VictorJuiz/thesis huggingface dataset:
Energetics of protein interactions in the membrane via computer simulations

Protein-lipid interactions underpin the biological activities in cell membranes. However, the energetic aspect of these interactions is notoriously difficult to study. Here, I performed a number of enhanced sampling simulations on biologically-interesting systems using different collective variables to provide converged estimates of protein binding affinities in the membrane.
Replica exchange umbrella sampling (REUS) simulations were performed using a distancebased collective variable on two biologically relevant interactions: the ANT-Cardiolipin (CL) and Kir2.2-PIP2. Converged PMFs were obtained for both systems; for the Kir2.2 R186A channel mutant, the potential of mean force (PMF) well-depth is reduced, in qualitative agreement with experimental data, where the mutation reduces conductance. These results demonstrate that REUS methodology can be robustly used to estimate protein-lipid binding interactions with the coarse-grained model, on different binding pockets and lipid types.
The REUS methodology was then extended to study prototypical transmembrane (TM) helix-helix interactions. A series of model helix-helix dimers was studied, experimentally known to span a range of affinities, including the Glycophorin A (GpA) TM fragment and a number of different Receptor Tyrosine Kinase (RTK) TM fragments. The coarsegrained MARTINI model correctly predicts the bound state to be most stable, for GpA. Unexpectedly the non-dimerizing GpA mutant was just as stable as the wild-type. Similarly, for RTKs, the calculated affinities were similar, in contrast to semi-quantitative TOXCAT data that suggests a range of affinities.
Using the collective variable developed to study the coarse-grained helix-helix systems, an all-atom PMF was calculated for wild-type GpA in a 1-palmitoyl,2-oleoyl-sn-glycero-3- phosphocholine (POPC) bilayer. Unexpectedly, the dimer state was found to be metastable, with the CHARMM36 and AMBER force fields, with the unbound state being the global energy minimum. Two simple corrections were proposed for the CHARMM36 force field, which stabilize the bound state making the model consistent with experiment.

Advisor: Best, R
Sansom, M
'Two congenial beings of another sphere': Peter Sterry as a theological precursor to William Blake

This thesis seeks to explicate, and develop an appropriate method for the elucidation of, the antecedents to the theology of William Blake in the writings of the seventeenth-century divine, Peter Sterry (1613-1672). While the radical religious scene of the English Revolution has long been recognised as offering important antecedents to Blake’s thought, Sterry is a figure who has largely been overlooked. The exception to this is an essay, published in 1929, in which Vivian de Sola Pinto asserted the existence of ‘startling affinities’ between their ideas. Pinto’s study was, however, limited by its failure to consider, firstly, the implications of its findings for our general understanding of the antecedents to Blake’s thought in the seventeenth century and, secondly, the insight Sterry’s writings may be able to offer into Blake’s theological vision. These are the very questions at the heart of this dissertation. By addressing them, it seeks to shed new light on the nature of Blake’s theology and its anticipations in earlier English thought. Given the lack of evidence that Blake read Sterry, and the limited effectiveness of the ‘genealogical’ method when it comes to Blake, it pioneers a bespoke ‘analogical’ method for the exploration of these issues. It proposes that Sterry is actually closer to the intellectual milieu of Commonwealth radicalism than one might expect and that his writings function effectively as a lens through which it is possible to discern how Blake consistently uses ‘dualistic’ language and imagery in an ethical and epistemological sense. The first finding suggests that the established view of the radical religious environment in Blake studies needs to be extended; the second challenges the widespread perception that Blake’s thought is ultimately dualistic in an ontological sense, thus contributing to the elucidation of a perennial problem for Blake scholarship. Together, they underline Sterry’s importance as a neglected theological precursor to the thought of William Blake.

Keywords: Theology
Analogy
Contraries
Dualism
Advisor: Rowland, C
Vector correlations in the inelastic scattering of NO(X) with atoms and diatoms

