VictorJuiz/thesis huggingface dataset:
Modification and application of glycosidases to create homogeneous glycoconjugates
Keywords: antibody-drug conjugate
oligosaccharide
glycosidase
glycoprotein
endo-beta-N-acetylglucosaminidase
glycosynthase
glycan trimming

In the post-genomic era, recognition of the importance of sugars is increasing in biological research. For the precise analysis of their functions, homogeneous materials are required. Chemical synthesis is a powerful tool for preparation of homogeneous oligosaccharides and glycoconjugates. Glycosidases are potent catalysts for this purpose because they realize high stereo- and regio- selectivities under conditions benign to biomolecules without repetitive protection/deprotection procedures.
A glycosynthase is an aritificial enzyme which is derived from a glycosidase and is devised for glycosylation reaction. To suppress the mechanistically inherent oligomerization side reaction of this class of biocatalysts, a glycosidase with plastic substrate recognition was engineered to afford the first α-mannosynthase. This novel biocatalyst showed low occurrence of oligomerized products as designed and was applied to prepare a wide range of oligosaccharides.
Glycosidases are also valuable tools for glycan engineering of glycoconjugates, which is a pivotal issue in the development of pharmaceutical agents, including immunoglobulin G (IgG)-based drugs. EndoS, an endo-β-N-acetylglucosaminidase from Streptococcus pyogenes, natively cleaves N-glycans on IgG specifically. When the latent glycosylation activity of this enzyme was applied, the N-glycan remodelling of full-length IgG was successfully achieved for the first time and a highly pure glycoform was obtained using the chemically synthesized oxazoline tetrasaccharide as glycosyl donor. This biocatalytic reaction allows development of a novel type of antibody-drug conjugates (ADCs) in which drug molecules are linked to N-glycans site-specifically. For this purpose, glycans with bioorthogonal reaction handles were synthesized and conjugated to IgG. A model reaction using a dye compound as reaction partner worked successfully and the synthetic method for this newly designed ADC was validated.
Glycan trimming of glycoproteins expressed from Pichia pastoris was performed using exoglycosidases to derive homogeneous glycoform. Jack Bean α-mannosidase (JBM) trimmed native N-glycans down to the core trisaccharide structure but some of the glycoforms were discovered to be resistant to the JBM activity. Enzymatic analyses using exoglycosidases suggested that the JBM-resistant factor was likely to be β-mannoside. In summary, this work advanced application of modified glycosidases for preparation of oligosaccharides and also demonstrated biocatalytic utility of glycosidases to produce biologically relevant glycoconjugates with homogeneous glycoforms.
Advances in electrochemical simulation and its application to electroanalysis
Keywords: Electrochemistry
Electroanalysis
Computational electrochemictry

This thesis is concerned with the simulation of various electrochemical experiments and its application to electroanalysis.
Chapter 1 outlines the fundamental principles of electrochemistry which are of importance for the reading of this thesis. Chapter 2 then outlines the methods used in the numerical simulation of electrochemical experiments.
Chapters 3 and 4 are concerned with the electrochemistry of nanoparticles, and how this is affected by the presence of near wall hindered diffusion. In Chapter 3, a computational model to simulate anodic particle coulometry of nanoparticles in the presence of hindered diffusion is developed, and the effect of this hindered diffusion investigated. The model is then applied to simulate experimental data. Chapter 4 looks at the effect of hindered diffusion on the adsorption of nanoparticles on electrode surfaces, and investigates the effects of this adsorption on electrochemical experiments with nanoparticles generally.
Chapters 5, 6 and 7 are concerned with band electrodes in isolation, in a pair and in an array respectively. In Chapter 5, a model to simulate double potential step chronoamperometry at an individual band electrode is developed, and used to successfully simulate experimental data. Chapter 6 looks at dual band electrodes used in generator-collector mode, and how this can be used to simultaneously measure the concentration of two species in solution. Chapter 7 looks at interdigitated arrays of band and ring electrodes in generator-collector mode, and develops a model to simulate cyclic voltammetry in both cases, as well as investigating under what conditions interdigitated ring arrays may be modelled as interdigitated band arrays.
Chapter 8 develops a model to simulate chronoamperometry and cyclic voltammetry at porous electrodes, and investigates the consequences for electroanalysis of having a porous layer.
Finally, Chapter 9 investigates the Marcus-Hush theory of electron transfer kinetics, and looks at the effect of the kinetically limited currents resulting from this theory to the equivalence relation between microdisc electrodes and sphere-on-a-surface electrodes.
Characterisation of global regulators that control expression of a flagella system in Rhodobacter sphaeroides
Keywords: Fla1
Rhodobacter sphaeroides
Rhodobacter
flagella
chemotaxis
Fla2

