Incorporation of nitrogen into ¢»-¢½ materials such as GaAsN and InGaAsN, have recently drawn much attention, due to the unique properties as well as potential device applications of such materials. The purpose of this thesis is to probe microscopic compositions and electronic structures in a series of N-based semiconductor compounds. For the material and electronic structure characterizations, X-ray photoelectron spectroscopy (XPS) with synchrotron radiation beam was adopted to analyze the sample quality under different growth and post-growth thermal annealing. Through detection of samples of InGaAsN in comparison with a series of samples of GaAsN, InAsN, InN, GaN, InGaAs and GaAs, the experimental result and analysis. Now X-ray photoelectron spectroscopy investigation on ¢»-¢½alloys containing a few percentage of nitrogen demonstrated the success of nitrogen incorporation. X-ray photoelectron spectroscopy investigation on InGaAsN films and curve fitting analysis, it can provide evidence of the existence of two principle N configurations, indicating the formation of N-In, N-Ga bonds. Through an estimation of the sample surface composition was made on the basis of the peak area: N-In/N-Ga larger than 3, it can provid direct evidence of the presence of preferential bonding of N to In. The incorporation of atomic nitrogen was added during the annealing. Right through X-ray photoelectron spectroscopy in annealed InGaAsN film can N-In and N-Ga bonds be observed to be increase, but N-In/N-Ga larger than 2, The bonds of atomic nitrogen is still N-Ga bonds.

Malaria is a disease that causes more than 1 million deaths per year world wide and more than 400 million clinical cases. Due to the acquired resistance of Plasmodium falciparum to the drugs used to control the infection, searching for new anti-malaria drugs is necessary in modern days. Recent studies have shown that the parasite synthesizes fatty acids using a fatty acid synthase type II (FAS-II) instead of a type-I fatty acid synthase (FAS-I) that is present in other eukaryotes. Plasmodium falciparum enoyl reductase (PfENR) is responsible for the last step of fatty acid biosynthesis in the parasite. This enzyme is located within the apicoplast, a plastid-like organelle that is responsible for several important metabolic pathways, including fatty acid biosynthesis. It is known that triclosan is an inhibitor of ENR in bacteria and we and others have shown that it is also effective against ENR in apicomplexan organisms such as P. falciparum. However triclosan cannot be used to treat malaria in humans because it has metabolic liability (glucoronidation) which limits its inhibitory potency. We have used X-ray crystallography and a Structural Activity Relationship (SAR) strategy to design and cocrystallize a tertiary complex of PfENR with NAD+ and triclosan derivatives to improve their properties as drugs to treat malaria. More than five hundred triclosan derivatives were synthesized, and their in vitro and in vivo inhibitory activity evaluated. Furthermore, structural studies were made of their affinity to interact with residues in PfENR active sites, as well as with the cofactor NAD+. A total of six PfENR-NAD+-triclosan analog/complexes structures were determined. Analogs which had replacements of chloride groups at position 5 of ring A and 4' of ring B were determined, allowing the structural analysis of the binding of these triclosan analogs to PfENR. In addition, the urea derivatives (modification at position 1) as well as phenylsulphonamides (modification at position 2') have shown to be more potent inhibitors than triclosan in the in vivo assay. The analysis of the inhibitory properties and the structure of these analogs bound to PfENR will provide novel compounds in the search for new anti-malarial drugs.

Thesis (Ph. D.)--Open University. BLDSC no. DXN041011.

Thesis (Ph.D)--Rochester Institute of Technology, 2009. / Typescript. Includes bibliographical references (p. 201-206).

Thesis (Ph. D.)--University of Canterbury, 2008. / Typescript (photocopy). Includes bibliographical references (p. 126-133).

Thesis (M. Phil.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves [86]-88).

Thesis (Ph. D.)--University of Queensland, 2002. / Includes bibliographical references.

