VictorJuiz/thesis huggingface dataset:
Macroautophagy, alpha-synuclein and dopamine neurotransmission: implications for Parkinson’s disease
Keywords: Parkinson's disease
Autophagy
Neurology

Parkinson’s disease (PD) is an incurable neurological disease characterised by impairment of motor function, death of substantia nigra pars compacta (SNc) dopamine (DA) neurons and accumulation of the protein α-synuclein. Macroautophagy, a major process by which deleterious cellular contents are degraded, is implicated in both sporadic and genetic PD, and macroautophagy inducers are currently in PD clinical trials. However, little is known about the interaction between α-synuclein and macroautophagy in vivo.
In this thesis, the interaction between impaired macroautophagy in DA neurons and α-synuclein was studied by generating novel transgenic mice. Mice were bred featuring conditional knockout of ATG7, a gene essential for macroautophagy, in DA neurons (ATG7cKODAT-IRES-cre), and expressing the full-length human α-synuclein gene (hSNCA). Mice carrying the ATG7cKODAT-IRES-cre genotype developed key features of PD, including loss of SNc DA neurons, reductions in caudate-putamen DA and the development of protein aggregates in DA neurons. Presence of the hSNCA gene had minimal effect on histological phenotypes. Paradoxically, ATG7cKODAT-IRES-cre mice displayed improvements in some elements of motor function, including increased locomotion, increased gait swing speed and improved motor coordination in old age. There was no effect of the hSNCA gene on behavioural phenotypes.
In order to determine a physiological basis for the discrepancy between the neuropathological and motor phenotypes associated with the ATG7cKODAT-IRES-cre genotype, DA neurotransmission was examined using fast-scan cyclic voltammetry (FCV). FCV demonstrated that the ATG7cKODAT-IRES-cre genotype increased evoked DA levels, reduced the rate of DA reuptake, and increased evoked DA in response to repeated stimuli. The finding that impaired macroautophagy in DA neurons enhances DA neurotransmission was confirmed in a second transgenic mouse model. These data demonstrating that impaired macroautophagy enhances dopamine neurotransmission, thus improving behavioural phenotypes while worsening some pathological phenotypes, has direct implications for PD pathogenesis, drug discovery and clinical trials.
Between scripture and human reason: an intellectual biography of Muḥammad ibn Ismāʿīl al-Bukhārī (d.256/870)
Keywords: Hadith criticism
Bukhari
early kalam
Islamic law

By the dawn of the fifth/eleventh century, al-Bukhārī (d. 256/870) was recognized as the most highly regarded hadith scholar and his Ṣaḥīḥ as the most authoritative book, after the Qurʾan. This canonical status promoted a romanticized version of al-Bukhārī that does not reflect the reality that his pre-canonical historical record presents. This study recovers the reality of al-Bukhārī and provides a critical biography of him, tracing the progress of his career and detailing the objectives of his work. It provides a re-assessment of al-Bukhārī’s own juridical, theological, and hadith-criticism principles based on an analysis of his own works, arguing that al-Bukhārī was shaped by the split between hadith and raʾy. It distinguishes three stages in his career: early education under raʾy authorities, conversion to hadith-based school, and his critique of the raʾy-based scholars in Transoxania. Al-Bukhārī was a significant contender of theology and law in his own day and certainly promoted a moderate position in theology and law that proved crucial to his future renown. He appears to have been Medinese in law and Iraqi in hadith criticism. His legal theory adopts some of Mālik ibn Anas’ (d. 179/795) views and al-Shāfiʿī’s (d. 204/820) hermeneutical concepts. His legal method and positive law appear to be systematically anti-raʾy and exhibit a virulent disparage of Abū Ḥanīfa (d. 150/767) and al-Shaybānī (d. 192/804-5). It appears that al-Bukhārī composed the Ṣaḥīḥ over a long period, at least a decade, as the Ṣaḥīḥ itself tends to confirm a chronological progress. This progress, the author contends, was the outcome of al-Bukhārī’s long project in Transoxania, combating raʾy and promoting hadith. Al-Bukhārī achieved prominence within hadith-based circles for his unique transmitter-criticism (rijāl) works, particularly al-Tārīkh, but when he conceded that one’s utterance (lafẓ) of the Qurʾan is created, he was immediately denounced by the hadith-based school. This controversy caused the collapse of al-Bukhārī’s career, leading to his demise in Khartank near Samarqand in 256/870.
The Armenians in the Ottoman Empire after the First World War (1918-1923)
Keywords: Armenians
Ottoman Empire
Armistice years
First World War