The α-proteobacterium Rhodobacter sphaeroides expresses one ﬂagellar system (Fla1) and two chemotaxis operons (cheOp2 and cheOp3) under laboratory conditions. It has another ﬂagellar system (Fla2) with a proposed cognate chemotaxis operon (cheOp1) which until recently had not been seen to be expressed. Here we characterised Fla2 motility and show that cheOp1 can be expressed under Fla2-inducing conditions. Putative Fla2&plus; strains AM1 and N29 were incubated on Sistrom's media and expression of the Fla2 system was conﬁrmed with western blotting and mass spectrometry. The Fla2 motility pattern was signiﬁcantly different to Fla1 when measured on soft nutrient agar and by analysing free swimming cells. Fla2&plus; strains swam in a corkscrew-like pattern which may favour movement through bioﬁlms. Fla2&plus; AM1 and N29 were signiﬁcantly deﬁcient in their capacity to form bioﬁlms compared to Fla1&plus; WS8N. AM1 and N29 were found to contain mutations in cckA and plasmids expressing these mutations were able to switch expression of Fla1 in WS8N to Fla2. Expression of mutant cckA also affected cheOp2 and cheOp3 expression and induced expression of cheOp1. Some members of the α-proteobacteria are known to engage in lifestyle switches from motile to sessile growth. It is suggested that a similar switch occurs in R. sphaeroides which uses the Fla1 system for motility in liquid environments and for the initial attachments to surfaces and the Fla2 system for movement through the highly-viscous bioﬁlm. For the ﬁrst time we have also shown expression of cheOp1 which may engage in cross-talk with the cheOp2 and cheOp3-expressed chemotaxis system. These results have implications for the regulation of dual ﬂagellar systems in the α-proteobacteria.
Football and immigrant communities: transnational diaspora politics, Identities, and integration in Turkish-speaking ethnic football in London
Keywords: diaspora politics
Turkish-speaking community in London
ethnic football
gender and masculinity
integration through sport

This thesis is on the Turkish-speaking community, comprising Turkish-Cypriots, Turks from Turkey, and Kurds from Turkey, and ethnic community football in London, which has been conceptualised as a transnational social field. It is intended as a contribution in the debates on the growing importance of issues of diasporic communities, their identity politics, and cultural integration in a context of ‘super-diversity’.
There are three major analytical themes. The first is transnational diaspora politics, which is redefined to comprise any relationship of power or interest by mobilising diasporic connections. I argue that the Turkish-speaking community uses ethnic football as a means for communal mobilisation around and representation of their ethnic identity in the public space of London, a city of unique political-economic and symbolic significance for the Cyprus Conflict which helped create the Turkish and Greek Cypriot football leagues in London. I show that the Turkish-speaking community has ever since used football to create and maintain a bridge between London and all the different locations of the community including Cyprus, Turkey, Germany, and beyond.
The second major theme is collective identities and how they are (re)produced, represented, and manifested in the diaspora. I argue that the nature of the field of ethnic football as a familiar, open, and welcoming space conveniently positioned between the Turkish-speaking private sphere and the British/Londoner public space has been a major factor accounting for the effectiveness of various identity projects to be pursued within this field. Lastly, after presenting the historical link between modern competitive sports and masculinity, I claim that the one defining aspect of all the ethnic identities reproduced within the field is their masculine character.
The last analytical theme is the cultural integration of immigrant communities. Without adopting a normative definition of cultural integration, I have considered the implications of involvement in ethnic community football in terms of belonging, social inclusion, marginalisation, and the psychological development and well-being of the individuals involved. The presented and analysed discussion rejects any automatic causal link between involvement in sports and integration or that involvement in mono-ethnic sporting organisations and segregation. Having reviewed a few exemplary organisations, which used football for integration purposes, and the nature of the ethnic community leagues, I have also argued in this thesis that the field of ethnic community football, again due to its specific nature, structure, and position between the private and public spaces, offers a great potential to be engaged by local and national governments in the service of integration policies.
A study of viral and cellular factors in the regulation of the influenza virus RNA-dependent RNA polymerase
Keywords: RNA polymerase
RNA synthesis
influenza

