VictorJuiz/thesis huggingface dataset:
Translational relevance of AIPL1 and NUB1 in cancer
Keywords: Neddylation
chaperone
ubiquitin

Background: Aryl Hydrocarbon Receptor Interacting Protein-Like 1 (AIPL1) interacts with NUB1 and restricts the entry of NUB1 protein into the nucleus. The interferon-induced NEDD8 ultimate buster (NUB1) protein causes degradation of neddylated and FAT10ylated proteins through the ubiquitin proteasome system. We observed AIPL1 were frequently down-regulated in various cancers compared to normal tissues. The mechanistic roles of AIPL1 and NUB1 protein in cancer cell cycle regulation remain unexplored.
Results: Meta-analysis of cancer databases revealed that expression transcripts of chaperones, including AIPL1, were down-regulated in lung, pancreatic cancer and breast cancer relative to the adjacent normal tissues. Opposite levels of both AIPL1 and NUB1 transcripts were observed in the breast cancer. So it triggers the in vitro experiments using breast cancer cells. METABRIC breast cancer clinical cohort highlighted that patients with low NUB1 transcripts had poor survival in the ER-negative subgroup (but not in ER-positive) of breast cancer patients: hazard ratio (HR)=0.66, 95% confidence interval (CI)=0.5-0.87, p=0.003 and triple negative subgroup of breast cancer patients: HR=0.67, 95% CI=0.47-0.96, p=0.028. NUB1 silencing significantly inhibits in vitro cell growth in MDA-MB-231 and MCF7 under hypoxia. AIPL1 protein forms multimers in cancer cells. NUB1 protein moved into the nucleus in hypoxia (0.1% O2 48hrs) with final confluency at 80-90%. p21 (marker of senescence) & p27 (marker of cell cycle arrest) accumulated in NUB1-silent MDA-MB-231 and RCC4 cells. It suggested that low NUB1 nuclear localisation in hypoxia cause cancer cell cycle arrest. In MDA-MB-231 cell, upon hypoxia, neddylation inhibitor (MLN4924) treated and siNUB1 transfected cells showed decreased CUL1 and further accumulated p21 & p27. The evidence suggested lower neddylated CUL1 and reduced NUB1 cooperatively stabilise p21 and p27 as the substrate of CUL1-ubiquitin ligase. The neddylation inhibitor MLN4924 treated and NUB1 knockdown group exhibited more cells in sub-G1 stage as compared to the control group. In connection to higher p21/p27, it is associated with prolonged arrested cellular aging with depletion. After silencing of NUB1, the increases in cell death of cancer cells upon hypoxia happen through the neddylation-dependent CUL1-p27-p21 and CUL2-VHL axis. We then demonstrated that HIF1α protein could be both neddylated and FAT10ylated upon reoxygenation. In a tissue microarray study of breast cancer, lower cytoplasmic expression (n=57) had worse overall survival than higher cytoplasmic expression (n=57): HR=1.779, 95% CI=1.006-3.346, p=0.048.
Conclusions: AIPL1 and NUB1 proteins exert a role in cell cycle regulation in breast cancer. Low cytoplasmic NUB1 levels are observed in the G1-S transition of cancer cells. NUB1 depletion causes G0/G1 phase arrest due to CUL1 and CUL2 ubiquitin E3 ligase-dependent pathways.
Octave flutes in England 1660-1800
Keywords: Flageolet
Recorder

