VictorJuiz/thesis huggingface dataset:
Investigating the mechanism of non-catalytic tyrosine-phosphorylated receptor triggering
Keywords: StrepTactin
Non-catalytic tyrosine-phosphorylated receptor
Strep-Tag II

Non-catalytic tyrosine-phosphorylated receptors (NTRs) are a large group of leukocyte receptors that bind to surface-associated ligands and include both activating and inhibitory members. They contain, or associate with adaptor molecules which contain, tyrosine residues within conserved cytoplasmic motifs that are phosphorylated and dephosphorylated by extrinsic kinases and phosphatases respectively. The mechanism by which NTR-ligand engagement leads to sustained phosphorylation of receptor tyrosinebased motifs and initiation of downstream signalling (termed "receptor triggering"), is as yet unknown.
Our hypothesis is that the NTRs signal using the kinetic-segregation (KS) model. The model proposes that large inhibitory phosphatases, but not inner leaflet-bound activating kinases, are segregated in a size-dependent manner from engaged receptors upon ligand binding. This favours kinase activity and drives sustained receptor phosphorylation.
To systematically test whether predictions of the KS model hold for all NTRs, we have developed an artificial generic ligand system in which biophysical and biochemical properties of NTR-ligand interactions can be manipulated. These include NTR-ligand dimensions, ligand densities and valency. Our system exploits the interaction between a Strep-Tag II, which is attached to the ectodomain of the NTR, and StrepTactin protein. We first demonstrate that representative NTRs, both activating and inhibitory, can be triggered through ligation of this Strep-Tag II. In agreement with a key KS model prediction, we next show that only ligation by surface-associated ligand leads to triggering, whilst ligation by soluble ligand does not. Additionally, by altering ligand valency and mobility, we provide evidence that receptor clustering can enhance activation. Also in agreement with the KS model, we show that elongation of the artificial ligand dramatically affects activation of a representative NTR. Finally, we provide evidence to suggest that increased receptor clustering may be able to compensate for ligand elongation-mediated defects in NTR signalling.
The flexibility of this system will allow us to analyse other NTRs, test further predictions of the model, and investigate the role of other properties of NTR signalling.
Correlation methods in the statistical analysis of financial trading data
Keywords: Trading Latency
Latency
Asynchronous correlation
High Frequency Trading
Big data
Correlation
High-Frequency Covariance Estimates With Noisy
Financial data
Asynchronous Financial Data
Statistical Learning
Machine Leaning
Correlation methods in the statistical analysis of financial trading data
Lagged correlation
Volatility

This thesis considers problems associated with the statistical analysis of correlation in financial trading data. Sources of data are identified and their characteristics are described. Nowadays most financial transactions are carried out electronically on automated exchanges or electronic communication networks and active participants in the market re- quire sophisticated computing infrastructure to compete effectively. These data are shown to present novel statistical challenges both in retrospectively analysing the vast stores of accumulated historical data and also in online processing of high-bandwidth multiple data streams arriving on millisecond time-scales. We show that computational speed dictates the range of statistical tools that are available for high-speed calculation.
The measurement and interpretation of correlation is a dominant concern in the analysis of high-frequency financial data. We compare and develop methods for assessing volatility, cross-asset correlation and lead-lag effects. For volatility estimation we consider a class of estimates that can accommodate noisy irregularly spaced data. We derive explicit expressions for the variance of these estimators and show how the estimators can be modified to obtain infill consistency. We then consider the problem of covariance estimation and develop a new estimator, demonstrating its superior performance. We explore the problems of quantifying lead-lag relationships and show that our new covariance estimator provides a sharper estimate of lead-lag delay. We then develop a method of exploring lead-lag structure in depth and demonstrate how to obtain a maximum likelihood estimator of the delay structure. The final chapter briefly describes ongoing research questions relating to the design of hedging strategies at times of market disruption.
Infrared spectroelectrochemical study of E. coli NiFe hydrogenase 1
Keywords: hydrogenase
in situ spectroelectrochemistry
protein film electrochemistry
H2 activation

