VictorJuiz/thesis huggingface dataset:
Biophysical characterisation of the mechanisms regulating sarcoplasmic reticulum K+ channel gating

Intracellular Ca2+-release from the sarcoplasmic reticulum (SR) occurs through highly specialised Ca2+-release channels called ryanodine receptors (RyR) in a process known as excitation-contraction coupling (EC-coupling) in striated muscle.
The RyR is the main ion-channel mediating Ca2+-release from the SR but the SR also contains many other ion-channels and proteins, with many of unknown physiological role. For example, two SR K+ channels, TRIC-A and TRIC-B, have recently been identified and are thought to play a key role in supporting intracellular Ca2+ movements across the SR. The TRIC double knockout (DKO) mouse dies in embryonic heart failure and the TRIC-B knockout (KO) dies in respiratory failure immediately after birth, highlighting their important roles in different tissue types. The TRIC-A KO mouse survives until adulthood, however, there are SR structural abnormalities and compromised Ca2+ release.
I have focused on characterising and comparing the single-channel properties of the native SR K+ channels from WT and TRIC-A KO mouse skeletal muscle. I have investigated if the SR K+ channels can gate in a cooperative manner when multiple SR K+ channels are present in the bilayer. Since TRIC and RyR channels are both located in high abundance in the junctional SR regions, I have examined whether the SR K+ and RyR channels also gate in a cooperative manner when both are present in a bilayer. In addition to voltage-regulation of native SR K+ channels, I have characterised the pH sensitivity of the SR K+ channels from WT and TRIC-A KO tissue. Finally, I investigated if the mouse isoform of TRIC-A could be purified using the Wheat germ cell-free system and incorporated into bilayers without loss of function.
In summary, this thesis describes novel mechanisms of regulation of ion-channels that are involved in the process of Ca2+-release from the SR. By focusing on the biophysical properties of SR K+ channels, I have highlighted the complexity of the ionic fluxes that are thought to be required to maintain normal EC-coupling in striated muscle.

Advisor: Sitsapesan, R
Playing the game: a study of transnational Turkish football fans, imaginations and the internet

This thesis is about transnational Turkish football communities and how they come to be imagined through internet technologies. The research is based on an ethnography of one particular group of Turkish football fans in Europe. The team is Beşiktaş, one of Turkey's top teams, and the fans make up Çarşi Berlin, their largest supporters' club in Europe. Founded in 2003 in Berlin, the group has grown to consist of 600 members, with branches from London to Switzerland.
The thesis explores the internet and its effects at a specific historic juncture on the fashioning of Çarşi Berlin. I approach the topic via three routes, namely, the effects of internet technologies on: football fandom; the spaces in which it occurs; and the cultural forms and practices by which it is instantiated. In the process I contribute to current scholarly debates across sub-disciplines both within and outside anthropology: those of sport and globalisation, enchantment, publics, personhood and the imagination. I argue that football communities are increasingly imagined in ways that are distracted, ephemeral and playful and that, contrary to common conceptions, fun, affect-laden imaginings can have the power to alter conceptions of concepts such as the nation or family. In the process, I contribute greater appreciation of the experience of being a diasporan football fan and its salience for broader understandings of how we imagine belonging in the twenty-first century.

Keywords: Turkey
social media
internet
football
diaspora
Advisor: Keith, M
Berg, M
Role of the nuclear envelope in regulation of ageing