The small recorders, the flageolet, the fife, and the piccolo are octave flutes, sounding at four-foot pitch. The bulk of the literature relating to the recorder in the late seventeenth- and eighteenth-century England focuses on the alto (treble), for this was the most commonly used member of the family, but octave recorders have never been the subject of detailed scrutiny. There is no comprehensive study of the flageolet or of the fife in England during this period, and virtually nothing has been written on the early use of the piccolo. The thesis examines the organology of the four instruments, with most attention being given to the recorder, the dominant octave flute of the era; the changes in the instrument from the sixteenth to the eighteenth century are described, and related to changes in assigned music. The reasons for the displacement of the flageolet by the recorder in the late seventeenth century and the recorder's substantial displacement by the German flute in the eighteenth are explored. Duct flutes have long been the particular province of amateur musicians, who often studied from a self-instructor, and examples of these tutors are examined, together with a representative repertoire. Particular note is made of the English 'small flute concerti' and the use of the sopranino recorder in the late eighteenth century. A chapter examines social, financial, and performance aspects (including performance venues); professional and amateur usage of the instruments and gender differences are discussed. A comparison is made of the usage of the instruments in Continental Europe and England, where differing practices are observed regarding tutors, repertoire, and, in particular, the usage of the piccolo. The introductory review of extant literature indicates thirteen matters in which I consider the literature on octave flutes 1660–1800 to be deficient. The thesis explores these lacunae.
State and parameter estimation of physics-based lithium-ion battery models
Keywords: identifiabilility
state estimation
extended Kalman filter
parameter estimation
Chebyshev orthogonal collocation
electrochemical modelling
lithium-ion battery
single particle model
pseudo-two dimensional model

This thesis investigates novel algorithms for enabling the use of first-principle electrochemical models for battery monitoring and control in advanced battery management systems (BMSs). Specifically, the fast solution and state estimation of a high-fidelity spatially resolved thermal-electrochemical lithium-ion battery model commonly referred to as the pseudo two-dimensional (P2D) model are investigated. The partial-differential algebraic equations (PDAEs) constituting the model are spatially discretised using Chebyshev orthogonal collocation enabling fast and accurate simulations up to high C-rates. This implementation of the P2D model is then used in combination with an extended Kalman filter (EKF) algorithm modified for differential-algebraic equations (DAEs) to estimate the states of the model, e.g. lithium concentrations, overpotential. The state estimation algorithm is able to rapidly recover the model states from current, voltage and temperature measurements. Results show that the error on the state estimate falls below 1% in less than 200s despite a 30% error on battery initial state-of-charge (SoC) and additive measurement noise with 10mV and 0.5°C standard deviations.
The parameter accuracy of such first-principle models is of utmost importance for the trustworthy estimation of internal battery electrochemical states. Therefore, the identifiability of the simpler single particle (SP) electrochemical model is investigated both in principle and in practice. Grouping parameters and partially non-dimensionalising the SP model equations in order to understand the maximum expected degrees of freedom in the problem reveals that there are only six unique parameters in the SP model. The structural identifiability is then examined by asking whether the transfer function of the linearised SP model is unique. It is found that the model is unique provided that the electrode open circuit voltage curves have a non-zero gradient, the parameters are ordered, and that the behaviour of the kinetics of each electrode is lumped together into a single parameter which is the charge transfer resistance. The practical estimation of the SP model parameters from frequency-domain experimental data obtained by electrochemical impedance spectroscopy (EIS) is then investigated and shows that estimation at a single SoC is insufficient to obtain satisfactory results and EIS data at multiple SoCs must be combined.
Improving sensitivity and specificity in diffusion MRI group studies
Keywords: diffusion mri
computational neurology
group studies
machine learning

Diffusion MRI provides a unique opportunity to study the brain tissue architecture at a microscopic level. More specifically, it allows to infer biophysical properties of the axons in the white matter in-vivo. Microstructural parameters are widely used in multi-subject studies to track pathological processes, follow normal development and aging, or investigate behaviour. This thesis aims to identify and potentially address the limitations and pitfalls in voxelwise comparison of diffusion MRI parameters across subjects.
To allow for accurate matching of brain structures across subjects, non-linear transformation that spatially aligns the data is required. We demonstrate that using advanced registration methods, we can outperform the standard registration-projection approach both in terms of sensitivity and specificity.
The coarse resolution of the data typically causes partial volume effects that bias the diffusion parameters and potentially mislead the interpretation of a group study outcome. We provide evidence that these effects can be addressed by constraining the diffusion model parameter space, which leads to marginally lower sensitivity, but allows an accurate interpretation of the results. Additionally, we suggest that additional information inferred with a data driven approach might mitigate the loss in sensitivity.
Finally, we design an original tract-specific modelling framework that enables to estimate microstructural parameters unbiased by the presence of foreign fibre populations or tissues. We demonstrate the sensitivity of our method in a study relating microstructure and behaviour.
Dancing on the devil’s staircase: the synchronization of the quasi-biennial oscillation in the tropical stratosphere
Keywords: Synchronization
Stratosphere
Quasi-Biennial Oscillation

