VictorJuiz/thesis huggingface dataset:
Single molecule studies of seven transmembrane domain proteins
Keywords: conducting atomic force microscopy (C-AFM)
wavelength-sensitivity
molecular conductance photoswitching
bacteriorhodopsin (BR)

This work aimed at studying biophysical properties of two membrane proteins, one of potential nanotechnological use, bacteriorhodopsin, and one potential drug target, the NTS1 neurotensin receptor, at the single molecule scale.
Bacteriorhodopsin (BR) is the only protein in the purple membrane (PM) of the halophilic organism Halobacterium salinarium. It is a light-driven proton pump converting light into a transmembrane proton gradient through isomerization of its retinal chromophore. Its stability, as well as its photoactivity remaining in dry protein layers, has made BR an attractive material for biomolecular devices. Numerous studies have been published on this topic; however, they have all used BR within the PM, on relatively large (µm-wide) surfaces.
Here, conducting-probe atomic force microscopy (C-AFM) analysis was performed after removing most of the membrane lipids. For the first time, it was shown that the molecular conductance of BR can be reversibly photoswitched with predictable wavelength sensitivity. Intimate and robust coupling to gold electrodes was achieved by using a strategically engineered cysteine which, combined with partial delipidation, generated protein trimers homogenously orientated on the surface. Numerous controls using biophysical (SPR, ellipsometry, Kelvin-probe AFM) and chemical (photocurrent, cyclic voltammetry) techniques confirmed the wavelength specificity of the photoswitch, the anchoring role of the mutation and the homogenous orientation of the protein on the gold surface.
Neurotensin is a brain and gastrointestinal 13 amino acid peptide acting as a neuromodulator in the central nervous system and as a hormone in the periphery. Its wide range of biological activities is primarily mediated through its binding to the neurotensin type 1 receptor (NTS1). NTS1 expressed in E.coli was purified and inserted into 100 nm brain polar lipid liposomes in a conformation which retained its ligand-binding capabilities. Initial AFM characterisation was performed as a prelude for ligand-receptor interaction studies, including high resolution imaging, force spectroscopy and solid state NMR approaches.
Multiparametric cardiovascular magnetic resonance for the assessment of cardiac function and metabolism in hypertrophy and heart failure
Keywords: aortic stenosis
metabolism
cardiovascular magnetic resonance
cardiac function
dilated cardiomyopathy

Both hypertrophied and failing hearts are characterised by pathological left ventricular (LV) remodelling, impaired myocardial energy status and alteration in substrate metabolism. Cardiac magnetic resonance imaging (CMR) and magnetic resonance spectroscopy (MRS) are powerful tools in the characterisation of these disease conditions. More recent techniques have allowed assessment of myocardial steatosis using 1H-MRS and tissue oxygenation using blood oxygen level dependent (BOLD) CMR.
In hypertrophy and heart failure, studies on steatosis and the relationship with other parameters such as myocardial function and fibrosis, especially in humans are limited. I therefore investigated the presence of steatosis in severe aortic stenosis (AS) and dilated cardiomyopathy (DCM), and further assessed its relation to contractile function. This study found that myocardial triglyceride (TG) content is increased in both symptomatic and asymptomatic AS patients (lipid/water ratio 0.89±0.42% in symptomatic AS; 0.75±0.36% in asymptomatic AS vs. controls 0.45±0.17%, both p<0.05) and DCM patients (lipid/ratio 0.64±0.44% vs. controls 0.40±0.13%, p=0.03). Circumferential strain was lower in both AS (-16.4±2.5% in symptomatic AS; -18.9±2.9% in asymptomatic AS vs. controls 20.7±2.0%, both p<0.05) and DCM patients (-12.3±3.4% vs. controls -20.9±1.7%, p<0.001). In AS, myocardial contractility is related to the degree of steatosis, and were both reversible following aortic valve replacement (AVR), lipid/water ratio 0.92±0.41% vs. pre AVR 0.45±0.17%, p=0.04 and circumferential strain -17.2±2.0% vs. pre AVR -19.5±3.2%, p=0.04. A novel finding of this study was significant correlation of MRS-measured TG content with histological staining of TG of the myocardium, taken from endomyocardial biopsy during AVR. In DCM, myocardial TG was independently associated with LV dilatation and correlated significantly with hepatic TG, which suggests that both cardiac and hepatic steatosis might be a common feature in the failing heart.
Additionally, although the hypertrophied heart is characterised by impaired perfusion, it is unknown if this is severe enough to translate into tissue deoxygenation and ischaemia. I assessed this by using adenosine vasodilator stress test and BOLD-CMR in patients with severe AS. It was found that AS patients had reduced perfusion (myocardial perfusion reserve index-MPRI 1.0±0.3 vs. controls 1.7±0.3, p<0.001), and blunted tissue oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change 4.8±9.6% vs. controls 18.2±11.6%, p=0.001) during stress. Importantly, there was a substantial improvement in perfusion and oxygenation towards normal after AVR, MPRI 1.5±0.4, p=0.005 vs. pre AVR and BOLD SI change 16.4±7.0%, p=0.014 vs. pre AVR.
Overall, the work in this thesis supports the powerful role of CMR in assessing LV function and elucidating metabolic mechanisms in the hypertrophied and failing heart.
Subsequent use of documents disclosed in civil proceedings
Keywords: Civil Procedure
Disclosure
Subsequent use
Discovery of documents

