The client/server paradigm is a common means of implementing an application over a computer network. Servers provide services, such as access to files, directories, or web pages, and clients make use of those services. The communication between the clients and servers takes the form of a network protocol. These network protocols are often rigid and inflexible due to standardization, and because they are often implemented in the operating system kernels of the clients and servers. It is difficult to add new features to existing services without having complete control of all the clients and servers in question. Virtualization is a technique that can be used to alter the properties of a network service without requiring any modifications to the clients or servers. Virtualization is typically performed on an intermediate computer that is interposed between the clients and servers, such as a programmable router. This dissertation motivates the need for virtualization and presents several different examples of successful virtualizations. These virtualizations include translation, aggregation, replication and fortification. Virtualization is demonstrated both on commodity hardware, which has the advantage of low cost, and on a specialized network processor, which offers the advantage of high performance.

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is important in post-injury scar formation but its role in scar-free regeneration remains relatively unexplored. This study investigates vascular regeneration during tail regeneration in the leopard gecko (Eublepharis macularius). It is hypothesized that blood vessel regeneration follows a conserved sequence of events similar to physiological angiogenesis. To test this hypothesis the onset and pattern of expression of common vascular and angiogenic proteins (von Willebrand factor, α-smooth muscle actin, vascular endothelial growth factor, thrombospondin-1 and cluster differentiation 36) was investigated. The effect of the anti-angiogenic peptide ABT-510 on tail regeneration was also explored by documenting changes in vascular morphology and histology of regenerate tails. Results show that the proteins of interest are expressed in a conserved sequence consistent with physiological angiogenesis. ABT-510 did not consistently prevent tail regeneration, but did have some small-scale effects. These results provide the basis for further investigations into the importance of angiogenesis during multi-tissue regeneration.

Thermophysiological traits of two isolated Hoplodactylus maculatus populations were investigated to test adpatations to climate. Geckos were collected from Craigieburn (high altitude, generally cooler site) and Banks Peninsula. If climatic conditions at respective sites influenced physiology, I expected geckos from Craigieburn to exhibit cold-adapted physiological traits, whilst Banks Peninsula geckos would exhibit traits more characteristic of a warmclimate species. To this end I investigated four thermophysiological parameters: metabolism (SMR), preferred body temperature (PBT), locomotory performance and critical thermal minimum (CTMin). I hypothesized that if climate had an effect on SMR, Craigieburn geckos would exhibit higher levels of SMR which typically characterise other coolclimate reptiles. Craigieburn geckos displayed an average relative elevation of SMR over Banks Peninsula geckos of 26%. Furthermore, Craigieburn geckos appeared to be 'geared' towards lower body temperatures and exhibited a greater acclimatory and acclimatizatory ability of SMR. The PBT of Craigieburn geckos was consistently elevated above Banks Peninsula geckos. This finding was somewhat paradoxical in light of previous studies of this parameter. A closer examination of the ecology of the two populations is required to clarify the adaptive significance of a higher PBT in geckos from a cooler climate. With respect to locomotory performance, I hypothesized that if thermal extremes influenced activity, Craigieburn geckos would exhibit activity patterns which help ameliorate the adverse effects of cold temperature. Craigieburn geckos did in fact have greater independence of activity to temperature than Banks Peninsula geckos, especially over lower body temperatures. The final parameter investigated, that of the critical thermal minimum, failed to distinguish the populations decisively. However there was some evidence of a greater acclimatizatory and acclimatory range in Craigieburn geckos, providing somewhat limited support for a population difference. Investigations into all four parameters lead me to conclude that populations of Hoplodactylus maculatus from Craigieburn and Banks Peninsula are physiologically distinct and warrant a revision of nomenclature.

