VictorJuiz/thesis huggingface dataset:
The origin and development of the Pleistocene LSA in Northwest Africa: A case study from Grotte des Pigeons (Taforalt), Morocco
Keywords: Later Stone Age
Maghreb
Middle East
Iberomaurusian
North Africa
Epipalaeolithic

This thesis examines variation within the microlith industries of the Later Stone Age (LSA) of Northwest Africa, around the time of the Last Glacial Maximum (LGM) until the onset of the Holocene, between &Tilde;25 - 11.5 ka. The traditionally held view is that whilst there is variation amongst the lithic assemblages, this can all be accommodated by a single definable industry, known as the Iberomaurusian. This thesis indicates an alternative scenario.
Based on the typo-technological analysis of 16,689 lithic artefacts recovered from recent excavations at the site of Grotte des Pigeons (Taforalt, Morocco) and the re-analysis of published data using the multivariate statistical approach of correspondence analysis (CA), this thesis shows that there was much greater variation than previously proposed within the Pleistocene LSA.
This thesis indicates that the LSA industries can be sub-divided into four chronologically distinct variants, an Initial LSA time-coincident with the first appearance of microlithic technology from &Tilde;25 ka and lasting up until Heinrich event 2, a succeeding Early LSA at &Tilde;22 ka that continued until Heinrich event 1, a Middle LSA marking a shift in technologies around this event at &Tilde;16 ka, and an Upper LSA occurring with the climatic amelioration of the Bølling-Allørod at &Tilde;14.5 ka.
The proposed chronological model provides a new framework for categorising variation within the LSA, which is a necessary pre-requisite for potential future research addressing wider anthropological and archaeological issues, such as reasons for shifts in subsistence and settlement.
Double object constructions and 'bill' verbs in English
Keywords: mainstream generative syntax
double object constructions
objecthood
lexical functional grammar
objects
syntax

This thesis empirically tests the two predominant views concerning which object in a DOC is the ‘true’ one by applying Hudson’s (1992) eleven objecthood diagnostics to verbs that pattern like ‘bill’ in a corpus search and a grammatical acceptability survey. Only two tests showed statistically significant results: passivization and extraction. Passivization indicated that the first positional object (O1) behaves most like the monotransitive object (O0). Extraction indicated that, by a small margin, the second positional object (O2) behaves more like O0. For most of Hudson’s objecthood tests, however, there was no clear patterning of O0 with either the first or second object for ‘bill’ verbs. This calls into question whether it is possible to determine which of the objects in a DOC is the ‘true’ object by employing such diagnostics, and has significant implications for notions of objecthood, especially within Lexical Functional Grammar. The study indicates that a substantial rethink is needed with regards to traditional views about objecthood.
The nouveau roman in Britain, 1957-73
Keywords: nouveau roman
postwar British literature

