VictorJuiz/thesis huggingface dataset:
The complexity and expressive power of valued constraints
Keywords: valued constraints
pseudo-Boolean optimisation
min-cut
submodularity
complexity
CSP
MRF
expressive power

This thesis is a detailed examination of the expressive power of valued constraints and related complexity questions. The valued constraint satisfaction problem (VCSP) is a generalisation of the constraint satisfaction problem which allows to describe a variety of combinatorial optimisation problems. Although most results are stated in this framework, they can be interpreted equivalently in the framework of, for instance, pseudo-Boolean polynomials, Gibbs energy minimisation, or Markov Random Fields. We take a result of Cohen, Cooper and Jeavons that characterises the expressive power of valued constraint in terms of certain algebraic properties, and extend this result by showing yet another connection between the expressive power of valued constraints and linear programming. We prove a decidability result for fractional clones. We consider various classes of valued constraints and the associated cost functions with respect to the question of which of these classes can be expressed using only cost functions of bounded arities. We identify the first known example of an infinite chain of classes of constraints with strictly increasing expressive power. We present a full classification of various classes of constraints with respect to this problem. We study submodular constraints and cost functions. Submodular functions play a key role in combinatorial optimisation and are often considered to be a discrete analogue of convex functions. It has previously been an open problem whether all Boolean submodular cost functions can be decomposed into a sum of binary submodular cost functions over a possibly larger set of variables. This problem has been considered within several different contexts in computer science, including computer vision, artificial intelligence, and pseudo-Boolean optimisation. Using a connection between the expressive power of valued constraints and certain algebraic properties of cost functions, we answer this question negatively. Our results have several corollaries. First, we characterise precisely which submodular polynomials of degree 4 can be expressed by quadratic submodular polynomials. Next, we identify a novel class of submodular functions of arbitrary arities that can be expressed by binary submodular functions, and therefore minimised efficiently using a so-called expressibility reduction to the (s,t)-Min-Cut problem. More importantly, our results imply limitations on this kind of reduction and establish for the first time that it cannot be used in general to minimise arbitrary submodular functions. Finally, we refute a conjecture of Promislow and Young on the structure of the extreme rays of the cone of Boolean submodular functions.
The propagation of ultra high energy cosmic rays
Keywords: Ultra High Energy Cosmic Rays
Nuclei
Secondaries

This thesis presents theoretical work on the propagation of ultra high energy cosmic rays, from their source to Earth. The different energy loss processes, resulting from cosmic ray interactions with the radiation fields, are addressed. The subsequent uncertainties in the energy loss rates and the effect produced on the arriving cosmic ray spectrum are highlighted.
The question of the composition of ultra high energy cosmic rays remains unresolved, with the range of possibilities leading to quite different results in both the secondary fluxes of particles produced through cosmic ray energy loss interactions en route, and the arriving cosmic ray spectra at Earth. A large range of nuclear species are considered in this work, spanning the range of physically motivated nuclear types ejected from the cosmic ray source.
The treatment of cosmic ray propagation is usually handled through Monte Carlo simulations due to the stochastic nature of some of the particle physics processes relevant. In this work, an analytic treatment for cosmic ray nuclei propagation is developed. The development of this method providing a deeper understanding of the main components relevant to cosmic ray nuclei propagation, and through its application, a clear insight into the contributing particle physics aspects of the Monte Carlo simulation.
A flux of secondary neutrinos, produced as a consequence of cosmic ray energy loss through pion production during propagation, is also expected to be observed at Earth. This spectrum, however, is dependent on several loosely constrained factors such as the radiation field in the infrared region and cosmic ray composition. The range of possible neutrino fluxes obtainable with such uncertainties are discussed in this work.
High energy cosmic ray interactions with the radiation fields present within the source may also occur, leading to cosmic ray energy loss before the cosmic ray has even managed to escape. The secondary spectra produced are investigated through the consideration of three candidate sources. A relationship between the degree of photo-disintegration in the source region and the neutrino flux produced through p γ interactions is found.
The case of the magazine Careta in Lima Barreto's journalistic oeuvre (1915-1922)
Keywords: Magazines
Rio de Janeiro
Brazil
Modernism
Illustrated periodicals
Lima Barreto
Satire
Brazilian Literature