Cellular senescence is a phenomenon characterised by stable and durable states of proliferative arrest induced by various stress stimuli. The abundance of senescent cells in tissues increases over a lifetime and, among other functions, they have been proposed to play a pivotal role in ageing. Hutchinson-Gilford progeria syndrome (HGPS) is a disease characterised by segmental premature ageing. It is caused by the expression of a persistently farnesylated lamin A isoform. Strikingly, HGPS patients show an increased abundance of senescent cells. Therefore the relationship between the farnesylated lamin A precursor, prelamin A, and senescence was studied in this thesis.
Cellular models of ageing in human dermal fibroblasts were established. They relied on either replicative exhaustion or prelamin A accumulation. An unbiased genome-wide transcript analysis of the ageing models revealed that a significant part of the common senescence programme during cellular ageing can be replicated in young cells by accumulating prelamin A. The most prominent and overlapping expression changes were observed in pathways regulating inflammation, lipid metabolism and cholesterol homeostasis. Six genes, identified as underexpressed consistently across the studied ageing models, were tested functionally in the context of senescence regulation by prelamin A. The ability of prelamin A-accumulating cells to induce inflammation has also been demonstrated by multiplexed detection of secreted cytokines, chemokines and other factors. This confirms that a significant overlap between replicative and prelamin A-induced senescence exists not only at mRNA level changes, but is also observed at the level of secreted proteins. Finally, nuclear morphology was studied in the ageing models, with a particular interest in the formation of a nucleoplasmic reticulum. We identified NOGO/Reticulon-4 as a new protein involved in the process of NR formation, and also demonstrated that new NR channels require incorporation of newly synthesised lipid and protein components. The research presented in this thesis offers a new insight into a role of the prelamin A maturation process in senescence and ageing.

Keywords: Senescence
Prelamin A
Reticulons
Nucleoplasmic Reticulum
SASP
Advisor: Vaux, D
Patient outcomes following discharge from secure hospitals

Background: Despite limited evidence for service benefit, the demand for forensic psychiatric beds is growing. Some studies have reported rates of serious adverse outcomes post-discharge, however, the role of psychiatric diagnosis as a determinant of these outcomes needs to be clarified to ensure patients are managed in the most appropriate way.
Aims: The first aim of this thesis is to summarize evidence on key adverse outcomes, and to provide comparative information for public health and policy. The second aim of this thesis is to elucidate the role of diagnosis and comorbidity in the risk of some adverse outcomes.
Methods: The first study is a systematic review and a meta-analysis of investigations that followed patients discharged from secure hospitals, and reported data on key adverse outcomes after discharge. The second is a historical cohort study of forensic patients discharged from Swedish secure hospitals between 1972 and 2009, which examines the role of psychiatric diagnosis in risk of some adverse outcomes.
Results: Thirty-six studies from 10 countries were included. Mortality rates were lower in studies from England and Wales (crude rate=1,239, 95% CI 932-1,547) compared to other countries (2,331; 1,738-2,925). Readmission rates were higher in samples with a bigger proportion of patients with a diagnosis of mental illness (β=105.57, [se(β)]=54.90, p=0.070) as opposed to personality disorder (β=-181.45, [se(β)]=90.59, p=0.070). Reoffending rates were lower in more recent studies (β=-101.15, [se(β)]=43.34, p=0.026). Compared with different cohorts of discharged prisoners matched on gender, age, and type of offence, reoffending rates were lower for the forensic psychiatric samples (UK prevalence ratios 1.4-7.7 in UK studies)
In the Swedish study, substance use was associated with increased risk of death (HR=1.783, 95% CI=1.556-2.044, p&LT;.000) and violent offending (HR=1.980, 95% CI=1.740-2.254, p&LT;.000). Schizophrenia increased the risk of readmission. Bipolar disorder (HR=1.461, 95% CI=1.196-1.785, p&LT;.000 and personality disorder (HR=1.496, 95% CI=1.345-1.663, p&LT;.000) were associated with increased risk of violent offending.
Conclusions: Treatment and post-discharge support strategies should take into account primary and comorbid diagnosis. Services should provide better overall care to improve patients' general health aiming to reduce premature mortality. Better health could also improve social functioning of these patients reducing readmissions and post-discharge offending in the long-term.