This thesis considers the early dissemination and critical/cultural/literary reception of the nouveau roman in Britain, roughly between the years 1957–73. The nouveau roman is considered in its capacity as an avant-garde grouping of writers and texts coming from France, and as articulated at the interface of the novel and its theoretical metalanguage; the main nouveaux romanciers considered are Michel Butor, Marguerite Duras, Robert Pinget, Alain Robbe-Grillet, Nathalie Sarraute, and Claude Simon. Particular attention is paid to the ways in which the nouveau roman's status as nouveau was presented in Britain in the period in question. One of the major arguments of the thesis is thus: that the question of the nouveauté of the nouveau roman became a nodal point for negotiations over the legacy of modernism, and over the meaning of the 'contemporary' in literature in the postwar period.
Part I charts the emergence of the nouveau roman in Britain. It looks first at the origins and the methods of the nouveau roman's initial dissemination, drawing on a range of previously undocumented archival sources. The main focus here is Calder & Boyars – the nouveau roman's main British publisher – and in particular the notions of publics that framed its activities involving the nouveau roman. Subsequently, the nouveau roman's British reception is considered with reference to an extensive survey of periodicals and books.
Part II looks at the literary impact of the nouveau roman. First, a range of novels is considered as bridging the critical and the literary response in Britain to the nouveau roman. The authors considered are: Pamela Hansford Johnson, J. I. M. Stewart, Muriel Spark, John Fowles, J. B. Priestley, William Cooper, Rayner Heppenstall, and Christine Brooke-Rose. Then, other novels are considered more directly within the domain of the nouveau roman, seen against the background of Robbe-Grillet's approach to objects and materiality, and with reference to notions of 'project-work' in Butor's novels. Novels are considered by: Brian W. Aldiss, Muriel Spark, Denis Williams, Eva Figes, B. S. Johnson, and Alan Sheridan. Finally, the nouveau roman is looked at in relation to an emergent avant-garde in the British novel. Here, the nouveau roman is seen as providing terms with which British writing from the period in question was able to present itself as avant-garde beyond the manifestations of individual works. The conclusion briefly surveys more peripheral and non-novelistic British responses to the nouveau roman, considering the way in which they inscribe the nouveau roman as 'contemporary'. The thesis turns finally to the legacy of the nouveau roman for the British novel of the present day.
Asymmetric synthesis of α-alkylated aldehydes using chiral enamines
Keywords: terminal epoxides
aldehydes
asymmetric synthesis
alkylation
enamines

Direct generation of enantioenriched mono-α-alkylated aldehydes by intermolecular nucleophilic substitution is a general and long-standing problem in synthesis, and is of importance due to the diverse reactions such aldehydes undergo for introducing asymmetry into molecules.
The work described in this thesis initially details the development of the first lithium amide capable of efficiently converting terminal epoxide into enamine functionality, where the latter also demonstrates effective C-alkylation activity. Not only addition to Michael acceptors, but more notably substitution using activated organohalides (α-bromoacetates, benzyl, allyl and propargyl bromide) gave the corresponding α-substituted aldehydes in good to excellent yields. Alkylation with propargyl bromide yielded only the propargyl-substituted aldehyde with none of the corresponding allene observed; this result shows that N-alkylation followed by [3,3] sigmatropic rearrangement is not occuring. Importantly, a range of short-, longer-chain and secondary unactivated alkyl iodides also proved viable.
Significantly, with chiral lithium amides, the corresponding chiral enamines could be alkylated with strongly electrophilic benzyl, allyl and propargyl (no allene seen) bromides in very good yields, and with short chain alkyl iodides – MeI and EtI in satisfactory yields, to provide the first direct access to α-alkylated aldehydes with high asymmetric induction by intermolecular nucleophilic substitution.
Regulation of the human RNA nucleotidyl transferase ZCCHC11
Keywords: Molecular Pathology

Terminal uridylation of RNA 3ꞌ ends has recently been recognised as an important biological regulatory mechanism. The human terminal uridyl transferase ZCCHC11 was shown previously to uridylate and thereby regulate replication-dependent histone mRNAs and several miRNA precursors and mature miRNAs. Studies in cancer cell lines, mouse models and patient samples suggest that ZCCHC11 is a potential oncogene. However, very little is known about regulation of its expression and subcellular localisation. In this study, the regulation of the expression of ZCCHC11 was investigated, especially in relation to the roles played by the untranslated regions of its mRNA. The second aim of this study was to investigate the subcellular localisation of ZCCHC11, both under physiological conditions and under cellular stress. The results presented show that ZCCHC11 expression is regulated negatively through its 5ꞌ and 3ꞌUTRs. Upstream open reading frames in the 5ꞌUTR decrease its translation, while regulation through the 3ꞌUTR involves the combined activity of positive and negative factors. In this study it was shown that HuR positively regulates ZCCHC11 expression, whereas TTP contributes to its negative regulation. An homologous enzyme, ZCCHC6, negatively regulates ZCCHC11 expression. Regulation through the 3ꞌUTR of ZCCHC11 is particularly marked following S-phase arrest. ZCCHC11 expression increases under cellular stress and both UTRs take part in this regulation. Regulation under cellular stress also involves an alteration in sub-cellular localisation. ZCCHC11 is predominantly cytoplasmic in unstressed cells, but re-localises to p-bodies and stress granules under cellular stress. Mutating one of three zinc knuckle motifs within ZCCHC11 significantly decreased differential co-localisation with stress granule marker TIA-1 under oxidative stress. Taken together, the data presented provide insights into the post-transcriptional regulation of this post-transcriptional regulatory protein and its subcellular localisation, especially under cellular stress.
Free curves on varieties
Keywords: vector bundles on curves
etale fundamental groups
rationally connected varieties
free curves