Rule 31.22 of the Civil Procedure Rules 1998 provides, as a general rule, that those who receive documents through disclosure during civil proceedings may use them only for the purpose of the proceedings at hand. The general rule is subject to three exceptions, and judges have discretion to authorise subsequent use for other purposes. However, the foundational presupposition underpinning CPR 31.22 is that subsequent use, generally speaking, is improper.
The thesis has two primary aims: (1) to demonstrate that the rule governing subsequent use (as developed in the case law) is theoretically and practically flawed, and that maintaining a blanket, general rule against subsequent use is unsound in principle, unjust, and procedurally inefficient; and (2) to generate a normative and procedural framework suitable for reform.
Part I outlines the content, origins and operation of CPR 31.22. Through historical analysis, it suggests that presumptively categorising as improper all forms of subsequent use beyond the original litigation contradicts traditional authority. By identifying and examining the three principal rationales said to justify the modern rule, it argues that none affords sound justification. By analysing the exceptions to the rule, including judicial discretion, it seeks to show that such measures are incapable of remedying the defects in the underlying rule.
Part II attempts to formulate a theoretically defensible, procedurally viable model for reforming CPR 31.22. It suggests that the presumption against subsequent use should be abolished, and the law reoriented around two central norms: the harm principle and a balancing approach. It tests this theoretical model by applying it to seven paradigmatic categories of subsequent use. Finally, it outlines a possible structure for procedural reform.
Characterisation of the transcriptomes of Leishmania mexicana promastigotes and amastigotes
Keywords: leishmania
dual RNA seq
amastigote
trypanosoma
differentiation
RNA sequencing
trypanosomatids
Leishmania mexicana
promastigote
macrophage

