Exploring the role of the “glycan-shield” of human immunodeficiency virus in susceptibility to, and escape from, broadly neutralising antibodies

Philosophiae Doctor - PhDThe HIV-1 envelope (Env) glycoprotein is the primary target of the humoral immune response and a critical vaccine candidate. However, Env is densely glycosylated and thereby substantially protected from neutralisation. Despite the importance of the HIV- 1 Env glycans, limited computational analyses have been employed to analyse these glycans. Here, the Env glycans of two HIV-1 wild-type subtype C isolates are examined, in detail, using computational approaches. These particular strains were used since in vitro data showed that the removal of a single glycan had a substantially different impact on the neutralisation sensitivity of the two strains. Molecular dynamics simulations, and the subsequent analyses, were carried out on the computationally determined, fully glycosylated, Env structures of these two wild-type strains and their N301A mutant counterparts. Detailed comparison of the molecular dynamics simulations demonstrated that unique glycan dynamics and conformations emerged and that, despite shared HXB2 reference sequence positions, the glycans adopted distinct conformations specific to each wild-type model. Furthermore, different changes in conformations were observed for each wild-type model compared to its N301A mutant counterpart and, interestingly, these N301A mutant model-specific glycan conformations were directly associated with the protein residues ultimately found to be exposed, which may explain the varied resistance to neutralising antibodies observed, in vitro, for the two N301A mutant strains

Discrete Element Modeling of Cone Penetration in JSC-1A Lunar Regolith Simulant

NASA plans to return back to the Moon for a long term presence and use of the Moon as a launch station for further space exploration to other planets. This scenario increases the importance of determining the geotechnical properties of the lunar surface. However, due to the limited availability of lunar regolith and its high scientific value, a simulant material which closely matches the composition and grain size distribution and other characteristics of the lunar regolith has become an indispensable need to benefit in hardware development as well as estimating lunar regolith properties. Therefore, JSC-1A lunar regolith simulant, which was produced by Orbitec Company under the guidance of NASA, was provided for researchers to investigate soil parameters. Previous studies about JSC-1A utilized from conventional laboratory experiments. This thesis aims to examine the behavior of JSC-1A and auxiliary Ottawa sand against cone penetration testing (CPT). CPT is a fast and reliable method to characterize soil properties. Experimental work is augmented with numerical simulation to take advantage of powerful capabilities of discrete element method (DEM). Experimental work is mainly composed of two sets of tests. Firstly, CPT is conducted on JSC-1A in the field using a CPT truck and soil classification and internal friction angle analyses were estimated based on the test results. However, the limited data and high boundary effects on the container made a strong case to provide reliable reference for DEM simulations. Therefore, miniature CPT experiments were conducted for JSC-1A and Ottawa sand with distinctive densities using two size cylindrical containers. Ottawa sand which is a uniform silica sand is also included in the analysis to obtain supplementary data. Finally, DEM in 3D was used to model the response of two soils to cone penetration. Microscale changes such as contact force, displacement, velocity and stress variation of individual soil particles were monitored throughout the simulation process. In conclusion, CPT results show that each soil exhibits a characteristic response to cone penetration under different conditions. Its response is affected by various parameters such as soil density, boundary conditions, homogeneity, grain size and shape. It was found that boundary condition influence the results significantly. DEM results have a good agreement with laboratory experiments except the fluctuations in simulation data. The penetration of the cone produces a considerable variation in velocity and displacement field. Contact forces and deformation pattern of the granular material are mainly governed by the relative position of particles to the penetrometer

CURRENT ACCOUNT DEFICIT SUSTAINABILITY IN TRANSITION COUNTRIES

The current account balance represents the most important measurement of acountry's economic performance and it is important to keep the current account deficit within sustainable levels. Over the last decade, the importance of asustainable current account deficit has been major concern of policy makers and investors. In this paper, we investigate the sustainability of the current account deficit in transition countries over the period from 1995:01 through 2011:03, using intertemporal solvency model. According to this approach, the existence of aco integrating relationship between exports and imports + (including imports, netinterest payments and net transfer payments) gives that countries do not violate their intertemporal budget constraint. To achieve our objective, the cointegration test which recently developed in the presence of two potentially unknown structural breaks, is carried out. These breaks are taken into account in our analysis by considering that the long run relationship between related series might change andthe shifts can occur in the cointegrating vector. The obtained results suggest that there is evidence of cointegration for selected transition countries, implying sustainability

Revealing Seed Coat Colour Variation and Their Possible Association with Seed Yield Parameters in Common Vetch ( Vicia sativa