This thesis presents a joint experimental and theoretical study of the state-to-state resolved rotationally inelastic scattering of NO(X) with atoms and homonuclear diatoms. Emphasis is placed on measuring the correlations between the vectors which describe the system: k and k' the initial and final relative velocities, respectively, r the initial NO bond axis orientation, and j' the final rotational angular momentum of NO. Experimentally, the initial f Δ-doublet state of NO(X) is selected using a Hexapole state selector, and the scattered NO detected using (1+1') REMPI.
In the first part of this thesis the k-k' correlation in the scattering of NO(X) with O2(X) is presented. A modified onion peeling algorithm is used to extracted the (partially) pair correlated angular distributions from the experimental ion images, as well as the relative populations of O2 rotational states populated during scattering. Strong similarities are observed between the scattering of NO with Ar and O2.
The second part of this thesis focuses on steric effects (the r - k - k' correlation); the initial orientation of the NO bond axis is controlled using a static electric field, such that the collision partner approaches either the ‘ends’ or the ‘sides’ of the NO molecule. A new quantum mechanical theory is presented to describe the scattering of a symmetric top molecule in the presence of an arbitrarily directed electric field. The scattering of NO(X) with Ar at a collision energy of Ecoll = 651cm-1 is presented for ‘end-on’ and ‘side-on’ scattering on the spin-orbit changing and conserving manifolds, respectively. In both cases good agreement with full quantum mechanical calculations is observed. Scattering resulting in only weak deflection is shown to be very sensitive to the orientation of the NO bond axis prior to collision, and is maximised for collisions at the 'side' of the molecule. The integral steric asymmetry for scattering of NO with N2(X) and O2(X) is also presented, and information about the potential energy surfaces for such interactions inferred.

Advisor: Brouard, M
Characterisation of microbubble-membrane interactions in ultrasound mediated drug delivery

Cancer imposes a significant disease burden and constitutes a major societal challenge. Despite being widely used, chemotherapy suffers numerous disadvantages, including off- target drug toxicity, poor tumour penetration, and drug resistance. The use of ultrasound in combination with contrast agents has shown promise in enhancing outcomes in the treatment of cancerous and non-cancerous diseases. However, the underlying biophysical processes that underpin their interactions with tissues remain poorly understood. The aim of the research presented in this thesis is to develop methods to elucidate these processes.
Development is hindered by the difficulties involved in isolating cellular parameters, noninvasively quantifying biological features at the molecular scale, and recreating a predictable and repeatable ultrasound field. To overcome these challenges, giant unilamellar vesicles made with 1,2-dioleoyl-sn-glycero-3-phosphocholine and cholesterol were used initially as cell models and exposed to therapeutically relevant conditions in a purpose-built acoustofluidic device. The resulting effects on the hydration and permeability of the vesicle membranes and the dynamics of their intravesicle milieu were characterised in situ using quantitative microscopy.
Results show that flow, ultrasound, and microbubbles led to an increase in vesicle membrane hydration, while dehydration was seen only in the presence of microbubbles. An increase in permeability was observed for all exposure conditions, and was accentuated when microbubble shell fragments were incorporated in the vesicle bilayer. These findings thus indicate that ultrasound-mediated delivery is governed by a combination of physical and chemical mechanisms that influence the permeation of molecules through lipid membranes. Further, it was shown that exposure to the same conditions led to the onset of streaming flows within the vesicles’ lumen. An experimental proof-of-concept for extending the study in vitro was also presented. Actuating the motion of cytoplasmic constituents may potentially induce a broad range of underexplored and therapeutically relevant bioeffects.

Advisor: Stride, E
Coussios, C
Architectures for fault-tolerant quantum computation

Quantum computing has enormous potential, but this can only be realised if quantum errors can be controlled sufficiently to allow quantum algorithms to be completed reliably. However, quantum-error-corrected logical quantum bits (qubits) which can be said to have achieved meaningful error suppression have not yet been demonstrated. This thesis reports research on several topics related to the challenge of designing fault-tolerant quantum computers. The first topic is a proposal for achieving large-scale error correction with the surface code in a silicon donor based quantum computing architecture. This proposal relaxes some of the stringent requirements in donor placement precision set by previous ideas from the single atom level to the order of 10 nm in some regimes. This is shown by means of numerical simulation of the surface code threshold. The second topic then follows, it is the development of a method for benchmarking and assessing the performance of small error correcting codes in few-qubit systems, introducing a metric called 'integrity' - closely linked to the trace distance -- and a proposal for experiments to demonstrate various stepping stones on the way to 'strictly superior' quantum error correction.
Most quantum error correcting codes, including the surface code, do not allow for fault-tolerant universal computation without the addition of extra gadgets. One method of achieving universality is through a process of distilling and then consuming high quality 'magic states'. This process adds additional overhead to quantum computation over and above that incurred by the use of the base level quantum error correction. The latter parts of this thesis report an investigation into how many physical qubits are needed in a `magic state factory' within a surface code quantum computer and introduce a number of techniques to reduce the overhead of leading magic state techniques. It is found that universal quantum computing is achievable with &Tilde; 16 million qubits if error rates across a device are kept below 10-4. In addition, the thesis introduces improved methods of achieving magic state distillation for unconventional magic states that allow for logical small angle rotations, and show that this can be more efficient than synthesising these operations from the gates provided by traditional magic states.