Thermophysiological traits of two isolated Hoplodactylus maculatus populations were investigated to test adpatations to climate. Geckos were collected from Craigieburn (high altitude, generally cooler site) and Banks Peninsula. If climatic conditions at respective sites influenced physiology, I expected geckos from Craigieburn to exhibit cold-adapted physiological traits, whilst Banks Peninsula geckos would exhibit traits more characteristic of a warmclimate species. To this end I investigated four thermophysiological parameters: metabolism (SMR), preferred body temperature (PBT), locomotory performance and critical thermal minimum (CTMin). I hypothesized that if climate had an effect on SMR, Craigieburn geckos would exhibit higher levels of SMR which typically characterise other coolclimate reptiles. Craigieburn geckos displayed an average relative elevation of SMR over Banks Peninsula geckos of 26%. Furthermore, Craigieburn geckos appeared to be 'geared' towards lower body temperatures and exhibited a greater acclimatory and acclimatizatory ability of SMR. The PBT of Craigieburn geckos was consistently elevated above Banks Peninsula geckos. This finding was somewhat paradoxical in light of previous studies of this parameter. A closer examination of the ecology of the two populations is required to clarify the adaptive significance of a higher PBT in geckos from a cooler climate. With respect to locomotory performance, I hypothesized that if thermal extremes influenced activity, Craigieburn geckos would exhibit activity patterns which help ameliorate the adverse effects of cold temperature. Craigieburn geckos did in fact have greater independence of activity to temperature than Banks Peninsula geckos, especially over lower body temperatures. The final parameter investigated, that of the critical thermal minimum, failed to distinguish the populations decisively. However there was some evidence of a greater acclimatizatory and acclimatory range in Craigieburn geckos, providing somewhat limited support for a population difference. Investigations into all four parameters lead me to conclude that populations of Hoplodactylus maculatus from Craigieburn and Banks Peninsula are physiologically distinct and warrant a revision of nomenclature.

Acute myeloid leukemia (AML) is a disease characterized by overproduction of abnormally differentiated, hyper-proliferative myeloid cells known as blasts in bone-marrow and blood. Our laboratory has previously demonstrated that loss of epigenetic repression by the polycomb repressive complex 2 (PRC2), which is mediated by complex member metal response element binding transcription factor 2 (MTF2), drives chemo-resistance resulting in refractory AML. In this study, to identify MTF2-specific synthetic lethal interactions, a genome-scale CRISPR Knock-out (GeCKO) synthetic lethal screen was performed in matched MTF2-deficient and rescued THP-1 cells both in the absence and presence of the induction chemotherapeutic cytarabine. Following careful analysis of screening data using specialized software, 104 highly significant MTF2-specific synthetic lethal interactions as well as 15 cytarabine-specific synthetic lethal interactions were identified. Reduced stringency upon analysis helped to identify an additional seven MTF2-specific synthetic lethal interactions that could be targeted with commercially available small-molecule inhibitors. Among eight small molecule inhibitors, two DNA Polymerase A/Ribonucleotide Reductase Catalytic Subunit M1 (POLA/RRM1) dual inhibitors (clofarabine and fludarabine) were shown to induce toxicity with specificity for MTF2-deficient THP-1 cells at low concentrations only in the absence of cytarabine. In the future, further testing of the therapeutic potential of clofarabine and fludarabine in treating MTF2-deficient AML will be conducted in patient derived bone-marrow aspirates which better represent the true clonal and hierarchical nature of this life-threatening malignancy. Furthermore, lentiviral delivery of short-hairpin RNAs (shRNAs) targeting highly significant, non-enzymatic MTF2 and cytarabine-specific synthetic lethal interactions will be performed in both THP-1 cells as well as in patient derived bone-marrow aspirates. Eventually, in vitro validated targets will be validated under in vivo conditions using a patient derived xenograft (PDX) preclinical animal model of AML using immunocompromised NOD scid gamma (NSG) mice.

The common gecko, Hoplodactylus pacificus (Gray, in McCann (1955) ), is widely distributed throughout New Zealand. As yet no specific ecological study of this lizard has been published, though Sharell (1966) mentions habitat preferences and hibernation behaviour, and Whitaker (1968) has published some data for H. pacificus on Poor Knights Islands (mentioned in this report) and describes their observed foraging behaviour. In this study, carried out from late March through to May 1970, I have recorded information on snout-vent lengths, weights, individual movements, and habitat preference, and have also estimated the population density. This particular lizard does not seem to be active during the Autumn months and no observations of food preferences and foraging behaviour were able to be made.