Advisor: Fazel, S
Toward robust algebraic multigrid methods for nonsymmetric problems

When analyzing symmetric problems and the methods for solving them, multigrid and algebraic multigrid in particular, one of the primary tools at the analyst's disposal is the energy norm associated with the problem. The lack of this tool is one of the many reasons analysis of nonsymmetric problems and methods for solving them is substantially more difficult than in the symmetric case. We show that there is an analog to the energy norm for a nonsymmetric matrix A, associated with a new absolute value we term the "form" absolute value. This new absolute value can be described as a symmetric positive definite solution to the matrix equation A&ast;&verbar;A&verbar;-1A = &verbar;A&verbar;; it exists and is unique in particular whenever A has positive symmetric part. We then develop a novel convergence theory for a general two-level multigrid iteration for any such A, making use of the form absolute value. In particular, we derive a convergence bound in terms of a smoothing property and separate approximation properties for the interpolation and restriction (a novel feature). Finally, we present new algebraic multigrid heuristics designed specifically targeting this new theory, which we evaluate with numerical tests.

Keywords: nonsymmetric
absolute value
algebraic multigrid
Advisor: Wathen, A
Self and society in Mary McCarthy's writing

My thesis analyses the oeuvre of the American writer Mary McCarthy (1912-1989), with the focus on the figure of the outsider looking in. McCarthy uses outsider figures in her texts as prisms through which distinctive historical moments as well as problems of gender, race and religion are studied against the backdrop of the changing climate of the American "red" 1930s, the anxious '50s, and the late '60s torn by the Vietnam war. Examples of McCarthy's recurring protagonists are the New York Bohemian girl of the '30s in the predominantly male world marred by the Great Depression, the Jewish character stereotyped as the Other by the poorly hidden anti-Semitism of the American society of the early 1940s, and the orphan child exposed to adult cruelty, who finds her only solace in the Catholic religion. Their position of being outsiders who live in a society not their own by birthright, is shown to be crucial for their acquisition and knowledge of truth, and links insight to marginality, which is reinforced by McCarthy’s technique of ironically detached observation, the "cold eye” of her prose. McCarthy herself appears as an outsider character throughout her writing, both as the historical figure and as the protagonist of her autobiographies. Her self-image, shaped by her orphaned childhood and her youth as a Bohemian girl among leftist intellectuals, is subject to conflicting impulses of confession and concealment. McCarthy's wide use of autobiographical details in her fiction and elements of fiction in her autobiographies led most critics to study her work from a chiefly biographical point of view. My own approach to Mary McCarthy’s writing takes their findings into consideration, and includes the analysis of the historical, political, and social contexts of McCarthy’s texts, as well as the intertextual dialogue with a few select writings by McCarthy’s contemporaries such as Philip Roth and Sylvia Plath.

Keywords: American 1930s and 1950s
Psychoanalysis
Jewishness
Auto/biography
20th century American Women's Writing,
Advisor: Marcus, L
Investigating the effect of  melanopsin gene therapy in the degenerate retina

Retinal degenerations such as retinitis pigmentosa affect 1 in 3000 people causing visual loss and blindness. In these conditions, photoreceptors are lost whereas other retinal cells and central visual pathways remain largely intact. A strategy for restoring vision in patients with end-stage disease would be to introduce a light sensitive protein into remaining inner retinal cells to make them directly light sensitive.
The aim of this thesis was to assess whether the human photopigment melanopsin, normally present in intrinsically photosensitive ganglion cells, could be delivered to other residual cells of the degenerate retina using an adeno-associated viral (AAV) vector, and whether this could restore visual function.
Several AAV serotypes were tested in the rd1 mouse model of end-stage retinal degeneration. The most effective was found to have a single tyrosine to phenylalanine mutation in the AAV capsid (rAAV2/8 Y733F), and this vector was also able to transduce bipolar cells in human retinal samples cultured ex-vivo. Further evaluation of the vector was then performed to identify whether delivery using a ubiquitous or bipolar cell specific promoter gave optimal expression, and that comparing a wild type to a codon optimised sequence was also assessed. Longevity of expression was also assessed with robust levels of melanopsin seen in the degenerate retina fifteen months after a single subretinal injection.
Retina transduced using the optimised vector was tested for functional light responses using ex-vivo multi-electrode array recordings and in vivo light pulsing, with results from both highly indicative of functional photosensitivity mediated by expressed melanopsin. Furthermore, laser speckle cortical imaging demonstrated a light-dependent change in blood flow in the visual cortex of treated mice.
Finally to assess whether visual function was restored, in vivo testing of the pupil light response revealed augmented pupil constriction compared to controls two months after subretinal injection of the vector. This effect was maintained and even greater at thirteen months. Further behavioural testing demonstrated that following vector administration both two and thirteen months previously, mice were able to detect a change in visual environment, whereas control rd1 mice were not.
These data indicate that the increased photosensitivity derived from expression of human melanopsin in the degenerate retina can generate functionally useful information, which can restore light-driven responses and even enhance performance in a test that relies on image–forming vision in mice with end-stage retinal degeneration. Therefore with further development, this optogenetic strategy has great potential for the treatment of patients with end-stage retinal degeneration.