In this thesis we study various ways in which every two general points on a variety can be connected by curves of a fixed genus, thus mimicking the notion of a rationally connected variety but for arbitrary genus. We assume the existence of a covering family of curves which dominates the product of a variety with itself either by allowing the curves in the family to vary in moduli, or by assuming the family is trivial for some fixed curve of genus g. A suitably free curve will be one with a large unobstructed deformation space, the images of whose deformations can join any number of points on a variety. We prove that, at least in characteristic zero, the existence of such a free curve of higher genus is equivalent to the variety being rationally connected. If one restricts to the case of genus one, similar results can be obtained even allowing the curves in the family to vary in moduli. In later chapters we study algebraic properties of such varieties and discuss attempts to prove the same rational connectedness result in positive characteristic.
The body through the lens: anatomy and medical microscopy during the enlightenment
Keywords: microscope history
history of medical microscopy
eighteenth-century microscopes

This thesis examines the role of microscope technology in informing medical and anatomical knowledge during the Enlightenment. Past historians have claimed that microscopy generally stagnated until the popularisation of achromatic microscopes and cell theory in the middle of the nineteenth century. As evidence for this decline, historians have pointed to the poor quality and slow development of microscope designs until the popularisation of achromatic microscopes in the 1820s. In contrast, this thesis highlights the role of specific Enlightenment-era microscopes in answering medical and anatomical questions. It suggests that medical microscopy was far more advanced than previous scholarship has ascertained. Thus far, instrument historians have focused more attention on competing instrument makers as opposed to rival instrument users. This thesis presents several case studies which explore both makers and users. These concern the histories of Enlightenment-era epidemiology, reproduction theory, anatomy, and physiology as well as the different types of microscopes which influenced these fields.
In terms of methodology, this thesis neither follows nor casts doubt on any particular theory of historical development; rather, it attempts to shed further light on available primary sources and their contexts. Presenting key case studies illustrates the difficulties that early microscope users faced in acquiring and publishing new observations. To explore the practice of early microscopy further, this thesis presents re-enactments of these case studies using Enlightenment-era microscopes and modern tissue samples. Thus, this thesis is a call to broaden the scope of primary sources available to historians of science and medicine to include instruments and re-enactments.
This thesis finds that technological advances did not correlate to microscopical discovery in medicine or anatomy. Both simple and complex microscope designs aided anatomical and medical research. Broader advances in anatomy, physiology, and medical etiology dictated the utility of medical microscopy. Although various groups, such as the French clinicians, saw little need for microscopy towards the end of the eighteenth century, microscope-based evidence continued to play a diagnostic role among lesser-known practitioners despite its lack of visibility in medical literature.
Knowledge of God in Philo of Alexandria with special reference to the Allegorical Commentary
Keywords: law of nature
divine incomprehensibility
divine beneficence
Exposition of the Law
exegesis
laws of Moses
Allegorical Commentary
human rationality
Plato
Aristotle
Protagoras of Abdera
epistemology
philosopher-king
mystery initiation
Philo of Alexandria
post-Hellenistic philosophy
divine inspiration