The seed coat colour variation of 70 common vetch genotypes were determined by using uniform colour scale (L⁎a⁎b⁎) and their possible correlation with seed yield parameters including the number of pods per plant, the number of seeds per pod, pod dimension, and seed yield (kg/da) was determined. The results revealed presence of highly significant (p<0.01) variations for both the seed yield and the seed coat colour parameters measured. The number of pods per plant, the number of seeds per pod, and seed yield ranged from 5.8 to 16.03, from 5.2 to 7.66, and from 143.37 to 531.1, respectively. The lightness value varied from 19.00 to 40.28 while chromaticity a⁎ and b⁎ values ranged from −0.16 to 8.99 and from 0.79 to 22.11, respectively. The highest correlation coefficients were determined between b⁎ and L⁎ (r=0.73), and a⁎ and L⁎ (r=0.55). The seed coat colour traits and seed yield parameters generally showed weak negative correlations. Seed yellowness (b⁎) and seed yield had correlation coefficient of −0.25, while correlation between L⁎ and seed yield was determined as −0.23. The results indicated that lightness and yellowness of seed coat may be used as an important parameter to prescreen high yield genotypes of common vetch

Activation Energy of Metastable Amorphous Ge2Sb2Te5 from Room Temperature to Melt

Resistivity of metastable amorphous Ge2Sb2Te5 (GST) measured at device level show an exponential decline with temperature matching with the steady-state thin-film resistivity measured at 858 K (melting temperature). This suggests that the free carrier activation mechanisms form a continuum in a large temperature scale (300 K - 858 K) and the metastable amorphous phase can be treated as a super-cooled liquid. The effective activation energy calculated using the resistivity versus temperature data follow a parabolic behavior, with a room temperature value of 333 meV, peaking to ~377 meV at ~465 K and reaching zero at ~930 K, using a reference activation energy of 111 meV (3kBT/2) at melt. Amorphous GST is expected to behave as a p-type semiconductor at Tmelt ~ 858 K and transitions from the semiconducting-liquid phase to the metallic-liquid phase at ~ 930 K at equilibrium. The simultaneous Seebeck (S) and resistivity versus temperature measurements of amorphous-fcc mixed-phase GST thin-films show linear S-T trends that meet S = 0 at 0 K, consistent with degenerate semiconductors, and the dS/dT and room temperature activation energy show a linear correlation. The single-crystal fcc is calculated to have dS/dT = 0.153 {\mu}V/K for an activation energy of zero and a Fermi level 0.16 eV below the valance band edge.Comment: 5 pages, 5 figure

Investignation of applicability of solid state phantom SP34 for orthovoltage X-Ray

It is now widely used two types of tissue-equivalent phantoms: Solid and water. Water is the "gold standard" in accordance with the recommendations of the IAEA as a medium for measurements of absorbed dose for both photon and electron beams for, as the water has the most similar to human tissue characteristics. However, from a practical standpoint, water phantom is not always convenient to use, because it requires much time for preparation work. The output in such a situation would be to use a solid-state phantom with coefficients that take into account the difference between the electronic and physical material density against distilled water

Evolution of particle breakage studied using x-ray tomography and the discrete element method

Particle breakage can significantly change the fabric (size and shape of particles and contact network) of a granular material, affecting highly the material's macroscopic response. In this paper, oedometric compression tests are performed on zeolite specimens and x-ray computed micro-tomography is employed, to acquire high resolution 3D images of the specimens throughout the test. The images are processed, to describe breakage spatially and quantify it throughout the test and gain information about the mechanisms leading to particle breakage. In addition to the image processing, the discrete element method (DEM) is used to study the initiation and likelihood of particle breakage, by simulating the experimental test during the early stages of loading and using quantitative results from the images to inform and validate the DEM model. A discrete digital image correlation is used, in order to incrementally identify intact grains and simultaneously get results about the strain field within the specimen, as well as the kinematics of individual grains and fragments. In the initial stages of breakage, there is a clear boundary effect on the spatial distribution of breakage, as it is concentrated at the moving boundary (more than 90% of total breakage) and circumferentially (more than 70% of total breakage) close to the apparatus cell. The DEM model can reproduce the bulk response of the material until the point where substantial breakage governs the macroscopic response and it starts to soften. Additionally, there is an initial indication that the spatial distribution of the force network matches the localisation of breakage radially, but it does not seem to localise close to the loading platen. This analysis will enrich our understanding of the mechanisms and evolution of particle breakage