VictorJuiz/thesis huggingface dataset:
Preimplantation genetic diagnosis - new methods for the detection of genetic abnormalities in human preimplantation embryos

Preimplantation genetic diagnosis (PGD) refers to the testing of embryos produced through in vitro fertilization (IVF) in order to identify those unaffected by a specific genetic disorder or chromosomal abnormality. In this study, different methodologies were examined and developed for performance of PGD. Investigation of various whole genome amplification (WGA) methods identified multiple displacement amplification as a reliable method for genotyping single cells. Furthermore, this technology was shown to be compatible with subsequent analysis using single nucleotide polymorphism (SNP) microarrays. Compared to conventional methods used in this study to perform single cell diagnosis (e.g. multiplex PCR), WGA techniques were found to be advantageous since they streamline the development of PGD protocols for couples at high risk of transmitting an inherited disorder and simultaneously offer the possibility of comprehensive chromosome screening (CCS). This study also aimed to develop a widely applicable protocol for accurate typing of the human leukocyte antigen (HLA) region with the purpose of identifying embryos that will be HLA-identical to an existing sibling affected by a disorder that requires haematopoietic stem cell transplantation. Additionally, a novel microarray platform was developed that, apart from accurate CCS, was capable of reliably determining the relative quantity of mitochondrial DNA in polar bodies removed from oocytes and single cells biopsied from embryos. Mitochondria are known to play an important role in oogenesis and preimplantation embryogenesis and their measurement may therefore be of clinical relevance. Moreover, real-time PCR was used for development of protocols for CCS, DNA fingerprinting of sperm samples and embryos and the relative quantitation of telomere length in embryos (since shortened telomeres might be associated with reduced viability). As well as considering the role of genetics in terms of oocyte and embryo viability assessment and the diagnosis of inherited genetic disorders, attention was given to a specific gene (Phospholipase C zeta) of relevance to male infertility. A novel mutation affecting the function of the resulting protein was discovered highlighting the growing importance of DNA sequence variants in the diagnosis and treatment of infertility.

Keywords: HLA-typing
phospholipase C zeta
multiplex PCR
whole genome amplification
single cell
preimplantation genetic diagnosis
DNA fingerprinting
microarray
telomere
mitochondria
aneuploidy
real time PCR
Advisor: Wells, D
Publishing Chinese art: issues of cultural reproduction in China, 1905-1918

This thesis is an enquiry into the conditions in which various understandings of the newly introduced but vaguely grasped Western notion of ‘art’ emerged and sustained themselves in the name of cultural reproduction in early twentieth-century China. This Western concept of art was translated into Chinese as ‘meishu’, a neologism originally coined in Japanese kanji, and regarded as the embodiment of the ‘national essence’. Through a close examination of five art-related publishing events—the publication of the nationalistic journal Guocui xuebao; the launch of the art periodical Shenzhou guoguangji; the endeavours to compile a book collection on art, Meishu congshu; the making of the text Zhonguo yishujia zhenglüe which claimed to be a history book of Chinese ‘meishu’; and an example of image appropriation from Stephen Bushell’s Chinese Art—this thesis explores the ways in which different ‘neologistic imaginations’ of the term ‘meishu’ were constructed through publishing practices attempting to preserve and reproduce the ‘national essence’, by creating from the existent tradition a category of ‘art’ equivalent to that in the European West. Unlike previous scholarship, which deems any understanding of ‘meishu’ that deviated from the ‘authentic’ European model a ‘misconception’, this thesis sees these disparate understandings of ‘meishu’ as equally valid statements competing for dominance in the discursive field of art. This thesis thus argues that there existed at least three modes of utterances regarding the notion of ‘meishu’ in early twentieth-century China, and that the success of any such given utterance depended upon the acceptance of the authentic quality argued in its strategy of cultural reproduction. This thesis hence not only offers a detailed analysis of each publishing event, but also provides an interpretative framework within which the recognition of these utterances can be analysed by their strategic approaches to claiming cultural authenticity.

