Placental contribution to the origins of sexual dimorphism in health and diseases: sex chromosomes and epigenetics

Sex differences occur in most non-communicable diseases, including metabolic diseases, hypertension, cardiovascular disease, psychiatric and neurological disorders and cancer. In many cases, the susceptibility to these diseases begins early in development. The observed differences between the sexes may result from genetic and hormonal differences and from differences in responses to and interactions with environmental factors, including infection, diet, drugs and stress. The placenta plays a key role in fetal growth and development and, as such, affects the fetal programming underlying subsequent adult health and accounts, in part for the developmental origin of health and disease (DOHaD). There is accumulating evidence to demonstrate the sex-specific relationships between diverse environmental influences on placental functions and the risk of disease later in life. As one of the few tissues easily collectable in humans, this organ may therefore be seen as an ideal system for studying how male and female placenta sense nutritional and other stresses, such as endocrine disruptors. Sex-specific regulatory pathways controlling sexually dimorphic characteristics in the various organs and the consequences of lifelong differences in sex hormone expression largely account for such responses. However, sex-specific changes in epigenetic marks are generated early after fertilization, thus before adrenal and gonad differentiation in the absence of sex hormones and in response to environmental conditions. Given the abundance of X-linked genes involved in placentogenesis, and the early unequal gene expression by the sex chromosomes between males and females, the role of X- and Y-chromosome-linked genes, and especially those involved in the peculiar placenta-specific epigenetics processes, giving rise to the unusual placenta epigenetic landscapes deserve particular attention. However, even with recent developments in this field, we still know little about the mechanisms underlying the early sex-specific epigenetic marks resulting in sex-biased gene expression of pathways and networks. As a critical messenger between the maternal environment and the fetus, the placenta may play a key role not only in buffering environmental effects transmitted by the mother but also in expressing and modulating effects due to preconceptional exposure of both the mother and the father to stressful conditions.

Exploring processes of indeterminate determinism in music composition, programming and improvisation

This portfolio consists of 15 original musical works. Taking the form of electronic and acousmatic music, multimedia, and scores, these chamber works serve as a result of experimentation and improvisation with individually built computer interfaces. The accompanying commentary provides discourse on the conceptual practice of these interfaces becoming a compositional entity that present a multi-interpretative opportunity to explore, engage, and personalise. Following this, the commentary examines the path of creative decisions and musical choices that formed both these interfaces and the resulting musical and visual works. This portfolio is accompanied by interfaces used, transcoded interfacing behavioural information, and documented improvisational findings.

Practical programming for static average-case analysis: the MOQA investigation

This work considers the static calculation of a program’s average-case time. The number of systems that currently tackle this research problem is quite small due to the difficulties inherent in average-case analysis. While each of these systems make a pertinent contribution, and are individually discussed in this work, only one of them forms the basis of this research. That particular system is known as MOQA. The MOQA system consists of the MOQA language and the MOQA static analysis tool. Its technique for statically determining average-case behaviour centres on maintaining strict control over both the data structure type and the labeling distribution. This research develops and evaluates the MOQA language implementation, and adds to the functions already available in this language. Furthermore, the theory that backs MOQA is generalised and the range of data structures for which the MOQA static analysis tool can determine average-case behaviour is increased. Also, some of the MOQA applications and extensions suggested in other works are logically examined here. For example, the accuracy of classifying the MOQA language as reversible is investigated, along with the feasibility of incorporating duplicate labels into the MOQA theory. Finally, the analyses that take place during the course of this research reveal some of the MOQA strengths and weaknesses. This thesis aims to be pragmatic when evaluating the current MOQA theory, the advancements set forth in the following work and the benefits of MOQA when compared to similar systems. Succinctly, this work’s significant expansion of the MOQA theory is accompanied by a realistic assessment of MOQA’s accomplishments and a serious deliberation of the opportunities available to MOQA in the future.