VictorJuiz/thesis huggingface dataset:
Retroactive recharacterisation of crimes: the principles of legality and fair labelling in international criminal law
Keywords: Non-retroactivity
International Criminal Law
International Criminal Court
Legality
Fair Labelling

The principle of legality is one of the most fundamental principles of criminal law. It requires crimes and penalties to be established by law at the time of the conduct. In international criminal law, it applies as a rule of custom, treaty and a general principle of law. Nonetheless, the principle sits uneasily with some unique features of the international legal order, particularly its multiple adjudicative and prescriptive authorities. This has led to a frequent but overlooked practice known as ‘retroactive recharacterisation of crimes’. This occurs when, upon charging, convicting or sentencing the accused, an international or domestic tribunal substitutes new rules of criminal law for those applying at the time of the conduct. Retroactive recharacterisation of crimes has been justified on the basis of a cursory reading of the principle of legality in general international law, which, on closer look, does not seem to accommodate some of its problematic outcomes. It is also unclear whether this phenomenon is consistent with the principle of fair labelling, which necessitates criminal labels to be representative of the accused’s blameworthiness. This thesis seeks to answer two principal research questions. First, how are the principles of legality and fair labelling to be applied in international criminal law generally and in the specific context of the International Criminal Court? Second, to what extent is the phenomenon of retroactive recharacterisation of crimes consistent with them, bearing in mind their elements, scope and rationales? Its central claim is that, although not per se contrary to both principles, changes in the applicable criminal law which substantively affect the fundamental rights of the accused, including the imposition of more stigmatising labels, may be unlawful. To address this, the substantive criminal law binding on the accused at the crime of the conduct ought to be applied as such.
Becoming families: a study of same-sex couples' rights in the Anglo-Saxon countries
Keywords: Ireland
Australia
same-sex marriage
Anglo-Saxon Countries
social policy
marriage policy
United Kingdom
LGBT
New Zealand
politics
Canada

The politics surrounding the recognition of same-sex couples has found uneven analysis in the extant literature. While the dynamics in the United States and Western Europe are well-documented, the processes in the Anglo-Saxon countries is less advanced. This oversight is two-fold. First, the empirical record regarding the historical evolution of same-sex couples’ rights is wanting. Second, the theoretical framework of morality policymaking is unevenly theorised and therefore ill-equipped in dealing with this set of countries. This set of countries, therefore, is chosen to advance the extant theories regarding the politics of same-sex couples’ rights. In short, this thesis aims to add to the empirical evidence and advance the theorisation of morality policy in ‘secular’ countries; that is countries which do not feature a politically relevant state-church conflict.
The thesis pursues this goal through four cases studies that each rely on qualitative research methods. First, it develops a theoretical framework to show the secularisation and contractualisation of opposite-sex marriage and outlines these processes’ importance for same-sex marriage advocacy. Second, it uses the experience of the Anglo-Saxon countries to develop a new judiciary-based mode of international policy transfer. Third, it uses the case of same-sex union recognition in Australia to develop the morality policy framework in regard to secular countries. This analysis expands to the extant understanding of morality policymaking in particular regarding parliamentary democracies of the Westminster type. Fourth, the thesis analyses the Adoption and Children Act 2002 in England and Wales to understand why same-sex couples were granted joint adoption rights before any form of formal union recognition.
The results of these case studies indicate that the morality policy framework is only partially useful for explaining the politics in Anglo-Saxon countries. In setting the parliamentary agenda, the executive has very strong albeit not absolute control. In the legitimation of policy, the competition between ‘progressive’ and ‘traditionalist’ frames is confirmed, as is the ability of the executive to reinforce its preferred policy definition in the case of latent morality policies. However, the treatment of manifest morality policy requires the careful analysis of intra-party fractions and vested interests. Further research is required to test the theoretical frameworks built in this thesis and in particular the applicability of the morality policy framework in similar countries.
Epidemiology of environmental enteric dysfunction, malnutrition and intestinal microbiota amongst children in Kilifi, Kenya
Keywords: Environmental Enteropathy
Small intestinal bacterial overgrowth
Environmental Enteric Dysfunction
Tropical medicine
Childhood malnutrition
Intestinal microbiota

