Milton's Hellenism

This thesis investigates the Hellenism of the English poet John Milton from his student writings at Cambridge through to Paradise Lost. It explores Milton’s engagement with classical, Hellenistic, Byzantine, and Early Modern Greek texts and it considers Milton’s reading of Greek scholarship and interactions with Greek scholars and Hellenic scholarship. Chapter 1, ‘Milton’s Cambridge Greek’, consists of two sections: ‘Protestant Hellenism at Milton’s Cambridge: A Case Study of James Duport’s Greek Paraphrase of the Book of Job, Threnothriambos (1637)’ and ‘Greek and the “Lady of Christ’s College”: Latin–Greek Code-Switching in Milton ‘Prolusion VI’’. Chapter 2, ‘Milton Among the Hellenists in England and Italy’ considers the role that Greek played in Milton’s correspondence and poetic exchanges with Charles Diodati and Lucas Holstenius; it also considers the nature of Milton’s own Hellenic research at libraries in Rome and Florence during his travels in Italy from 1638–39. Chapter 3 considers the political and polemical roles that Greek texts played for Milton from the mid-1640s to 1660 and consists of three sections: ‘Marshall’s Ignorant Hand: Milton’s Greek Epigram and the 1645 Poems Frontispiece and the First Edition of Langbaine’s Longinus (1636)’; ‘O Soul of Sir John Cheek: Milton and the Legacy of Sixteenth-Century Greek Humanism’; and ‘John Milton, Leonard Philaras, and Early Modern Advocacy for Greece’s Liberation from the Ottoman Empire’. The final, fourth chapter explores the influence of Greek texts—ranging from the Homeric epics and the fragmentary Epic Cycle through to Byzantine and Early Modern Greek texts—upon Milton’s design of Books 1 and 2 of Paradise Lost

Understanding the experience of ‘brain fog’ in coeliac disease: an interpretative phenomenological analysis

This thesis is submitted by Emily May Ahmed in partial fulfilment of the degree of Doctor of Clinical Psychology at the University of Birmingham. The thesis is comprised of three chapters. The first chapter is a meta-analysis which aims to provide a current prevalence estimate of depression in adults with coeliac disease, including evaluation of risk of bias factors. Additionally, it includes a brief secondary analysis, within the appendix, describing prevalence and relative risk estimates for other mental health disorders associated with coeliac disease. The second chapter is a qualitative empirical study which uses interpretative phenomenological analysis (IPA) methodology to explore the complex lived experiences of one of the lesser-known symptoms associated with coeliac disease – ‘brain fog’, in seven participants. Both the meta-analysis and empirical studies have clear clinical implications for the cognitive and psychological support that individuals with coeliac disease should be offered during and after diagnosis. Finally, the third chapter is comprised of two press release documents, which provides an accessible summary of the main findings of both the meta-analysis and the empirical research study

