Active regulation of the epidermal calcium profile

A distinct calcium profile is strongly implicated in regulating the multi-layered structure of the epidermis. However, the mechanisms that govern the regulation of this calcium profile are currently unclear. It clearly depends on the relatively impermeable barrier of the stratum corneum (passive regulation) but may also depend on calcium exchanges between keratinocytes and extracellular fluid (active regulation). Using a mathematical model that treats the viable sublayers of unwounded human and murine epidermis as porous media and assumes that their calcium profiles are passively regulated, we demonstrate that these profiles are also actively regulated. To obtain this result, we found that diffusion governs extracellular calcium motion in the viable epidermis and hence intracellular calcium is the main source of the epidermal calcium profile. Then, by comparison with experimental calcium profiles and combination with a hypothesised cell velocity distribution in the viable epidermis, we found that the net influx of calcium ions into keratinocytes from extracellular fluid may be constant and positive throughout the stratum basale and stratum spinosum, and that there is a net outflux of these ions in the stratum granulosum. Hence the calcium exchange between keratinocytes and extracellular fluid differs distinctly between the stratum granulosum and the underlying sublayers, and these differences actively regulate the epidermal calcium profile. Our results also indicate that plasma membrane dysfunction may be an early event during keratinocyte disintegration in the stratum granulosum.

The role of law in responding to climate change : emerging regulatory, liability and market approaches

Climate change presents as the archetypal environmental problem with short-term economic self-interest operating to the detriment of the long-term sustainability of our society. The scientific reports of the Intergovernmental Panel on Climate Change strongly assert that the stabilisation of emissions in the atmosphere, to avoid the adverse impacts of climate change, requires significant and rapid reductions in ‘business as usual’ global greenhouse gas emissions. The sheer magnitude of emissions reductions required, within this urgent timeframe, will necessitate an unprecedented level of international, multi-national and intra-national cooperation and will challenge conventional approaches to the creation and implementation of international and domestic legal regimes. To meet this challenge, existing international, national and local legal systems must harmoniously implement a strong international climate change regime through a portfolio of traditional and innovative legal mechanisms that swiftly transform current behavioural practices in emitting greenhouse gases. These include the imposition of strict duties to reduce emissions through the establishment of strong command and control regulation (the regulatory approach); mechanisms for the creation and distribution of liabilities for greenhouse gas emissions and climaterelated harm (the liability approach) and the use of innovative regulatory tools in the form of the carbon trading scheme (the market approach). The legal relations between these various regulatory, liability and market approaches must be managed to achieve a consistent, compatible and optimally effective legal regime to respond to the threat of climate change. The purpose of this thesis is to analyse and evaluate the emerging legal rules and frameworks, both international and Australian, required for the effective regulation of greenhouse gas emissions to address climate change in the context of the urgent and deep emissions reductions required to minimise the adverse impacts of climate change. In doing so, this thesis will examine critically the existing and potential role of law in effectively responding to climate change and will provide recommendations on the necessary reforms to achieve a more effective legal response to this global phenomenon in the future.