Environmental Enteric Dysfunction (EED) is a chronic intestinal inflammatory disorder that is highly prevalent amongst children in tropical low-income settings and associated with stunting (low height-for-age). I undertook two studies in coastal Kenya that aimed to explore the aetiology of EED. Firstly, in a cross-sectional survey across 12 villages, 509 under-fives from 229 randomly selected homesteads underwent anthropometry and provided a stool sample. Participant sociodemographic and health characteristics were determined by questionnaire. 419 stool samples underwent enzyme-linked immunosorbent assay (ELISA) for three markers of EED: alpha-1-antitrypsin, myeloperoxidase and neopterin. EED risk factors identified included older age, geophagy and recent acute illness. Secondly, in a birth cohort of 99 participants aged zero to nine months, 839 dual sugar absorption tests and 934 breath hydrogen tests were carried out at monthly intervals to measure EED and small intestinal bacterial overgrowth (SIBO) respectively. Stool samples were collected bi-weekly and 434 underwent ELISA for alpha-1-antitrypsin, myeloperoxidase and neopterin. Acute illness and antibiotic episodes were captured by active and passive surveillance. Breastfeeding status was recorded weekly. EED increased with age and was associated with stunting. In a multivariable model, EED was not associated with SIBO, acute illnesses, household water/sanitation/hygiene or antibiotics. In the same model, adjusted for age, EED was worse amongst those who had ceased exclusive breastfeeding, and for one EED biomarker this association was only seen during the rainy season.
Doing good badly? Philosophical issues related to effective altruism
Keywords: Hilary Greaves
moral philosophy
William MacAskill
cause prioritisation
happiness
saving lives
Peter Singer
effective altruism

Suppose you want to do as much good as possible. What should you do? According to members of the effective altruism movement—which has produced much of the thinking on this issue and counts several moral philosophers as its key protagonists—we should prioritise among the world’s problems by assessing their scale, solvability, and neglectedness. Once we’ve done this, the three top priorities, not necessarily in this order, are (1) aiding the world’s poorest people by providing life-saving medical treatments or alleviating poverty itself, (2) preventing global catastrophic risks, such as those posed by nuclear war or rogue artificial intelligence, and (3) ending factory farming.
These claims are both plausible and striking. If correct, they should prompt a stark revision of how we approach our altruistic activities. However, the project of determining how to do the most good—as opposed to say, whether we should do the most good—has only recently, within the last ten years, become the subject of serious academic attention. Many key claims have not yet been carefully scrutinised. This is a cause for concern: are effective altruists doing good badly?
In this thesis, I critique and develop some of the latest claims about how individuals can do the most good. I do this in three areas: the value of saving lives (preventing premature deaths), how best to improve lives (making people happier during their lives), and cause prioritisation methodology (frameworks for determining which problems are the highest priorities). In each case, I raise novel theoretical considerations that, when incorporated, change the analysis.
Roughly speaking, my main conclusions are (1) saving lives is not as straightforwardly good we tend to suppose, may not be good at all, and is not clearly a priority; (2) happiness can be measured through self-reports and, based on the self-reported evidence, treating mental health stands out as an overlooked problem that may be an even more cost-effective way to improve lives than alleviating poverty; (3) the cause prioritisation methodology proposed by effective altruists needs to be moderately reconceptualised and, when it is, it turns out it is not as illuminating a tool as we might have thought and hoped.
Isolated singular points and the Gauss-Manin connection
Keywords: Gauss-Manin
connection
points
singularities
hypersurfaces
singularity
polynomials
Bernstein
connections
singular

This thesis studies the Gauss-Manin connection for the Milnor fibration of a complex hypersurface with an isolated singular point. Using the formalism developed by Brieskorn and Malgrange, we give an explicit basis, with respect to which the connection has a simple pole and its residue matrix has a manageable form. We calculate the residue for several examples. The method of calculation enables us to give some examples relevant to questions arising in Malgrange's work on the Bernstein polynomial. We also make several conjectures related to the monodromy theorem.
Design, synthesis and properties of multivalent DNA nanomaterials for cancer diagnostics and therapeutics
Keywords: DNA nanoflower
Aptamers
Chemical ligation
Cancer diagnostics and therapeutics
RCA
Cyclic oligonucleotides