Keywords: print culture
20th-century Chinese art
art as national patrimony
transcultural appropriation
photography
art reproduction
collotype printing
meishu
Advisor: Clunas, C
Beyond culture

This dissertation examines Friedrich Nietzsche's theory of culture. Nietzsche held that all beliefs were arbitrary and culturally contingent; cultures were distinct, organic, homogeneous entities, whose values were mutually incommensurable. I trace the origins of this theory to Nietzsche's experience as a philologist; but I claim that, in deriving his theory from historical data, Nietzsche drew false conclusions. As a mature philosopher, Nietzsche developed a somewhat more subtle theory, according to which cultures functioned like the underlying rules of a game. Thus any cultural world-view was arbitrary, but served as a necessary precondition for thought and communication. I argue that Nietzsche's mature theory led to contradictions and depended upon false inferences which he drew from history.
Several of Nietzsche's doctrines including perspectivism, the Eternal Return, and the Overman depend upon his mature theory of culture. A similar theory underlies the work of two representative followers of Nietzsche, Leo Strauss and Jacques Derrida; and I discuss its consequences for their work. I then propose an alternative theory which explains the phenomenon of historical diversity without invoking Nietzsche's picture of reified cultures. Instead of imagining cultures as organic wholes, this alternative paradigm views the cultural background of any person as a heterogeneous collection of ideas and prejudices, often derived from diverse sources. Thus "cultures" are simply ways of categorizing people according to similarities in their backgrounds; and we belong simultaneously to numerous overlapping cultures. This paradigm, I argue, provides support for pluralist and democratic cultural ideals which Nietzsche and his followers have repudiated. Finally, I trace Nietzsche's reasons for criticizing humanistic scholarship to his theory of culture; and I defend humanism on the basis of my alternative paradigm.
Poetry of inner space

This study examines the presence of poetic form in First and Second Generation New York School Poetry. Because New York School writing—where its existence is conceded—seems formless, it has yet to be viewed under a formal lens. Therefore, this study is the first of its kind.
In what follows, works by Frank O’Hara, Ted Berrigan, Alice Notley and Ron Padgett are contextualized and closely read for form, with an attention to the shaping propensity of inhabited spaces. While it is agreed that the external environment has the potential to influence shapes and forms of writing, domestic spaces also offer parameters which are traceable onto the page.
New York School poets lived in and wrote from alternative domestic spaces—untidy, disordered, congested apartments in downtown New York City. The forms of their poems are accordingly untraditional. New York School stanzas often take on the contours of these spaces, becoming linguistic rooms riddled with the tensions of indoor urban life. After outlining New York School poetry and addressing contemporaneous urban theories, this study asks: what role does the space of writing have on the shape of writing? More specifically, are New York City apartments reflected in the forms of New York School poems? Through close-reading and formal analysis, it becomes possible to affirm that New York School Poetry is formal, and that its form is distinctive in that in its variances, it makes it possible for the tensions and dynamics of living within the constraints of inner urban spaces to be fully pronounced and inflected. This is a study of the formal representations of those inflections.

Keywords: Frank O'Hara
Poetry
Space
Poetics of Space
New York School
Advisor: O'Donoghue, B
The analysis of homologous recombination pathways in Saccharomyces Cerevisiae

