresponding to the nation-state) as being instrumentalized to serve the political goals of non-democratic regimes. The participatory political-theological model is seen as corresponding to the conditions of the constitutional democratic state. The research is justified by the fact the Eastern Orthodoxy has been a dominant religiouscultural force in the European South East for centuries, thus playing a significant role in the process of creation of the medieval and modern statehood of the SEE countries. The analysis employs comparative constitutional perspectives on democratic transition and consolidation in the SEE region with the theoretical approaches of political theology and Eastern Orthodox theology. The conceptual basis for the political-theological synthesis is found in the concept and doctrines of the Eastern Orthodoxy (theosis and synergy, ecclesia and Eucharist, conciliarity and catholicity, economy and eschatology) which emphasize the participatory, personalist and communal dimensions of the Orthodox faith and practice. The paradigms of revealing the political-theological potential of these concepts are the Eucharistic ecclesiology and the concept of divine-human communion as defining the body of Orthodox theology. The thesis argues that with its ethos of openness and engagement the participatory political theology presupposes political systems that are democratic, inclusive, and participatory, respecting the rights and the dignity of the person. The political theology developed here calls for a transformation and change of democratic systems towards better realization of their personalist and participatory commitments. In the context of the SEE countries the participatory political theology addresses the challenges posed by alternative authoritarian political theologies practiced in neighboring regions.

Down scaling to regional assessment of greenhouse gas emissions to enable consistency in accounting for emissions reduction projects and national inventory accounts for northern beef production in Australia

This paper explores the effect of using regional data for livestock attributes on estimation of greenhouse gas (GHG) emissions for the northern beef industry in Australia, compared with using state/territory-wide values, as currently used in Australia’s national GHG inventory report. Regional GHG emissions associated with beef production are reported for 21 defined agricultural statistical regions within state/territory jurisdictions. A management scenario for reduced emissions that could qualify as an Emissions Reduction Fund (ERF) project was used to illustrate the effect of regional level model parameters on estimated abatement levels. Using regional parameters, instead of state level parameters, for liveweight (LW), LW gain and proportion of cows lactating and an expanded number of livestock classes, gives a 5.2% reduction in estimated emissions (range +12% to –34% across regions). Estimated GHG emissions intensity (emissions per kilogram of LW sold) varied across the regions by up to 2.5-fold, ranging from 10.5 kg CO2-e kg–1 LW sold for Darling Downs, Queensland, through to 25.8 kg CO2-e kg–1 LW sold for the Pindan and North Kimberley, Western Australia. This range was driven by differences in production efficiency, reproduction rate, growth rate and survival. This suggests that some regions in northern Australia are likely to have substantial opportunities for GHG abatement and higher livestock income. However, this must be coupled with the availability of management activities that can be implemented to improve production efficiency; wet season phosphorus (P) supplementation being one such practice. An ERF case study comparison showed that P supplementation of a typical-sized herd produced an estimated reduction of 622 t CO2-e year–1, or 7%, compared with a non-P supplemented herd. However, the different model parameters used by the National Inventory Report and ERF project means that there was an anomaly between the herd emissions for project cattle excised from the national accounts (13 479 t CO2-e year–1) and the baseline herd emissions estimated for the ERF project (8 896 t CO2-e year–1) before P supplementation was implemented. Regionalising livestock model parameters in both ERF projects and the national accounts offers the attraction of being able to more easily and accurately reflect emissions savings from this type of emissions reduction project in Australia’s national GHG accounts.

Emerging Gender Regimes and Policies for Gender Equality in a Wider Europe

This article addresses some implications for gender equality and gender policy at European and national levels of transformations in family, economy and polity, which challenge gender regimes across Europe. Women’s labour market participation in the west and the collapse of communism in the east have undermined the systems and assumptions of western male breadwinner and dual worker models of central and eastern Europe. Political reworking of the work/welfare relationship into active welfare has individualised responsibility. Individualisation is a key trend west − and in some respects east − and challenges the structures that supported care in state and family. The links that joined men to women, cash to care, incomes to carers have all been fractured. The article will argue that care work and unpaid care workers are both casualties of these developments. Social, political and economic changes have not been matched by the development of new gender models at the national level. And while EU gender policy has been admired as the most innovative aspect of its social policy, gender equality is far from achieved: women’s incomes across Europe are well below men’s; policies for supporting unpaid care work have developed modestly compared with labour market activation policies.Enlargement brings new challenges as it draws together gender regimes with contrasting histories and trajectories. The article will map social policies for gender equality across the key elements of gender regimes – paid work, care work, income, time and voice – and discuss the nature of a model of gender equality that would bring gender equality across these. It analyses ideas about a dual earner–dual carer model, in the Dutch combination scenario and ‘universal caregiver’ models, at household and civil society levels. These offer a starting point for a model in which paid and unpaid work are equally valued and equally shared between men and women, but we argue that a citizenship model, in which paid and unpaid work obligations are underpinned by social rights, is more likely to achieve gender equality.