VictorJuiz/thesis huggingface dataset:
Essays on macroeconomic policy
Keywords: structural reforms
political economy
currency mismatch
expenditure Switching
currency invoicing
monetary policy cooperation
dilemma
unconventional monetary policy
exchange rates flexibility
effective lower bound
structural VAR
monetary policy
foreign exchange liabilities
trilemma
product market deregulation
global financial cycle

This dissertation consists of four self-contained chapters which discuss topics related to challenges and the design for macroeconomic policy in the aftermath of the Global Financial Crisis 2007-2008. The first two chapters consider the implications of the global financial cycle (GFC) to monetary policy in two-country open market dynamic stochastic general equilibrium models where the dominant role of the reserve currency in trade and global financial transactions can account for the cross-border transmission of U.S. monetary policy shocks. Chapter 1 evaluates the gains from international monetary policy cooperation between the financial centre and periphery countries. The key finding is that although monetary policy cooperation may improve the global welfare, the asymmetric policy spill-overs through the global financial markets create winners and losers from cooperation at the individual country level. Chapter 2 discusses whether exchange rate regime matters in the presence of the GFC with a similar model estimated to match the empirical evidence from a panel vector autoregressive (VAR) model. We find that even with a GFC, a peg substantially increases macroeconomic volatility. Conversely, the introduction of an additional policy instrument to manage capital flows dampens economic fluctuations. A tax on domestic credit achieves nearly equivalent results. Chapter 3 examines the effectiveness of unconventional monetary policy (UMP). We develop a theoretical model that underpins the `irrelevance hypothesis,' which states that UMP may make the effective lower bound (ELB) on the short-term interest rate irrelevant. We then test and firmly reject this hypothesis for Japan and the United States using a structural VAR model with the ELB. However, we find that UMP has had strong delayed effects. Chapter 4 analyses the factors that hinder the implementation of structural reforms using a macroeconomic political economy model. In the model, the effects of product market deregulation create its own resistance, and the resistance generates endogenous political costs to impair deregulation. In addition, adverse initial conditions, better risk-sharing among workers, and a lower share of temporary workers weaken opposition and help deregulation.
Immuno-molecular profiling and modulation of donor livers during normothermic machine perfusion

Keywords: reperfusion injury
transplantation
organ preservation

Normothermic machine perfusion (NMP) is an increasingly adopted preservation strategy in liver transplantation that facilitates organ assessment, safely prolongs preservation and is associated with reduced ischaemia reperfusion injury (IRI) related complications. However, these IRI-related benefits are less apparent in higher risk organs, which maintain a propensity to develop severe preservation injury despite NMP. The underlying mechanisms and contributory factors associated with this persistent injury are unclear, but may be related to molecular processes occurring during NMP or other preservation factors such as the length of cold ischaemia prior to NMP. This thesis aims to characterise the immunological and molecular processes occurring during NMP and devise interventions targeting these processes to reduce preservation injury. Through an evaluation of samples from clinical trials of human liver perfusion, I have demonstrated that ex situ reperfusion injury/inflammation (ERI) is an immunologically and molecularly distinct entity observed consistently across livers preserved with NMP. I have shown that the presence and length of prior static cold storage (pSCS) can impact the molecular signature of donor livers affecting key pathways and processes involved in mitochondrial function and cellular energetics. I have found that circulating damage associated molecular patterns (DAMPs), constitute an important element in ERI and alongside immune cells and inflammatory cytokines within the perfusate, propagate injury and inflammation ex situ, likely impacting the immunogenicity of the graft. I developed a large animal model to investigate these observations and explore possible modulatory interventions. Finally, I demonstrated that by mitigating ERI, ex situ graft function could be improved and preservation injury reduced in a porcine NMP model. This is achieved by the removal of highly pro-inflammatory nuclear DAMPs (neutrophil extracellular traps (NETs)/nucleosomes, free histones and cell free DNA) from the circulating perfusate during NMP with a specialised column.
Metabolic engineering of Clostridium saccharoperbutylacetonicum for improved solvent production
Keywords: biofuel
butanol
Clostridium saccharoperbutylacetonicum
metabolic engineering
flux balance analysis
Clostridium