This thesis is a historical study of the Ottoman Armenians in the Ottoman Empire from 1918-1923. It seeks to delineate how the Ottoman Armenians reorganised their political position against the massive socio-political crises that led to the collapse of the Ottoman Empire. The thesis analyses the transformation of the Armenian political position by examining the Ottoman Turkish and Armenian press. The study contends that the Ottoman Armenians struggled to reorganise their political and social life after the First World War and established alliances with the Allied Powers to create an independent ‘Western Armenia’, which would ultimately unite with the Armenian state in the Caucasus. The Ottoman Armenians developed a patriotic approach that sought unification with their compatriots in the Caucasus. However, after the defeat of the Greek army by the Nationalist troops in Anatolia in 1922, the collective approach among the Ottoman Armenians changed significantly. After the Nationalist victory had become inevitable, the Ottoman Armenians sought reconciliation and peace with the Turks. This reconciliation was only possible through the acceptance of 'Turkish supremacy' by the Ottoman Armenians. In other words, the Armenians who chose to remain within the boundaries of Turkey preferred to pledge loyalty to the newly established Nationalist government in Ankara. The establishment of the Türk-Ermeni Teali Cemiyeti (Turkish Armenian Ascent Association) and the reconciliation attempts of the Ottoman Armenians with the Muslim Turks is an example of the transformation of the Armenian collective position among the Ottoman Armenians. This study employs Armenian and Ottoman Turkish media sources published in Istanbul and Anatolia during the Armistice years (1918-1923) to track the post-war interrelationship of Ottoman society in general and the Armenian community in particular, the social and political reorganisations of the Armenian community and the transformation of the Armenian political position in the last years of the Ottoman Empire. By doing so, the thesis challenges both Ottoman/Turkish and Armenian historiographies, and attempts to bring these two historiographic approaches together with a new approach to understand this historical period.
Questioning neutrality: Sino-Portuguese relations during the war and the post-war periods, 1937-1949
Keywords: Portugal
Second Sino-Japanese War
Second World War
China
Macau

This thesis is a study of neutrality and collaboration during the Second World War in East Asia. It analyses the relations between China and Portugal during the conflict and the immediate post-war period, with a particular focus on the enclave of Macau, the only foreign-administered territory in China not to be occupied by Japan. It argues that the practice of Portuguese neutrality in East Asia was marked by great ambivalence and used by different actors for their own, often conflicting, ends. In social history terms, Macau was part of the war, with comparable experiences to other cities in China, including a massive refugee influx, as well as everyday experiences of hunger, popular mobilisation for relief, and urban crime. Wartime Macau was marked by multiple layers of collaboration involving Chinese, Portuguese, British, Japanese, and others. This thesis also argues that wartime issues left unsolved had an impact on Sino-Portuguese relations after the war. Its dealings with a small European imperial power reveal China’s attempts and difficulties to exercise its regained sovereignty and new international status.
The politics of performance in Viking Age skaldic poetry
Keywords: Dialogic
Skaldic
Old Norse
Performance
Diplomacy
Óðal
Viking Age
Politics