Discovery of selective saccharide receptors via Dynamic Combinatorial Chemistry

The diagnosis of various diseases and pathological conditions can be accomplished by screening and detecting glycans in cells. Certain glycans serve as excellent biomarkers, being related to cell malfunctioning, while other structurally similar glycans perform completely different functions and are naturally present in healthy cells. Despite the theoretical feasibility of using glycans as biomarkers for early disease detection, our current inability to discriminate between them limits their use. One promising approach to distinguishing between glycans is targeting their dissimilarities in saccharide chains. However, designing selective receptors for saccharides is challenging due to the complexity of these molecules. Their vast diversity, the fact that they exist in many interconvertible forms, their lack of recognisable functional groups, or the fact that they are normally heavily solvated in aqueous environments have made the design of receptors for saccharides a challenge that has kept the scientific community busy for the last 35 years. Although there have been ground-breaking discoveries in the field, improvements are needed to enhance our disease detection and risk stratification tools. To address this challenge, we employed a technique known as Dynamic Combinatorial Chemistry (DCC). DCC enables the self-formation and self-selection of the best possible receptor for a given target from a pool or library of potentially good ligands. DCC has been effective for creating receptors for biomolecules such as DNA, RNA, and proteins, but its use for discovering sugar receptors is less explored. In this work, we filled this gap by implementing DCC for screening common saccharides (glucose, galactose, mannose, and fructose) using small, simple, and inexpensive building blocks. Our results indicated that molecule 2DD, which consists of a benzene ring with 2 units of amino acid aspartic acid derivatives connected in positions 1 and 3, is the best receptor in a library of very similar structures for the saccharides glucose, galactose, and mannose. For fructose, molecule 1P, a benzene ring linked to just one unit of the amino acid phenylaldehyde, was appointed as the best receptor. The differential behaviour of fructose can provide insight into the relatively unknown processes behind molecular recognition of sugars. Molecules 2DD and 1P, as well as some other library members as negative controls, were then synthesised for further testing and DCC results were then validated by Isothermal Titration Calorimetry (ITC) and NMR techniques, proving the effectiveness of DCC as a molecular recognition tool for the creation of receptors for saccharides. Moreover, molecule 1P was found to have a high binding constant (K$_{a}$ = 1762 M$^{-1}$) and selectivity (50-100 times over other sugars) for fructose, which is surprisingly good considering the simplicity of the receptor. A much more challenging approach was attempted by employing short peptides as scaffolds in DCC experiments. The benefits of using peptides are numerous but can be summarised in three bullet points: customisability, flexibility, and easiness in their synthesis. Unfortunately, we encountered many difficulties for the complete functionalisation of the peptides within the Dynamic Combinatorial Library (DCL) and this approach did not yield the desired results before the research project came to an end. However, we believe in its potential and the knowledge that we gained on the topic helped to stablish the foundations on which new research will be carried out in the near future within the research group. In summary, this thesis reports the development of a rapid methodology for the discovery of selective receptors for monosaccharides, employing a library of simple and inexpensive starting building blocks. While this was a proof-of-concept study, it can be scalable to larger library sizes and to target more complex biomolecules, becoming a useful tool that could accelerate the discovery of new molecules with biomedical applications

Dinuclear Lanthanide(III) complexes for light emitting surfaces and plasmonic nanomaterials

Lanthanide(III) luminescence is extremely valuable for the development of optical devices. The long luminescence lifetimes, high photostability and narrow and characteristic emission peaks of lanthanides(III) are accompanied by low molar absorption coefficients, demanding sensitisation from light harvesting units via the antenna effect. In addition to careful ligand design, nanostructured plasmonic materials can enhance lanthanide(III) luminescence and overcome some of the most common limitations of luminescent materials and particularly near infrared (NIR) emission, such as poor signal to noise ratios and low quantum yields and brightness. Here, we present novel surface active bis β-diketonatelanthanide(III) complexes for the fabrication of visible and NIR emitting materials. The incorporation of thioacetate units in the ligand scaffold enables the complexes to be anchored on metallic substrates. The characteristic visible and NIR luminescence is retained upon coating on gold (Au) surfaces, and the preparation of a handheld sensing device is demonstrated as a response of the Eu(III) surfaces to F- coordination. Incorporation of the complexes to plasmonic substrates is determined to be an excellent approach for the enhancement of both visible and NIR luminescence. Plasmonic Au (pGold) surfaces, in particular, lead to exceptional resolution and intensity of NIR Nd(III) and Yb(III) emission, driving the progress of lanthanide(III) NIR light to advanced applications. Finally, the complexes are anchored on Au nanoparticles (AuNPs), producing highly emissive H2O dispersed nanomaterials. An alternative approach for the preparation of surface active bis β-diketonates is demonstrated by coordination of functionalised 1,10-phenanthroline units, also optimising the luminescent output of both the complex in solution and on AuNPs

Investigating the role of complement in the pathogenesis of pre-eclampsia in previously healthy pregnant women, and in high-risk groups.

