VictorJuiz/thesis huggingface dataset:
A gene's eye vew: W.D. Hamilton, the science of society, and the new biology of enlightened self-interest, 1950-1990

W.D. Hamilton has been celebrated as the twentieth-century Darwin. His extension of evolutionary theory to explain social behaviours has been extensively documented. Current accounts, however, have often overlooked the extent to which his early research goals were tied to his desire to see that a better world was created through a scientific understanding of society. In fact, when his interests in humans, and especially his eugenic concerns, have been acknowledged, they have been distanced from his scientific achievements and treated separately. Using new sources to reexamine the development of Hamilton’s most famous idea, the theory of inclusive fitness, we may better understand how his perception of cultural upheaval shaped his reading of social behaviours as evolved characters following universal laws.
Understanding this, we may see that however successful Hamilton was, he never realized his original dream, which was to devise a theory that would inform the human world, replacing religious and ideological beliefs. As he sought to solidify his career in the 1970s, he moved away from publicly disclosing his more controversial ideas. This meant that by the time the science of social behaviour inspired heated debates, he was almost always absolved from political critiques. Many assumed that his theory was derived from observations of insects, and his eugenic ideas were forgotten, ignored, or not understood. He was therefore well positioned to become the objective figurehead of a new discipline, sociobiology. This does not mean that his desire to understand society as the result of genetic laws subsided, and by placing inclusive fitness against its social and political background, we might reimagine its trajectory and its impact in new ways. We might also begin to see Hamilton not as an isolated scholar unengaged with society but as an individualist whose extra-scientific beliefs paralleled his scientific theories in meaningful ways.

Keywords: genetics
evolution
sociobiology
inclusive fitness
Advisor: Corsi, P
Synthetic approaches to functionalised piperidines

This thesis is concerned with the synthesis of functionalised piperidines. The piperidine unit is found in numerous alkaloids and other natural products, and has also been incorporated into synthetic compounds of significant therapeutic or strategic synthetic potential. Although numerous syntheses of individual piperidine compounds have been published, there are few general routes to this class of compounds, and there is therefore a need for such routes to be developed.
Bicyclic lactams derived from (S)-pyroglutamic acid have been shown to be useful synthons in the synthesis of pyrrolidines. An analogous bicyclic lactam was therefore synthesised from (S)-lysine. Alkylations at the carbon atom a- to the lactam carbonyl group were studied in detail. A number of different groups could be introduced in good to excellent yield, and with moderate to good stereoselectivity. The selectivity of these reactions was believed to depend on the shape of the bicyclic system, and a stereoelectronic effect of the nitrogen lone pair.
The bicyclic lactam was further elaborated to an activated enone. This was shown to be relatively unreactive to cycloaddition reactions. It is believed that this is because the activating ester group is not conjugated with the carbon-carbon double bond. However, conjugate addition could be achieved in high yield and excellent stereoselectivity using a zinc enolate Reformatsky reagent. An epoxide could also be formed in excellent yield and with excellent stereoselectivity. The Reformatsky adduct was shown to be a suitable substrate for a Pb(IV)-mediated arylation reaction.
Examples of the functionalised lactams were deprotected to give hydroxymethyl piperidinones and cyclic amino acids. This route therefore allows access to the desired novel compounds.

Advisor: Maloney, M
The outer atmospheres of 'hybrid' giants

This Thesis is concerned with the physical nature of the outer atmospheres of the 'hybrid' bright giants. These stars show C IV emission and evidence of cool, fast winds - unlike giants of similar effective temperature, which possess only cool chromospheres. The K3 II star ι Aur is studied in detail.
Chapter 1 discusses the importance of these stars in the context of the HR diagram. Chapter 2 examines the evolutionary status of the 'hybrid' bright giants and sets out the physical parameters which are adopted in the atmospheric modelling.
In Chapter 3, the high and low resolution IUE data extracted for ι Aur are discussed. In Chapter 4, the emission line fluxes and profiles are analysed and an emission measure distribution is calculated. Simple hydrostatic models of the transition region and corona are constructed.
Chapter 5 describes the methodology employed to construct model chromospheres using non-LTE radiative transfer. In Chapter 6, computations of the chromospheric structure of a 'hybrid' star are presented for the first time. Calculations made for the first time show that the excitation of the Fe I y5Go3 level by the Mg II k line can produce the observed emission in other transitions from the J = 3 level.
In Chapter 7, non-isothermal Alfvén wave driven wind models are calculated. It is shown that ι Aur proves to be a severe test of these models and that the transition region and the cool wind are physically separate.
A brief resumé, and possible future research topics are given Chapter 8.