This thesis examines the political functions of the performance of skaldic poetry during the Viking Age. It aims to establish the vital role that skaldic verse plays in the establishment and maintenance of power, as well as the importance of skaldic performance in the negotiation of that power in the inter-community relations between various courts both within and outside of Viking Age Scandinavia. The first chapter provides a contextual understanding of Viking Age power structures by considering the central ideological constructs surrounding the concept of óðal (ancestral property). Óðal-derived power, it will be shown, is based on ruler-presence (which extends to ancestral presence) in the landscape, which is perceived as a crucial element in the legitimisation of authority and power. My second chapter will consider the political significance of skaldic performance within the context of ruler itinerancy, which develops in response to political practices based on the importance of óðal-derived legitimacy. Of particular importance in this respect, will be the use of ‘presencing’ proper- and praise-names in skaldic poetry that effect both spatial and temporal itinerancies in a highly distributable format. My third chapter will establish the representational features of skaldic performance and elaborate on the definition of Performance not only as action (in the Austinian sense), but also as a type of action that is defined by its artifice, its temporal continuity and its emergent dialogism. This will provide the theoretical context for my fourth and final chapter which will aim to examine the employment of skaldic Performance in Viking Age diplomatic praxes. Here the phenomenologically perceived ‘binding’ of the Self through the dialogic rhythmicity that arises out of skaldic ambiguity and crypticism will be of central importance.
Elucidating the principal role of cholecystokinin neurons of the ventromedial hypothalamic nucleus in energy homeostasis
Keywords: hyperglycemia
cholecystokinin
glucose
hypothalamus
appetite
obesity

The central nervous system (CNS) has a crucial role in the maintenance of energy homeostasis by orchestrating a plethora of signals from peripheral organs about the state of energy stores and the current energy intake needed to match energy expenditure. These signals converge into the hypothalamic regions and its complex local circuitry. CNS-derived cholecystokinin (CCK) is acting at central level to modulate energy balance by regulating the neuronal activity of hypothalamic neuronal populations that regulate food intake, energy storage and consumption. Moreover, our recent published work identifies CCK neurons as key integrators of the neuroendocrine negative feedback of glucocorticoids to the PVN. Glucose sensing neurons of the Ventromedial Hypothalamus (VMH) are integrating energy signals and are essential for mounting a counter-regulatory response and glucose homeostasis. VMH is also important in energy expenditure by regulating body weight and thermogenesis. CCK neurons are present in high density in the VMH.The source of endogenous CCK that acts on distinct neuronal components has not been elucidated. The research so far does not address the purpose of CCK neurons in the hypothalamus and their potential role in the network dynamics regarding energy homeostasis.
In this study, we untangle the role of CCK neurons in the VMH nucleus by employing stereotactic intracranial delivery of adeno-associated viruses that result in cell-type specific chemogenetic inhibition or ablation of these neurons. Acute silencing of their neurotransmission with the cre-dependent AAV expression of the chemogenetic tool of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) increases their daily food intake due to increased meal numbers and eating frequency without meal size or meal duration being affected. CCK ablation by a newly generated double-recombinase-mediated Diphtheria Toxin Receptor (DTR) mouse line or AAV-DTA-mediated ablation resulted in hyperphagia, obesity and hyperglycaemia. We conclude that CCKVMH neurons are implicated in the regulation of food intake, body weight and glucose homeostasis in the adult brain.
Titanium and zirconium permethylpentalene chemistry: ethylene polymerisation and small molecule activation
Keywords: Permethylpentalene
Polymerisation
Pentalene
Mechanism
Ethylene

Chapter One
provides an introduction to the chemistry of pentalene and its derivatives encompassing ligand synthesis, organometallic chemistry, and in particular ethylene polymerisation. In the second half, cationic polymerisation is introduced encompassing both main-group and transition-metal initiated polymerisations. The limitations of cationic ethylene polymerisation are highlighted.
Chapter Two
describes the synthesis of a series of related complexes based on the Pn*MCpR(X) motif for application as ethylene polymerisation catalysts. The products are characterised by NMR spectroscopy, single crystal X-ray diffraction, elemental analysis and, where relevant, EPR spectroscopy.
Chapter Three
details the application of aforementioned Pn*MCpR(X) complexes as ethylene polymerisation catalysts, tested in solution co-catalysed by methylaluminoxane, and in the slurry phase, immobilised on a variety of inorganic supports. Very high activities are observed for the zirconium congeners of this non-classic polymerisation motif, with the Cp ligand observed to affect activity more dramatically than the "X" ligand.
Chapter Four
gives an account of mechanistic investigations examining the activity of the Pn*MCpR(X) catalysts. Pre-catalyst activation studies implicate the formation of cationic derivatives, which are rationally synthesised. The unexpected activity of [Pn*ZrCp]+ towards ethylene polymerisation is investigated by in-situ gas uptake measurements and small molecule activation studies, which do not readily accommodate a coordination-insertion mechanism. An alternative cationic initiation mechanism is proposed and explored.
Chapter Five
describes the synthesis of titanium and zirconium hydride and deuteride complexes. Using either LiAlH4/D4 or H2/D2 as the hydrogen source, trimetallic hydride clusters are synthesised. Preliminary investigations into their reactivity with small molecules is presented.
Chapter Six
details the synthesis of reduced permethylpentalene titanium complexes. Chlorine atom abstraction, scrambling of the Pn* ligand, and dinitrogen activation was observed depending on the nature of the reducing agent and the stoichiometry employed.
Chapter Seven
provides experimental details and characterising data for the complexes presented in the preceding five chapters.
Papers on the polarization of congress
Keywords: elections
polarization
political parties
congress