The expression, regulation and function of kallikrein 4 in prostate cancer

Prostate cancer is a significant health problem faced by aging men. Currently, diagnostic strategies for the detection of prostate cancer are either unreliable, yielding high numbers of false positive results, or too invasive to be used widely as screening tests. Furthermore, the current therapeutic strategies for the treatment of the disease carry considerable side effects. Although organ confined prostate cancer can be curable, most detectable clinical symptoms occur in advanced disease when primary tumour cells have metastasised to distant sites - usually lymph nodes and bone. Many growth factors and steroids assist the continued growth and maintenance of prostatic tumour cells. Of these mitogens, androgens are important in the development of the normal prostate but are also required to sustain the growth of prostate cancer cells in the early stage of the disease. Not only are androgens required in the early stage of disease, but also many other growth factors and hormones interact to cause uncontrolled proliferation of malignant cells. The early, androgen sensitive phase of disease is followed by an androgen insensitive phase, whereby androgens are no longer required to stimulate the growth of the tumour cells. Growth factors such as transforming growth factor  and  (TGF/), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), insulin-like growth factors (IGFs), Vitamin D and thyroid hormone have been suggested to be important at this stage of disease. Interestingly, some of the kallikrein family of genes, including prostate specific antigen (PSA), the current serum diagnostic marker for prostate cancer, are regulated by androgens and many of the aforementioned growth factors. The kallikrein gene family is a group of serine proteases that are involved in a diverse range of physiological processes: regulation of local blood flow, angiogenesis, tissue invasion and mitogenesis. The earliest members of the kallikrein gene family (KLK1-KLK3) have been strongly associated with general disease states, such as hypertension, inflammation, pancreatitis and renal disease, but are also linked to various cancers. Recently, this family was extended to include 15 genes (KLK1-15). Several newer members of the kallikrein family have been implicated in the carcinogenesis and tumour metastasis of hormone-dependent cancers such as prostate, breast, endometrial and ovarian cancer. The aims of this project were to investigate the expression of the newly identified kallikrein, KLK4, in benign and malignant prostate tissues, and prostate cancer cell lines. This thesis has demonstrated the elevated expression of KLK4 mRNA transcripts in malignant prostate tissue compared to benign prostates. Additionally, expression of the full length KLK4 transcript was detected in the androgen dependent prostate cancer cell line, LNCaP. Based on the above finding, the LNCaP cell line was chosen to assess the potential regulation of full length KLK4 by androgen, thyroid hormone and epidermal growth factor. KLK4 mRNA and protein was found to be up-regulated by androgen and a combination of androgen and thyroid hormone. Thyroid hormone alone produced no significant change in KLK4 mRNA or protein over the control. Epidermal growth factor treatment also resulted in elevated expression levels of KLK4 mRNA and protein. To assess the potential functional role(s) of KLK4/hK4 in processes associated with tumour progression, full length KLK4 was transfected into PC-3 cells - a prostate cancer cell line originally derived from a secondary bone lesion. The KLK4/hK4 over-expressing cells were assessed for their proliferation, migration, invasion and attachment properties. The KLK4 over-expressing clones exhibited a marked change in morphology, indicative of a more aggressive phenotype. The KLK4 clones were irregularly shaped with compromised adhesion to the growth surface. In contrast, the control cell lines (parent PC-3 and empty vector clones) retained a rounded morphology with obvious cell to cell adhesion, as well as significant adhesion to their growth surface. The KLK4 clones exhibited significantly greater attachment to Collagen I and IV than native PC-3s and empty vector controls. Over a 12 hour period, in comparison to the control cells, the KLK4 clones displayed an increase in migration towards PC-3 native conditioned media, a 3 fold increase towards conditioned media from an osteoblastic cell line (Saos-2) and no change in migration towards conditioned media from neonatal foreskin fibroblast cells or 20% foetal bovine serum. Furthermore, the increase in migration exhibited by the KLK4 clones was partially blocked by the serine protease inhibitor, aprotinin. The data presented in this thesis suggests that KLK4/hK4 is important in prostate carcinogenesis due to its over-expression in malignant prostate tissues, its regulation by hormones and growth factors associated with prostate disease and the functional consequences of over-expression of KLK4/hK4 in the PC-3 cell line. These results indicate that KLK4/hK4 may play an important role in tumour invasion and bone metastasis via increased attachment to the bone matrix protein, Collagen I, and enhanced migration due to soluble factors produced by osteoblast cells. This suggestion is further supported by the morphological changes displayed by the KLK4 over-expressing cells. Overall, this data suggests that KLK4/hK4 should be further studied to more fully investigate the potential value of KLK4/hK4 as a diagnostic/prognostic biomarker or in therapeutic applications.

Efficient and secure self-escrowed public-key infrastructures

A self-escrowed public key infrastructure (SE-PKI) combines the usual functionality of a public-key infrastructure with the ability to recover private keys given some trap-door information. We present an additively homomorphic variant of an existing SE-PKI for ElGamal encryption. We also propose a new efficient SE-PKI based on the ElGamal and Okamoto-Uchiyama cryptosystems that is more efficient than the previous SE-PKI. This is the first SE-PKI that does not suffer from a key doubling problem of previous SE-PKI proposals. Additionally, we present the first self-escrowed encryption schemes secure against chosen-ciphertext attack in the standard model. These schemes are also quite efficient and are based on the Cramer-Shoup cryptosystem, and the Kurosawa-Desmedt hybrid variant in different groups.

Crime is in the air : air pollution and regulation in the UK

This latest briefing by Professor Reece Walters in the What is crime? series, draws attention to an area of harm that is often absent from criminological debate. He highlights the human costs of air pollution and failed attempts to adequately regulate and control such harm. Arguing for a cross disciplinary ‘eco-crime’ narrative, the author calls for greater understanding of the far-reaching consequences of air pollution which could set in train changes which may lead to a ‘more robust and meaningful system of justice’. Describing current arrangements in place to control and regulate air pollution, Walters draws attention to the lack of neutrality in current arrangements and the bias ‘towards the economic imperatives of free trade over and above the centrality of environmental protection’. While attention is often given to direct and individualised instances of ‘crime’, the serious consequences of air pollution are frequently neglected. The negative effects of pollution on health and well-being are often borne by people already experiencing a range of other disadvantages. In a global and national context, it is often the poor who are affected most. Ultimately, political and economic imperatives have historically helped to shape legal and regulatory regimes. Whether this is an inherent flaw in current systems or something that can be overcome in favour of dealing with more wide-ranging harms is an area that requires further discussion and debate.