Advisor: Jordan, C
Novel molecular markers for assessment of human embryo competence

In vitro fertilization treatments are responsible for 1-5% births in industrialized countries. The safest way to generate a pregnancy is to transfer a single embryo to the mother, reducing the likelihood of multiple gestations. Hence, in order to maximize the chance of success, it is extremely important that the embryo prioritised for transfer is the most capable within the cohort of embryos generated by the patient. Along with cytogenetic components, it has been suggested that embryo protein expression patterns may correlate with its ability to implant. However, embryo proteomics strategies have not been easy to harness mainly due to the complexity of the media the embryos are cultured in, and the low concentration of the proteins that are secreted.
In this study, the use of the blastocentesis procedure, which allows the safe retrieval of embryo inner fluid (blastosol), was described. The use of the blasocoel fluid as a source of embryonic DNA for preimplantation genetic assessment was also investigated. From this highly purified embryonic sample, a comprehensive catalogue of proteins present in the human blastosol was generated using standard and custom- made mass spectrometry strategies. The embryonic origin of these proteins was validated by gene expression microarray and RNASeq analysis. These experiments also allowed the identification of differentially expressed genes in the first two cell lineages, the Inner Cell Mass and the Trophectoderm. Finally, a targeted proteomics strategy able to measure part of the previously described protein targets in single blastosol samples was employed. The correlation between the presence and abundance of proteins of interest in single blastosols and several biological characteristics of the embryo, including its chromosomal status, was assessed.
These data are of major interest for the understanding of human embryo development. The validated embryo-derived protein catalogue and blastocyst gene expression profiles generated in this study, provides access to a thorough document for consultation in human embryology proteomics-based experiment design, paving the way to next-generation proteomic-based embryo assessment.

Keywords: human embryology
genetics
proteomics
Advisor: Wells, D
Child, T
Strategies for enhancing the therapeutic targeting of phosphatidylserine in oncological disorders and viral infections

Phosphatidylserine (PS) is exposed on a variety of tumour cell types, virus-infected cells and virions. Bavituximab, a PS-targeting antibody with a human immunoglobulin G (IgG) constant region, possesses anti-viral and anti-cancer activity that is mainly mediated by antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC of therapeutic antibodies is naturally limited in vivo by the prevailing serum concentrations of IgG which compete for Fcγ receptor (FcγR) binding. The binding of bavituximab to FcγRIIIA is shown here to be reduced in the presence of either whole serum or polyclonal IgG. However, the use of IdeS, a highly specific IgG-cleaving enzyme derived from Streptococcus pyogenes, presents a potential solution to this problem. IdeS cleaves in the hinge region of IgG between amino acid residues Gly236 and Gly237 but is thought to possess an additional binding interface with its IgG substrate. Firstly, the location of the IdeS–IgG binding interfaces was investigated using truncated IgG1 variants and systematic amino acid mutagenesis. IdeS bound an IgG1 fragment crystallisable (Fc) domain lacking the hinge region, thereby confirming the presence of a secondary binding site. Secondly, residues involved in the IdeS–IgG interaction were mutated to create an IdeS-resistant form of bavituximab. Pre-treatment of competing IgG with IdeS fully restored binding of IdeS-resistant bavituximab to FcγRIIIA, while pre-treatment of serum produced a partial improvement in binding. Lastly, bavituximab, the PS receptor TIM-1, and the related protein TIM-4 were tested for binding to a model alphavirus, Semliki Forest Virus. Only TIM-1, the smallest of these constructs, was found to bind the virus: this implies that receptor size may be an important consideration in the design of PS-targeting anti-viral agents. Overall, these data suggest possible methods for improving the therapeutic targeting of PS, either by optimisation of antigen binding regions or by enhancement of FcγR binding.

