Triggered fragmentation in gravitationally unstable discs: forming fragments at small radii

We carry out three dimensional radiation hydrodynamical simulations of gravitationally unstable discs using to explore the movement of mass in a disc following its fragmentation. Compared to a more quiescent state before it fragments, the radial velocity of the gas increases by up to a factor of ~2-3 after fragmentation. While the mass movement occurs both inwards and outwards, the inwards motion can cause the inner spirals to be sufficiently dense that they may become unstable and potentially fragment. Consequently, the dynamical behaviour of fragmented discs may cause subsequent fragmentation at smaller radii after an initial fragment has formed in the outer disc.Comment: Submitted to the conference proceedings of: Instabilities and Structures in Proto-Planetary Disks. 5 pages; 4 figure

Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species

Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates

Non-convergence of the critical cooling timescale for fragmentation of self-gravitating discs

We carry out a resolution study on the fragmentation boundary of self-gravitating discs. We perform three-dimensional Smoothed Particle Hydrodynamics simulations of discs to determine whether the critical value of the cooling timescale in units of the orbital timescale, beta_{crit}, converges with increasing resolution. Using particle numbers ranging from 31,250 to 16 million (the highest resolution simulations to date) we do not find convergence. Instead, fragmentation occurs for longer cooling timescales as the resolution is increased. These results suggest that at the very least, the critical value of the cooling timescale is longer than previously thought. However, the absence of convergence also raises the question of whether or not a critical value exists. In light of these results, we caution against using cooling timescale or gravitational stress arguments to deduce whether gravitational instability may or may not have been the formation mechanism for observed planetary systems.Comment: Accepted for publication by MNRAS Letters. 6 pages, 3 figure

Large grains can grow in circumstellar discs

We perform coagulation & fragmentation simulations to understand grain growth in T Tauri & brown dwarf discs. We present a physically-motivated approach using a probability distribution function for the collision velocities and separating the deterministic & stochastic velocities. We find growth to larger sizes compared to other models. Furthermore, if brown dwarf discs are scaled-down versions of T Tauri discs (in terms of stellar & disc mass, and disc radius), growth at the same location with respect to the outer edge occurs to similar sizes in both discs.Comment: Submitted to the conference proceedings of the IAU Symposium 299 - Exploring the formation and evolution of planetary systems. 2 pages; 2 figure

Accounting for genetic interactions improves modeling of individual quantitative trait phenotypes in yeast.

Experiments in model organisms report abundant genetic interactions underlying biologically important traits, whereas quantitative genetics theory predicts, and data support, the notion that most genetic variance in populations is additive. Here we describe networks of capacitating genetic interactions that contribute to quantitative trait variation in a large yeast intercross population. The additive variance explained by individual loci in a network is highly dependent on the allele frequencies of the interacting loci. Modeling of phenotypes for multilocus genotype classes in the epistatic networks is often improved by accounting for the interactions. We discuss the implications of these results for attempts to dissect genetic architectures and to predict individual phenotypes and long-term responses to selection