In order to avert irreversible damage to the global climate, the global community has committed to reaching net zero carbon emission in the coming years. To meet this ambitious target, substantial changes will be needed. To minimise the disruption to people’s lives, there is a need for renewable technologies which are compatible with existing infrastructure, such as biofuels and drop in chemical compounds. A compound which can fulfil both roles is n-butanol. Clostridium are natural butanol producers but have fallen out of use as they have been unable to compete with fossil fuel-based production methods.
The aim of this thesis was to improve the production of butanol in an asporogenic strain of Clostridium saccharoperbutylacetonicum N1-4. A systems scale approach was taken to improve butanol production. Combined analysis of Clostridium metabolism using flux balance analysis and 13C-metabolic flux analysis was used to guide metabolic engineering strategies, with the aim of increasing butanol production in asporogenic C. saccharoperbutylacetonicum N1-4 spo0AI261T.
Flux balance analysis was used to gain an understanding of Clostridium metabolism and to explore manipulations that could lead to increased butanol production in wild type C. saccharoperbutylacetonicum N1-4. Key features of in silico engineered strains were compared to experimental data and identified an increase in NADH generation and key butanol synthesising genes as targets for increasing butanol production. A second round of flux balance analysis identified further manipulations relevant to C. saccharoperbutylacetonicum N1-4 spo0AI261T, mainly that the rate of glucose uptake appeared to be limiting butanol production. Simulations of strains with increased glucose uptake and butanol production suggested that ATP consuming enzymes would have to be engineered into the asporogenic strain to balance ATP.
Additional investigation was performed using 13C-metabolic flux analysis, which was able to resolve intracellular fluxes of asporogenic C. saccharoperbutylacetonicum N1-4. It also identified a feature of C. saccharoperbutylacetonicum N1-4 spo0AI261T metabolism that was unexpected, that ATP was in excess to biomass synthesis requirements, resulting in a futile cycle. The results from this flux analysis confirmed the rationale of the flux balance analysis guided strategies.
In the final chapter, the developed strategies were incorporated into the asporogenic strain of C. saccharoperbutylacetonicum N1-4. These mutant strains were analysed in fermentations. While none of the strains produced more butanol than the parent strain, this work incorporated several novel approaches to increase butanol production in Clostridium and will serve as a starting point for future metabolic engineering work.
Unravelling the roles of CRTH2+ cells in asthma pathogenesis
Keywords: fevipiprant
CRTH2
Tc2
basophil
mepolizumab
prostaglandin D2
eosinophil
IL-5
asthma

Prostaglandin D2 (PGD2) receptor 2 (as known as chemoattractant receptor homologous to the T helper 2 cell, CRTH2) is expressed on various human immune cells including but not limited to type 2 helper T (Th2) cell, type 2 cytotoxic T (Tc2) cell, group 2 innate lymphoid cell (ILC2), eosinophil and basophil. These CRTH2+ cells are highly associated with type 2 (T2) immune response, the severity and the endotype of asthma. In this research, I demonstrated the importance of three types of CRTH2+ cells, Tc2 cells, basophils, and eosinophils, in inflammation and asthma. PGD2 induced cell migration, adhesion and survival, evoked the production of proinflammatory cytokine and fibrotic factors, and mediated autocrine/paracrine production of PGD2 in cultured human Tc2 cells. Using the CRTH2-specific antagonist fevipiprant as a tool, I observed the inhibition of the aforementioned PGD2-mediated activities in vitro, suggesting the anti-inflammatory and anti-fibrotic roles of CRTH2 antagonism in asthma. In the second study, the numbers of basophils that highly express CRTH2 were found to be significantly increased in blood and sputum from patients with severe eosinophilic asthma. Chemotaxis, interleukin (IL)-4/IL-13 production, granule histamine release and CD63/CD203c expression in basophils could be induced by PGD2, which could be suppressed by CRTH2 antagonism. The RNA sequencing revealed potential unique roles of the PGD2-CRTH2 pathway in basophils. In the third study, blood eosinophils from patients with eosinophilic asthma showed increased responses to the inducers of chemotaxis and degranulation ex vivo and in vitro, compared to those from non-eosinophilic asthma and healthy subjects. These enhanced responses were reversed after treatment with the anti-IL-5 monoclonal antibody mepolizumab. Mepolizumab also repressed the phosphorylation level of AKT, MERK and p38 in blood eosinophils, which was confirmed with single-cell RNA sequencing. These findings provided a better understanding of the roles of CRTH2+ cells in the pathogenic mechanisms of asthma.
Social science research in India: traversing the 'local' and 'global' terrain
Keywords: knowledge production
international relations in India
coloniality
qualitative methodology
universities in India
center-periphery
think tank culture
global higher education
transanational research system