This dissertation, a collection of independent papers, explores the polarization of the United States Congress through the lens of primary elections, campaign finance, and party structures during a pivotal moment in American political history. Paper 1 focuses on the top two primary format and its potential in producing moderate candidates and legislators, while Paper 2 expounds on the deleterious consequences it poses for the party system as a whole, particularly in this modern era of both high polarization and high fragmentation. Paper 3 examines the Downsian median voter theorem from the perspective of primary election voters, asking if general election wins/losses beget the nomination of more ideological/moderate nominees next cycle. Ultimately, the article illustrates that the parties instead retain consistent records through both election wins and losses, linked to credibility concerns from position changes as well as the inability of members to disentangle from national party identities. Its companion paper, Paper 4, takes that Downsian question to elites in Washington, D.C. Through original interviews with twenty-three individuals including former members of Congress, leadership, congressional staff, and think tank scholars, I describe the electoral and legislative pressures that prevent officeholders from responding to their median voter, especially among those in swing districts most exposed to the risks of partisan behavior. Paper 5, the final paper, brings together the themes of those preceding it by analyzing the ways in which outside interference, specifically political action committees and more inclusive primary elections, propagates legislative caucus fragmentation and weakens official leadership. This work plays one minor role in providing prescriptive steps to improve and empower channels of dialogue in the U.S. legislative branch—in spite of larger systemic sorting along geographical and partisan lines—and ensure the mediation of ideology between voters and their elected representatives results in policy solutions rather than gridlock.
Reflections on the intellectual foundations for metaphysical ground
Keywords: Facts
Explanation
Grounding
Causation
Ontology
Metaphysics
Determination relation
Philosophy

"This essay is a plea for ideological toleration", wrote Rosen (2010) on the idioms of metaphysical dependence, and especially '(metaphysical) ground'. This thesis is likewise a plea for ideological clarity. Much work on ground has connected it to "metaphysical explanation" – perhaps distinct from its causal cousin – and maintained that ground is somehow ineluctably wrapped up with it. Unfortunately, there is hardly consensus about what "explanation" is; the term 'explanation' is itself highly ambiguous, and is used by many philosophers in various guises, often without recognition and in theoretically risky ways.
It is my aim here to bring some lucidity to debates about ground vis-à-vis "explanation". To do so, I will do a few things. I will begin by trying to home in on the phenomenon of interest in the literature on ground – which I refer to as constitutive determination,/em> – absent potentially distracting talk of "explanation". Next, I will consider the varieties of "explanation" relevant to ground-theoretic discourse, imposing some basic conditions on constraints on things that may plausibly be so named. Given these considerations, I will then try to throw into relief some metaphysical and greater philosophical commitments of several of ground's biggest supporters – including and centrally those regarding the nature of "explanation" – drawing connections between them when possible, and demonstrating their (dis)agreements too. Ultimately, I believe that certain significant beliefs about "ground" may illicitly trade in ambiguities of "explanation", intentionally or not, leading to either erroneous theoretical posits, or the right ones for the wrong reasons. As such, I will offer what I take to be the most promising position for the realist who recognizes a seemingly unified phenomenon of constitutive determination – namely, that of a metaphysical dependence relation holding between entities or phenomena of arbitrary ontological category – and attempt to demonstrate where I think some philosophers who instead offer a more restricted relation, such as one holding only between facts, have been led astray. All told, without recognition of vital distinctions among the varieties of explanation, "explanation"-talk may be more harmful than helpful in theorizing about "ground".
Void and spatiality in Epicurus’ letter to Herodotus
Keywords: Epicurus
Space
Void