This thesis examines the articles the Brazilian writer Lima Barreto (1881-1922) published in the popular satirical magazine Careta. It argues that Careta epitomises Lima Barreto’s aim to create social impact through literature, as it provided him with the largest readership he enjoyed in his lifetime, reaching hundreds of thousands of readers weekly nationwide and internationally. The thesis expands the knowledge about the strategies Lima Barreto used to convey his ideas, showing how he endeavoured to engage with mass audiences in order to combat social fragmentation and intellectual alienation in early twentieth century Brazil.
The significance of this thesis is evident on two levels. First, I demonstrate throughout the chapters that Barreto fully engaged with Careta to convey his ideas to a mass audience, choosing the magazine as his main periodical voice in the last years of his life. This argument challenges the idea that Lima Barreto was a marginal writer in the First Republic. Second, the originality of this thesis lies in locating and uncovering almost one hundred and fifty hitherto unknown texts, most of them published pseudonymously in Careta.
Chapter one discusses the militancy of Barreto's works. Chapter two argues that Barreto elected magazines, more than newspapers, to convey his message to a large audience. Chapter three relates the early history of Careta. Chapter four suggests that Barreto incorporated pictorial strategies into his articles. Chapter five argues that Barreto embraced Careta's central theme derived from the Commedia dell'Arte. Chapter six discusses systematically the pseudonyms attributed to Barreto in Careta and provides robust evidence that he published many hitherto unknown texts pseudonymously. Finally, I conclude that Careta encapsulates Barreto's efforts to reach a mass readership and communicate with readers beyond literary circles.
Ion-pair and anion recognition by macrocycles and interpenetrative assemblies
Keywords: host-guest
ion-pair
macrocycle
Supramolecular
anion
recognition

This thesis investigates the design and synthesis of macrocycles and examines their ion-pair recognition, anion recognition and interpenetrative assembly capabilities.
Chapter One introduces the field of supramolecular chemistry. Key concepts in host–guest complexation and self-assembly are outlined, with particular emphasis on the design of host systems for anion and ion-pair recognition.
Chapter Two details the synthesis and binding properties of a heteroditopic 1,2,3-triazole- containing macrocycle that exhibits cooperative ion-pair recognition. Solution and solid-state evidence shows that the triazole motif simultaneously binds anions and cations. The exten- sion of this work towards the formation of interlocked structures containing an expanded heteroditopic macrocycle and threading components is explored.
Chapter Three discusses the design and syntheses of series of electron-deficient macrocycles based on imidazolium, pyridinium and triazole. These are investigated for anion binding ability and assembly of interpenetrative assemblies with electron-rich threading components.
Chapter Four describes research into the formation of interpenetrative assemblies using neutral components. Their design is based around aromatic donor–acceptor interactions and halogen bonding.
Chapter Five presents some conclusions from the research undertaken.
Chapter Six provides titration protocols, Job plot approximations, experimental procedures and characterisation of the compounds described in this thesis.
Appendix details additional X-ray crystallographic data.
Probing the molecular basis of melanopsin induced light sensitivity
Keywords: siRNA
pupillometry
ophthalmology
melanospin

It has been demonstrated that retinal photoreception among mammals extends beyond rods and cones to include a small number of intrinsically photosensitive retinal ganglion cells (pRGCs), which are capable of responding to light due to expression of the melanopsin (OPN4) photopigment. OPN4 may have therapeutic potential if ectopically expressed in the degenerate retina in cases where photoreceptors are lost, but the other molecules involved in this light induced transduction cascade are less well characterized. Therefore I sought to probe further the mechanism of OPN4 mediated light sensitivity by siRNA mediated knock down of specific molecules in two mice models in which complete loss of rods and cones renders them almost exclusively dependent on the OPN4 pathway for light sensitivity.
I generated siRNA probes against the long transcript variant of murine Opn4 mRNA and first tested these probes on the murine Neuro2A (N2a) cell line, before assessing effects in C3H/HeN rd and rodless/coneless rd/rd cl mice. siRNA was injected intravitreally into one eye and pupillometry was assessed, combined with molecular analyses at various timepoints. Reverse transcription polymerase chain reaction (RT-PCR) analysis in N2a cells confirmed Opn4 knockdown and immunolabelling techniques identified >85% silencing with siRNA. Pupil responses in the rd and rd/rd cl mice were inhibited by the siRNA injections in vivo which confirmed the functional effect of Opn4 silencing detected by molecular analysis.
I therefore present a novel reproducible in vivo model in which siRNA induced silencing of the melanopsin pathway can be assessed by pupillometry and compared to levels of mRNA and protein at specific timepoints. Probes against other putative candidate genes, such as TRPC3, may unravel the molecular interactions of this pathway. This may help in future to induce light sensitivity in other retinal neurons in patients who are completely blind from photoreceptor loss.
Dynamics of the Milky Way: tidal streams and extended distribution functions for the galactic disc
Keywords: methods: numerical
Galaxy: kinematics and dynamics
Galaxy: structure
galaxies: kinematics and dynamics
Galaxy: solar neighbourhood