In this thesis we investigate the variability of the Quasi-Biennial Oscillation (QBO), which is the dominant mode of variability in the tropical stratosphere. In particular, we study the susceptibility of the QBO to the phenomenon of synchronization; that is, the adjustment of the rhythms of the QBO under the influence of a periodic external force. We approach the problem using a combination of theoretical analysis, numerical modelling, and observational study. The dynamics of the QBO are studied in detail using the Holton-Lindzen partial differential equation. We introduce various forcing terms to this equation, to simulate the effects of the Brewer-Dobson circulation, the Semi-Annual Oscillation, the Inter-Tropical Convergence Zone, and tropical wave forcing variations on the QBO. We find that the QBO enters a state of synchronization in its interactions with all of the above forcing terms, with the exception of the Semi-Annual Oscillation. The general structure of QBO synchronization takes the form of either exact frequency locking, discrete multi-cycle periods, or quasiperiodic behaviour. By recasting the Holton-Lindzen equation into the form of a descent rate model, we demonstrate that the dynamics of the QBO period can be described using a simple one-dimensional ordinary differential equation, which is shown to be closely related to the circle map. This simplification greatly reduces the complexity of the model, whilst retaining all the key observed features of synchronization.
We study the dynamics of the QBO in reanalysis and general circulation model datasets, using a combination of Extended Empirical Orthogonal Function analysis and analytic phase techniques. We show that the descent rate of the QBO correlates with the strength of tropical upwelling. Further, by defining a statistical measure for QBO synchronization based on the evolution of QBO periods, we demonstrate that both the observed and modelled QBOs behave in a way that is consistent with synchronization to the annual cycle. The observed QBO is found to be phase synchronized with the Brewer-Dobson circulation, and we find that it jumps irregularly between the 2 : 1, 5 : 2, and 3 : 1 synchronization ratios. We find evidence that the phase slips of the observed QBO tend to occur during periods when the El Niño Southern Oscillation is in a strong positive phase.
Our results make a robust case in favour of the proposition that the QBO is synchronized to the annual cycle via seasonal and inter-annual variations in tropical upwelling strength and tropical wave activity.
Ecological and evolutionary significance of crassulacean acid metabolism in the montane genus puya (Bromeliaceae)
Keywords: Andes
Puya
CAM
Crassulacean acid metabolism
South America

Little is known about the evolution and ecology of crassulacean acid metabolism (CAM) in the genus Puya Molina. CAM is a photosynthetic pathway typified by nocturnal CO2 fixation and is regarded as a water-saving mechanism. Puya is one of the largest genera in the pineapple family (Bromeliaceae), with 226 species distributed across the Andes to Costa Rica and the Guiana Shield, and from sea level to 5000 m. About 21% of Puya species are CAM and at least 10 of these CAM species occur above 3000 m. The main aim of this thesis was to uncover new evidence to understand the ecophysiology and evolution of CAM in the montane genus Puya. The prevalence of CAM and C3 species in Puya was estimated from carbon isotope values of 161 species. The climatic niche of constitutive CAM species and C3 species of Puya was modelled using georeferenced herbarium records and climatic variables to evaluate the differences between their niches.
The evolution of CAM in Puya was investigated by reconstructing the ancestral photosynthetic pathway on an AFLP phylogeny and by studying positive selection in the genes encoding the key enzyme phosphoenolpyruvate carboxylase (PEPC). The coldresistance and the thermal lability of PEPC was investigated for high- and low- elevation CAM species of Puya to explore the potential molecular adaptations of CAM plants in high-elevation environments. The present study concludes that the common ancestor of Puya was a cold-resistant plant. This is suggested to explain the prevalence of Puya at highelevations.
The evolution of CAM was correlated with changes in the climatic niche, and occurred multiple times in Puya. These multiple origins were not independent because the common ancestor of Puya was likely to be a weak CAM plant (based on a diagnostic Arg679 residue in the PEPC sequence). It is likely that populations of P. chilensis gained CAM by introgression with P. alpestris ssp. zoellneri. Weak CAM photosynthesis and coldxv resistance allowed Puya to colonise the Andes from the south to the north; and, in the process, constitutive CAM and C3 evolved. The later-evolving species in the genus are suggested to have lost their capacity for CAM as they radiated into more mesic habitats during their colonisation of the northern Andes.
Philosophical readings in Virgil's Aeneid
Keywords: Virgil
Philosophy
Aeneid