This thesis is a context-sensitive study of key epistemological commitments and concerns presented in Philo’s two series of exegetical writings. The major conclusion advanced in this thesis is that two theological epistemologies, distinct yet related, can be detected among these writings. The first epistemology is specific to the Allegorical Commentary. The second epistemology is specific to the ‘Exposition of the Law.’
The epistemology of the Allegorical Commentary reflects a threefold conviction: the sovereignty of God, the creaturely contingency of the human mind and its inescapable limitations. In conversation with key epistemological notions of his day, Philo develops this threefold conviction in exegetical discourses that are grounded in Pentateuchal texts portraying the God of Moses as both possessing epistemic authority and aiding the aspiring mind to gain purification and perfection in the knowledge of God. Guided by this threefold conviction, Philo enlists key metaphors of his day – initiation into divine mysteries and divine inspiration, among others –in order to capture something of the essence of Moses’ twofold way of ascending to the divine, an approach which requires at times the enhancement of human reason and at other times the eviction of human reason.
The epistemology of the ‘Exposition’ reflects Philo’s understanding of the Pentateuch as a perfect whole partitioned into three distinct yet inseverable parts. Philo’s knowledge discourses in the ‘creation’ part of the ‘Exposition’ reflect two primary movements of thought. The first is heavily invested with a Platonic reading of Genesis 1.27 while the second invests Genesis 2.7 with a mixture of Platonic and Stoic notions of human transformation and well-being. Philo’s discourses in the ‘patriarchs’ segment reflect an interest in portraying the three great patriarchs as exemplars of the virtues of instruction (Abraham), nature (Isaac), and practice (Jacob) which featured prominently in Greek models of education. In the ‘Moses’ segment of the ‘Exposition,’ many of Philo’s discourses on knowledge are marked by an interest in presenting Moses as the ideal king, lawgiver, prophet and priest who surpasses Plato’s paradigm of the philosopher-king. In keeping with this view, Philo insists that the written laws of Moses represent the perfect counterpart to the unwritten law of nature. The life and laws of Moses serve as the paradigm for Philo to understand his own experiences of noetic ascent and exhort readers to cultivate similar aspirational notions and practices.
Role of OX40-OX40L interactions in the immune response to solid organ allografts
Keywords: Treg
costimulation
OX40
T cells
mice

Transplantation is the treatment of choice for end stage organ failure however current immunosuppressive therapies whilst effective at preventing acute allograft rejection, fail to prevent late graft loss due to chronic rejection and are associated with an increased risk of infection and malignancy. Therefore there is a clear unmet clinical need for improved strategies to prevent allograft rejection.
OX40 is a member of the TNFR superfamily that has potent costimulatory properties. Although the impact of blockade of the OX40-OX40L pathway has been well documented in models of autoimmune disease, its effect on the rejection of allografts is less well defined. Therefore the aim of this thesis was to determine the impact of OX40 blockade on conventional and regulatory T cell responses to allografts.
We found that activation of CD4+ and CD8+ naïve and memory T cells resulted in the induction of OX40 expression and that blockade of OX40-OX40L interactions partially inhibited the response of alloreactive T cells in vitro and prevented skin allograft rejection but did not result in the induction of tolerance. OX40 blockade was found to have no effect on the activation and proliferation of T cells but rather effector T cells failed to accumulate and migrate to skin allografts. This was shown to be the result of an enhanced degree of cell death amongst proliferating effector cells.
In addition, blockade of OX40-OX40L interactions at a time of exposure to alloantigen resulted in a pool of Treg with an enhanced ability to suppress T cell responses to alloantigen in vitro and in vivo. Counter-intuitively, OX40 blockade was found to increase the potency of alloreactive Treg by promoting survival following re-activation.
Finally, although OX40 blockade impacted both conventional and regulatory T cell responses, anti-OX40 administration did not promote skin or heart allograft survival in immunocompetent recipients and failed to synergise with blockade of other costimulatory molecules to prevent allograft rejection. In conclusion, these data demonstrate that blockade of OX40-OX40L interactions can attenuate naïve and memory T cell responses to alloantigen whilst promoting the survival of alloreactive Treg. Therefore, we propose that anti-OX40 would be a worthwhile adjunct to pre-existing strategies to induce tolerance.
The role of ephrinB2 in hematopoietic stem/progenitor cell differentiation from an arterial hemogenic endothelium
Keywords: EphrinB2