This thesis analyses the notion of void (to kenon) in Epicurus’ Letter to Herodotus: I argue that void should not be identified with space, but only with the empty intervals between bodies.
The thesis is composed by four chapters. In Chapter 1, I maintain that the Epicurean void is meant to fulfil two different functions (that I call the ‘elemental’ and the ‘spatial’ functions): I discuss the historical roots of the attribution of these functions to the void, and suggest how they could be brought together in a unitary, hybrid conception.
In Chapter 2, I examine how void, interpreted in this way, could make motion possible. I focus on the eixis of void, which I do not interpret in terms of receptivity, and draw a comparison with a contemporary metaphysical theory of holes to show that the resulting conception is coherent.
In Chapter 3, I discuss the theory of the minimae partes in the atom, offering an original interpretation of the notions of 'part' and 'division' on which the theory relies.
In Chapter 4, I analyse the consequences of this theory for the structure of void. I argue that the theory of minima naturally leads to suppose that motion is quantized: because of the Isomorphism Thesis, also time and spatial magnitudes must be composed by minima. However, I conclude that void in itself has not a granular structure, but is affected by the quantization only in a very peculiar and restricted sense.
Powder based processing of novel dispersion strengthened copper alloys for fusion applications
Keywords: Dispersion Strengthened
Copper
Divertor
Fusion

Copper (Cu) has high thermal conductivity and is thus ideal for high heat flux, thermal heat sink applications in fusion power applications. Divertor designs for future fusion power plants will expose Cu alloys to extreme thermal (>10 MW m−2) and neutron fluxes (200 dpa) that destabilise the microstructure of Cu. To improve stability, strength and creep resistance, alloying additions are used commercially, but these compromise thermal conductivity. Dispersed oxide particles may offer the opportunity for improved mechanical stability and creep resistance even at very low volume fractions (<1%) while avoiding large reductions in thermal conductivity. However there are few studies on the processing-performance of oxide dispersion strengthened Cu alloys.
In this thesis, novel oxide dispersion strengthened Cu alloys were prepared by room temperature mechanical alloying of Y2O3 and the mechanism of dispersion investigated. A small fraction of Y2O3, up to 1%, was shown to disperse effectively during mechanical alloying at room temperature in Cu. Both severe fragmentation and some local disassociation of the Y and O occurred, allowing for re-precipitation of fine nanoparticles <10 nm during consolidation and exposure to elevated temperatures. A model alloy of Cu-2 wt.% Y2O3 alloy had a mean oxide particle diameter of 7.1 ± 6.0 nm and a mean particle number density of 8.24 × 1022 m−3 following consolidation.
Ternary Ti additions were investigated for nanoparticle refinement and best design alloy with a composition of Cu-0.25Y2O3-0.25Ti was produced that had a mean nanoparticle diameter of 3.2 ± 1.5 nm and a mean particle number density of 2.36 × 1023 m-3 , which after thermal ageing for 545 h at 350 ◦C, was largely unchanged iii at 3.8 ± 1.7 nm, and 1.74 × 1023 m-3 respectively. Comparing favourably with commercial Al2O3 dispersion strengthened Cu, the alloy had a narrower particle size distribution and a higher particle number density. The fine dispersed oxide nanoparticles gave good grain boundary pinning, retaining an ultrafine mean grain size of 220 nm after thermal ageing. Thermal conductivity of the Ti-containing alloy was 332 ± 16W m−1 K−1 , and the addition of Ti increased the thermal conductivity with increasing temperature. The creep resistance was evaluated by small punch testing and in-house produced alloys outperformed commercial alloys at 350 ◦C. The work in this thesis indicates that mechanically alloyed Cu-Y2O3 or Cu-Y2O3-Ti alloys, with further development and evaluation, have potential as thermal heat-sink materials for fusion divertor application.