The segmented negative-sense vRNA genome of influenza A virus is replicated via a complementary RNA (cRNA) intermediate by the viral RNA-dependent RNA polymerase (RdRP). The replicative intermediate has been thought to exist as a complementary ribonucleoprotein (cRNP) complex. Development of an RNA-based affinity-purification strategy for the isolation of viral ribonucleoprotein complexes enabled the structural and functional characterisation of the previously uncharacterised cRNP complex. The cRNP exhibits a filamentous double-helical organisation with defined termini, containing the viral RdRP at one end and a loop structure at the other end. In vitro characterisation of cRNP activity led to a proposal of a model of vRNA synthesis that relies on a trans-activating RdRP.
The viral RdRP is an important host range determinant indicating that its function is affected by interactions with cellular factors. However, the identities and the roles of most of these factors remain unknown. Affinity-purification followed by mass spectrometry was performed to identify cellular proteins that interact with the viral RdRP. 171 cellular proteins were found to co-purify with the viral RdRP, the most abundant of which were chaperones, cytoskeletal proteins, importins, proteins involved in ubiquitination, kinases and phosphatases, mitochondrial and ribosomal proteins. Among the phosphatases, three subunits of the cellular serine/threonine-protein phosphatase 6 (PP6) were identified. PP6 was found to interact directly with the PB1 and PB2 subunits of the viral RdRP, and siRNA-mediated knockdown of the catalytic subunit of PP6 in infected cells resulted in the reduction of viral RNA accumulation and the attenuation of virus growth. Taken together, these results suggest that PP6 interacts with and positively regulates the activity of the influenza virus RdRP.
Magnetism in quasi-low-dimensional systems investigated with muon spin rotation and high magnetic fields
Keywords: superconductivity
muon spin rotation
magnetism
quasi-low-dimensional systems
coordination polymers
high magnetic fields
transition metal oxides

This thesis presents the investigation of magnetism in a selection of low-dimensional systems and its relation to other physical properties, such as superconductivity. The techniques employed are muon spin rotation and pulsed magnetic field magnetisation. The ability of muons to directly probe the local field is used to study SrFeAsF, which is a parent compound of the high-temperature superconducting pnictides. This revealed that the magnetic and structural transitions are separated in this system. I then demon- strate the coexistence of magnetism and superconductivity in NaFeAs for the first time. This discovery is of great interest since the interplay between magnetism and supercon- ductivity is thought to play an important role for high-temperature superconductivity. I further investigate the effect of partially replacing Fe with Co in NaFeAs. I study the ordering and spin reorientation in the Mott insulator Sr₂IrO₄, which has been suggested as a possible high-temperature superconductor. The complex magnetism observed in this system is contrasted to that in related iridates Ca₄IrO₆, Ca₅Ir₃O₁₂ and Sr₃Ir₂O₇. By combining pulsed-field magnetization and low magnetic field experiments with μSR on a series of coordination polymers. I am able to determine the size and direction of the magnetic exchange interaction. I demonstrate how it is possible to adjust the in- teractions by altering the molecular architecture of these Cu-based spin- 1 2 compounds. This is a significant contribution since it will lead to the targeted design of magnetic systems that can be utilized to experimentally test fundamental theories of magnetism.
American ways and their meaning: Edith Wharton’s post-war fiction and American history, ideology, and national identity
Keywords: 1930s
globalization
Americanization
World War I
Scott Fitzgerald
Edith Wharton
flapper
1920s
'The Age of Innocence'
' modernism
Jazz Age
American Dream
'Twilight Sleep
'The Buccaneers'
Sinclair Lewis