Keywords: Melanopsin, gene therapy
Advisor: Hankins, M
MacLaren, R
Understanding the role of Neuregulin 1-erbB signalling in microglia in the context of neuropathic pain.

Neuregulin 1 (NRG1) is a growth factor required for peripheral nerve development and functional recovery following nerve injury. However, its importance in regulating neuropathic pain via microglial signaling remains unclear. Previous pharmacological studies suggest NRG1 regulates microglial proliferation, mechanical allodynia and cold hypersensitivity through binding to extracellular tyrosine kinase receptors (e.g. erbB2, erbB3 and erbB4) found on microglia.
The aim of this thesis was to further dissect the role of NRG1 in regulating pain behaviour during neuropathic pain by using transgenic systems that conditionally ablate NRG1 expression in adulthood or erbB receptor expression specifically within microglia. In our hands it was determined that the CX3CR1 Cre is more efficient than the Cd11b Cre system in effectively targeting tissue specific gene ablation.
Using animal models of nerve injury, gene expression analysis showed that NRG1 and erbB gene expression levels are dysregulated in the peripheral nervous system and the spinal cord, in neuropathic pain models. A novel cold pain behaviour assay was optimised to measure cold pain behaviour. With conditional NRG1 ablation, and the use of the spared nerve injury model, it was determined that NRG1 regulates cold hypersensitivity in the delayed stages of nerve injury but does not regulate mechanical hypersensitivity or attenuate microglial proliferation. Similarly, conditional ablation of erbB3 and erbB4 receptors in microglia suggests that the NRG1-erbB signaling pathway does not regulate mechanical hypersensitivity or microglial proliferation. However, NRG1-erbB signaling does regulate cold hypersensitivity in the delayed stages of nerve injury through microglia. The work presented in this thesis has further refined the role of the NRG1-erbB signaling pathway in the context of peripheral nerve injury neuropathic pain.

Keywords: microglia
animal behaviour
neuropathic pain
spared nerve injury
Advisor: Bennett, D
Large markets: asymptotic arbitrage and portfolio optimisation

