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Vacuum induction melting investment casting is a process used to produce metal components. The procedure comprises of induction melting of a billet under vacuum conditions, followed by direct pouring into a casting mould. Castings made by this method are prone to defects such as misrun, inclusions and porosity. In this work, the impact of piping defects within IN713C billets is examined, specifically their size and location on flow characteristics during pouring and defect occurrence in finished castings. Manufactured holes were introduced in concast billets as a controlled method of exploring the effect of piping on alloy pouring flow characteristics. Using a Design of Experiments approach, an L9 array of two-piece billets was used to investigate the impact of disc height, hole diameter and hole position. A bespoke vacuum induction melting chamber was designed and fabricated with viewing ports which enable non-contact temperature measurements and high-speed images to be recorded during the heating and pouring processes, respectively. The L9 array was reproduced in numerical models of electromagnetic induction heating, and thermal fluid flow during alloy pouring, created using the in-development EMAG module for ESI ProCAST. Thermal results from electromagnetics models were used as initial conditions for alloy pouring, and additional mould filling and solidification simulations. The experimental data served as validation for numerical models and demonstrates that the modelling approach delivers representative results, while minimising computational demand. Knowledge of the temperature distribution within the billet from electromagnetic simulations is found to be key for accurate defect prediction. By interrogating defect criteria in post-processing, the impact of piping on defect occurrence is understood. Using a 15 mm disc, or 'penny', resulted in a reduction of defect instances, consistent with anecdotally reported improvements observed in the casting industry. Through this modelling, this is explained by reductions in the maximum alloy pouring temperature.

This thesis explores the synchrony and diachrony of auxiliary ellipsis (AE) in Early Modern German (1350-1800), focusing mostly on the afinite construction (AC) but also taking into account coordination ellipsis (CE). I seek to investigate whether AC was constrained synchronically by language external and/or internal factors, as well as understanding when, how and why AE (both AC and CE) came to be used so frequently, and when, how and why AC and non-parallel CE fell from use. To do this, I undertook a search of three corpora: GerManC (1650-1800), parts of the Bonn Corpus of Early New High German (1350-1600) and a corpus of texts from 1490-1550 which I put together myself. As regards the synchronic constraints, I argue that both language internal and external factors constrained AC at its peak according to the data. Language internal factors can be generalized in terms of frequency (the more frequent a type of construction, the higher the AC rate), and I link this with developments in style at the time. In terms of language external factors, genre was found to play a key role, with more 'print-oriented' genres such as legal and humanities texts containing a much higher rate of AC. In addition, I show that previous appeals to text complexity and pragmatic backgrounding (Admoni, 1990; Breitbarth, 2005) as a function of AC are not supported by the GerManC data by testing hypotaxis levels and the factivity of verb complements. I also make some claims about the theoretical treatment of AC, suggesting that it should be viewed as a separate phenomenon from Swedish ha-deletion. In terms of the rise of AE, I argue that AE was used supra-regionally in the legal genre as a stylistic feature to avoid the use of multiple auxiliaries in quick succession in the latter half of the fifteenth century. After 1500, AE spread to other genres in East Central German, before becoming commonplace in other regions in the seventeenth century, when it was targeted by metalinguistic commentary as irrational. Regarding its fall, I noted that region and genre did not constrain AC in the period 1750-1800 in the way they had done in earlier periods. I argue that a supra-regional style of writing was developing in this period, and AC and non-parallel CE was seen as contrary to that style. I searched a number of contemporary grammarians' works for comments on AE and found that fewer comments in the seventeenth century correlated with a higher AC rate, and more comments in the eighteenth century with a lower AC rate. I suggest that the grammarians themselves were probably reacting to a stylistic change that was already underway. Lastly, I consider what AE can tell us more generally about diachrony by discussing the AE results in the light of Kroch's (1989) Constant Rate Effect and Postma's (2010; 2015) 'failed changes'. Because AE cannot easily be categorized as grammatical or ungrammatical, I suggest that it is best analyzed as an example of a learned stylistic feature rather than grammatical change.

The mechanism by which antigens are processed and presented to T cells exerts a powerful influence on all immune responses, including those directed against pathogens. Knowledge of the peptides produced by antigen presenting cells for presentation to T cells is important in understanding why individuals have different abilities to combat infection and may prove critical in the design of new vaccines. The aim of this project was to attempt to use a novel metabolic labelling technique to enable biochemical identification of potential T cell epitopes in bacterial antigens. The technique is based upon labelling antigens with the stable isotope carbon-13, and subsequent identification of antigen-derived peptides using mass spectrometric isotopic composition analysis. The ultimate goal of the work was to pulse antigen presenting cells with labelled bacteria and identify MHC class II-associated bacteriaderived peptides with the objective of identifying potential vaccine candidates. Towards this goal, outer membrane proteins were prepared and analysed by polyacrylamide gel electrophoresis and immunoblotted with serum from healthy individuals. The results showed that the serum antibodies bound to a number of outer membrane proteins, confirming that they contained B cell epitopes. As a first step to demonstrate that the outer membrane proteins also contained T cell epitopes, it was shown that whole bacteria and bacterial antigens can be successfully labelled with carbon-13 such that all derived peptide fragments may be distinguished by isotopic analysis. However, due to the complexity of the peptide mixture generated by a tryptic digest of the outer membrane proteins, it was critical to combine isotope analysis with excellent chromatographic resolution in order to identify carbon-13 labelled peptides. To address this problem, a new high sensitivity 2D nanoflow liquid chromatography system was developed and its capabilities compared with conventional ID reverse phase chromatographic techniques. Two dimensional separation prior to mass spectral analysis substantially improved the separation of complex biological mixtures leading to an improvement in the identification of carbon-13 labelled peptides in such mixtures. Two dimensional chromatography and carbon-13 labelling was then applied to investigate the processing of tetanus toxin C fragment (TTCF) by lysosomes isolated from EBV transformed B lymphoblastoid cell lines. Whilst large TTCF fragments were demonstrably generated during processing, small (< 3kd) peptides suitable for binding to MHC class II molecules were extremely scarce. Further experiments suggested that this was unlikely to be a consequence of insufficient sensitivity of the carbon-13 technique, but probably a consequence of rapid destruction of the smaller fragments by lysosomal enzymes and high stability of the larger digestion fragments of TTCF. It was concluded from these studies that the metabolic labelling of bacterial proteins with carbon-13 is applicable to the analysis of processed products of bacterial antigens in complex peptide mixtures. Small peptides, with sizes in the range bound to MHC class II molecules, appear to be very sparse in processing compartments, presumably because of rapid proteolysis. Peptides bound to MHC class II are known to be relatively resistant to proteolysis so in future work it is proposed to examine TTCF-derived peptides bound to MHC class II molecules rather than free within lysosomes.