Aptamer-functionalised DNA nanostructures have been developed as drug nanocarriers for targeted cancer therapy and other in vivo applications. Among them, hierarchical DNA nanoflowers (DNA-NFs) with densely packed DNA that can self-assemble using rolling circle amplification (RCA) hold promise for cancer therapy. To expand the functionality of DNA-NFs, the inorganic core of the nanoflowers was chemically modified through substitution of Mg2+ with either Mn2+ or Co2+ during the RCA process, resulting in formation of nanomaterials in a range of morphologies. These nanoconstructs retain the stability against enzymatic degradation of their magnesium counterparts and the Mn2+ and Co2+ DNA-NFs were endowed with magnetic properties. Cyclic nucleic acid templates are essential substrates in RCA reactions, and are most commonly obtained via enzymatic cyclisation. However, the cyclisation efficiency mainly depends upon the length of the linear precursor and is inefficient when the linear oligonucleotide has complex secondary structures. To circumvent the limitations of enzyme-catalysed DNA cyclisation, three different chemical cyclisation approaches were explored for the preparation of single-stranded cyclic DNA constructs. These chemical cyclisation methods are cheaper and easier to carry out in a large scale than their ligase-mediated counterpart. They can also be carried out under denaturing conditions and are therefore particular valuable for cyclic DNA templates containing complicated secondary structure. The resulting cyclic DNA templates contain a single unnatural backbone linkage at the ligation site (triazole, phosphoramidate or amide). They were compared to unmodified cyclic DNA templates in RCA reactions using Ф-29 and Bst 2.0 DNA polymerases. The phosphoramidate-modified cyclic templates were particularly well tolerated by Ф-29 DNA polymerase, consistently performing as well as the unmodified natural backbone in RCA. In contrast, the cyclic templates containing a triazole backbone linkage generally showed lower and more variable yields of RCA products, a significant proportion of which were double-stranded DNA side-products. The performance of the amide-modified cyclic templates fell in between those of the triazole- and phosphoramidate-modified cyclic templates. Moreover, all cyclic templates containing modified backbone linkage could be used to produce DNA-NFs during the RCA process.
Molecular mechanisms relevant to the maintenance of locomotor control
Keywords: Enkephalinergic neurons
Striatum
locomotor behavior

The striatum, consisting of enkephalin-positive (Penk+) and substance P-positive subpopulations of medium spiny neurons (MSNs), integrates and drives information and function of the basal ganglia circuits, which is crucial for maintaining normal movement. Preferential degeneration of the Penk+ MSNs has been observed at early stage of Huntington disease (HD). Recently, selective deletion of TrkB, high affinity receptor of brain derived neurotrophic factor (BDNF), specifically in the Penk+ MSNs (TrkbPENK-KO) led to an age-dependent spontaneous hyperlocomotion, but not to neuronal loss, indicating that TrkB is essential to maintain normal locomotor control. However, the underlying molecular mechanism still remains unknown. Dissecting the molecular changes induced in the Penk+ MSNs in the context of absence of TrkB is imperative to understand mechanism of normal locomotor maintenance. We, therefore, have performed transcriptomics analysis by next generation sequencing (RNA-seq) on the purified Penk+ MSNs with and without ablation of TrkB at two ages. Subsequent bioinformatics analysis has revealed early energy metabolism and mitochondrial dysfunction specifically to the Penk+ MSNs, leading to the severe energy deficiency at later stage. We have then validated hits from the RNA-seq data by optimising comprehensive validation approaches. Interestingly, the bioinformatics analysis led to the discovery of dopamine dysregulation in mutants at early age that could contribute to an age-dependent hyperlocomotor phenotype. Amongst the hits we validated, an enzyme involved in the glutathione metabolism, was identified as a key gene with unique expression pattern driving transcriptomic changes of the Penk+ MSNs. Furthermore, by creating a Cre-dependent shRNA lentiviral vector, we selectively knocked down specific gene expression in the Penk+ MSNs in vivo at presymptomatic age. Excitingly, this significantly rescued the hyperlocomotor phenotype of the TrkbPENK-KO mice. These findings add knowledge to the molecular mechanisms underlying normal locomotor maintenance, and they also highlight related pathway as a potential target for the development of novel treatments to movement disorders.
Practising the Irish enlightenment:  the role of medical men in Ireland’s learned societies, 1683-1801
Keywords: Republic of Letters
Medical Practitoners
Ireland
Enlightenment
Learned Societies and Academies
History of Medicine