This study examines how and why Virgil makes reference to philosophy and engages with contemporary philosophical debate in the Aeneid. Each of the six chapters has a different philosophical focus, and offers literary analyses of the poem that are supported and enriched by situating it within its philosophical context. Cicero and Lucretius are our principal sources for Roman philosophy during the 1st c. BC, and Stoics, Epicureans and Academics were the most influential philosophical schools. The topics I explore include: the relationship between words, especially names, and their referents; the characterization of fate in the Aeneid as Stoic, and the meaning of F/fortuna; Virgil's engagement with Lucretius' explanation of visual perception, which I argue embodies a refutation of the materialism integral to Epicurean philosophy; and, given that Cicero and Lucretius provide the first extant references to 'free will' (libera...voluntas Lucr. 2.256-7; voluntate libera Cic. Fat. 20) in Western literature, the articulation of this concept in the Aeneid. I conclude that Virgil's use of philosophy is both politically and poetically motivated: he shows that poetry and literature are valuable philosophical and political tools by demonstrating that our experience of reality is fundamentally mediated through language and texts.
Diagnosis and prognosis of degradation in lithium-ion batteries
Keywords: Diagnostics
Open circuit voltage
Battery management
Degradation

Lithium-ion (Li-ion) batteries are the most popular energy storage technology in consumer electronics and electric vehicles and are increasingly applied in stationary storage systems. Yet, concerns about safety and reliability remain major obstacles, which must be addressed in order to improve the acceptance of this technology. The gradual degradation of Li-ion cells over time lies at the heart of this problem. Time, usage and environmental conditions lead to performance deterioration and cell failures, which, in rare cases, can be catastrophic due to res or explosions. The physical and chemical mechanisms responsible for degradation are numerous, complex and interdependent. Our understanding of degradation and failure of Li-ion cells is still very limited and more limited yet are reliable and practical methods for the detection and prediction of these phenomena.
This thesis presents a comprehensive approach for the diagnosis and prognosis of degradation in Li-ion cells. The key to this approach is the extraction of information on electrode-speci c degradation through open circuit voltage (OCV) measurements. This is achieved in three stages. Firstly, a parametric OCV model is created, which computes the OCV of each electrode. Secondly, a diagnostic algorithm is devised, through which the OCV model is tted to OCV measurements recorded on Li-ion cells at various stages throughout their cycle life. The algorithm identi es the nature and quanti es the extent of degradation experienced by the cells. Lastly, the outputs of the algorithm are used to identify the likely failure modes of the cells and predict their end-of-life.
The presented methods improve safe operation and predictions of remaining useful cycle life for commercial Li-ion cells. Greater certainty about the reliability, safety, required maintenance and depreciation of Li-ion battery systems can signi cantly enhance the competitiveness of battery electric storage in both automotive and stationary applications. The ndings presented in this work are therefore not only of technological but also of commercial interest.
Calabi-Yau manifolds, discrete symmetries and string theory
Keywords: Calabi-Yau Manifolds
Heterotic String Compactification
Symmetries