Homologous recombination (HR) is essential for the repair of DNA doublestrand breaks (DSBs) and damaged replication forks. However, HR can also cause gross chromosomal rearrangements (GCRs) by producing crossovers (COs), resulting in the reciprocal exchange of sequences between non-sister chromatids. Therefore, HR-mediated GCRs are suppressed via the promotion of HR pathways that favour noncrossover (NCO) formation, such as the synthesis-dependent strand annealing (SDSA) and dissolution pathways, which are modulated by Mph1 and Sgs1 helicases, respectively. The mismatch repair (MMR) pathway is intricately associated with HR via its roles in repairing mismatches on heteroduplex DNA that can arise during HR and in preventing homeologous recombination. Using a plasmid break-repair assay, we have revealed a novel, MMR-independent role of MutSα in promoting the formation of a subset of COs that is specifically supressible by Mph1, during HR between two completely homologous sequences. In contrast, the MMR-dependent function of MutSα, together with Mph1 and Sgs1, was shown to be required for the suppression of CO formation during homeologous recombination. These data indicate that Mph1 can both antagonise and promote the functions of MutSα during DSB repair, depending on the levels of homology between the two recombining sequences.
COs are generated by the resolution of Holliday junction (HJ) intermediates formed at the terminal stages of HR. Several S.cerevisiae proteins such as Yen1, Mus81, Slx1 and Rad1 have been implicated in HJ resolution. However, the in vivo roles of these proteins in HJ resolution remain to be confirmed. To directly and quantitatively monitor in vivo HJ resolution in S.cerevisiae, a transformation-based HJ resolution assay using a plasmid-borne HJ substrate has been developed. Using this system, we have demonstrated an in vivo HJ resolution function of Yen1, which acts redundantly with Mus81. Moreover, these redundant activities of Yen1 and Mus81 are essential for survival during replication stress, but are dispensable for DSB repair. An Slx4 and Rad1-dependent in vivo HJ resolution activity was also observed in the absence of Yen1 and Mus81 that was suppressed by presence of Slx1. Models describing how the nucleases interact to process HJs in vivo will be discussed.

Keywords: Holliday junction
Saccharomyces cerevisiae
homologous recombination
mismatch repair pathway
DNA repair
Advisor: Wu, L
God’s non-capricious no: Karl Barth’s “purified infralapsarianism” in development 1920-1953 

This dissertation comprises three parts, setting forth the thesis that Karl Barth’s mature doctrine of election, though avowedly supralapsarian, is in fact basically the opposite. I trace the development of Barth’s lapsarian thinking from its inception in 1920 (Romans II) to its maturation in 1936-42 (Gottes Gnadenwahl to CD II/2), and further developments up to 1953 (CD IV/1). The thesis of my dissertation comprises two aspects, one concerning what lapsarian position, Christological and predestinarian, underlies the Christocentric doctrine of election Barth developed in 1936-42, and the other concerning how he came to develop this lapsarian view. Part I examines the lapsarian position of Barth’s mature doctrine of election set forth in CD II/2 against the background of the Lapsarian Controversy in seventeenth-century Reformed orthodoxy, arguing that he has misunderstood some seventeenth-century terms and that his position is in fact basically in line with infralapsarianism in that for him both election and the incarnation presuppose humankind’s fallenness. Part II traces the development of Barth’s lapsarian position from its inception in 1920 to its Christological reorientation in 1936-42. In a nutshell, my thesis in Part II is that Christology and predestination started out as two loosely related doctrines in Barth’s theology, but as predestination, which was inconsistently supralapsarian during the first phase of the development, was drawn closer to Christology, which carried infralapsarian tendencies at first and became infralapsarian in the 1920s, Barth’s doctrine of predestination became more and more infralapsarian, and then in 1936-42 the two doctrines merged and became inseparable, and he became basically infralapsarian in both Christology and predestination. Part III comprises two chapters exploring doctrinal implications and further developments of Barth’s Christological-predestinarian infralapsarianism up to 1953 (CD IV/1). I argue that in developing what I suggest we call his “purified infralapsarianism” in a deeply historical-actualistic direction, the basically infralapsarian character of Barth’s understanding of election in Christ becomes more radical in that he leaves no room for the possibility of homo nondum lapsus as the obiectum praedestinationis.