This thesis examines the neglected practice of Enlightenment in Ireland through a study of the institutional character of Ireland’s Republic of Letters. It focuses on the unique and fundamental contribution made by medical men to the life of Ireland’s learned societies. It argues that Ireland had an Enlightenment and it was Irish. It contends that medicine and medical practitioners constituted a vitally important, yet unexamined, part within it.
It suggests that Ireland experienced a moderate Enlightenment (c.1683-1790), which was founded on the notion of improvement and a radical Enlightenment (c.1791-1801), which was rooted in republicanism and revolution. It proposes that Ireland’s learned societies institutionalised a vibrant patriotic and cosmopolitan Republic of Letters between 1683 and 1801 and that their members were self-conscious engines of the Irish Enlightenment.
It argues that Ireland’s men of letters shared a common identity and fundamental commitment to the concept of improvement and were united by their belief in the advancement of knowledge, peaceful reform and, as the century progressed, to the notion of increased religious toleration. It maintains that Ireland’s medics were the leading animators and beating heart of these learned societies. It demonstrates that Ireland’s medics were engaged in ambitious programmes of social, economic and political reform. It concludes that while the pursuit of medical and natural knowledge was not the only concern of the Irish Enlightenment, it was, nevertheless, a vital component and suggests that a medical Enlightenment was taking place in long eighteenth-century Ireland.
This thesis shows, not just that the ideas of the Enlightenment had been transferred, jug to mug style, into Ireland from abroad but that the flow of knowledge was never just one way. It demonstrates how Ireland’s medics contributed to key Enlightenment debates and were active participants in a transnational Republic of Letters and Enlightenment.
The paribhāṣā, yadāgamās tadguṇībhūtās tadgrahaṇena gṛhyante in the Pāṇinian tradition
Keywords: paribhāṣā
Sanskrit
Pāṇini
yadāgamaparibhāṣā
āgama
vyākaraṇa
grammar
Aṣṭādhyāyī

The current work studies a paribhāṣā “metalinguistic rule” about āgama “augment” within the scope of the Pāṇinian tradition of Sanskrit grammar (vyākaraṇa). One of the forms in which this paribhāṣā (“the yadāgamaparibhāṣā”) is found is yadāgamās tadguṇībhūtās tadgrahaṇena gṛhyante (e.g. #11 in Paribhāṣenduśekhara). The current work discusses various aspects of āgama (Chapter 2), translates and explains the texts found in the Mahābhāṣya and five Pāṇinian paribhāṣā treatises that deal with the yadāgamaparibhāṣā (Chapter 3-8), and presents, based on the treatment of these texts, evaluation and remarks (Chapter 9). It argues that Pāṇini must have assumed the effect of the yadāgamaparibhāṣā, but he may not necessarily have assumed an additional paribhāṣā like yadāgamās tadguṇībhūtās tadgrahaṇena gṛhyante or tadbhaktas tadgrahaṇena gṛhayate to achieve this effect, because this effect can already be achieved through elements within the Aṣṭādhyāyī itself, i.e. sūtra 1.1.46 and 1.1.56. Therefore, such an additional paribhāṣā can be assumed, but is not necessary. The current work may thus contribute to a better understanding of: <1> the concept and function of āgama in the Aṣṭādhyāyī system; <2> the yadāgamaparibhāṣā; <3> through the previous two points, the working of the Aṣṭādhyāyī system itself; and <4> the Pāṇinian paribhāṣā literature, e.g. how a paribhāṣā is interpreted and argued about by the commentators.
Mathematical modelling of lead-acid batteries
Keywords: lead-acid batteries
asymptotics