Keywords: quantum error correction
magic states
surface code
Advisor: Benjamin, S
Atrial cardiomyocytes development from human induced pluripotent stem cells

Cardiovascular diseases are the leading cause of death around the globe. Despite ongoing progress, a shortage in the primary source of human cardiac tissue still presents a major limiting factor in relevant research. Human induced pluripotent stem cells (iPSCs) hold great promise in cardiovascular disease mechanistic research and treatment as they can provide an unlimited supply of cardiomyocytes. Nevertheless, so far, the cardiomyocytes derived from human iPSCs disproportionately recapitulated immature ventricular characteristics, which has hindered the application of iPSC-based models in studying atrial-specific diseases and developing relevant therapies. In the current study, the effectiveness of a combined treatment of Gremlin 2 and retinoic acid (RA) in directing atrial cardiomyocyte differentiation from human iPSCs and driving the in vitro maturation of those derived cardiomyocytes was explored.
Morphologically, human iPSC-derived cardiomyocytes treated with Gremlin 2 and RA recapitulated human adult atrial cardiomyocyte features. The treated cardiomyocytes showed elevated expressions of cardiac genes, atrial-specific genes, inward rectifier potassium channel coding genes and the β1-adrenergic receptor coding gene. However, no significant differences in gene expressions were identified between the treated cells and untreated cells. In addition, the treated cells displayed increases in calcium transient amplitude after α1- and β- adrenergic stimulations and they showed atrial-type action potentials with mature cardiomyocyte features as well. In conclusion, the above results are insufficient to determine the effectiveness of the combined treatment of Gremlin 2 and RA in directing atrial specification and driving in vitro cell maturation, but evidence has been provided that this treatment combination has the potential to produce mature atrial-type cardiomyocytes from human iPSCs with further optimization.

Advisor: Lei, M
The education of American Muslims: knowledge and authority in intensive Islamic learning environments

This ethnographic study explores the ways in which religious teachers use intensive Islamic learning environments as sites to reshape understandings of Islam amongst American Muslims of Sunni orientation. The absence of longstanding traditional Islamic educational institutions in the United States poses challenges for Muslims looking to learn about Islam beyond parental teachings and Sunday schools. However, a range of innovative transmedial learning environments, bridging offline and online spaces, have emerged in recent decades. This is the first ethnographically informed study of such spaces which attends to the role of knowledge and the multidimensional nature of authority in the education of American Muslims.
Using 10 months of fieldwork in Canada, the United States, and Turkey, I draw on and explore narratives of students and teachers, revealing the bodies of knowledge that teachers deem relevant for the development of an American Muslim self and how these teachers situate their authority within a tradition of knowledge transmission. These narratives demonstrate how students seek out certain types of knowledge to develop their religious identities, and the ways teachers respond by selecting and deploying these and other bodies of knowledge in their teaching. Teachers and their associated educational programmes use various pedagogical techniques and accessories to link students to the imagined international Muslim community. This leads to an understanding of how teachers situate their authority within a tradition of knowledge transmission. These teachers ground narratives of self and place within religious and regional histories to define religious practice that is ethical and culturally relevant, and justify their own authority.
This research contributes to debates on the challenges of intra-Muslim dialogue in relation to the umma. It is a ground-breaking empirical study illustrating how, despite the tense geopolitics surrounding Islam and Muslims, American Muslim communities in the 21st century sustain Islamic tradition by developing an Islamic pedagogy relevant to its historical roots and contemporary possibilities in a digital age.

Keywords: American Muslims
authority
Islamic knowledge
muslims
ethnography
religious authority
narrative ehtnography
islam
Advisor: Fancourt, N
Mills, D
Summoning the believers as the Christians did? Religious differentiation in Muslim sources until the third/ninth century.