In this thesis, we aim to shed some light on the intricate behaviour of large, correlated financial markets, the existence or absence of asymptotic arbitrage in such a model and its connection to optimal investing. Therefore we will approximate these finite large markets by infinite-sized markets, and derive strategies describing how to invest optimally, based on the modelling coefficients. Our correlated finite real world market, spanning n ∈ &Nopf; single secu- rities as well as at most the fixed number of J ∈ &Nopf;, global assets is similar to the approach known from the well-established Capital Asset Pricing Model (CAPM) and can be viewed as an increasing sequence of smaller sub-markets, which can be interpreted as a collection of sectors or a set of different economies, where each is endowed with its own market risk factor.
The core problem we want to tackle in this thesis is to find out how an agent can optimally distribute his positive initial endowment over a large or infinite number of securities in order to build the optimal portfolio which can maximise his expected utility of terminal wealth. We will give both general as well as explicit solutions for a power utility function using optimal control methods.
If we are going to approximate large markets by infinite ones, we need to carefully consider the limiting arbitrage conditions, namely the asymptotic arbitrage. Our main result provides a new link between the two concepts, no asymptotic arbitrage and the existence of a finite limiting value function in the infinite market. We succeed to prove that, for measurable and adapted coefficients, there is no asymptotic arbitrage if the value function solving the optimisation problem exists and is finite in the limit for an infinite number of stocks.
In addition, we present a weak convergence result in terms of market models and look at asymptotic expansions of our optimisation results. Fundamentally, we manage to show that asymptotic arbitrage in our CAPM-style model always occurs, unless Sharpe ratios with respect to the global market of the single securities are close to the same, homogeneous value.
The thesis is concluded by a real life investment example which attempts to generate wealth by investing according to our optimal portfolio proportions.

Advisor: Hambly, B
Rewriting context-free families of string diagrams

String diagrams provide a convenient graphical framework which may be used for equational reasoning about morphisms of monoidal categories. However, unlike term rewriting, which is the standard way of reasoning about the morphisms of monoidal categories, rewriting string diagrams results in shorter equational proofs, because the string diagrammatic representation allows us to formally establish equalities modulo any rewrite steps which follow from the monoidal structure.
Manipulating string diagrams by hand is a time-consuming and error-prone process, especially for large string diagrams. This can be ameliorated by using software proof assistants, such as Quantomatic.
However, reasoning about concrete string diagrams may be limiting and in some scenarios it is necessary to reason about entire (infinite) families of string diagrams. When doing so, we face the same problems as for manipulating concrete string diagrams, but in addition, we risk making further mistakes if we are not precise enough about the way we represent (infinite) families of string diagrams.
The primary goal of this thesis is to design a mathematical framework for equational reasoning about infinite families of string diagrams which is amenable to computer automation. We will be working with context-free families of string diagrams and we will represent them using context-free graph grammars. We will model equations between infinite families of diagrams using rewrite rules between context-free grammars. Our framework represents equational reasoning about concrete string diagrams and context-free families of string diagrams using double-pushout rewriting on graphs and context-free graph grammars respectively. We will prove that our representation is sound by showing that it respects the concrete semantics of string diagrammatic reasoning and we will show that our framework is appropriate for software implementation by proving important decidability properties.

Keywords: graph rewriting
formal methods
string diagram
monoidal category
quantum information
quantum computing
Advisor: Abramsky, S
Coecke, B
Kissinger, A
Spectroscopy and imaging of gas-phase transition metal clusters

The field of transition metal clusters has proven to be fertile ground for study in recent years due to their interesting properties and reactivity. In this thesis, Velocity Map Imaging (VMI) has been used alongside spectroscopic techniques to study a range of diatomic metal-containing molecules which have relevance to cluster chemistry.
The photodissociation of Ag-RG complexes (RG = Ar, Kr, Xe), as well as AgO, have been studied in the 29900–31700 cm-1 spectral region using VMI. The electronic states of the fragments produced have been assigned in each case and new values for the dissociation energies determined. These are presented as an update to the most recent experimental values for each molecule, about which doubts have been expressed.
VMI has also been used to study the photodissociation dynamics of isotopically-selected 98MoO and 52CrO in multiple spectral regions. Assignments have been proposed for the processes generating the observed features, and values for the dissociation energies of these species determined which are consistent with literature values from other, older experimental techniques, or indirect measurements.
Finally, a comparison has been made of different image reconstruction algorithms in order to determine which is best suited to analysing the data recorded in our group. The experimental data from the rest of this thesis have been reanalysed using various approaches, and it is demonstrated that recently-developed maximum entropy programs produce better results than the onion peeling algorithm previously used.

Keywords: Metal Clusters
Photodissociation
Velocity Map Imaging
Advisor: Mackenzie, S