No description available.

No description available.

No description available.

No description available.

In Myanmar, Plasmodium falciparum malaria is important because of both the burden of disease and the emergence of parasites resistant to artemisinin-based therapies. In 2012, concomitant with the lifting of international economic sanctions, funding for malaria control and elimination in Myanmar rose significantly. The University of Oxford was asked to support priority setting by assessing the relative cost-effectiveness of insecticide- treated bed nets and community health workers, particularly with respect to planning in the Myanmar Artemisinin Resistance Containment region along the east of the country. In the context of rising artemisinin resistance and, later, the goal of regional malaria elimination by 2030, reduction in malaria transmission was an important consideration in prioritising between interventions. A cost-effectiveness analysis was undertaken using both a static decision tree model and a dynamic disease transmission model. Supporting work towards this analysis included a systematic review of dynamic-transmission economic-evaluations and the creation of a data repository to collate governmental and non-governmental malaria case records. In addition, initially unplanned work on economic evaluation methodology was completed; identifying challenges in the application of cost utility analysis to this decision problem and proposing a framework for budget-based geographic resource allocation as an adaptation of standard methods. The results of this work include a tripling of the number of malaria diagnostic reports available between 2012 and 2014 (71% increase in Plasmodium falciparum cases) with this data showing a decrease in Plasmodium falciparum cases over time, alongside rising testing rates. Cost utility analysis found that, in general, malaria community health workers are more costly yet more effective than insecticide treated bed nets, though in both cases cost effectiveness is very much context dependent. Geographic allocation analyses using both static and dynamic models illustrate the potential for economic evaluation to provide both more detailed and more practical policy recommendations. Parameter uncertainty was explored in both cases. Some township recommendations were robust to both parameter uncertainty and model variation (structural uncertainty). Viewed through the lens of the Reference Case for Economic Evaluation in Low and Middle Income Countries (published during the course of this DPhil), budget-based geographic resource allocation largely adheres to the healthcare economic evaluation principles and offers improvements to dealing with heterogeneity and resource constraints. This DPhil recommends that Myanmar malaria policy is tailored to reflect geographic variation in intervention cost-effectiveness, rather than focusing on universal coverage, and illustrates a framework for economic evaluation to support budget-based geographic allocation.

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

Two experiments explore the application of plasmonic nanoparticles to cellular pathology. The first devised a platform by which gold-silver nanoparticles act as differentiable labels for cell surface receptors under dark field imaging. By conjugating particles of various constitutions with receptor-targeting antibodies, particles scatter characteristically according to their plasmon peak. The second experiment programmed receptor placement via the patterning of two substrates and used the binding of SERS nanoparticles to explore the quantification of such targets at high-density. On one substrate, anchor pairs established receptors at specified distances in order to define the relationship between scattering intensity and the distance between SERS particles. On the second, anchor regions are filled with increasing densities of receptors and the particle-saturated substrates are probed to relate scattering intensity to particle density. This should discover the density-threshold between linear and non-linear scattering and inform the quantification of particles in the exponential density regime.

Two experiments explore the application of plasmonic nanoparticles to cellular pathology. The first devised a platform by which gold-silver nanoparticles act as differentiable labels for cell surface receptors under dark field imaging. By conjugating particles of various constitutions with receptor-targeting antibodies, particles scatter characteristically according to their plasmon peak. The second experiment programmed receptor placement via the patterning of two substrates and used the binding of SERS nanoparticles to explore the quantification of such targets at high-density. On one substrate, anchor pairs established receptors at specified distances in order to define the relationship between scattering intensity and the distance between SERS particles. On the second, anchor regions are filled with increasing densities of receptors and the particle-saturated substrates are probed to relate scattering intensity to particle density. This should discover the density-threshold between linear and non-linear scattering and inform the quantification of particles in the exponential density regime.

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe3O4 molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review. Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy tissue, exhibit properties similar to those of an isothermal barrier. As a result, target cells experience limited gross heating, which is localized to the area directly surrounding the active magnetic nanoparticle within the cytoplasm. The effects of isothermal barriers and HSP up regulation on particle-based hypothermia are profound and prevent therapeutic temperatures from being achieved in single cell heating limiting the applications for Fe3O4 magnetic nanoparticle hyperthermia applications. It has been shown that reaching a certain magnetic nanoparticle density within the cell can result in a larger heating capacity, though this effect is also dependent on the particle dispersion pattern within cytoplasm. It has yet to be concluded whether ferromagnetic particles or super-paramagnetic particles are superior or more practical for hyperthermic treatments as they each have distinct benefits, and further study is needed. Finally, the popular targeting mechanism associated with magnetic nanoparticle research, monoclonal antibodies, require that they have an organic coating (such as starch) as a means of both providing an organic binding point and as camouflage for avoiding host filtration pathways. Forgoing this organic coating could lead to increased particle density within the cell and the adoption of a more specific targeting mechanism such as virus like particles (VLPs) altered to target HSP’s could lead to an increase in yield. Furthermore the up regulation of HSPs in response to therapeutic temperature is problematic for the therapies practically.

This diploma thesis provides an overview and basic principles of satellite communication systems. Further is description of specific aerial satellite communication system ARINC 791. The practical part includes proposals of the system for automated verification targeting functionality of an air satellite antenna, which has been carried out in Honeywell laboratory conditions. The selected implementation is realized and used for automated verification targeting functionality of an air satellite antenna. The results are graphically evaluated.