The Muslim tradition tells us that when Muslims migrated to Medina and their number increased, they felt the need for an efficient means to convoke the community for the daily prayers. Jews and Christians both had well-established summoning rituals involving different instruments, that Muslims considered adopting. They eventually developed a distinct, simple ritual consisting of a small set of chanted formulæ, which became known as the adhān, the Islamic call to prayer. This is the narrative thread that we find in all major Sunnī collections of aḥādīth – reported sayings of Muḥammad and his companions – which recount the introduction of the adhān. The present work postulates that this thread or ‘proto-narrative’ was used by several narrators, transmitters, and collectors until the third/ninth century who modified it and added new elements in order to settle political and religious controversies of their times. This proto-narrative is outlined in the main chapter (chap. 3), which highlights how it was modified and why, using close textual analysis of both Sunnī and Shīʿī texts with data-dense graphs of relations, locations, and times produced via network visualisation tools. Five major Sunnī legal treaties from the second/eighth century onwards were also scrutinised (chap. 4) to better understand the general context in which the aḥādīth about the introduction of the adhān were being circulated and confirm the results obtained through the textual analysis. The conclusions reveal specific mechanisms used in the formation and transmission of aḥādīth. In the case of the adhān, aḥādīth represent half of a ‘conversation’ between people, students, or rulers on one side, asking questions about the origins and the right form of the call to prayer, and on the other side, scholars or jurists who answer with adapted narratives. Only the latter was preserved, yet the present thesis shows that it is often possible to reconstruct, to a certain extent, the former part of this ‘conversation’.

Keywords: Islam
Adhan
Hadith
Islamic Law
Advisor: Sinai, N
Melchert, C
Early Irish kingship

This is not a piece of original research. It is merely an attempt to see what an anthropologist, using the discipline of modern social anthropology, can make of the material that has already been published on pro-Conquest Ireland. The earlier of the chapters on Ireland are little more than a rewriting (and not , I hope, a misrepresentation) of recent specialist publications. The later sections (especially those concerned with the virtues of the kings, and the symbolism associated with Irish kingship) involve a certain amount of analysis that has not, so for as I know, been attempted before in quite the some form, though, as I think, all the main points on which it is supported have been made before by others. It arises in particular from the work of Domézil on Indo-European concepts of sovereignty, of Hocart on kingship, and, in part, from Myles Dillon's consideration of the concept of "Truth" in Irish literature. This being so, and considering also the purpose for which this is written (i.e. for social anthropologists), it would be both ludicrous and pretentious to include extensive quotations in the little known language of Irish. Many (not all) of the quotations given have been referred to in Irish. but they are consistently given here in English. I have not, however, been able to prevent several Irish words and phrases from creeping in. A brief glossary of the most constantly used Irish terms is included for ease of reference, though it has not been possible to standardise the spelling throughout.

Keywords: Irish
Ireland
kings
rulers
kingship
Perception and predication: a synchronic and diachronic analysis of dutch descriptive perception verbs as evidential copular verbs

Descriptive perception verbs have failed to receive a uniform analysis in previous verb classifications (cf. Chomsky 1965, Rogers 1974, Hengeveld 1992, Levin 1993, Van Eynde et al. 2014). This thesis argues that the descriptive perception verbs in Dutch (i.e. eruitzien ‘look’, klinken ‘sound’, voelen ‘feel’, ruiken ‘smell’, and smaken ‘taste’) should be classified as copular verbs, much like lijken ‘seem’ and schijnen ‘seem’. This classification is supported by both the synchronic and diachronic behaviour of these verbs in Dutch. Synchronically, proposing that Germanic copular verbs (as opposed to copulas) are defined by their syntax rather than their (empty) semantics, I discuss that the Dutch descriptive perception verbs behave like stereotypical copular verbs: they require a predicative complement, usually in the form of an adjective. Semantically, the Dutch descriptive perception verbs are much like the copular verbs blijken ‘turn out’, lijken ‘seem’ and schijnen ‘seem’ in terms of epistemicity and evidentiality. Diachronically, I hypothesize that the Dutch descriptive perception verbs have evolved from one of the following two origins: either from intransitive verbs (as is the case for klinken and ruiken), much like English remain, through grammaticalization processes of semantic bleaching and reanalysis; or from cognitive perception verbs (as is the case of eruitzien and voelen), as found in Latin, Japanese and Zulu, through the process of argument reordering. The origin of smaken is not clear, and is left for future research. I show that other Germanic evidential copular verbs (i.e. lijken, schijnen ‘seem’, scheinen ‘seem’, seem) have developed diachronically in a uniform fashion, suggesting the following grammaticalization path: from a lexical verb to a copular verb, to taking a that-complement, an infinitival complement or a like-complement, and eventually being used in parenthetical constructions. The results of this thesis indicate that the Dutch descriptive perception verbs are only at the beginning of this grammaticalization path, but are on their way to becoming grammaticalized evidential copular verbs.

Keywords: Germanic languages
Copular Verbs
Diachronic change
Epistemicity
Dutch
Grammaticalization
Evidentiality
Advisor: Dalrymple, M
Asudeh, A