This study aims to analyse the global research environment, in the field of social science, from the perspective of International Relations researchers based in India. The study attempts to understand how these scholars translate the knowledge of their local realities to the global pool of knowledge. In this journey, the scholars traverse the local, national and global dynamics of knowledge production. They also navigate through the structures of the global science system that circulate, recognise, legitimate and value research.
For understanding the phenomena from the perspectives of the researchers, I conducted 16 in-depth interviews with research scholars based in India. For the interviewees, I formulated an equity with respect to various factors such as gender, interviewee profile, experience, current role, educational background, professional assignments and university type.
The study explores how the participants develop a close understanding of their local realities, employ existing methodologies and creatively use theories to navigate the global dynamics of knowledge production. In this journey, they also influence the prevalent global designs of the discipline. They thus attempt to establish a dialogic space in the global domain of knowledge production. While some scholars benefit from interaction with the global science, some participants felt the need to delink from these systems of recognition that they felt constrained the space for epistemic difference.
The ASCEND-Eye study: effect(s) of aspirin and omega-3 fatty acids on eye disease
Keywords: age-related macular degeneration
diabetic retinopathy
aspirin
randomised trial
omega-3 fatty acids

Background
Aspirin and omega-3 fatty acids (FAs) have potential disease-modifying roles in diabetic retinopathy (DR) and age-related macular degeneration (AMD), but randomised evidence of these effects is limited. This thesis describes the rationale, methods and results of ASCEND-Eye; a sub-study of the ASCEND double-blind, 2x2 factorial design, randomised, placebo-controlled trial, which compared the effects of 100mg aspirin daily and, separately, 1g omega-3 FAs daily for the primary prevention of serious cardiovascular events, in 15,480 UK adults with diabetes.

Methods
Events were derived from three sources: 1) six-monthly follow-up questionnaires for ASCEND or a one-off eye questionnaire sent to a subset of participants after the parent trial ended, 2) electronic NHS Diabetic Eye Screening Programme (DESP) data and 3) responses to the National Eye Institute’s Visual Function Questionnaire-25 (NEI-VFQ-25). The primary efficacy outcome was the first occurrence of referable disease in either eye during the scheduled treatment period, a composite of referable diabetic retinopathy (≥R2) or referable diabetic maculopathy (M1), based on grading criteria defined by the National Screening Committee. The primary safety outcome was the first sight-threatening eye bleed. Secondary outcomes included incident diagnoses of AMD and the NEI-VFQ-25 composite score. Logrank methods were used for intention-to-treat analyses of time until the primary efficacy, safety, and AMD outcomes, between groups in each treatment arm. Ordinal data from the NEI-VFQ-25 were analysed using proportional odds regression methods.