Leishmania spp. undergo substantial adaptations from being promastigotes, found in sandflies, to being amastigotes, residing in parasitophorous vacuoles within mammalian macrophages. In the past, microarray studies have sought to elucidate these adaptations using axenic amastigote systems or amastigotes purified from host-cells, raising the question whether the observed transcriptomic signatures were a true reflection of intracellular amastigotes. Moreover, with ever-improving genome annotations being available, it is clear that these studies failed to address the transcriptomic behaviour of a considerable number of transcripts.
In the work presented herein, I employed RNA-sequencing to obtain transcriptomic profiles of Leishmania mexicana axenic promastigotes (PRO), axenic amastigotes (AXA) and intracellular amastigotes (AMA) in murine bone-marrow derived macrophages. The intracellular amastigotes were not purified from host cells, but instead sequencing reads assigned to a hybrid L. mexicana - Mus musculus genome and the transcriptomes separated in silico. We were able to map pre-mRNA processing sites, thereby defining transcript boundaries, proposing 184 truncations and 1253 extensions of existing gene models as well as discovering 936 novel genes. Mass-spectrometric evidence was obtained for both proposed extended and novel proteins. Using this improved genome annotation, we generated gene expression profiles for AMA, AXA and PRO, identifying 3832 differentially expressed transcripts between PRO and AMA as well as 2176 between PRO and AXA and 1234 between AXA and AMA. Transcripts differentially expressed between AMA and PRO correlated well with previous reports, were enriched for novel transcripts identified in this study and contained an unprecedented wealth of yet uncharacterised transcripts.
Guided by these data, I performed a GFP-tagging screen identifying two proteins which may play an important role in L. mexicana biology, LmxM.16.0500, a member of a small, divergent, amastin-derived gene family, which appears to be released from the cell body of PRO, and LmxM.09.1330 a specific marker of the amastigote flagellar pocket.
Tradition and innovation in the Mamluk period: the anti-bid‘a literature of Ibn al-Ḥājj (d. 737/1336) and Ibn al-Naḥḥās (d. 814/1411)
Keywords: innovation
Intellectual history
Islam
Islamic law
tradition
Mamluk period

This study seeks to contribute to a growing discussion about Islamic intellectual endeavours in the Middle Periods, providing new evidence from the genre of anti-innovation tracts (anti-bid‘a tracts) that has hitherto received relatively little modern scholarly attention. Specifically, this thesis examines tradition and innovation in Islam during the Mamluk period (648/1250 – 922/1517) through the lens of two jurists and their anti-innovation tracts. Ibn al-Ḥājj (d. 737/1336) was a Mālikī from North Africa who wrote Madkhal al-shar‘ al-sharīf. Ibn al-Naḥḥās (d. 814/1411), by contrast, was a Shāfi‘ī (and former Ḥanafī) from Damascus, who wrote a tract contained within his Tanbīh al-ghāfilīn, a work concerned with the duty of commanding right and forbidding wrong, and with naming and briefly discussing various sins and innovations.
Ibn al-Ḥājj’s and Ibn al-Naḥḥās’ anti-innovation tracts are studied here for the first time in their own right, together with English translations of representative passages of their work that allow the reader to gain a direct impression of them. In addition to this, this thesis makes three unique arguments. First, anti-innovation tracts should be read as prescriptive yet flexible examples of furū‘. Second, the authors of the tracts investigated here, Ibn al-Ḥājj and Ibn al-Naḥḥās, were both ‘outsiders’ to Mamluk Egypt, who used this genre to define and regulate correct Muslim practices, in less formal ways that were both new and continuous with earlier thinking. Ibn al-Ḥājj’s programme - urging fledgling scholars, in almost encyclopaedic fashion, to know about and teach against innovative practices - was more important for him than addressing the topics of intention and innovation that feature in the full title of his work. Ibn al-Naḥḥās is an interestingly obscure figure. In an abbreviated and direct style, he urged non-specialists in Mamluk lands to censure innovations, and even to prevent them. Third, Ibn al-Ḥājj and Ibn al-Naḥḥās conceived of loyalty to their legal school in ways that require us to expand the terms of modern scholarly debates about such loyalty.
This study contributes to the relatively recent, and fast-growing, literature on the Mamluk period in general, and its legal literature in particular. It supports a recent perspective on the Mamluk period, by illustrating the continuity and evolution of legal thinking during this period, which is both predicated upon, and differs substantially from, earlier periods of Islamic history. and deserves study in its own right.
Quantitative verification of real-time properties with application to medical devices
Keywords: Probability
Approximation Algorithms
Model Checking
Computing
Algorithms
Verification