This thesis investigates the catalytic mechanism of NiFe hydrogenases. The specific enzyme studied in this work, E. coli Hyd-1, is an efficient catalyst for H2 oxidation even in the presence of O2. A method for studying the chemistry of the active site of this enzyme, under catalytic conditions, is developed. The combination of IR spectroscopy with protein film electrochemistry in situ is demonstrated. This was achieved by adsorbing the hydrogenase on a high surface area carbon nanoparticle electrode; and by the design of a spectroelectrochemical flow cell that provides efficient mass transport conditions.
A complete redox characterisation of the active site for a hydrogenase immobilised on a carbon electrode is described for the first time. The study of the effect of pH on the distribution of redox states demonstrates the existence of a pH equilibrium between the Ni-C and the Ni-L states. It is shown that the active site responds to the pH of the external solution, and that the increase in pH acts as a driving force that removes the proton further away from the active site. Studies under electrocatalytic conditions provides direct evidence of intermediates of the catalytic cycle. The role of Ni-SI, Ni-R, and Ni-C is confirmed. Furthermore, Ni-L is detected under turnover conditions and therefore shown to be an important intermediate in the cycle. The detection of different protonation states of Ni-L and Ni-R is proposed to provide information on the transport of the protons as they start to move away from the active site.
In the investigation of O2 inhibition, Ni-B (detected spectroscopically) is directly related to the loss in activity upon the attack of O2 for the first time. Also, the formation of solely Ni-B from the reaction with O2 (no other O2-damaged species are detected) provides further evidence on the ability of O2-tolerant hydrogenases of having an effective mechanism for dealing with O2 tolerance. A thorough study on the interaction of CO with Hyd-1 proves unequivocally that this O2-tolerant hydrogenase does bind CO, and that CO does inhibit its catalytic activity (both H2 and H+ reduction). This helps clarify how CO interacts with O2-tolerant hydrogenases.
Overall, the work in this thesis contributed to the understanding of key mechanistic aspects in O2-tolerant hydrogenases. The technique for combining protein film electrochemistry with IR spectroscopy in situ shall provide valuable opportunities for providing new insight into the mechanisms of hydrogenases and other metalloenzymes that bind small molecules.
Occupants' interaction with low-carbon retrofitted homes and its impact on energy use
Keywords: energy efficient measures
deep refurbishment
Low-carbon retrofit
socio-technical approach

Current regulatory and other policy trends in housing refurbishment relating to low-carbon performance standards tend to involve complex technologies and systems as well as innovative solutions to achieve 80% emissions reduction in line with the UK national target for 2050. Indicators of domestic energy performance tend to assume ideal performance of materials, complex systems and services, and that they are installed to high standards and under specific conditions, as well as rational occupant behaviour and interactions. Previous studies exploring the influence of socio-technical factors on the UK’s domestic energy use highlight that one of the main reasons for under-performance of individual projects is the lack of understanding of how people interact with domestic technology. Considering this, and given that there is still little evidence on deep refurbishments that implement low-carbon 'whole house' approaches in the UK, this research explored occupants' interaction with heating and ventilation measures as these were designed, installed and operated. The main concern was to identify the type of interactions that occur between occupants (social housing tenants) and building systems (mainly low-carbon heating and ventilation systems), and how that influences actual energy use. Using a sample of 26 social housing properties involved in the Retrofit for the Future competition in the UK, the study employed an socio-technical mixed methods approach, in which qualitative and quantitative empirical data were explored together, cross-checking occupants' 'doings' and 'sayings'. A combination of theories was used to analyse the complex interrelated factors involved in users’ interaction with building systems. The analysis identifies key factors that affect significantly occupants’ everyday practices and their interactions with the new measures: thermal comfort and pastexperiences with measures and controls; knowledge and skills (of both occupants and those involved in the project); design of the technical interventions (systems/measures) and quality of their installation. The findings from this research showed that active measures (such as intelligent and conventional heating controls, MVHR boosters, etc.) fostered direct interaction with active users when there were no design or installation faults. On the contrary, low-carbon measures that are designed and installed to be passive (such as MVHR systems operation) tend, in practice, to involve indirect interactions with active users. The research findings provide an insight into the 'in-use' factors, demonstrating to policy makers and implementers of mass refurbishment programmes the need for a framework where critical combinations of different measures and design solutions are targeted on specific house types, locations and households, in order to achieve maximum savings. Higher standards in installation of the new measures and improved quality control are also found to be a key part of refurbishment policies.
Individual pains and social gains: the personal and social consequences of collective dysphoric rituals
Keywords: Ritual
Extreme Ritual
Dysphoria

This thesis presents the results of a multi-method exploration of the effects of collective dysphoric rituals on self-identification, group affiliation, and prosocial behaviour. Findings are presented from a worldwide sample of martial artists, student participants in artificial ritual experiments, and observers and performers of Shinto firewalking festivals in Japan. The thesis tests recent predictions of the Modes of Religiosity theory in regards to the psychological processes that underpin shared dysphoric rituals and various costly signalling theories concerning the group orientated consequences of participating in extreme ritual events. The results from the studies raise questions with the broader generalisability of recent findings linking collective dysphoric rituals and inclusive self- identification and urge for a more nuanced appraisal of associations with prosocial behaviour. Furthermore, the role of subjective positive assessment of dysphoric experiences is shown to be a topic that has been unduly overlooked and preliminary evidence is provided for a potential relationship with identity fusion. Methodologically the thesis presents a series of novel artificial ritual studies that offer initial evidence in support of shared dysphoria’s ability to enhance cooperation and promote positive ingroup association.
Stem cell culture on 3D-scaffolds for cardiac regenerative medicine and in vitro studies
Keywords: tissue engineering
regenerative medicine
heart
stem cells

