The aims of this thesis are two-fold. The first is to develop computer graphics that allow quantitative manipulation of complex visual stimuli. The second is to show that such techniques have utility in the domain of perceptual psychology. There are three main sections to this thesis. The first section creates methods for performing transformations of facial appearance along particular perceptual dimensions. This work begins with 2-D image manipulations and then extends the general principles to 3-D. Effectiveness of the techniques is illustrated with plates showing transformation in age, gender and identity. The second section uses Genetic Algorithms to control the appearance of 3-D computer graphics objects and investigates methods of evolving objects that embody various consumer concepts. Computer graphic models of shampoo bottles are successfully evolved to satisfy a selection of aesthetic and perceptual characteristics. The final section returns to facial stimuli and extends the Genetic Algorithm approach to investigate aesthetic preference for 3-D facial surfaces. The study shows that individual human subjects can evolve facial surfaces based upon their own attractiveness preferences. The faces evolved are non-average and there is consistency between subjects about preferred characteristics. The three parts of this thesis have different theoretical backgrounds and literature relevant to each topic is therefore reviewed at the start of each section.

The cellular integrity of the blood is maintained by the cellular output of the haematopoietic stem cell population which produces the specialized precursors and differentiated cells which constitute the blood. The investigation of haematopoietic stem cell behaviour and regulation has been hampered by both the difficulty in their identification and the development of relevant assay systems. The purpose of this investigation was to study the behaviour and regulation of the haematopoietic stem cell population in normal and leukaemic haematopoiesis using an in vitro assay of a primitive haematopoietic precursor. The use of a combination of haematopoietic colony-stimulating factors [interleukin 3 (IL3)/multi-CSF and macrophage colony-stimulating factor (M-CSF/CSF-1)] in semi-solid agar culture of murine haematopoietic tissue, stimulated the proliferation of a haematopoietic colony-forming cell, defined as the "HPP-CFCIL3+CSF-1" population, which was characterized by a high proliferative potential, a multipotency and behavioural and regulatory properties consistent with its being a primitive haematopoietic precursor and possibly a component of the haematopoietic stem cell population. The proportion of the in vitro HPP-CFCIL3+csf-1 population in S-phase in normal murine marrow, was determined to be relatively low at approximately 10%, increasing to approximately 40% in sublethally X-irradiated, regenerating murine marrow and the respective presence of the haematopoietic stem cell proliferation inhibitor and stimulator was demonstrable by the induction of appropriate kinetic changes in the in vitro HPP-CFCIL3+CSF-1 population. In leukaemic haematopoiesis, leukaemic proliferation often occurs at the expense of apparently suppressed normal haematopoiesis. In vitro HPP-CFCIL3+CSF-1 assay of the haematopoietic stem cell proliferation regulators in a number of murine, myeloid leukaemic cell lines, failed to demonstrate either increased levels of the haematopoietic stem cell proliferation inhibitor, or evidence of a direct-acting, leukaemia- associated proliferation inhibitor, however, evidence of a leukaemia- associated impairment of inhibitor and stimulator production was observed and this may be a possible mechanism by which the leukaemic population develops a proliferative advantage over normal haematopoietic tissue. The identification of a possible mechanism of leukaemic progression and suppression of normal haematopoiesis may subsequently allow the development of potentially more effective disease treatment and management regimes. The endogenous haemoregulatory tetrapeptide: Acetyl-N-Ser- Asp-Lys-Pro [AcSDKP, Mr=487 amu] is reported to prevent the G0-G1 transition of haematopoietic stem cells into S-phase. The mechanism of action of AcSDKP and a number of related peptides, was investigated in relation to the stem cell proliferation stimulator and inhibitor. AcSDKP demonstrated no direct haemoregulatory role against the in vitro HPP-CFCIL3+CSF-1 population, which is consistent with reports that AcSDKP is not active against cells already in late G1, or S-phase, rather it appeared to act indirectly by impairing the capacity of the haematopoietic stem cell proliferation stimulator to increase the proportion of the in vitro HPP-CFCIL3+CSF-1 population in S-phase. An apparent impairment of stimulator action may explain the reported AcSDKP-associated 'block' of haematopoietic stem cell recruitment. A putative endogenous AcSDKP precursor and synthetic and degradative enzyme systems have been reported and the possible physiopathological role of AcSDKP in a number of myeloproliferative disorders has been implicated. The potential application of AcSDKP as a 'haemoprotective' agent administered prior to the use of S-phase- specific chemotherapy may be of clinical significance. The in vitro HPP-CFCIL3+CSF-1 assay of a primitive haematopoietic precursor cell population, which may be a component of the haematopoietic stem cell population, should play a significant role in the investigation of haematopoietic stem cell behaviour and regulation in both normal and aberrant haematopoiesis. With the characterization of the mechanism(s) of action of the haematopoietic stem cell proliferation inhibitor and stimulator and the haemoregulatory tetrapeptide AcSDKP, the manipulation of the haematopoietic system to clinical advantage can be envisaged, while the identification of the aberrant regulatory mechanism(s) in haematopoietic dysfunction may allow, the development of more effective disease treatment and management regimes.