During development, hematopoiesis develops in temporally distinct waves in the yolk sac (YS) and embryo proper, culminating in the emergence of definitive hematopoietic stem cells (HSCs) from the hemogenic endothelium (HE) of the dorsal aorta. The close association of this aortic endothelium with definitive hematopoiesis suggests a functional relationship between arteriogenesis and blood development, but this association is not fully understood. To gain insight into this relationship, we have chosen to study the role of the “arterial” marker, EphrinB2 (EfnB2) in hematopoietic specification. EfnB2 is a transmembrane protein critical for the development of the arterial vascular system. We find that EfnB2 is expressed in the VE-Cadh+CD41- HE in Day 2 BL-CFC (blast-colony forming cell) culture and Day 6 EBs (embryoid bodies), and that EfnB2 expression in ES cell differentiation enriches for endothelial cells with greater hemogenic capacity. Knock-down experiments in ES cells showed that EfnB2 is not required for endothelial cell commitment and survival. It is also not required for early hematopoietic commitment and differentiation from EBs or BL-CFCs. However, we find that EfnB2 is required for the maturation of ES cells into CD41+/CD45+ hematopoietic cells in OP9 co-culture and for definitive hematopoietic colony formation in MethoCult3434 medium. This requirement for EfnB2 expression was confirmed by peptide-mediated blocking of EfnB2 binding to its cognate receptors and by forced expression of a phospho-tyrosine signaling-deficient EfnB2. These results provide evidence for an essential role of endothelial EfnB2 in hematopoiesis.
Optimising the quality and effectiveness of risk: benefit appraisal methodologies utilised in randomised control trials
Keywords: risk
Randomised control trials

This investigation systematically assesses the quality and effectiveness of risk:benefit appraisal methodologies implemented in the analysis of published randomised controlled trials for pre-licensure biomedical innovations – therapeutics, devices and surgical procedures. The key finding is that, to date, reported applications of risk:benefit methodologies are highly heterogeneous and poorly reflective of the stakeholder needs assessed in the investigation.
[Abstract continues in thesis]
Investigating carbon nanotube - polymer blends for organic solar cell applications
Keywords: ultrafast
organic photovoltaics
carbon nanotubes
polymers
organic solar cells
charge transfer

This thesis describes studies on nanohybrid systems consisting of single-walled carbon nanotubes (SWNTs) with monolayer coatings of semiconducting polymers. Steady-state and time-resolved optical and high-resolution microscopy experiments were used to investigate the blends. These materials show promise for use in organic photovoltaics (OPVs) owing to the high carrier mobilities and large aspect ratios of SWNTs, the controllable solubilisation of tubes with various polymers and the broad light-harvesting abilities of organic polymers.
Chapters 1 and 2 introduce the theory and background behind the work and present a literature review of previous work utilising carbon nanotubes in OPV devices, revealing poor performances to date. The experimental methods used during the thesis are detailed in Chapter 3 and the solution processing techniques used to prepare the polymer–nanotube blend samples are described in Chapter 4.
Chapter 5 describes a study on a nanotube blend with a thiophene polymer, a system previously unsuccessfully implemented into OPV devices. Ultrafast spectroscopic measurements showed that electrons can transfer on a 400 fs time scale from the polymer to nanotubes and the conditions to allow long-lived free charges to be produced were found. The study is extended in Chapter 6 to show that nanostructures consisting of a nanotube coated in one polymer can then be coated by a second polymer and that these nano-engineered structures could be implemented into OPV devices. The use of a competition binding process to isolate purely semiconducting nanotubes dispersed with any desired polymer is then described in Chapter 7. Finally, Chapter 8 introduces systems consisting of chains of porphyrin units, nature’s light-harvesting systems, bound to nanotubes and the blends were found to exhibit the required electronic alignment for use in OPVs.
The work described in this thesis provides an explanation for the poor device behaviour of nanotube–polymer blends to date and, in particular, demonstrates several nanohybrid systems that show particular promise for improved OPV applications.