Advisor: Crispin, M
Sattentau, Q
Arene transition metal complexes in synthesis

This thesis deals with the applications of organopalladium and organochromium chemistry to the functionalisation of the benzopyran ring system, at a variety of oxidation levels.
Section I demonstrates the functionalisation of 3-, 6-, and 8-bromochromones via palladium (0) insertion into the C-Br bond. The resultant arylpalladium species are shown to undergo addition to the least substituted end of a variety of olefins including methyl acrylate, acrylonitrile and styrene. Subsequent palladium-hydride elimination leads to overall palladium catalysed vinylation of the chromone and the synthesis of a number of novel compounds. Vinylation occurs regiospecifically at the site of chromone bromination and is shown to allow clean substituent introduction into each of the three sites. The palladium catalysed reaction of 3,6-dibromo-chromone with methyl acrylate leads to vinylation at both the C3 and C6 positions. Carbonylation of the 6-bromochromone in ethanol or butanol leads to the 6-ethyl or 6-butyl esters respectively. The palladium catalysed vinylation of the 6-bromochromone with ethyl vinyl ether leads to a mixture of products from addition of the chromone to either end of the olefin. With p-bromophenol or p-bromo-N,N-dimethylaniline the reaction gives exclusively the acetylated product arising from addition to the more substituted end of the olefin. This change in orientation is rationalised by considering the polarisation of the olefin and the arylpalladium species.
Section II demonstrates the functionalisation of chroman and 4-chromanol via coordination to the Cr(CO)3 moiety. (η6-Chroman)Cr(CO)3 is synthesised and is shown to undergo regiospecific ring deprotonation at C8 under kinetic conditions or regiospecific benzylic deprotonation at C4 under thermodynamic conditions. The resultant anions are quenched with alkyl halides, aldehydes, Eschenmoser's salt and methyl disulphide resulting in selective functionalisation of either site. No mixed products are observed. The uncomplexed arene is shown to be totally unreactive under identical conditions. (η6-4-Chromanol)Cr(CO)3 is synthesised and is shown to undergo regiospecific C8 ring deprotonation by comparison with authentic samples of the C5 and C8 methylated alcohols. Protection of the hydroxyl group as its methyl, t-butyldimethylsilyl or methoxymethyl ethers is found not to alter the regiochemistry of deprotonation. The 4-chromanol t-butyldimethylsilyl and tri-i-propylsilyl ethers are synthesised and coordinated to the metal unit. Cleavage of the silyl ethers is shown to proceed with loss of stereochemistry, indicating C-0 bond cleavage.

Advisor: Davies, S
Statistical and Computational Methodology for the Analysis of Forensic DNA Mixtures with Artefacts

This thesis proposes and discusses a statistical model for interpreting forensic DNA mixtures. We develop methods for estimation of model parameters and assessing the uncertainty of the estimated quantities. Further, we discuss how to interpret the mixture in terms of predicting the set of contributors.
We emphasise the importance of challenging any interpretation of a particular mixture, and for this purpose we develop a set of diagnostic tools that can be used in assessing the adequacy of the model to the data at hand as well as in a systematic validation of the model on experimental data.
An important feature of this work is that all methodology is developed entirely within the framework of the adopted model, ensuring a transparent and consistent analysis.
To overcome the challenge that lies in handling the large state space for DNA profiles, we propose a representation of a genotype that exhibits a Markov structure. Further, we develop methods for efficient and exact computation in a Bayesian network. An implementation of the model and methodology is available through the R package DNAmixtures.

Keywords: probabilistic expert system
DNA mixture analysis
probability propagation
forensic genetics
statistics
gamma distribution
Bayesian network
Advisor: Lauritzen, S
Rule and identity in a diverse Mediterranean society: aspects of the county of Tripoli during the twelfth century

The county of Tripoli (Lebanon) was one of four “crusader states” established in the Levant after the First Crusade (1095-99). Compared to the other states, the county of Tripoli has suffered from a disproportionate level of historiographical neglect. What has been produced has taken an institutional and Eurocentric approach to the subject and its sources. The present thesis jettisons this in favour of a post-institutional methodology, approaching the county from the perspectives of geography and demographics, which together ensure that it is treated within its proper Syro-Lebanese context. Chapter one looks at the role of local geography in shaping the political frontiers of the county of Tripoli and its neighbours, arguing that topography was more important than the agency of the European settlers. Chapter two continues to challenge traditional assumptions regarding European influence, arguing that the specifically southern French origins of many of the county’s settlers were of little significance. Chapter three analyses the use of Arabic by the Frankish government of the county, informed by an awareness of diglossia. It argues that the Franks were more likely to know spoken Arabic than written, but remained reliant upon local intermediaries when ruling over Arabophones. Chapter four looks at popular religion, arguing that the cross-fertilisation of religious beliefs and practices was widespread but poorly understood by the contemporary intelligentsia, upon whose sources historians rely. As a whole, the thesis argues that the county’s inhabitants lacked a distinctive culture, identity, religion or language. The sole justification for viewing the county as an integrated unit is geographical.

