432 research outputs found
The choice of sire breed and slaughter weight for lamb production
International audienc
The sodium-chlorinity ratio of ocean waters from the Northwest Pacific
Ocean water is a complex solution of many ions. The concentration of this solution varies considerably from place to place but it has been repeatedly shown that the relative concentration of the ions to each other is remarkably constant…
A novel optogenetics-based therapy for obstructive sleep apnoea
Obstructive sleep apnoea (OSA) is characterised by repeat upper airway narrowing and/or collapse during sleep. Many patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel, optogenetics-based therapy, that enables light-stimulation induced upper airway dilator muscle contractions to maintain airway patency.
The primary aims of this thesis were to determine feasibility in a rodent model of OSA, and identify effective optogenetic constructs for activating upper airway muscles. Chapters 2 and 3 outline the development of a novel construct for the expression of light-sensitive proteins (opsins) in upper airway muscles, comparing two promotors and two recombinant adeno-associated virus capsids (rAAV) for optogenetic gene transfer. Results show that a muscle-specific promotor (tMCK) was superior to a non-specific promotor (CAG). With tMCK, opsin expression in the tongue was 470% greater (p=0.013, RM-ANOVA), brainstem expression was abolished, and light stimulation facilitated a 66% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA (p<0.001, linear mixed model) (Chapter 2). Moreover, a novel, highly myotropic rAAV serotype, AAVMYO, was superior to a wild-type serotype, AAV9. The AAVMYO serotype driven by tMCK facilitated a further increase in muscle activity with light stimulation to 194% of that recorded during unstimulated breaths (p<0.001, linear mixed model) (Chapter 3). Finally, ultrasound imaging confirmed that the optimised construct was able to generate effective light-induced muscle contractions and airway dilation (Chapter 4).
A secondary aim was to advance preclinical trials for the proposed therapy. To this end, a surgical protocol for chronic implantation of light delivery hardware and recording electrodes in rodents was developed (Chapter 5). The final protocol will allow us to determine the effects of acute and chronic light stimulation on opsin-expressing upper airway muscles during natural sleep.
In summary, Chapters 2 to 4 provide proof-of-concept for a non-invasive optogenetics-based OSA therapy. The combination of a muscle-specific promotor and a muscle-specific viral vector presents a novel and highly effective method of inducing light sensitivity into skeletal muscle and facilitating light-evoked airway dilation. Finally, Chapter 5 commences the development of a surgical protocol that will aid ongoing preclinical trials
Barbarian nations in a civilizing empire: naturalizing the nation within the British Empire 1770-1870
This thesis examines the emergence of the nation in the British Empire in the process of thinking about empire, economy and biology during the late-Enlightenment and the nineteenth century. A key aspect of this, Knapman argues, was concern over the dialectic of civilization and order as it related to the barbarian and the savage. The notion of the barbarian grounded the European nations in time and therefore constructing a sense of origin and particularism. Equally the savage and the barbarian placed non-European cultures in time. The thesis draws on a range of writers from eighteenth and nineteenth centuries such as Adam Smith, Edward Gibbon, David Hume, Thomas Malthus, John Stuart Mill, Charles Darwin, James Cowles Prichard, Robert Knox and many other lesser-known figures. This is related to an examination of the nation in British representations of Southeast Asia, including colonial officials such as Stamford Raffles, John Crawfurd, and James Brooke who produced encyclopaedic accounts of their experiences in Asia. The thesis argues that while the complex grammar of the British Empire divided the world into spheres of civilisation and barbarism, it retained a special place for barbarians within the core and thus allowed for the naturalisation of nations within the context of an empire of civilizing others
Zeta Functions in Brane World Cosmology
We present a calculation of the zeta function and of the functional
determinant for a Laplace-type differential operator, corresponding to a scalar
field in a higher dimensional de Sitter brane background, which consists of a
higher dimensional anti-de Sitter bulk spacetime bounded by a de Sitter
section, representing a brane. Contrary to the existing examples, which all
make use of conformal transformations, we evaluate the zeta function working
directly with the higher dimensional wave operator. We also consider a generic
mass term and coupling to curvature, generalizing previous results. The
massless, conformally coupled case is obtained as a limit of the general result
and compared with known calculations. In the limit of large anti-de Sitter
radius, the zeta determinant for the ball is recovered in perfect agreement
with known expressions, providing an interesting check of our result and an
alternative way of obtaining the ball determinant.Comment: 14 pages, 1 figur
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