Results
DESP data were obtained for 48% of those randomised in ASCEND (n=7360). During their 6.5 years of follow-up, 539 [14.6%] participants assigned to active aspirin developed referable disease compared to 522 [14.2%] in the placebo group (rate ratio 1.03; 95% confidence interval: 0.91-1.16; P = 0.64). There was no statistically significant difference in the proportion of primary efficacy events by omega-3 FA allocation. Similarly, neither treatment had a statistically significant effect on incident AMD events (n=15,480) or composite scores from the NEI-VFQ-25 (n=8839); aspirin did not increase the risk of sight-threatening eye bleeds (n=15,480).

Conclusions
ASCEND-Eye overcomes some of the methodological limitations of previous studies, providing reliable, randomised evidence of the eye-related effects of two inexpensive treatments commonly taken by those with diabetes, older people, or both. Overall, the data exclude any clinically meaningful benefits of aspirin or omega-3 FAs for DR or AMD but provide some reassurance regarding the ophthalmological safety of aspirin.
Utilisation of metabolic resources in Arabidopsis thaliana suspension culture
Keywords: NAD(P)H
growth respiration
arabidopsis thaliana
netabolic flux analysis
central carbon metabolism
gas chromatography mass spectrometry
MFA
tricarboxylic acid cycle
mannitol
mass spectrometry
mannose
pentose phosphate pathway
biosynthesis
glycolysis
maintenance respiration
carbon metabolism
growth costs
suspension culture
maintenance cost
decreased temperature
ATP
respiration paradigm

Appreciating the relationship between growth rate and metabolism is important for understanding plant growth dynamics in laboratory and agricultural settings. This project uses steady-state 13C-metabolic flux analysis (MFA) to investigate the relationship between growth rate and flux distribution through the network of central carbon metabolism in heterotrophic cells of Arabidopsis thaliana.
Two different conditions were used to slow the growth rate of Arabidopsis cell suspension cultures; growth at mildly decreased temperatures and growth in medium supplemented with mannose. The results showed that a decreased growth temperature slowed the growth rate and induced minor alterations in flux distribution. Supplementation with mannose also slowed the growth rate and induced a more widespread rearrangement of fluxes through the central network of carbon metabolism. The effect of mannose was likely due to sequestration of inorganic phosphate as mannose 6-phosphate.
The flux solutions also showed that growth at mildly decreased temperature did not alter the relative allocation of ATP and reductant (principally, NAD(P)H) to growth and maintenance processes. In contrast, supplementation with mannose induced a significant increase in the proportion of ATP and reductant available for maintenance processes.
Slowed growth rate was associated with decreased flux through the glucose 6-phosphate dehydrogenase reaction. This effect was independent of the effect of altered allocation of ATP and reductant between growth and maintenance.
This project introduces a novel modelling approach for quantifying ATP and NAD(P)H production/utilisation in plant MFA. The results suggest that the growth rate and the allocation of resources to growth and maintenance have independent effects on the central carbon metabolism. This conclusion highlights the need to consider the general effect of altered growth rates when investigating the specific effects of imposed stress on the metabolic response of plant cell to an environmental perturbation.
Transcriptional analysis of chIFITM knock-out cell lines
Keywords: PGC
DF-1
influenza
RNA-seq
CRISPR
chIFITM

Interferon-inducible transmembrane (IFITM) proteins are restriction factors known to confer antiviral resistance against a wide range of viral pathogens. The chicken IFITM locus is found on Gallus gallus chromosome 5. It contains 4 genes of chIFITM family: chIFITM1, 2, 3, and 5. They have been shown to restrict avian influenza virus in vitro and significantly ameliorate clinical signs in animals in vivo. Here I hypothesise that chIFITM knock-out models could support higher viral titres due to the ablation of chIFITM genes. I develop two models: chIFITM KO DF-1 and chIFITM KO PGC. chIFITM KO DF-1 fibroblasts representing ubiquitous avian fibroblast line used in veterinary research and chIFITM KO PGC modelling an approximation to an animal model. chPGCs are chicken primordial germ cells: precursors of sperm and ova which are very amenable to gene editing and for that reason frequently used for production of transgenic animals in research. Subsequent to gene editing they were differentiated into fibroblasts to facilitate comparison with the DF-1 fibroblasts. The study focussed on the investigation of the effects of the chIFITM KO on the permissiveness of the cells to the influenza virus and their ability to support viral replication. Differential expression analysis and the subsequent pathway analysis was conducted on the differentially expressed genes in native conditions as well as during the influenza infection for both models to compare and contrast differentially regulated pathways for each model.
Development of data-driven constitutive models for aerospace materials
Keywords: material modelling
constitutive models
data-driven
plasticity
surrogate model
machine learning