Probabilistic model checking is a powerful technique used to ensure the correct functioning of systems which exhibit real-time and stochastic behaviours. Many such systems are embedded and used in safety-critical situations, to mention implantable medical devices. This thesis aims to develop a formal model-based framework that is tailored for the analysis and verification of cardiac pacemakers. The contributions are novel approaches for the automatic verification and validation of real-time properties over continuous-time models, which are applicable to software embedded in medical devices.
First, we address the problem of model checking continuous-time Markov chain (CTMC) models against real-time specifications given in the form of temporal logic, namely, metric temporal logic (MTL) and linear duration properties (LDP), or as timed automata (TA). The main question that we address is “given a continuous-time Markov chain, what is the probability of the set of timed paths that satisfy the real-time property under consideration?”. We provide novel algorithms to approximate the probability through generating systems of linear inequalities over variables that represent the waiting times in system states, and then solving multidimensional integrals over this set.
Second, we present a model-based framework to support the design and verification of pacemakers against real-time properties. The pacemaker is modelled as a network of timed automata, whereas the human heart is modelled either as a network of timed automata or as a network of hybrid automata. Our framework can be instantiated with personalised heart models whose parameters can be learnt from patient data, and we have done so to validate our approach. We introduce property patterns and the counting metric temporal logic (CMTL) in order to specify the properties of interest. We provide new verification algorithms for networks of timed or hybrid automata against property patterns and CMTL.
Finally, we pose and solve the parameter synthesis problem, i.e., given a network of timed automata containing model parameters, an objective function and a CMTL formula, find the set of parameter valuations, whenever existing, which satisfy the CMTL formula and maximise the objective function. The framework has been implemented using Simulink, Matlab and Python code. Extensive experimental results on pacemaker models have been carried out and discussed in detail. The techniques developed in this thesis can assist in the design and verification of software embedded in medical devices.
On cleavability
Keywords: ordinal
scattered
compact
cleavability
LOTS
homeomorphic
continuous

This thesis concerns cleavability. A space X is said to be cleavable over a space Y along a set A subset of X if there exists a continuous function f from X to Y such that f(A) cap f(X setminus A) = emptyset. A space X is cleavable over a space Y if it is cleavable over Y along all subsets A of X.
In this thesis we prove three results regarding cleavability.
First we discover the conditions under which cleavability of an infinite compactum X over a first-countable scattered linearly ordered topological space (LOTS) Y implies embeddability of X into Y. In particular, we provide a class of counter-examples in which cleavability does not imply embeddability, and show that if X is an infinite compactum cleavable over ω1, the first uncountable ordinal, then X is embeddable into ω1.
We secondly show that if X is an infinite compactum cleavable over any ordinal, then X must be homeomorphic to an ordinal. X must also therefore be a LOTS. This answers two fundamental questions in the area of cleavability. We also leave it as an open question whether cleavability of an infinite compactum X over an uncountable ordinal λ implies X is embeddable into λ.
Lastly, we show that if X is an infinite compactum cleavable over a separable LOTS Y such that for some continuous function f from X to Y, the set of points on which f is not injective is scattered, then X is a LOTS.
In addition to providing these three results, we introduce a new area of research developed from questions within cleavability. This area of research is called almost-injectivity.
Given a compact T2 space X and a LOTS Y, we say a continuous function f from X to Y is almost-injective if the set of points on which f is not injective has countable cardinality. In this thesis, we state some questions concerning almost-injectivity, and show that if lambda is an ordinal, X is a T2 compactum, and f is an almost-injective function from X to lambda, then X must be a LOTS.
Out of many, one: epigram anthologies in pre-modern Arabic literature
Keywords: Epigrams
Poetry Anthologies
Arabic Poetry