Evidence of the last glaciation of the Shetland Islands, UK, is re-examined and combined with new data on terrestrial glacigenic deposits and recent offshore data from the continental shelf to produce a dynamic, integrated model of the history of the whole ice cap. It is shown that evidence which has previously been attributed to last glacial, or earlier, Scandinavian ice incursion, might be explained by the eastwards migration of local ice sheds. At its maximum, the ice sheet reached the continental shelf edge to the west of the islands, at least 75 km east, at least 50 km north and might be seen as a peninsular extension of the Scottish ice sheet to the south. The changing patterns of ice flow during deglaciation are reconstructed, implying an early phase of deglaciation at the west and northwest margins (possibly accounting for the suggested eastern migration of the ice shed), followed by retreat at more northern, then eastern, then southern margins. It is suggested that the above pattern reflects tidewater calving controlled by bathymmetric variation around the ice sheet. During a later phase of deglaciation, the margin of the ice cap may have grounded at around the current -100m bathymmetric contour and from there retreated terrestrially. The importance of topographic control on patterns of deglaciation as ice retreated towards the island group is clearly established. Some minor moraines in parts of Shetland are due to active ice margins but their age is unknown. Radiocarbon dates reported here show that the last glaciation was Late Weichselian and that the maximum northern extent was at least 50 km north of the islands. The concepts of an eastwards migrating ice shed and an early, extensive ice cap retreating to a grounding point, could have parallels elsewhere in Scotland during the last glaciation. The methodology applied in this study of Shetland - integrating onshore and offshore data, and developing a dynamic picture of the whole ice cap - needs to be applied to the last Scottish ice sheet also.

The development of a stereotyped pattern of neural connectivity depends upon the behavior of growth cones, motile structures at the tips of axons that propel axon growth and steer the axon to its targets. When growth cones reach their appropriate target cells, they halt and ultimately remodel into stationary presynaptic boutons. The influence of extracellular cues in directing growth cones to their targets is well studied, but cell-intrinsic factors are also increasingly appreciated for their role in driving much of growth cone behavior. Dual leucine zipper kinases (DLKs) promote growth cone motility and must be kept in check to ensure normal development. PHR (Pam/Highwire/RPM-1) ubiquitin ligases therefore target DLK for proteosomal degradation unless axon injury occurs. Overall DLK levels decrease during development, but how DLK levels are regulated within a developing growth cone has not been examined. We analyzed the expression of the fly DLK Wallenda (Wnd) in R7 photoreceptor growth cones as they halt at their targets and as they remodel into presynaptic boutons. We found that Wnd protein levels are repressed by the PHR protein Highwire (Hiw) during R7 growth cone halting, as has been observed in other systems. However, during remodeling, Wnd levels are further repressed by a temporally-expressed transcription factor, Tramtrack69 (Ttk69). Previously unobserved negative feedback from JNK also contributes to Wnd repression. We conclude that maturing neurons progressively deploy additional mechanisms to keep DLK off and thereby protect their connectivity. We use live imaging to directly probe the effects of Wnd and Ttk69 on remodeling R7 growth cones and conclude that Ttk69 coordinates multiple regulators of this process. Preliminary results indicate that excess Wnd signaling requires the transcription factor Fos to disrupt growth cone remodeling in R7s. This opens up new strategies to identify how Wnd exerts its motility-promoting effects on growth cone cytoskeletons. Additional findings point to a later requirement for Wnd in normal R7 synapse development, suggesting that Wnd expression is not fully silenced in R7s. Further investigation into these findings would greatly advance our understanding of how the neuronal cytoskeleton is regulated as neurons undergo profound morphological and functional changes while developing. This dissertation includes both unpublished and published co-authored material. This dissertation also includes supplemental movie files, which can be found online and are described in Appendix B.

This thesis is divided into two parts; Part I consisting of the theory and Part II the experimental work. Part I is divided into three sections; in Section 1 a summary is given of collision processes and how they have been used to explain various experimental results; this is followed in Section 2 by the author's interpretation of some previous experimental observations; a summary of the wave mechanical theory of collisions is given in Section 3. Part II consists of four sections; In Section 1an outline is given of the various ways of exciting spectra and this is followed by a description of the apparatus used by the author in Section 2; the results of the experiments with hydrogen and oxygen are given in Section 3, and the theoretical interpretation of these; the last Section deals with the experiments carried out with hydrogen and helium, and the facts which may be inferred from these experimental results.

In this thesis, applications of a numerical continuation method to two- and three-dimensional bifurcation problems are presented. The 2D problems are motivated by solar applications. In particular, it is shown that the bifurcation properties of a previously studied model for magnetic arcades depend strongly on the pressure function used in the model. The bifurcation properties of a straight flux model for coronal loops are investigated and compared with the results of linear ideal MHD stability analysis. It is shown that for line-tied boundary conditions, the method for the calculation of the equilibrium sequence determines whether the first or the second bifurcation point coincides with the linear stability threshold. Also, in this thesis, the 3D version of the continuation code is applied for the first time. The problems treated with the 3D code are therefore chosen with the intention to demonstrate the general capabilities of the code and to see where its limitations are. Whereas the code performs as expected for relatively simple albeit nonlinear bifurcation problems, a clear need for further development is shown by more involved problems.

