Pulmonary Tuberculosis: towards improved adjunctive therapies

The potential to improve pulmonary tuberculosis (PTB) treatment outcomes with adjunctive immunotherapies requires investigation. L-arginine and vitamin D have antimycobacterial properties which render them suitable candidates. Therefore the Arginine and Vitamin D Adjunctive therapy in Pulmonary TB (AVDAPT) trial evaluates these supplements in PTB. This trial commenced in June 2008 in Timika, Papua Province, Indonesia, through a collaboration between the International Health Division, Menzies School of Health Research (Darwin, Australia), the National Institute for Health Research and Development (Ministry of Health, Indonesia), and the Australian National University (Canberra)...This thesis provides the basis for continuation of the AVDAPT study, produces original findings relating to clinico-immunological aspects of PTB, and provides information of major local importance to help guide TB service provision in Timika.National Health and Medical Research Council for providing a Postgraduate scholarship and a 2009 research grant, and the Australian Respiratory Council and the Royal Australasian College of Physicians (Covance award) which generously provided funds for the project

Physiological responses of Daphnia pulex to acid stress

<p>Abstract</p> <p>Background</p> <p>Acidity exerts a determining influence on the composition and diversity of freshwater faunas. While the physiological implications of freshwater acidification have been intensively studied in teleost fish and crayfish, much less is known about the acid-stress physiology of ecologically important groups such as cladoceran zooplankton. This study analyzed the extracellular acid-base state and CO₂partial pressure (<it>P</it>_CO2), circulation and ventilation, as well as the respiration rate of <it>Daphnia pulex </it>acclimated to acidic (pH 5.5 and 6.0) and circumneutral (pH 7.8) conditions.</p> <p>Results</p> <p><it>D. pulex </it>had a remarkably high extracellular pH of 8.33 and extracellular <it>P</it>_CO2of 0.56 kPa under normal ambient conditions (pH 7.8 and normocapnia). The hemolymph had a high bicarbonate concentration of 20.9 mM and a total buffer value of 51.5 meq L^-1pH^-1. Bicarbonate covered 93% of the total buffer value. Acidic conditions induced a slight acidosis (ΔpH = 0.16–0.23), a 30–65% bicarbonate loss, and elevated systemic activities (tachycardia, hyperventilation, hypermetabolism). pH 6.0 animals partly compensated the bicarbonate loss by increasing the non-bicarbonate buffer value from 2.0 to 5.1 meq L^-1pH^-1. The extracellular <it>P</it>_CO2of pH 5.5 animals was significantly reduced to 0.33 kPa, and these animals showed the highest tolerance to a short-term exposure to severe acid stress.</p> <p>Conclusion</p> <p>Chronic exposure to acidic conditions had a pervasive impact on <it>Daphnia's </it>physiology including acid-base balance, extracellular <it>P</it>_CO2, circulation and ventilation, and energy metabolism. Compensatory changes in extracellular non-bicarbonate buffering capacity and the improved tolerance to severe acid stress indicated the activation of defense mechanisms which may result from gene-expression mediated adjustments in hemolymph buffer proteins and in epithelial properties. Mechanistic analyses of the interdependence between extracellular acid-base balance and CO₂transport raised the question of whether a carbonic anhydrase (CA) is involved in the catalysis of the <inline-formula><graphic file="1472-6793-9-9-i1.gif"/></inline-formula> reaction, which led to the discovery of 31 CA-genes in the genome of <it>D. pulex</it>.</p

Chemical bonding effects in Sc compounds studied using X-ray absorption and X-ray photoelectron spectroscopies

Advances on understanding the nature of the chemical bonding and electron correlation effects during the X-ray absorption process in ionic–covalent metal complexes has been achieved for most of the transition elements, except for scandium, due to the lack of a systematic series of spectroscopic reference spectra and the shortage of standard crystallographic data on scandium compounds. To close the gap, the chemical bonding effects in eight Sc compounds are studied using X-ray absorption spectroscopy (XAS) at Sc K and L2,3 absorption edges and X-ray photoelectron spectroscopy (XPS). Indeed, the fine structure of the XAS Sc K edge reflects the chemical sp3-like bond formed between scandium and the ligand while the L2,3 edge and the pre-edge features of the K-edge provide a direct insight into the crystal field parameters at the Sc site in the coordination compound. The XPS data provide the information on binding energies of the core electrons involved in the electron transitions caused by the absorption of high energy X-rays. XAS and XPS complement each other by accessing the information on Sc structure on bulk and the surface. Herein, comprehensive information on the electronic structure of well-known crystalline materials based on Sc is given with spectroscopic fingerprints X-ray data. This will help to predict the formation of chemical bonds in the unknown components via the systematic evaluation of the available spectroscopic fingerprints

