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Reversibly switchable fluorescent proteins (RSFPs) switch between a highly and weakly fluorescent state upon photoexcitation. This switching is known to be driven by reversible photoisomerisation and a change in protonation state of the chromophore. However, the exact sequence of events after optical excitation is unclear. In this thesis, time-resolved crystallography and vibrational spectroscopy are used to study the ultrafast dynamics of a new RSFP. Time-resolved serial femtosecond crystallography (TR-SFX) is used to probe the trans/cis reaction and reveals ultrafast sub-Angstrom motions of the chromophore and surrounding hydrogen bonding network. The addition of a stokes pulse (shown to dump the excited state population) increases these displacements and allows assignment of the light-induced signals to a vibrationally excited electronic ground state structure instead of an excited state structure. Temperature analysis of the steady-state switching rates resolves an intermediate ground-state structure using conventional crystallography which supports the TR-SFX assignments. Ultrafast pump-probe vibrational spectroscopy confirms that excited state photoisomerisation occurs (~70 ps), proceeded by rearrangement of a nearby arginine residue (~7 ps) with deprotonation (trans-neutral/cis-anion) occurring between 2 ns - 1 ms. An additional dump pulse is then shown to repress product formation and reforms the ground state, further supporting the structural observations of the pump-dump-probe crystallography measurements. These results improve our understanding of photoswitching in RSFPs and have important implications for structural assignments in future TR-SFX experiments. Time-resolved serial synchrotron crystallography (TR-SSX) is an accessible and emerging technique for studying protein dynamics on millisecond timescales. Here, the trans/cis isomerisation of an RSFP is probed at 10 ms with a range of pump intensities to demonstrate precise control of the cis-state formation yields. The population transfer is resolved crystallographically using quantitative analysis of the occupancy, showing excellent agreement with optical flash-photolysis measurements. The issue of X-ray induced heating, which leads to partial thermal recovery, is also addressed. A temperature increase of 82-112 K is extracted for the fixed-target sample delivery used, which should be accounted for in all future TR-SSX experiments. Finally, the effect of pH on the protonation step is investigated by studying a RSFP mutant with a destabilised ground state conformation. Structural and spectroscopic evidence is presented for a new class of reaction at low pH, involving a cis-neutral/trans-cation isomerisation, in contrasts to the typical cis-anion/trans-neutral reaction at neutral pH. These steady-state observations expand our understanding of acid/base equilibria in the photoreactions of RSFPs.

In this thesis, I return to the unsettled ground of Beckett’s influence over the emergence of postmodern fiction. Taking on board Peter Boxall’s piercing assertion that ‘one of the most significant of Beckett’s legacies [...] is a conception of legacy itself,’ (2009) I provide a narrative of inheritance in which the exhaustion of literary experiment glimpsed in Beckett provides a bequest that is simultaneously energising and enervating. In particular, I connect this to the strained relationship of Beckett regarding the U.S., enshrined in his statement that this is ‘somehow not the right country for me.’ (Knowlson, 1996) The first chapter details the practicalities of Beckett’s U.S. migration via the Grove Press periodical Evergreen Review. Beckett’s 16 (1957-1973) appearances in the American periodical serve as a core vehicle of the author’s deracination, contextualising his publisher Barney Rosset’s description of Beckett’s ‘nontogetherness.’ The second chapter focuses on the work of Thomas Pynchon, in which Beckett’s poetics of exhaustion is integrated alongside the vitalism of the popular Beat avant-garde staged in Evergreen. In particular, I argue that Beckett’s influence intersects with the postmodern problem of hermeneutics, dramatized through shared images of ending, ‘Zero,’ and entropy. The final chapter reframes the Beckettian disjuncture against the work of Don DeLillo and the author’s interrogation of ‘this whole global, yet American, postmodern culture.’ (Jameson, 1991) Framed by DeLillo as the ‘last writer to shape the way we think and see,’ (Mao II, 157) Beckett’s presence is one of termination; at the same time, it discloses a means whereby fiction might ‘extend into the world.’ (Adelman, 2004) Alongside developments in DeLillo’s spatial-poetics to a fiction set ‘nowhere in particular,’ I finally provide a view of Beckett’s problematic bequest as one that is integrated into the fabric of the text over time.

In recent years Java has been increasingly considered as a language for safety-critical embedded systems. However, some features of Java are unsuitable for such systems. This has resulted in the creation of Safety-Critical Java (SCJ), which facilitates the development of certifiable real-time and embedded Java programs. SCJ uses different scheduling and memory management models to standard Java, so it requires a specialised virtual machine (SCJVM). A common approach is to compile Java bytecode program to a native language, usually C, ahead-of-time for greater performance on low-resource embedded systems. Given the safety-critical nature of the applications, it must be ensured that the virtual machine is correct. However, so far, formal verification has not been applied to any SCJVM. This thesis contributes to the formal verification of SCJVMs that utilise ahead-of-time compilation by presenting a verification of compilation from Java bytecode to C. The approach we adopt is an adaptation of the algebraic approach developed by Sampaio and Hoare. We start with a formal specification of an SCJVM executing the bytecodes of a program, and transform it, through the application of proven compilation rules, to a representation of the target C code. Thus, our contributions are a formal specification of an SCJVM, a set of compilation rules with proofs, and a strategy for applying those compilation rules. Our compilation strategy can be used as the basis for an implementation of an ahead-of-time compiling SCJVM, or verification of an existing implementation. Additionally, our formal model of an SCJVM may be used as a specification for creating an interpreting SCJVM. To ensure the applicability of our results, we base our work on icecap, the only currently available SCJVM that is open source and up-to-date with the SCJ standard.

The question of whether psychopaths are morally responsible is a difficult one for philosophers and non-philosophers alike. In comparison to some other forms of mental illness, it is difficult to locate intuitions concerning what our attitudes to psychopaths should be and how they should be treated. This is because, unlike people with some other forms of mental illness, psychopaths (qua psychopaths) do not appear to be mistaken about the facts bearing on their choices, but they do appear to lack understanding of the world in an important way. Working within an understanding of moral responsibility as consisting in responsiveness to reasons, I argue that psychopaths lack responsiveness to certain kinds of reasons and are therefore not morally responsible for failing to act on reasons of these kinds. Based on a review of the empirical evidence, I conclude that psychopaths experience deficiencies of emotional engagement and of empathy, which are the result of events that are not under their control. I argue that these deficiencies lead ‘hardcore’ psychopaths (those at the high end of the scale for the deficiencies in question) to fail to develop the capacity to recognise entities other than themselves as sources of value, and thus to recognise that the rights, interests and concerns of others provide reasons which bear on their choices. These psychopaths are therefore not morally responsible for failing to act on such reasons. Nonetheless, I argue that these reasons apply to psychopaths’ choices in a way that they do not apply, for example, to the choices of non-human animals. Implications of these conclusions include 1) that some reactive attitudes, such as resentment or hurt feelings, are inappropriate when directed at psychopaths, and 2) that some justifications for punishment are unavailable in the case of psychopaths.