Pressure sensitive adhesive surfaces are often inspired by nature. Miming the toe-surface of gecko, engineered surfaces made of thousands of micro-pillars show promising adhesive properties. This surfaces, covered with cylindrical pillars arranged into a pattern have adhesive properties greatly dependent on the geometrical characteristics. In this thesis, have been studied successively two models of micro-patterned surfaces, one two-dimensional, the other in three-dimensional using a FEM tool. Varying geometry parameters, has been determined optimal geometries to improve adhesive strength on these biomimetic, micropatterned surfaces. This study concludes to the non-adaptability of one-level scale micropatterned surface to large area of adhesion, to the strong advantage from the point of adhesion per contact area for high aspect ratio at each level of the geometry and study the opportunity of hierarchical structures. Some further suggestions of improvements to adhesion properties are discussed in the final chapter.

The common gecko, Hoplodactylus pacificus (Gray, in McCann (1955) ), is widely distributed throughout New Zealand. As yet no specific ecological study of this lizard has been published, though Sharell (1966) mentions habitat preferences and hibernation behaviour, and Whitaker (1968) has published some data for H. pacificus on Poor Knights Islands (mentioned in this report) and describes their observed foraging behaviour. In this study, carried out from late March through to May 1970, I have recorded information on snout-vent lengths, weights, individual movements, and habitat preference, and have also estimated the population density. This particular lizard does not seem to be active during the Autumn months and no observations of food preferences and foraging behaviour were able to be made.

Geckos can freely climb on walls and ceilings against their body weight at speed of over 1ms-1. Switching between attachment and detachment seem simple and easy for geckos, without considering the surface to be dry or wet, smooth or rough, dirty or clean. In addition, gecko can shed dirt particles during use, keeping the adhesive pads clean. Mimicking this biological system can lead to a new class of dry adhesives for various applications. However, gecko’s unique dry self-cleaning mechanism remains unknown, which impedes the development of self-cleaning dry adhesives. In this dissertation we provide new evidence and self-cleaning mechanism to explain how gecko shed particles and keep its sticky feet clean. First we studied the dynamic enhancement observed between micro-sized particles and substrate under dry and wet conditions. The adhesion force of soft (polystyrene) and hard (SiO2 and Al2O3) micro-particles on soft (polystyrene) and hard (fused silica and sapphire) substrates was measured using an atomic force microscope (AFM) with retraction (z-piezo) speed ranging over 4 orders of magnitude. The adhesion is strongly enhanced by the dynamic effect. When the retraction speeds varies from 0.02 µm/s to 156 µm/s, the adhesion force increases by 10% ~ 50% in dry nitrogen while it increases by 15%~70% in humid air. A dynamic model was developed to explain this dynamic effect, which agrees well with the experimental results. Similar dynamic enhancement was also observed in aqueous solution. The influence of dynamic factors related to the adhesion enhancement, such as particle inertia, viscoelastic deformations and crack propagation, was discussed to understand the dynamic enhancement mechanisms. Although particles show dynamic enhancement, Gecko fabrillar hair shows a totally different trend. The pull off forces of a single gecko seta and spatula was tested by AFM under different pull-off velocities. The result shows that both the spatula and the seta have a rate independent adhesion response in normal retraction, which is quite different from micro-particles. Further research indicated the shape of the contact area was a key factor to the dynamic effect. In order to verify this hypothesis, artificial gecko spatula made of glass fibers was nanofabricated by a focus ion beam (FIB) and tested by AFM. These manmade spatulae also show a rate independent adhesion response. The dynamic adhesion of a single gecko seta and spatula were simulated with finite element analysis and the results also confirm the rate independent phenomena.. In conclusion, self-cleaning is induced by dynamic effect during gecko locomotion. The relative dynamic adhesion change between particles and seta makes it possible for gecko to shed the dirt particles while walking.Finally, the fatigue property of gecko seta was examined with the atomic force microscope under cyclic attachment/detachment process, mimicking gecko running. The adhesion force versus cycles has been tested and evaluated. Fatigue mechanism of gecko seta was also analyzed based on the experimental findings.

No description available.