Keywords: supralapsarianism
Barth
lapsarian controversy
infralapsarianism
Advisor: Rasmussen, J
Re-engineering bacterial two-component signalling systems

Bacteria use Two Component Systems (TCS) to sense and respond to changes in their external environment. TCS are used to navigate to nutrients or away from toxins (chemotaxis) and to adapt to changes in osmolarity (osomosensing). TCS are composed of a histidine protein kinase (HPK) which trans-autophosphorylates in response to environmental change, transferring the phosphoryl group to a cognate response regulator (RR). Phosphorylated RRs modulate an output response such as protein-protein interaction for chemotaxis, and transcription for osmosensing. RRs are composed of a conserved amino terminal REC domain, and where present a variable effector domain. CheY, the chemotaxis RR, contains only a REC domain, whilst OmpR, the osmosensing RR, also contains a DNA binding effector domain. Recently, TCS have been used in synthetic biology applications due to their modularity and conserved signalling mechanism.
This thesis aimed to investigate whether it was possible to design a synthetic TCS composed of fused chemotaxis and osmosensing components. Synthetic RRs were designed, fusing the highly conserved REC domains of CheY and OmpR upstream of the OmpR effector domain. REC domains were fused across the α4-β5-α5 region, a region which transmits REC domain phosphorylation into effector domain activation. Synthetic RRs were designed to undergo phosphotransfer to their fused REC domains from the chemotaxis HPK, CheA, activate the attached OmpR effector domain and bind promoter DNA.
Four chimeric RRs were created, although only three were structurally viable; F2, F3 and F4. Each fusion bound CheA, and F3 and F4 bound CheA with a significantly higher affinity than CheY. The chimeric RRs could all be phosphorylated byCheA-P; F4 and F3 were phosphorylated to wild-type levels. DNA binding affinitywas investigated with fluorescence anisotropy, hosphorylated and unphosphorylated F3 could not bind promoter DNA. F2 bound promoter DNA regardless of phosphorylation state. These data indicate that phosphorylation of the F2 REC domain does not lead to activation of the effector domain. F2 is likely to be constitutively active suggesting a previously unknown role for OmpR α5 as a mediator of effector domain activation. Furthermore, using a simple fusion approach to design RRs is not a viable method to create a synthetic TCS with a controllable output.

Keywords: two-component systems
synthetic biology
bacteria
Advisor: Wadhams, G
Armitage, J
Genetic and molecular studies of early embryogenesis in Drosophila

The Drosophila embryo is patterned by a complex interplay of zygotically expressed genes and maternally supplied components, a large number of which have been identified. However, many maternal components are encoded by essential zygotic genes whose maternal effects are not amenable to conventional genetic analysis. Investigation of such genes requires the generation of homozygous mutant germ cells in chimeric females, and analysis of their embryos. The recent development of techniques which allow the efficient generation of germline clones has made the screening of zygotic lethal mutations for maternal effects more feasible. I have generated a collection of X-linked zygotic lethal mutations and used FLP recombinase catalysed mitotic recombination to look for maternal effects affecting segmentation.
Two mutations have been recovered which have maternal effect phenotypes similar to those of the pair-rule segmentation genes. The leprechaun mutation affects oogenesis, so fertile females are very rare, preventing straightforward phenotypic analysis of the segmentation phenotype. Attempts to generate a rescuing duplication are described.
The second mutation, stunted (sun), initially gave rise to a segmentation cuticle phenotype. Subsequent attempts to reproduce the phenotype were unsuccessful as it was masked by a severe reduction in the amount of cuticle secreted, a phenotype characteristic of the neurogenic genes. Detailed analysis revealed that the primary lesion affects neither segmentation or neurogenesis. Rather, sun+ is required for cellularisation of the syncytial blastoderm and for the localisation of actin to 'caps' above the syncytial nuclei. Cloning of a candidate gene for stunted revealed a predicted protein product limited homology to cyclins.
In addition to searching for novel segmentation genes, potential proteinprotein interactions of the segmentation gene hairy's protein product were also investigated, and a model is presented for its mode of action as a transcriptional repressor.