Pre-eclampsia (PE) is a leading cause of obstetric morbidity and mortality. Certain groups of women, including those with chronic kidney disease (CKD) and those of sub-Saharan African (SSA) ethnicity, are at particularly high risk. There remains no definitive treatment other than expedited delivery of baby and placenta. Previous studies suggest a role for complement dysregulation in the pathogenesis of PE, but results are often conflicting, and it remains unclear whether changes in circulating complement concentrations reflect a general heightened inflammatory state in PE or are directly associated with placental complement-mediated injury. This thesis tested the hypothesis that PE is associated with excessive complement activation within placental tissue, with concurrent complement activation within the maternal and fetal circulation, and that groups with a high prevalence of PE, and of PE with severe features (women with CKD and women of SSA ethnicity) would exhibit a greater degree of systemic complement activation. Three arms of research were conducted, and I report: • In a cohort of previously healthy women, PE was associated with significant placental complement deposition, associated with concurrent changes in maternal and fetal circulating complement markers (reduced maternal properdin and C4, and elevated maternal and fetal Ba). Placental C4d deposition was strongly correlated with maternal properdin and C4, suggesting that those patients with the most excessive changes in circulating markers of complement activation also have the greatest extent of placental complement-mediated damage. • There was no evidence of excessive complement activation in the maternal circulation in superimposed PE in a cohort of women with CKD. However, raised Ba levels were associated with adverse pregnancy outcomes in women with CKD. • There was no evidence of excessive complement activation in PE in a Ghanaian cohort of women of SSA ethnicity when compared to healthy pregnant controls. However, pregnant women of SSA ethnicity did have significantly elevated levels of C5b-9, serum free light chains, and immunoglobulin G, when compared to the UK-recruited cohorts; suggestive of a baseline elevated inflammatory state. The results suggest that inhibition of complement activation is a potential therapeutic target for certain groups of women with PE. However, PE is a heterogenous syndrome and additional pathophysiological mechanisms may contribute to the development of disease in women with CKD and women of SSA ethnicity

Designing colloidal open crystals & empty liquids

Because their shape and interactions can be readily controlled, colloidal particles are particularly well suited to act as building blocks for the bottom-up fabrication of complex three-dimensional structures. The self-assembly of sub-micrometre colloidal particles has long been recognised as a promising approach to fabricate photonic materials that operate at visible wavelengths. Cubic diamond-structured colloidal photonic crystals are particularly sought after for their applications in visible light management because of their ability to support a complete photonic band gap at low refractive-index contrasts; however, their realisation via self-assembly pathways has proved to be a long-standing challenge. In this context, this thesis presents a body of computational studies that devise self- assembly routes for designer triblock patchy colloidal rods and tetrahedral patchy particles to yield colloidal diamond crystals by encoding ring selection rules to circumvent kinetic traps. We show that the photonic band gap of the resulting crystals assembled from the triblock patchy rods is robust to stacking faults, thus circumventing the requirement of polymorph selection in a scalable fabrication method. Additionally, using patterning sym- metry concepts, we present a bottom-up route to an enantiomorphic pair of single gyroid crystals comprising colloidal spheres, and demonstrate their assembly from rationally designed patchy spheres. We show that the single colloidal gyroid, and its inverse structure, supports a wide complete photonic band gap in addition to exhibiting rich chiroptical properties, making them attractive chiral photonic crystals. Colloids, traditionally seen as “big atoms” and more recently with the development of the concept of “colloidal molecules”, are also perfectly suited to act as model systems for atomic and molecular systems, and provide a window through which we can glean new insight into a number of fundamental problems in condensed matter physics. One such problem is the liquid-liquid phase transition – hypothesised to underpin the anomalous thermodynamic properties of water. We rationally design a colloidal analogue of water using triblock patchy particles, showcasing that this model displays the well-known water thermodynamic anomalies, as well as a liquid-liquid critical point. Using this model, we reveal that the liquid-liquid phase transition of tetrahedral networks can be described as a topological transition between an unentangled low-density liquid and an entangled high-density liquid, the latter containing an ensemble of topologically complex motifs. We show that this topological distinction between the low-density and high-density liquids also holds for molecular water in connection with the liquid-liquid phase transition