This thesis focuses on the radiation mechanisms of non-thermal X-rays and soft gamma-rays of two types of thousands year old spin-down powered pulsars. The thousands year old pulsars have distinct radiation behaviors from the middle-aged gamma-ray pulsars. In the magnetosphere of the pulsar, the particles are accelerated by the electric field resulting from the rotation of the neutron star. These accelerated particles move along the magnetic field lines and emit GeV gamma-ray curvature photons. For the middle-aged pulsars, most of the curvature photons, whose observed spectra are described well by power law with exponential cut-off, can escape out of the light cylinder. In X-ray band, the middle-aged pulsars usually have black body radiation with a weak non-thermal component described by power law. On the other hand, for the thousands-year-old pulsars, the curvature spectra in GeV band, which obey power law with exponential cut-off, are smeared out by the pair creation or missed by the line of sight. The secondary pairs generated by pair creation processes spiral around the magnetic field lines and emit synchrotron photons, and the young pulsars have stronger non-thermal X-ray and soft gamma-ray radiation than the middle-aged ones. Seven young pulsars have been studied here, they are the Crab pulsar, PSRs B0540-69, B1509-58, J1846-0258, J1811-1925, J1617-5055 and J1930+1852. These seven fall into two categories: the Crab-like pulsars and soft gamma-ray pulsars. The Crab-like pulsars include the Crab pulsar and the Giant Crab PSR B0540-69, and the soft gamma-ray pulsars include the other five. The main difference between the two types of young pulsars is that the Crab-like pulsars’ spectra peak at E ≤ 1MeV while the soft gamma-ray pulsars’ spectra (in units of MeV/cm2/s) peak at E ∼ 10MeV. Their spectra also have different photon indices in X-ray band. The physics behind is two different pair creations, the photon-photon pair creation and the magnetic pair creation. The former happens when a high energy photon collides with a soft photon, and the latter happens when a high energy photon penetrates through strong perpendicular magnetic field. In the outer gap of the pulsar, a large mount of pairs are generated around the null charge surface via photon-photon pair creation, and the electric field separates the two charges to move in opposite directions. Therefore, there are outflow and inflow of particles in the magnetosphere, whose curvature photons are converted to pairs by photon-photon pair creation and magnetic pair creation respectively. For the Crab-like pulsar, the non-thermal X-rays and soft gamma-rays are emitted by the outgoing secondary pairs generated by photon-photon pair creation in the outer magnetosphere; for the soft gamma-ray pulsar, the radiating secondary pairs are generated below the null charge surface by the magnetic pair creation. / published_or_final_version / Physics / Doctoral / Doctor of Philosophy

Malaria is a global health concern accounting for approximately 219 million cases and an estimated 660 000 deaths in 2010. The most fatal strain of malarial parasite, Plasmodium falciparum is found to contain 3 Adenylate Kinases (PfAK1, PfAK2 and PfGAK). Adenylate Kinases are important enzymes that essentially catalyze and regulate energy metabolism processes. PfAK1 and PfAK2 catalyze the reversible MG2+ reaction ATP + AMP ←→ 2ADP whereas, the PfGAK catalyzes the Mg2+ dependent reaction GTP+AMP ←→ ADP+GDP. Of all malarial strains, only the Plasmodium falciparum Adenylate Kinase 2 (PfAK2) was found to contain a N-myristoylation sequence and subsequently formed a stable heterodimer with Plasmodium falciparum N-myristoyl transferase (PfNMT). The myristoylation of PfAK2 by PfNMT is believed to help transport PfAK2 to the parasitophorous vacuole membrane (PVM) so that the enzyme can perform its essential functions. With these enzymes being key components in the parasite’s survival, the structural study of these enzymes would provide a lot of insight into targeting these proteins for drug design that would effectively kill the parasite without affecting the human host. In this study, PfAK1 was able to be expressed, purified and crystallized with a dataset collected at 4.3Å. PfGAK was expressed and purified. A GTP analogue called GP5A was used to soak the purified PfGAKand the PfGAK bound to GP5A was crystallized and diffracted. Moreover, PfAK2 and PfNMT was successfully expressed and co-purified. The purified PfAK2-PfNMT heterodimer are undergoing crystal screening for possible crystallization conditions. / published_or_final_version / Physiology / Master / Master of Philosophy

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