Advisor: Ish-Horowicz, D
The social mythology of medieval Icelandic literature

This thesis argues that the corpus of Old Norse-Icelandic literature which pertains to Iceland contains an intertextual narrative of the formation of Icelandic identity. An analysis of this narrative provides an opportunity to examine the relationship between literature and identity, as well as the potency of the artistic use of the idea of the past. The thesis identifies three salient narratives of communal action which inform the development of a discrete Icelandic identity, and which are examined in turn in the first three chapters of the thesis. The first is the landnám, the process of settlement itself; the second, the origin and evolution of the law; and the third, the assimilation and adaptation of Christianity. Although the roots of these narratives are doubtless historical, the thesis argues that their primary roles in the literature are as social myths, narratives whose literal truth- value is immaterial, but whose cultural symbolism is of overriding importance. The fourth chapter examines the depiction of the Icelander abroad, and uses the idiom of the relationship between þáttr (‘tale’) and surrounding text in the compilation of sagas of Norwegian kings Morkinskinna to consider the wider implications of the relationship between Icelandic and Norwegian identities. Finally, the thesis concludes with an analysis of the role of Sturlunga saga within this intertextual narrative, and its function as a set of narratives mediating between an identity grounded in social autonomy and one grounded in literature. The Íslendingasögur or ‘family sagas’ constitute the core of the thesis’s primary sources, for their subject-matter is focussed on the literary depiction of the Icelandic society under scrutiny. In order to demonstrate a continuity of engagement with ideas of identity across genres, a sample of other Icelandic texts are examined which depict Iceland or Icelanders, especially when in interaction with non-Icelandic characters or polities.

Keywords: Iceland
law and literature
literary criticism
Old Norse literature
Old Norse-Icelandic literature
sagas
literature and society
medieval civilization in literature
Advisor: O'Donoghue, H
The decision-making process in relation to British foreign policy, 1938-1941

The purpose of this thesis is to provide a case-study in the making of British foreign policy by relating a substantial body of historical evidence to problems raised by a comparative and analytical perspective. The particular period between Munich and the German invasion of the Soviet Union has been chosen because of its intrinsic interest and because it allows us to observe a democracy facing up to the most fundamental question of external relations, that of war or peace.
The thesis focusses on the political aspects of decision-making, at three levels: the Cabinet, at the apex of the system; the press, as the most extensive of all lobbies; and public opinion, arguably the ultimate source of legitimacy in British politics. The aim is to reveal the role of domestic factors in British foreign policy, which are usually acknowledged but not dwelt upon, and thereby to peel back some layers of the complex process of causation in history. The main hinge of the thesis is therefore the argument that neither the 'logic of events', nor some self-evident rationality, explains why the British government entered and remained in the war between 1939-41. While their importance must not be exaggerated, such decision-making factors as the operation of the Cabinet and the character of public debate, also helped to determine the British position towards Germany.
The other main theme of the thesis is the relative weakness of power-based explanations of decision-making. The roles of Prime Minister and Cabinet are not best described in terms of either's dominance; the press is sufficient of an insider in policy-making circles to complicate immensely any assessment of its separate influence; public opinion can barely be distinguished from the perceptions of politicians who defer to it. Some alternative interpretations are presented for the period under review; those working in different areas may find them suggestive.
Aspects to T-cell phenotype during infection with HIV, CMV and Hepatitis C virus

This work concerns itself with understanding the organisation of cellular immune responses to three major human pathogens - HIV, CMV and Hepatitis C (HCV). Each was studied to form three projects, each undertaken with a different approach - arrived at independently - and largely owing their origins to opportunity and circumstance as much as design. Each project led to exploration of a particular aspect of T-cell phenotype (that is the expression of particular molecular markers on T-cells) and its’ broader biological significance. I found that T-cell phenotype was strongly linked to the magnitude of T-cell responses (CMV) and the ability of T-cells to control infection (HIV). Finally I explored the significance of expression of a molecule known as CD161 on the surface of HCV specific CD8+ T-cells, indicating a phenotype of T-cell that may not follow the ‘normal rules’ applicable to T-cells in general.

Keywords: CMV
HIV
virus
Hepatitis C
T-cell
immunity
Advisor: Klenerman, P