Zinc as a potential therapy for Burkitt’s lymphoma

Burkitts lymphoma (BL) is a form of non-Hodgkin lymphoma (NHL) that arises from germinal center B cells. BL is characterized by translocations of the C-MYC oncogene to immunoglobulin light and heavy chain loci resulting in its constitutive deregulated expression. BL shows a rapid and aggressive growth pattern. There are three different forms of BL; sporadic BL (sBL), immunodeficiency-associated BL and endemic BL (eBL) which accounts for ~50% of all paediatric cancers in Sub-Saharan Africa. Due to financial restrictions, treatment and supportive care options are limited resulting in poorer outcomes in low - middle income countries (LMICs). Thus, there is a need to develop new affordable effective low toxicity treatments for eBL. Prior to this study, a panel of BL cell lines were tested against an in-house custom drug repurposing library developed in our lab (FMC Library) that contains ~100 approved and commonly used drug. This screen identified the nutritional supplement zinc acetate as an effective anti-BL candidate. Dose response studies showed that all BL cell lines tested had little/no response to zinc at 50 μM whereas 100 μM zinc killed all BL cell lines. In contrast, 100 μM zinc acetate induced no killing against a panel of non-BL cell lines including acute myeloid leukaemia (AML) which is a non BL cell tumour, diffuse large B cell lymphoma (DLBCL) which represent a B cell lymphoma that arise from germinal centre B cells and BV infected lymphoblastoid cell lines (LCL) as a control cells. The latter were used as karyotypically normal B cell controls. Cell death in BL cells was associated with positive flow cytometry staining for propidium iodide and annexin V and activation of caspase 3 and 9 (western blotting) indicating cell death by apoptosis. The proto-oncogene C-MYC is mutated or deregulated in >50% of cancers. In BL, deregulated expression occurs as a consequence of translocation of C-MYC on chromosome 8q24 to either the immunoglobulin heavy chain enhancer region on 14q32 (85% of cases) or the immunoglobulin kappa light chain or lambda loci on 2p12 or 22q11, respectively (15% of cases). Thus, the effect of zinc on C-MYC protein levels were studied. Western blot analysis showed that 100 μM zinc was able to reduce C-MYC protein levels rapidly and sustainably in BL cell lines whereas no change in C-MYC protein levels was observed in non-BL cell lines. Zinc-induced reduction of C-MYC protein levels was time-dependent, reducing by approximately 20% after 6 hours with little/no protein detectable after 24 hours. C-MYC protein levels were not reduced following treatment with 50 μM zinc. Quantitative real time PCR (qRT-PCR) also showed a rapid reduction in C-MYC mRNA levels in BL cell lines after 6 hours exposure to 100 μM but not upon exposure to 50μM. Again, no reduction in C-MYC mRNA levels was seen in non-BL cell lines. Translocations of other genes to the immunoglobulin loci occur in other forms of NHL. The DLBCL cell line SU-DHL-4 has a t(14;18) translocation resulting in deregulated expression of the protooncogene BCL2. Western blotting showed no decrease in BCL-2 protein levels in SU-DHL-4 in response to either 100 μM or 50 μM zinc acetate after 6 or 24 hours indicating a selectivity of zinc action against C-MYC protein in BL cells. To further investigate the role of altered C-MYC expression in zinc-mediated killing of BL cells, the eBL cell lines Raji and Namalwa were stably transfected with C-MYC using a piggyBac transposon system that allows gene expression under a constitutively active promoter. However, overexpression of C-MYC from an alternative promoter did not rescue BL cells from killing by 100μM zinc. Although western blotting showed that C-MYC protein levels were protected after 6 hours, protein reduction and loss of viability was again observed after 24 hours indicating that loss of C-MYC is important in zinc-mediated killing of BL cells. In a second approach to rescue C-MYC expression, the proteasome inhibitor Bortezomib was used to inhibit C-MYC protein degradation via the ubiquitin-proteasome system (UPS). Whilst increases were observed in overall ubiquitinated proteins indicating bortezomib was working, western blotting and flow cytometry showed no rescue of C-MYC protein levels. Furthermore, bortezomib did not rescue cells from zinc-mediated killing after 24 hours. In conclusion, findings from this study have identified that 100 mM zinc is effective at killing BL cell lines selectively, and that this killing is associated with activation of apoptotic markers. Treatment with zinc resulted in a rapid and sustained reduction in C-MYC mRNA and protein levels that could not be rescued through constitutive overexpression or the use of proteasome inhibitors. Given that zinc deficiency is common in sub-Saharan Africa and that zinc supplementation is safely used to treat diarrhoeal episodes in children, the studies proposed here indicate that zinc may safely be used as an adjunctive therapy to target C-MYC in BL