In this thesis we explore various aspects of Calabi-Yau (CY) manifolds and com- pactifications of the heterotic string over them. At first we focus on classifying symmetries and computing Hodge numbers of smooth CY quotients. Being non- simply connected, these quotients are an integral part of CY compactifications of the heterotic string, aimed at producing realistic string vacua. Discrete symmetries of such spaces that are generically present in the moduli space, are phenomenologically important since they may appear as symmetries of the associated low energy theory. We classify such symmetries for the class of smooth Complete Intersection CY (CICY) quotients, resulting in a large number of regular and R-symmetry examples. Our results strongly suggest that generic, non-freely acting symmetries for CY quotients arise relatively frequently. A large number of string derived Standard Models (SM) were recently obtained over this class of CY manifolds indicating that our results could be phenomenologically important. We also specialise to certain loci in the moduli space of a quintic quotient to produce highly symmetric CY quotients. Our computations thus far are the first steps towards constructing a sizeable class of highly symmetric smooth CY quotients.
Knowledge of the topological properties of the internal space is vital in determining the suitability of the space for realistic string compactifications. Employing the tools of polynomial deformation and counting of invariant Kähler classes, we compute the Hodge numbers of a large number of smooth CICY quotients. These were later verified by independent cohomology computations. We go on to develop the machinery to understand the geometry of CY manifolds embedded as hypersurfaces in a product of del Pezzo surfaces. This led to an interesting account of the quotient space geometry, enabling the computation of Hodge numbers of such CY quotients.
Until recently only a handful of CY compactifications were known that yielded low energy theories with desirable MSSM features. The recent construction of rank 5 line bundle sums over smooth CY quotients has led to several SU(5) GUTs with the exact MSSM spectrum. We derive semi-analytic results on the finiteness of the number of such line bundle models, and study the relationship between the volume of the CY and the number of line bundle models over them. We also imply a possible correlation between the observed number of generations and the value of the gauge coupling constants of the corresponding GUTs. String compactifications with underlying SO(10) GUTs are theoretically attractive especially since the discovery that neutrinos have non-zero mass. With this in mind, we construct tens of thousands of rank 4 stable line bundle sums over smooth CY quotients leading to SO(10) GUTs.
Subcritical turbulence in the Mega Ampere Spherical Tokamak
Keywords: fusion
ion temperature gradient
turbulence
flow shear
subcritical
plasma

The transport of heat out of tokamak plasmas by turbulence is the dominant mechanism limiting the performance of fusion reactors. Turbulence can be driven by the ion temperature gradient (ITG) and suppressed by toroidal equilibrium scale sheared flows. Numerical simulations attempting to understand, and ultimately reduce, turbulence are crucial for guiding the design and optimisation of future reactors.
In this thesis, we investigate ion-scale turbulence by means of local gyrokinetic simulations in the outer core of the Mega Ampere Spherical Tokamak (MAST).We perform a parameter scan in the values of the ITG and the flow shear. We show that nonlinear simulations reproduce the experimental ion heat flux and that the experimentally measured values of the ITG and the flow shear lie close to the turbulence threshold. We demonstrate that the system is subcritical in the presence of flow shear, i.e., the system is formally stable to small perturbations, but transitions to a turbulent state given a large enough initial perturbation. We propose a scenario for the transition to subcritical turbulence previously unreported in tokamak plasmas: close to the threshold, the plasma is dominated by a low number of coherent long-lived structures; as the system is taken away from the threshold into the more unstable regime, the number of these structures increases until they fill the domain and a more conventional turbulence emerges.
We make quantitative comparisons of correlation properties between our simulations and experimental measurements of ion-scale density fluctuations from the MAST BES diagnostic. We apply a synthetic diagnostic to our simulation data and find reasonable agreement of the correlation properties of the simulated and experimental turbulence, most notably of the correlation time, for which significant discrepancies were found in previous numerical studies of MAST turbulence. We show that the properties of turbulence are essentially functions of the distance to threshold, as quantified by the ion heat flux. We find that turbulence close to the threshold is strongly affected by flow shear, whereas far from threshold, the turbulence resembles a conventional ITG-driven, zonal-flow damped regime.