This thesis argues that Edith Wharton’s assessment of American ways and their meaning in her post-war fiction has been widely misread. Its title derives from French Ways and Their Meaning (1919), which she wrote to educate her countrymen about French culture and society. Making sense of America was as great a challenge to Wharton. Much of her later fiction was for a long time dismissed by critics on the grounds that she had failed to ‘make sense’ of America. Wharton was troubled by American materialism and optimism, yet she believed in a culturally significant future for her nation. She advocated – and wrote – an American fiction that looked critically at society and acknowledged the nation’s ties to Europe. Sometimes her assessment of American ways is reductive, and presented in a tone that her critics, then and since, found off- putting and snobbish. But her skepticism about American modernity was penetrating and prophetic, and has not been given its due.
In criticism over the last two decades, a case for the place of Wharton’s post-war fiction in canons of feminism and modernism has been persuasively made. The thesis responds to these positions, but makes its own argument that the post-war writing reflects broader shift in American identity and ideology. The thesis is broadly historicist in its strategy, opening with a discussionofthereputationofthesetextsandthatoftheauthormoregenerally. Afterthat entry-point, it is organized thematically, with four chapters covering topics that are seen as key components of American ideology in Wharton’s post-war writing. These include modernity, gender equality, the American Dream of social mobility, and American exceptionalism. The thesis concludes with an assessment of Wharton’s prognostications in the context of twenty-first century America.
Adverbs in conceptual semantics
Keywords: formal semantics
participant-oriented evaluative modification
predicate-oriented modification (by manner adverbs)
conceptual semantics
adverbs

The thesis discusses and evaluates semantic representations of predicate-oriented modification (specifically by manner adverbs) and participant-oriented evaluative modification (by so-called “subject-oriented” adverbs). Analyses are proposed within the framework of Conceptual Semantics.
Electronic structure/function relationships in metal nanowires: components for molecular electronics
Keywords: electron transport
DFT
NEGF

The dramatic expansion of the electronics industry over the past 40 years has been based on the progressive reduction in size of the silicon-based semiconductor components of integrated circuits. The miniaturisation of semi-conductor circuits cannot, however, continue indefinitely, and we are rapidly approaching the stage where quantum effects will prevent further dramatic improvements in computer performance using existing technology. As a result, the field of molecular electronics, which seeks to identify and develop much smaller molecular analogues of the transistors that make up integrated circuits, has expanded rapidly over the past few years.
Recent studies suggested that extended metal atom chains (EMAC) may have many potential applications in molecular electronics, but it is clear that this potential can only be realised if we establish a link between the fundamental electronic properties of these systems and the transport of electrons. For this reason the ultimate goal of this thesis is to relate the electronic structure of extended metal chains to their electron transport properties. We address the problem using non-equilibrium Green’s function, in conjugation with density functional theory.
In the results sections of this thesis we present calculations on tricobalt, trichromium and trinickel chains. Our data suggested that in the trimetal chains, the dominant electron transport channel is the σ manifold, while the π systems establish the contact with the electrodes. The implication of this is that even when the highly polarized π channels are strongly rehybridised by the applied electric field, current flow is not affected. In the trichromium systems we find that the distortion of the chain away from the symmetric equilibrium structure does not perturb the current flow but rather enhances it. Our rather counter intuitive conclusion is therefore that ‘broken wires’ (highly unsymmetric) are more efficient conductors than their symmetric counterparts. We have performed calculation on longer penta- and heptacobalt structures chains to establish the extent to which longer structures attenuate the conductance. Our calculations show significant oscillations of the conductance due to development of a one-dimensional band structure about the Fermi level. The evolution of the electron transport properties in cobalt chains with different length is a complex one, but it is clear that narrowing the band gap in longer chains makes it increasingly likely that the Fermi level will be in resonance with one or more of the orbitals of the extended metal atom chain.
Discovery of a conserved Plasmodium antigen on the surface of malaria-infected red blood cells
Keywords: conserved
membrane
aptamer
malaria