This study presents novel techniques to develop data-driven constitutive models. The adoption of data-based machine learning-driven models obtained from mechanical loading experiments allows for the accurate and computationally efficient prediction of the mechanical behaviour of materials eliminating the need for theoretical assumptions and potential constraints associated with traditional models.
The research is divided into four phases. In the first phase, uniaxial compression experimental data is used to develop surrogate models for the temperature and strain-rate dependent stress-strain response of a polymeric syntactic foam. In the second phase, the proposed techniques are applied to the history-dependent non-monotonic uniaxial response of commercially pure titanium. The third phase introduces a strategy to formulate data-driven constitutive models from random multiaxial experiments. The obtained surrogate constitutive models are capable of capturing the in-plane stress response of isotropic, elastic-plastic materials loaded by combined normal and shear stresses. The feasibility of this approach is evaluated by conducting virtual experiments by means of Finite Element (FE) simulations in which a hollow, cylindrical, thin-walled test specimen is subjected to random histories of axial displacement and rotation. Finally, in the fourth phase, the methodology developed in the third phase is applied to the real experimental combined normal and shear response of aluminium specimens.
To validate the surrogate models, their predictions are compared against experimental data not used in the training process. The results demonstrate a very good agreement between the measurements and the predictions of the data-driven surrogate models.
In conclusion, this research proposes an innovative approach to data analytics and materials constitutive modelling based on machine learning techniques, offering significant potential to enhance the accuracy and efficiency of predicting the mechanical behaviour of aerospace materials.
'Myth-makers to eternity': the idea of the poetic drama in England, 1897-1928
Keywords: English Verse Speaking Association (EVSA)
Herbert Beerbohm Tree
verse speaking
Gilbert Murray
Lascelles Abercrombie
William Archer
Gordon Bottomley
Stephen Phillips
new drama
John Drinkwater
Newbolt Report
twentieth-century social policy
British idealism
Oxford Recitations
Society for Pure English
Harley Granville-Barker
twentieth-century education
poetic drama
Fabianism
T.S. Eliot
W.W. Gibson
British Hegelianism
verse drama

This thesis examines a largely occluded and misunderstood movement in early twentieth century cultural history, when a significant number of poets and critics made repeated calls for the revival of ‘poetic drama,’ not as a coterie form, but as a viable alternative to the commercial theatre of their time. Throughout this period, writers including Stephen Phillips, Gordon Bottomley, John Drinkwater, Wilfrid Gibson, Lascelles Abercrombie and, ultimately, T.S. Eliot persistently delineated what they perceived as the need to restore to the theatre what had once been its more lofty functions. The theatre was a place where the real, it was suggested, could and should meet the ideal and renew the status of art as a crucial correspondence to an unassailable and timeless truth, restoring the ties of a fractured community.
The eventual demise of this movement left an extraordinary body of writing in a kind of limbo, where it has since received little attention. A few critical studies have focused on the plays as literary artefacts and with a qualitative eye. In doing so, they obscure the broader critical and philosophical discourse that had been carrying and giving meaning to creative experiments in poetic drama since the turn of the century. Without that frame, this thesis argues, such experiments make little if any sense.
This thesis places the story of the poetic drama in a broader history of ideas, with particular attention to the school of idealist metaphysics and moral philosophy that was dominant in the early decades of the twentieth century. In doing so it illuminates not only how very misunderstood the poetic dramatists have been from the point of view of cultural history, but also the riches that lie in their writings, both creative and critical, for our understanding of early twentieth century intellectual history more broadly.