Financial literacy and mental health

Being one of the essential skills in the 21st Century, financial literacy is important in its own right and for individuals’ life-long financial well-being. Financial literacy has been associated with a series of positive financial outcomes in previous literature. However, we still know little about how financial literacy is related to individuals’ mental well-being. This thesis aims to investigate the relationships between financial literacy, financial well-being and mental well-being among adults. To realise this, three empirical studies are conducted. The first empirical study examines the relationship between financial literacy and depressive symptoms, providing the first empirical evidence of the relationship between the two concepts in a middle-income setting: China. The second empirical study provides the first longitudinal investigation on the relationship between financial literacy and depression and its underlying economic pathways, using data from a nationally representative dataset: the Health and Retirement Study (HRS) based on the U.S.. The third empirical study investigates the moderating role of financial literacy in the association between financial shocks and depression aiming to further enclose the relationship between financial literacy and mental well-being. The findings highlight both positive and negative effects of financial literacy on mental well-being. On one hand, financial literacy is significantly associated with fewer depressive symptoms and financial literacy may positively impact individuals’ mental well-being either directly or indirectly operated through its influence on household finances such as income and wealth. On the other hand, when individuals experience financial shocks, financial literacy can magnify the negative effect of experiencing financial shocks on mental well-being. The findings suggest that investing in acquiring or sustaining financial literacy may have the potential to protect against depression and thus promote positive mental health in adults by assuring better financial well-being. However, the observed negative psychological effect of higher financial literacy suggests that the role of financial literacy on mental health is complex. Future research is needed to further understandings of the causal impact of enhancing financial literacy on mental well-being and of its complex and multifaceted underly mechanisms

4D quantifications of intermetallics in solidifying aluminium alloys

High-speed synchrotron X-ray tomography was used to investigate the growth dynamics and mechanisms of faceted intermetallic compounds (IMCs) in aluminium alloys under different solidification conditions (temperature gradients, cooling rates and external magnetic field). Different IMCs in four aluminium alloys are studied including Al13Fe4 in Al-5wt%Fe alloys, Al2Cu in Al-45wt%Cu alloys, Al3Ni in Al-10wt%Ni alloy and β-IMCs in W319 (Al-Si-Cu) based alloys. 4D quantifications (3D plus time) were achieved in determining the nucleation rates, nucleation densities, volume fractions and growth velocities of Al$_{13}$Fe$_4$ IMCs with various faceted morphologies. In both Al-45wt%Cu and Al-10wt%Ni, two stages of the formation processes were identified including the growth of the basic unit and the growth of the faceted dendrite. The transition of various morphologies of the basic unit was observed and the relationship between these morphologies was determined. The growth mechanism of the faceted dendrite was proposed to be self-repeated layer-by-layer stacking of the basic units (such as L-shaped in Al$_2$Cu or V-shaped in Al$_3$Ni). In addition, the work studied the effect of magnetic fields on solidification in Al-45wt%Cu and W319 alloys. A transverse magnetic field of 0.5T was used to control the solidification processes while the sample was rotating. Highly refined Al$_2$Cu intermetallic compounds were obtained including the in Al-45wt%Cu alloys which were much finer than those without the imposition of the magnetic field. Under the magnetic field, fine α-Al dendrite with smaller primary dendrite arm spacing in W319 alloys was obtained. The macro segregation zone was almost eliminated, while the solid/liquid interface was altered from tilted to flat. Gradient volume distribution of the secondary β-IMCs was observed. This work first reveals the growth mechanisms of different faceted IMCs with various morphologies. It also demonstrates that rotating the sample under a transversal magnetic field is a simple yet effective method of controlling the morphologies and volume distribution of crystals via altering the temperature and composition profiles in the melt

Gamma emission from clustered states in 16O nuclei

The experiment involving the reaction (α +12 C) → (16O∗ + γ) → (α +12 Cg.s.) was performed at the University of Birmingham MC40 cyclotron facility at a beam energy of 12.29±0.04 MeV to study the gamma to alpha emission ratio of a suspected clustered state in 16O at 16.272 MeV , J = 6+. Finding a reduced transition probability value of B(E2; 6+ → 4 +) = 3.316 ± 1.736w.u. = 7.942 ± 4.158 e2 fm4. This work also presents a method to create simulations of alpha-gamma coincidences with realistic detectors response, which is used to decompose and analyse the components of the detected gamma spectrum to extract the reduced transition probability. The methods described in this work can be employed to study nuclear structure properties by gamma emission of other light nucle