ePortfolios and eGovernment : from technology to the entrepreneurial self

We analyse the electronic portfolio (ePortfolio) in higher education policy and practice. While evangelical accounts of the ePortfolio celebrate its power as a new eLearning technology, we argue that it allows the mutually-reinforcing couple of neoliberalism and the enterprising self to function in ways in which individual difference can be presented, cultured and grown, all the time within a standardised framework which relentlessly polices the limits of the acceptable and unacceptable. We point to the ePortfolio as a practice of (self-) government, arguing that grander policy coalesces out of a halting, experimental set of technological instruments for thinking about how life should be lived.

Self-presentation and underachievement among young adolescents identified as gifted

Academically gifted students are recognised as possessing considerable achievement potential. Yet many gifted students fail to perform at a level commensurate with their ability. This phenomenon is known as underachievement and may have far-reaching personal and social costs. Underachievement is particularly prevalent during early adolescence, between the ages of 10 to 14 years, when declining levels of academic achievement are often apparent. Grouping for instructional purposes is advocated as a means of reducing underachievement for gifted students by providing opportunities for like-minded and like-ability individuals to learn together. Despite this, some gifted students continue to underachieve. For some, underachievement appears to be a deliberate choice making them a population of learners at-risk. This multiple case study examines the relationship between self-presentation and underachievement as experienced by three gifted adolescents. It reveals how students perceived and explained the discrepancy between their ability and performance. Further, the study identifies those self-presentation strategies adopted in response to underachievement. Findings may assist parents and educators to provide greater support for gifted adolescents.

Becoming a 'Bastion Against Tyranny' : Australian legal education and the government of the self

Research into legal education suggests that many students enter law school with ideals about using the law to achieve social change, but graduate with some cynicism regarding these ideals. It is often argued that law schools provide a negative, competitive, and conservative environment for students, pushing many away from social justice ideals towards more self-interested, vocational concerns. This article uses Michel Foucault’s work on the government of the self to suggest another way of understanding this process. It examines a range of prescriptive texts that provide students with advice about how to study law and ‘survive’ law school. In doing so, it posits that this apparent loss of social ideals does not necessarily always signify that the student has become politically conservative or has had a negative educational experience. While these legal personae may appear outwardly conservative, and indeed still reflect particular gendered or raced perspectives, by examining the messages that these texts offer students, this article suggests that an apparent loss of social ideals can be the result of a productive shaping of the self. The legal persona they fashion can incorporate social justice ideals and necessitate specific ways of acting on those ideals. This analysis adds to the growing body of research that uses Foucault’s work to rethink common narratives of power and the shaping of the self in legal education, and provides legal educators with new ways of reflecting on the effects of legal education.

Facet-controlled Self-assembly of ZnO Nanocrystals by Non-Hydrolytic Aminolysis and their Photodegradation Activities

We report a method for controlling the exposed facets and hence the dimensionality and shape of ZnO nanocrystals using a non-hydrolytic aminolysis synthesis route. The effects of changes to reaction conditions on ZnO formation were investigated and possible self-assembly mechanisms proposed. The crystal facet growth and hence morphologies of the ZnO nanocrystals were controlled by varying reaction temperature and the reactant ratio. Four distinct ZnO nanocrystal types were produced (nanocones, nanobullets, nanorods and nanoplates). The relative photocatalytic activities of the exposed facets of these ZnO nanostructures were also examined, which showed the activities obviously depended on the reactivity of exposed crystal facets in the order: {1011}>>{0001}, {1010}.

Scandals, public inquiries and health professional regulation

Since 1980 there has been an increasing incidence of the use of public inquiries as a process through which scandals raising patient safety and health care quality concerns can be subject to highly public scrutiny. The use of public inquiries and their impact on the governance of health or social systems, especially around issues of patient or client safety, has been examined by a number of commentators (Butler and Drakeford 2003, Masso and Eager 2009, Stanley and Manthorpe 2004, Walshe and Higgins 2002) but public inquiries into scandals in the health system also raise a question about the impact of these inquiries on public perceptions about the adequacy of the various mechanisms for health professional regulation...

Regulation of proteasome structure and function

Proteasomes are cylindrical particles made up of a stack of four heptameric rings. In animal cells the outer rings are made up of 7 different types of alpha subunits and the inner rings are composed of 7 out of 10 possible different beta subunits. Regulatory complexes can bind to the ends of the cylinder.We have investigated aspects of the assembly, activity and subunit composition of core proteasome particles and 26S proteasomes, the localization of proteasome subpopulations, and the possible role of phosphorylation in determining proteasome localization, activities and association with regulatory components.