Electrochemical and equivalent-circuit modelling are the two most popular approaches to battery simulation, but the former is computationally expensive and the latter provides limited physical insight. A theoretical middle ground would be useful to support battery management, online diagnostics, and cell design.
In this thesis, we present a porous-electrode model of a lead-acid battery, which includes an extension of concentrated-solution theory that accounts for excluded-volume effects, local pressure variation, and a detailed microscopic water balance.
Asymptotic analysis of the one-dimensional model in the limit of small discharge rate produces three reduced-order models, which relate the electrical behaviour to microscopic material properties, but simulate discharge at speeds approaching an equivalent circuit. A lumped-parameter model, which neglects spatial property variations, proves accurate for small discharge rates (below 0.1C), while a spatially resolved higher-order solution retains accuracy at higher discharge rates (up to 5C). The reduced-order models provide improved insight into the battery's behaviour. The models are fit to experimental data, showing good agreement.
We then consider the three-dimensional model and exploit the limit of small aspect ratio to decompose the through-cell and transverse dimensions. Further asymptotic analyses in the limit of high conductivity and/or small discharge rate give new simplified models that capture transverse non-uniformities at reduced computational cost. In the simplest case, the current collectors act as series resistors.
In order to explore the behaviour of a lead-acid battery during recharge, we return to a one-dimensional model and add an oxygen reaction to the model. We find that the oxygen recombination must be diffusion limited in the negative electrode, leading to non-monotonic voltage increase during constant-current recharge. Reduced-order models in the limit of slow recharge provide good approximations to the full charging model.
Investigating the role of the anti-malarial drug Atovaquone in anti-cancer therapy
Keywords: Cancer
Electron Transport Chain
Metabolism
Radiobiology
ETC
Atovaquone
OXPHOS Inhibition
Hypoxia

Radiotherapy (XRT) is used in over half of all cancer treatment regimens and can be administered alone or in tandem with chemotherapeutics to improve clinical outcomes. Sub-physiological levels of oxygen (hypoxia) is a feature of many solid tumours and can diminish the effectiveness of anti-cancer treatments. Though its detrimental impact on treatment efficacy was first realised over half a century ago, hypoxia endures as a significant barrier to improving clinical outcomes.
Historically, numerous approaches to alleviate or even exploit tumour hypoxia have been explored; however, none are in widespread clinical use today. Most strategies were predicated on therapeutic agents reaching hypoxic areas that are difficult to penetrate, yielding minimal clinical efficacy. Attempting to increase oxygen supply directly via hyperbaric chambers was similarly ineffective. An emerging alternative approach based on modulating cellular demand for oxygen was recently pioneered by our team. We theorised that reducing oxygen consumption of cells that are located in adequately perfused areas and peri-hypoxic regions might increase the concentration of unmetabolised oxygen able to diffuse across a tumour bed and into hypoxic areas.
Using a high-throughput small molecule screen, our team previously identified that the FDA-approved, anti-malarial drug Atovaquone (ATQ) reduces oxygen consumption, upregulates glycolysis, and alleviates tumour hypoxia in vivo. As a consequence of the alleviation of hypoxia, ATQ therapy was furthermore shown to synergise with XRT. ATQ is a ubiquinone analogue, suppressing oxidative phosphorylation via direct inhibition of Complex III subunit bc1 of the electron transport chain (ETC). ATQ is a well-studied anti-malarial agent and our team is actively undertaking multiple clinical studies to evaluate its suitability as a clinical hypoxia modifier.
This thesis builds on our teams’ previous work by exploring the broader effects of ATQ in an anti-cancer setting. The first experimental chapter (Chapter 3) probes the reversibility and tolerability of ATQ in vitro and in vivo before exploring preliminary mechanistic dependencies for how ATQ reverses hypoxia. Metabolic reprogramming towards a more glycolytic phenotype has long been implicated as a key promoter of aggressiveness and metastatic spread and so Chapter 4 probes the effects of ATQ on cancer cell migration in vitro and metastatic potential in vivo. In the last experimental chapter (Chapter 5), we reveal that ATQ potentiates the anti-cancer efficacy of platinum-class chemotherapy agents by modulating ETC-driven oxidative stress. Chapter 6 summarises the findings of the thesis as a whole and discusses future directions.
Together, the data presented in this thesis suggests that ATQ is a translationally viable and well-tolerated hypoxia modifying agent having pleotropic effects that are undoubtedly deserving of further study.