This is the study of a previously neglected genre in pre-modern Arabic literature: the (poetic) epigram anthology. The epigram anthology was pioneered by a handful of poets in 14th-century Syria, but the genre was soon taken up by anthologists across the pre-modern Middle East and soon became one of the most popular types of Arabic poetry up until the modern period. This study is divided into two parts. Part One deals with critical issues in literary history and comparative literature, while Part Two is made up of three encapsulated studies on specific aspects of the social and literary (structural and textual) composition of the texts. In Part One, the epistemological background of the terms epigram and anthology is surveyed and their suitability for application to pre-modern Arabic literature is evaluated. Part One also includes a comprehensive history of the maqāṭīʿ (sing. maqṭūʿ, also maqṭūʿah) genre in Arabic as well as a detailed explication of this style of poetry, its anthological context, its generic status in the Arabic literary tradition, and its relation to the wider world-literary category of epigram. The three chapters of Part Two are devoted to the social network of anthologists and poets, the structure and composition of the anthologies themselves, and the way in which anthologists used a technique, which is called ‘variation’ in this study, to link the cited poetic material into an organic whole respectively. NB: This is a literary-historical study informed by the discipline of comparative literature; it is not primarily a philolological, biographical, or codicological investigation. The literary material presented here is what has been deemed most relevant for the purposes of the larger generic discussion at the centre of this literary-historical study. An annotated bibliography of unpublished sources is provided in an appendix in order to help the reader navigate the tricky present status of many Mamluk and Ottoman era sources.
Exploring the reactivity of cationic rhodium xantphos complexes with amine-boranes
Keywords: dehydrocoupling
Amine-borane
Xantphos
rhodium

This thesis explores the reactivity of amine-boranes with the {Rh(Xantphos)}+ fragment, with the aim of gaining mechanistic insight into the catalytic dehydropolymerisation of the amine-borane H3B∙NMeH2 to yield the polyaminoborane [H2BNMeH]n.
Chapter 2 describes the synthesis of suitable RhIII and RhI Xantphos precursors to be used in this investigation. Moreover, the first example of the dehydrogenative B—B homocoupling of the tertiary amine-borane H3B∙NMe3 to form H4B2•2NMe3 is reported.
The synthesis of the RhI precatalyst introduced in Chapter 2 entails the hydroboration of tert-butylethylene by H3B∙NMe3. In Chapter 3, the ability of the {Rh(Xantphos)}+ fragment to mediate this hydroboration in a catalytic manner is explored, and a mechanism is presented in which reductive elimination is proposed to be turnover-limiting. Other alkenes and phosphine-boranes are also trialled to determine the scope of the hydroboration.
Chapter 4 investigates the catalytic dehydrocoupling of H3B∙NMe2H and H3B∙NMeH2 with {Rh(Xantphos)}+ to form the dehydrocoupling products [H2BNMe2]2 and [H2BNMeH]n, respectively, and the dehydrocoupling mechanisms are shown to be similar. Both involve an induction period in which the active catalyst is formed (thought to involve N—H activation), and saturation kinetics operate during the productive phase of catalysis. H2 is shown to inhibit the dehydrocoupling, and lead to production of shorter chain [H2BNMeH]n. Conversely, using THF as the dehydropolymerisation solvent instead of C6H5F results in longer chain [H2BNMeH]n.
Finally, Chapter 5 presents new dicationic {Rh(Xantphos)}-based dimers, the formation of which involves loss of a phenyl group from the Xantphos ligands by P—C activation. The dimers are produced by routes involving either dehydrogenative homocoupling of H3B∙NMe3, or dehydrocoupling of H3B∙NMe2H. One of these dimers was tested as a catalyst for the dehydrocoupling of H3B∙NMe2H, and the reaction kinetics appear closely related those obtained using {Rh(Xantphos)}+, suggesting that the active catalysts in each system may be related.
Brokers of uncertainty?: a sociology of law enforcement analysis
Keywords: policing

Law enforcement analysis is increasingly utilized by police organizations to help its warranted officials understand the public safety and security environment and make decisions about threats, harms and risks. While there is a well-developed practitioner literature and a number of evaluative studies about law enforcement analysis, there has been little empirical research into the day-to-day work practice of law enforcement analysis. This thesis utilizes participant observation and semi-structured interviews to construct an ethnography of the daily work practice of law enforcement analysis in three sites in the USA, Ireland and the UK. This empirical research at the intersection of the organizational structures and work cultures of both the law enforcement analytic units and the larger police organisation to which they belong helps explain not only how knowledge is created but also what knowledge and why. The thesis concludes that while law enforcement analysis produces valuable knowledge about current threats and harms and plays a role in organizational risk management, a variety of factors circumscribe the type of knowledge that is produced. The result is that the future is left largely unknown and that law enforcement analysts play a limited role in brokering organizational uncertainty about the public safety and security environment.