Most life years lost due to death and disability in the Western world arise from non-communicable diseases, such as cancer and cardiovascular disease. Myocardial infarction (MI) and heart failure (HF) still have a particular poor prognosis, despite the development of improved pharmacological therapy and surgical interventions. No cure, other than heart transplant, is available for patients with HF. As a result, further research into new treatment strategies is paramount. Many potential avenues have been suggested, but this thesis aimed to work towards using stem cells and tissue engineering strategies as tool for in vitro testing and in vivo therapy.
In the first place, the thesis aimed to develop a humanised Langendorff perfused heart as an in vitro testbed. The decellularised rat heart was chosen as biomaterial, because it allows perfusion, and cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPS) as cell source. Given the size of the constructs and to enable biomimetic mechano-electrical stimulation of the organoids, which may aid in the differentiation and maturation of the cardiomyocytes, a bioreactor was constructed for culturing the recellularised hearts. Finally, the feasibility and performance of culturing decellularised hearts seeded with iPS-CMs in the bioreactor under biomimetic conditions was assessed. The performance of this technique was currently insufficient for it to be used as an in vitro model of the heart. Hence, further improvements in bioreactor design and cell culture technique are required.
Secondly, the therapeutic benefit of a cell-loaded collagen scaffold was investigated in a rat ischaemia-reperfusion myocardial infarction (MI) model. A bilayer collagen scaffold was designed for this purpose and biocompatibility demonstrated both in vivo and in vitro. Cardiosphere-derived stem cells were used as cell source, given their potential to form cardiomyocytes and blood vessel structures, and their therapeutic benefit post-MI. In the present study, the cells were pre-conditioned with hypoxia, as this increased stemness and pro-angiogenic factor secretion, before implantation post-MI. However, a twelve week study using magnetic resonance imaging to study cardiac function failed to show significant improvements in function post-MI.
In summary, this thesis contributed to the development of technology for both in vitro and in vivo cardiac tissue engineering. However, further investigation and optimisation will be required before this technology can be applied in practice.
Playing the game: a study of transnational Turkish football fans, imaginations and the internet
Keywords: Turkey
social media
internet
football
diaspora

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.
Role of the nuclear envelope in regulation of ageing
Keywords: Senescence
Prelamin A
Reticulons
Nucleoplasmic Reticulum
SASP

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.
Toward robust algebraic multigrid methods for nonsymmetric problems
Keywords: nonsymmetric
absolute value
algebraic multigrid

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.
Zeolite frameworks with beta-cages
Keywords: beta-cages
Zeolite synthesis
Flexibility window
Sodalite cages
Zeolite frameworks
Zeolites

This study focuses on five zeolites: sodalite, zeolite A, linde type N, zeolite Y, and EMC-2, with SOD, LTA, LTN, FAU, and EMT framework topologies respectively. All of these zeolites have β-cages as the framework building units. The aims are to understand the conditions which control the formation of different zeolite phases and some of the physical properties of zeolite frameworks, mainly the framework exibility, and the capacity of β-cage to accommodate guest molecules such as water and methanol.
The hydrothermal and microwave syntheses of zeolite with no organic structure directing agents require precise control of synthesis conditions and form the fundamental part of this study. Reaction temperature and synthesis time control the phase purity in zeolite A synthesis. A transformation from zeolite A to sodalite is observed and is related to framework density and reaction temperatures. Microwave syntheses of sodalite show that the batch compositions and methods of preparation also affect the as-synthesised zeolite phases and a new sodalite morphology is found. By using microwaves instead of traditional hydrothermal methods, one of the most complex zeolites, linde type N zeolite, was synthesised. This is the first study to report this new method.
The newly defined extrinsic exibility window is studied on more depth in this work. While the intrinsic exibility is defined by the ability of an empty framework to flex with no distortions in the primary tetrahedral building units; the extrinsic exibility window is limited by the host-guest steric interactions between the framework and the extra framework contents. In zeolite Y, the extrinsic exibility window can be limited not only under compression, but also in expansion, as the β-cage in a maximally expanded framework lack the exibility to adapt to bulky contents such as a combination of methanol and water molecules. It is also found that the β-cage in zeolite Y can only accommodate a maximum number of two water molecules and one methanol molecule.
The same phenomenon is observed in sodalite under compression. In the sodium form, the framework remains within its intrinsic exibility window when fluorinert is used as pressure transmitting media, as fluorinert does not enter the zeolite pores. However, an extrinsic exibility window is observed in both the sodium and sodium bromide forms with methanol/ethanol/water mixture as pressure transmitting media.
An exception is seen in EMC-2. The intrinsic and extrinsic exibility windows are identical to each other. The presence of 18-crown-6 ether molecules in the pores does not affect the exibility window. The crown ether, despite its steric bulk, does not limit the geometric exibility of the framework since the cage of the EMT framework has enough space to accommodate the crown ether molecule and can adapt to the contraction. This shows that the extrinsic exibility window of zeolite frameworks is controlled not only by the extra framework contents, but also by the framework building units.