They Held Me Fearfully

Poe

Antony Gormley's Apple

Poem published in Neon Highway magazine. One of a collection of poems written on works of contemporary art

Please Inside-Out This

Through poetry of witness, this thesis explores the idea of truth as perception. The poems explore the themes of family, expatriate life, and identity in order to give voice to an alternate perspective

Analysis of conformational exchange processes using methyl-TROSY-based Hahn echo measurements of quadruple-quantum relaxation

Transverse nuclear spin relaxation is a sensitive probe of chemical exchange on timescales on the order of microseconds to milliseconds. Here we present an experiment for the simultaneous measurement of the relaxation rates of two quadruple-quantum transitions in 13CH3-labelled methyl groups. These coherences are protected against relaxation by intra-methyl dipolar interactions and so have unexpectedly long lifetimes within perdeuterated biomacromolecules. However, these coherences also have an order of magnitude higher sensitivity to chemical exchange broadening than lower order coherences and therefore provide ideal probes of dynamic processes. We show that analysis of the static magnetic field dependence of zero-, double- and quadruple-quantum Hahn echo relaxation rates provides a robust indication of chemical exchange and can determine the signed relative magnitudes of proton and carbon chemical shift differences between ground and excited states. We also demonstrate that this analysis can be combined with established Carr–Purcell–Meiboom–Gill (CPMG) relaxation dispersion measurements, providing improved precision in parameter estimates, particularly in the determination of 1H chemical shift differences

Estimating means of bounded random variables by betting

This paper derives confidence intervals (CI) and time-uniform confidence sequences (CS) for the classical problem of estimating an unknown mean from bounded observations. We present a general approach for deriving concentration bounds, that can be seen as a generalization (and improvement) of the celebrated Chernoff method. At its heart, it is based on deriving a new class of composite nonnegative martingales, with strong connections to testing by betting and the method of mixtures. We show how to extend these ideas to sampling without replacement, another heavily studied problem. In all cases, our bounds are adaptive to the unknown variance, and empirically vastly outperform existing approaches based on Hoeffding or empirical Bernstein inequalities and their recent supermartingale generalizations. In short, we establish a new state-of-the-art for four fundamental problems: CSs and CIs for bounded means, when sampling with and without replacement.Comment: 68 pages, 18 figures; Python implementation: https://github.com/wannabesmith/confse

Optimal design of adaptively sampled NMR experiments for measurement of methyl group dynamics with application to a ribosome-nascent chain complex

NMR measurements of cross-correlated nuclear spin relaxation provide powerful probes of polypeptide dynamics and rotational diffusion, free from contributions due to chemical exchange or interactions with external spins. Here, we report on the development of a sensitivity-optimized pulse sequence for the analysis of the differential relaxation of transitions within isolated 13CH3 spin systems, in order to characterise rotational diffusion and side chain order through the product S2τc. We describe the application of optimal design theory to implement a real-time ‘on-the-fly’ adaptive sampling scheme that maximizes the accuracy of the measured parameters. The increase in sensitivity obtained using this approach enables quantitative measurements of rotational diffusion within folded states of translationally-arrested ribosome–nascent chain complexes of the FLN5 filamin domain, and can be used to place strong limits on interactions between the domain and the ribosome surface

Cross‐Peaks in Simple Two‐Dimensional NMR Experiments from Chemical Exchange of Transverse Magnetisation

Two‐dimensional correlation measurements such as COSY, NOESY, HMQC, and HSQC experiments are central to small‐molecule and biomolecular NMR spectroscopy, and commonly form the basis of more complex experiments designed to study chemical exchange occurring during additional mixing periods. However, exchange occurring during chemical shift evolution periods can also influence the appearance of such spectra. While this is often exploited through one‐dimensional lineshape analysis (“dynamic NMR”), the analysis of exchange across multiple chemical shift evolution periods has received less attention. Here we report that chemical exchange‐induced cross‐peaks can arise in even the simplest two‐dimensional NMR experiments. These cross‐peaks can have highly distorted phases that contain rich information about the underlying exchange process. The quantitative analysis of such peaks, from a single 2D spectrum, can provide a highly accurate characterisation of underlying exchange processes

Critical Evaluation of Techniques for the Identification of Archaeological Bast Fibres: Flax, Hemp and Nettle

Fibre plants favour different growth conditions and require different levels of husbandry. However, the fibres share some physical and material properties, which make them difficult to distinguish in the archaeological record. This thesis evaluates the effectiveness of methods for characterising bast fibres including; fibre chemical analysis, mechanical testing and fibre morphology, to propose that longitudinal microfibrillar angle (MFA) and cross-sectional circularity (Ct) used in a two-step procedure to analyse selected modern fibres of nettle (Urtica dioica L.), flax (Linum usitatissimum L.) and hemp (Cannabis sativa L.) could offer an alternative approach. The reliability of MFA and Ct, as diagnostic features, was evaluated under a temperature accelerated degradation 48week trial with eight fibre types from three deposition soils Post deposition, surviving fibres were subjected to evaluation of changes in MFA and Ct. An additional check on the diagnostic efficacy was conducted within a blind-test protocol. Finally, the research programme employs MFA and Ct in the diagnosis of a range of archaeological textile fibres from museum collections and fibres from the Kasr el Yahud mass burial. The thesis includes recommendations to address future post thesis research programmes