Quantifying Security Risks in Cloud Infrastructures:A Data-driven Approach

Businesses increasingly outsource their ICT services to cloud environments, mostly driven by considerations about costs, processes and security. However concerns around cloud exposure against cyber-security attacks are also growing. This bring about the question if the cloud really makes us more secure, or if it merely changes the type of threats we are exposed to. This PhD project aims at addressing this question by focusing on cloud infrastructure security. Using Internet measurements, we will take a data-driven approach to identify vulnerabilities and single points of failure in cloud infrastructure. Based on our analysis, we will propose solutions to mitigate these vulnerabilities and enhance the overall security of cloud environments

Understanding the magnetic resonance spectrum of nitrogen vacancy centers in an ensemble of randomly-oriented nanodiamonds

Nanodiamonds containing nitrogen vacancy (NV-) centers show promise for a number of emerging applications including targeted in vivo imaging and generating nuclear spin hyperpolarization for enhanced NMR spectroscopy and imaging. Here, we develop a detailed understanding of the magnetic resonance behavior of NV- centers in an ensemble of nanodiamonds with random crystal orientations. Two-dimensional optically detected magnetic resonance spectroscopy reveals the distribution of energy levels, spin populations, and transition probabilities that give rise to a complex spectrum. We identify overtone transitions that are inherently insensitive to crystal orientation and give well-defined transition frequencies that access the entire nanodiamond ensemble. These transitions may be harnessed for high-resolution imaging and generation of nuclear spin hyperpolarization. The data are well described by numerical simulations from the zero- to high-field regimes, including the intermediate regime of maximum complexity. We evaluate the prospects of nanodiamond ensembles specifically for nuclear hyperpolarization and show that frequency-swept dynamic nuclear polarization may transfer a large amount of the NV- center's hyperpolarization to nuclear spins by sweeping over a small region of its spectrum.Comment: 6 pages, 5 figure

Spatial and temporal trends of iron and iron isotope cycling in the Peruvian oxygen minimum zone

Iron (Fe) is a key element in the global ocean’s biogeochemical framework because of its essential role in numerous biological processes. A poorly studied link in the oceanic Fe cycle is the reductive release of Fe from sediments in oxygen depleted ocean regions - the oxygen minimum zones (OMZs). Changing rates of Fe release from OMZ sediments may have the potential to modulate ocean fertility which has far-reaching implications considering the high amplitude oxygen fluctuations throughout earth history as well as the ongoing ocean deoxygenation projected for the near future. In order to explore spatial and temporal trends of Fe cycling in OMZs, we present here Fe isotope and speciation data for surface sediments from a transect across the Peruvian upwelling area, one of the most pronounced OMZs of the modern ocean. Because of continuous dissimilatory Fe reduction and diffusive loss across the benthic boundary, sediments within the OMZ are strongly depleted in reactive Fe components, and the little reactive Fe left behind has a heavy isotope composition. In contrast, surface sediments below the OMZ are enriched in reactive Fe, with the majority being present as Fe oxides with comparably light isotope composition. This lateral pattern of Fe depletion and enrichment indicates that Fe released from sediments within the OMZ is reoxidized and precipitated at the oxycline. First-order calculations suggest that the amount of Fe mobilized within the OMZ and that accumulated at the boundaries are largely balanced. Therefore, benthic Fe fluxes in OMZs should be carefully evaluated prior to incorporation into global models, as much of the initially released Fe may be reprecipitated prior to vertical or offshore transport. First XRF core scanning results for partly laminated piston cores from the OMZ boundaries reveal downcore oscillations in the content of reactive Fe and redox-sensitive trace metals that are attributed to past changes in OMZ extension. Ongoing work on these cores will focus on their dating and the downcore investigation of Fe and trace metal records in order to better understand past Fe cycling within the Peruvian OMZ and potential interactions with climate variability