No description available.

Neurons in the central nervous system are typically not replaced and must therefore maintain their choice of fate and their synaptic connections throughout the life of an organism. I have used Drosophila genetics to analyze genes that prevent neurons from switching fates and allow them to form synapses onto target neurons. The Drosophila fly eye is composed of approximately 750 ommatidia, each comprising eight photoreceptor neurons (R1-R8) surrounded by non-neuronal accessory cells. These photoreceptor neurons undergo a well-defined developmental specification process and form synapses at defined locations in the brain. I have taken advantage of this system to investigate two questions: 1) how do neurons maintain their fate after specification? and 2) how do neurons form stable synapses? For the first half of my dissertation, I have focused my research on a gene, Sce, that I have shown is essential to prevent R7 neurons from undergoing a late switch in cell fate. Sce is an integral component of the Polycomb Group (PcG) complex that is essential for maintaining repression of multiple genes throughout the genome. I found that PcGs are required to prevent R7s from derepression of the R8-specific transcription factor Senseless. For the second half of my dissertation, I focused on the gene syd-1 that was identified to be required for proper presynaptic formation of R7 neurons. Previous studies in Caenorhabditis elegans suggested that Syd-1 acts upstream of Liprin-α and that Liprin-α promotes presynaptic development by binding the kinesin Kif1a to promote axon transport. I used live image analysis to show that, unlike Liprin-α, Syd-1 is not necessary to promote axon transport. Instead, we show that in R7s, Syd-1 acts upstream of Trio, and our results suggest that Syd-1's function is to promote Trio activity. This dissertation includes both my previously published and co-authored materials. / 10000-01-01

Over the past twenty years molecules capable of templating their own synthesis, so called self–replicating molecules have gained prominence in the literature. We show herein that mixing the reagents for replicating molecules can produce a network of self–replicators which coexist and that the networks can be instructed by the addition of preformed template upon initiation of the reaction. Whilst self–replicating molecules offer the simplest form of replication, nature has evolved to utilise not minimal self–replication but reciprocal replication where one strand templates the formation of not an identical copy of itself but a reciprocal strand. Efforts thus far at producing a synthetic reciprocal replicating system are discussed and an alternative strategy to address the problems encountered is proposed and successfully implemented. The kinetic behaviour of a self–replicating reaction bears two distinctive time periods. Upon initiation, the reaction proceeds slowly as no template exists to catalyse the reaction. Upon production of the template, the reaction proceeds more rapidly via template direction. During this slow reaction period, the system is prone to mistakes as the reaction is slow and unselective. The creation of an [A•B] binary complex through non–covalent recognition of reagents allows for the reaction to proceed at an accelerated rate upon initiation however products of such a reaction are usually catalytically inert and do not promote further template directed reaction. A strategy to combine the desired behaviour of an [A•B] binary complex with the further template directed autocatalytic self–replicating reaction is described and implemented. Supramolecular polymers consist of repeating monomers which are held together by non–covalent interactions. The strong association of a self–replicating template dimer is comparable to that of supramolecular polymers reported thus far in the literature which are produced by cumbersome standard linear synthetic procedures. Herein the application of self–replication to the field of supramolecular polymer synthesis is discussed. As the autocatalytic reaction to produce the template monomers occurs under the same conditions as required to allow polymerisation to proceed, the polymer is able to spontaneously form in situ by self–replicating supramolecular polymerisation.

This thesis is a critique of the prominent strand of contemporary liberal political theory which maintains that liberal political authority must, in some sense, rest on the free consent of those subjected to it, and that such a consensus is achieved if a polity’s basic structure can be publicly justified to its citizenry, or to a relevant subset of it. Call that the liberal legitimacy view. I argue that the liberal legitimacy view cannot provide viable normative foundations for political authority, for the hypothetical consensus it envisages cannot be achieved and sustained without either arbitrarily excluding conspicuous sectors of the citizenry or commanding a consent that is less than free. That is because the liberal legitimacy view’s structure is one that requires a form of consent that carries free-standing normative force (i.e. normative force generated by voluntariness), yet the particular form of hypothetical consent through public justification envisaged by the view does not possess such force, because of its built-in bias in favour of liberalism. I also argue that the liberal legitimacy view is the most recent instantiation of one of two main strands of liberal theory, namely the nowadays dominant contract-based liberalism, which seeks to ground liberal political authority in a hypothetical agreement between the citizens. My case against the liberal legitimacy view, then, contributes to the revitalisation of the other main approach to the normative foundations of liberalism, namely the substantivist one, which legitimates liberal political authority through an appeal to the substantive values and virtues safeguarded and promoted by liberal polities.