During its intraerythrocytic stages (IE), Plasmodium falciparum, the causative agent of the deadliest human malaria, remodels the host red cell membrane with a poorly defined assortment of parasite-­encoded proteins that undergo antigenic variation. Despite the requirement for immunologic stealth, exported parasite proteins also mediate strain-independent functions such as endothelial sequestration that are critical for parasite survival and pathogenesis.
This thesis explores the hypothesis that P. falciparum displays novel structurally conserved proteins on the IE surface and these proteins may serve as useful antigens for a broadly effective anti-­malarial vaccine. In order to test this hypothesis, we developed an in vitro selection technique that sequentially incorporates unique P. falciparum isolates as the targets for Systematic Evolution of Ligands by EXponential enrichment (Serial-SELEX) to generate nucleic acid molecular probes, aptamers, capable of recognizing conserved cell surface determinants. Ten of 11 enriched aptamers were -parasite selective and three of these aptamers demonstrated strain-independent binding to P. falciparum. Aptamer recognition extended beyond the parasites used in Serial-SELEX to other laboratory and recent field isolates. Surprisingly the same three broadly binding aptamer selected against P. falciparum also recognized all laboratory-adapted and clinical isolates of P. vivax and P. knowlesi tested, strongly supporting our hypothesis that structurally conserved molecules are present on the surface IEs. Competition studies showed that the aptamers bound a single target which was confirmed as an IE membrane protein. Aptamer­‐mediated affinity purification and tandem mass spectrometry enabled identification of the aptamer target as parasite-encoded protein. Discovery of a protein conserved between the major human malarias may have implications for vaccine development and validates the Serial‑SELEX technique as a powerful tool for antigen discovery.
Electronic band structure of carbon nanomaterials
Keywords: Photoluminescence
Cyclotron Resonance
Nanotubes
Graphene

This thesis reports the study of electronic structures for single-walled carbon nanotubes, single layer graphene and thin graphite. A brief introduction is given in Chapter 1 for the geometric and electronic structures of the materials studied while a review for the theory and experimental results relevant to this thesis is given in Chapter 2.
The effects of hydrostatic pressure on surfactant-wrapped-single walled carbon nanotubes are studied in Chapter 3 by using photoluminscence and photoluminscence excitation mapping. It is found that the changes to the optical properties can be explained by the compression in carbon-carbon bonds, an effective uniaxial strain exerted on the nanotubes and changes in the surrounding environment leading to changes in the many-body interactions experienced by the nanotubes. Chapter 4 reports the study of cross-polarized photoluminescence of nanotubes isolated by conjugated polymers dispersed in solvents. The effects of Coulomb interactions on the optical bandgaps of the nanotubes are discussed here.
Chapter 5 reports Cyclotron resonances studies of graphene monolayers. It is found that a significant asymmetry exists between the electron and hole band structures near the Dirac point, and the asymmetry is bigger than that is expected in a simple tight-binding model. Chapter 6 reports a magnetoabsorption study of the electronic structures near the K- and H- points. It is found that the transitions are not describe well by the conventional Slonczewski-Weiss-McClure model, but can be described instead with a simplified asymmetric effective bilayer model.