Conceptual Modeling and Analysis of Drag-Augmented Supersonic Retropropulsion for Application in Mars Entry, Descent, and Landing Vehicles

The development of new decelerator technologies will be required as the desired payload mass for future Mars landing missions increases beyond the current state-of-the-art architecture capability. This thesis examines the potential for supersonic retropropulsion applied on entry, descent, and landing vehicles to increase the landed payload mass. Supersonic retropropulsion systems use rocket thrust directed into the free stream flow to decelerate the vehicle during descent. Under certain conditions the aerodynamic drag on the entry vehicle can be preserved or augmented using supersonic retropropulsion. The development of a model characterizing the drag augmentation capabilities of supersonic retropropulsion flow interactions is described. The model combines results from computational fluid dynamic simulations available in literature and analytic techniques to estimate the drag coefficient of a 70° sphere-cone aeroshell. The model is designed to capture the dominant flow physics of pressure conservation through various shock cascade structures more quickly than computational fluid dynamic simulations. This allows conceptual systems analysis to be performed across a wide range of input values beyond the current parameter space evaluated in experiments or computational simulations. The drag coefficient model developed is validated against available results from wind tunnel tests and computational simulations to within 10%. In addition, the sensitivity of the computed drag coefficient to inputs estimated from computational simulation results in literature is analyzed. A study of drag-augmented supersonic retropropulsion operation concepts for use in Mars entry, descent, and landing is presented. The feasible entry and payload masses for ballistic entries are determined for a range of supersonic retropropulsion operation intervals to illustrate the flight regimes where supersonic retropropulsion is most effective. The use of supersonic retropropulsion is shown to reduce the required propellant mass by 65% when the operation interval is focused in the region of maximum dynamic pressure. In addition, the feasibility of two concepts combining supersonic decelerator concepts is investigated: a combination of drag-augmented and high-thrust supersonic retropropulsion, and a combination of drag-augmented supersonic retropropulsion and inflatable aerodynamic decelerators. The potential for these hybrid solutions to increase the payload mass capability by up to 708% using each technology in the appropriate flight regime is demonstrated

Germline mutations and somatic inactivation of <i>TRIM28</i> in Wilms tumour

<div><p>Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in <i>TRIM28</i> predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of <i>TRIM28</i>, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. <i>TRIM28</i>-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of <i>TRIM28</i> provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis.</p></div

Somatic genetic changes in Wilms tumours.

<p>The left side shows the number of somatic non-synonymous and truncating mutations for each tumour detected by MuTect2. The single somatic variant in W117 is the <i>TRIM28</i> mutation. The right side shows the fractional length of aberrant copy number segments as determined by ADTEx.</p

DNA sequence and methylation of <i>TRIM28</i>.

<p>(<b>A</b>) Family 1. 2-bp deletion (c.525_526del) in the blood of case 39 (39B), the kidney of case 37 (37K) and the blood of their mother (37M). The father (37F) was unaffected. The tumours from cases 37 and 39 (37T and 39T) showed loss of heterozygosity. (<b>B</b>) Family 2. Germline deletion/insertion (c.1746_1747delinsC) in blood DNA from case 399 (399N) with loss of heterozygosity in tumours 399T and 249T. (<b>C</b>) Somatic deletion/insertion mutation (c.1935delinsGA) in W117 tumour (W117T) and reference sequence in the adjacent kidney (W117K). (<b>D</b>) The proportion of methylated CpGs in exon 1 of <i>TRIM28</i> in W117T as measured by targeted bisulfite PCR. For each CpG site the black portion of the bar shows the proportion of methylated reads.</p

Dendrogram from unsupervised hierarchical clustering of gene expression of 17 Wilms tumours.

<p>IGF2, refers to <i>IGF2</i> status where blue = loss of imprinting, and red = loss of heterozygosity at <i>IGF2</i>. Rests refers to the presence of nephrogenic rests (NR) were blue = intralobar NR, red perilobar NR and purple NR of unknown type. For each gene, red boxes indicate the presence of mutation, whereas the grey box denotes gene deletion.</p

Comparison of gene expression between S1 and other Wilms tumours.

<p>The upper panels show the five most down-regulated and five most up-regulated genes in the S1 subgroup (n = 11) compared to S2-S5 tumours (n = 213) in the study of Gadd et al. [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007399#pgen.1007399.ref030" target="_blank">30</a>]. The lower panels show expression of these genes in <i>TRIM28</i>-mutated tumours and 13 other tumours from this study. Red circles, S1 or <i>TRIM28</i>-mutated tumours. Blue circles, favourable histology tumours. Note that two tumours with anaplastic histology, both of which had <i>TP53</i> mutations, are not included to maintain comparability with the favourable histology tumours reported by Gadd et al. [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007399#pgen.1007399.ref030" target="_blank">30</a>].</p

TRIM28 immunohistochemistry.

<p>(<b>A</b>) Monomorphic epithelial Wilms tumours showing absence of TRIM28 expression in 37T and W117. (<b>B</b>) Absence of TRIM28 protein expression in tumour (T) but not in adjacent kidney (K) in case 39. (<b>C</b>) Positive control showing TRIM28 expression in two representative Wilms tumours. Black line = 50 μM.</p

Genetic, epigenetic and clinical features of monomorphic epithelial Wilms tumours.

<p>Genetic, epigenetic and clinical features of monomorphic epithelial Wilms tumours.</p