Keywords: Latin East
Tripoli (Lebanon)
crusader states
Outremer
crusades
Syria
Occitania
Lebanon
Advisor: Tyerman, C
Editors, artists and the changing status of manga in Japanese society, 1986-1995

The contemporary Japanese manga industry began in 1959 when the first weekly manga magazines were published. Throughout the 1960s publishing companies attracted a large adult readership by incorporating radical political themes and realistic drawing styles in manga magazines. The readership continued to expand throughout the 1970s and 1980s and manga became a mass medium on a similar scale to television or pop-music.
This thesis identifies two distinct trends in the cultural status of manga which were developing from the mid-1980s onwards. On the one hand, what had previously been seen as 'commercial' manga became respected as an 'art' form and highbrow communication medium. On the other, manga was vilified as pornography and as the extreme expression of an increasingly fragmented society. In the former trend, prestigious corporations sponsored a new category of 'information' manga, whilst in the latter, 'girls' and 'otaku' manga genres were censured by a quasi-governmental censorship movement. The amateur manga subculture in particular became the focus of a 'moral panic' where those involved were characterised as isolated and socially dysfunctional.
This thesis, based on ten months' participant observation and intensive interviews in 'Morning' manga magazine editorial office in 1994, examines how this editorial was influenced by the changing status of manga in Japanese society in the formulation of its editorial policy and production methods. Editors felt that in the 1990s social changes presented the manga industry with serious production problems - in particular, a dearth of 'good' artists who could produce social themes, and a shrinking readership. Morning editorial attempted to overcome these problems by pioneering a new form of artistic, high-quality and respectable adult manga, aimed at older and more socially-elite readers. By creating a new proactive intellectual role for manga editors at the same time as sponsoring experimental graphic styles, Morning editorial produced a distinctive new form of conservative, state-supporting social and political adult manga.
The re-definition of specific genres of manga as 'art' by Japanese institutions was paralleled by changes in commercial manga production which privileged the social and intellectual interests of editors over those of readers and artists. This study concludes that editors have become increasingly impo7tant in manga production between 1986 and 1995, and that there is a tight interrelationship between commercial cultural production and broader cultural and social discourses generally.

Keywords: Editors
Japan
Status
Manga
Artists
Magazines
Japanese
Advisor: Goodman, R
Stockwin, A
Public policy

This thesis is about the origins and implementation of the Equal Pay Act and Sex Discrimination Act in Britain. For historical and methodological reasons the subject is treated comparatively with similar American policies. British policy makers looked to the United States as an exemplar in this field. The thesis discusses one theory about innovation which predicts such a process. Accounts of policy formation and implementation are used as a method of comparing the general political processes of the two countries.
The first chapter introduces ideas about the study of policy and the pattern and timing of policy innovations. It also refers to early moves in the emancipation of women in Britain and America. Part I is about the origins of laws promoting equality of opportunity for working women. It deals with the problems the legislation was supposed to solve, the growth of interest in economic as well as political emancipation and with the actual provisions of the new laws. The emphasis is on Britain to which three chapters are devoted. Similar trends and events in America are dealt with more briefly in a single chapter. Part II discusses implementation in both countries, stressing the essentially political aspects of this process. That is to say, Chapters VI and VII consider the activities of the principle administrative agencies and departments and the courts.
The concluding chapter compares the different approaches of American and British institutions promoting equality in the light of variations in more general aspects of politics. Thus it attempts to contribute to the discipline of comparative politics.
The normative ethics of immigration detention in liberal states

This thesis explores the normative propriety of immigration detention in liberal states. In the first part of the thesis, I explore the development, current practice, and popular justifications for immigration detention in the United Kingdom. I argue that a crucial but unacknowledged role for immigration detention is to function as a political spectacle of the centralisation of power in liberal states. I find that the key motivation for detaining non-citizens is that they could abscond before their removals. I conclude that this basis for detention is normatively acceptable in only very limited cases and, even then, alternatives are often available and ethically preferable. Based on the fact that there is a normatively acceptable rationale, albeit circumscribed, for detention practices, I then propose a framework of minimum standards of treatment in detention that I advise all liberal states to follow.
After outlining my proposal, I turn in the second part of the thesis to an examination of the normative theories of immigration control and how they take account of detention. Normative theorists differ in how they balance their commitments to individual and state rights, yet I find the majority concedes the need for some degree of immigration admissions control. Such theories face a moral dilemma: there can be no immigration control without detention, and so detention becomes an implicit assumption for these normative theories to be coherent. A potential solution for combating the practical problems associated with the growing, worsening detention estates as well as the moral dilemma of incarcerating a non-citizen based on fear of absconding would be to open borders and eliminate immigration control. Given the reality of the sovereign right to control immigration, however, I argue that the more feasible normative answer is lobby liberal states to adopt my framework of minimum standards of treatment while simultaneously pressing for open borders as the long-term ethical goal.

Keywords: Asylum
Immigration detention
Liberalism
Practical ethics
State power
Immigration
Advisor: Anderson, B
Gibney, M