One of the key goals of Milky Way science is measuring the distribution of dark matter in the Galaxy. Through the study of Galactic dynamics, inferences can be made about the structure of the Galaxy, and hence the dark matter distribution. To this end, we present a study of methods useful for modelling and understanding dynamical systems in the Galaxy.
A natural choice of coordinate system when studying dynamical systems is the canonical system of angle-action coordinates. We present methods for estimating the angle-actions in both axisymmetric and triaxial potentials. These fall into two categories: non-convergent and convergent. The non-convergent methods are fast approaches, mostly based on approximations to Stäckel potentials. We investigate the accuracy of these methods for realistic Galactic potentials. The slower convergent methods operate by constructing generating functions to take us from simple analytically-tractable potentials to our target potential.
Tidal streams should prove useful for constraining the large-scale dark matter distribution in the Galaxy. Armed with our new angle-action tools, we investigate the properties of known streams in a realistic Galactic potential. We present a simple algorithm for constraining the Galactic potential using a tidal stream, which exploits the expected structure of a stream in the angle-frequency space of the true potential. We expand this approach into a fully probabilistic scheme that allows for handling of large errors, missing data and outliers.
We close by discussing another tool useful for modelling the dynamics of the Galaxy: extended distribution functions for the Galactic disc. We present a simple extension of an action-based distribution function from Binney (2010) that includes metallicity information, and compare the model predictions with current data. These models are essential for incorporating the selection effects of any survey, and reveal the important chemo-dynamic correlations that expose the history and evolution of the Galaxy.
Intracellular signalling, gene induction and histone modifications in Drosophila melanogaster
Keywords: Drosophila
MAPK signalling

In eukaryotes, histone H3 residues at the promoter and transcriptional start site of immediate early genes are phosphorylated at serine 10, a process mediated by histone kinases downstream of the p38 and ERK cascades. However, this phosphorylation event has not yet been investigated in Drosophila melanogaster, and the existence of an inducible histone kinase is uncertain.
To identify the kinases involved in the nucleosomal response in Drosophila, I first investigated the stimuli inducing MAPK signal transduction pathways. In mouse cells, anisomycin at sub-inhibitory concentration is a strong activator of JNK and p38, but no activation of MAPKs was observed in Drosophila. Peptidoglycan treatment induced JNK activation without altering histone H3 phosphorylation, demonstrating that this part of signal transduction is conserved between vertebrate and insect cells. However, in contrast to mammalian cells, inducing ERK activity by stimulation with hydrogen peroxide, insulin, serum or heat shock does not lead to histone H3 phosphorylation. Osmotic stress resulted in a strong increase in phosphoacetylated histone H3, suggesting that p38 is upstream of the histone H3 kinase in Drosophila, but the presence of p38 inhibitor SB203580 did not decrease histone H3 phosphoacetylation. Further evidence suggesting that the nucleosomal response in Drosophila is not conserved includes the absence of induction of classical immediate early gene jra after stimulation with either sorbitol or sodium arsenite. In summary, these results indicate that histone phosphorylation and IE gene induction differ in mammals and Drosophila and provide the basis for further experiments aiming to identify the relationship between histone phosphorylation and transcription.
Investigating high-affinity non-covalent protein-ligand interaction via variants of streptavidin
Keywords: biotin
mutagenesis
protein interactions
biochemistry
traptavidin
streptavidin
FtsK
crystallography

The Streptomyces avidinii protein streptavidin binds the small molecule biotin (vitamin H / B₇) with extraordinary stability, resulting in the streptavidin-biotin interaction being one of the strongest non-covalent interactions known in nature (Kd ~ 10-14 M). The stable and rapid biotin-binding, together with high resistance to heat, pH and proteolysis, has given streptavidin huge utility, both in vivo and in vitro. Accordingly, streptavidin has become a widely used tool in many different biotechnological applications. Streptavidin has also been the subject of extensive research efforts to glean insights into this paradigm for a high-affinity interaction, with over 200 mutants of the protein reported to date.
Despite the high stability of the streptavidin-biotin interaction, it can and does fail under certain experimental conditions. For example, streptavidin-biotin dissociation is accelerated by an increased temperature or lower pH (conditions often encountered in cellular imaging experiments), and by mechanical stress, such as the shear force arising from fluid flow (encountered when streptavidin is used as a molecular anchor in biosensor chips and arrays).
This study details efforts made at increasing further the utility of streptavidin, by increasing the stability of biotin and biotin-conjugate binding. A rational site-directed mutagenesis approach was used to create 27 mutants, with eight of these mutants possessing higher-stability biotin-binding. The most stable biotin-binding mutant was named traptavidin and was extensively characterised. Kinetic characterisation revealed traptavidin had a decreased dissociation rate from biotin and biotin-conjugates when compared to wildtype streptavidin, at both neutral pH and pH 5. Atomic force microscopy and molecular motor displacement assays revealed the traptavidin-biotin interaction possessed higher mechanical stability than the streptavidin-biotin interaction. Cellular imaging experiments revealed the non-specific cell binding properties of streptavidin were unchanged in traptavidin. X-ray crystallography was also used to generate structures of both apo- and biotinbound traptavidin at 1.5 Å resolution. The structures were analysed in detail and compared to the published structures of streptavidin, revealing the characteristics of traptavidin arose from the mutations stabilising a flexible loop over the biotin-binding pocket, as well as reducing the conformational change on biotin-binding to traptavidin.
Traptavidin has the potential to replace streptavidin in many of its diverse applications, as well as providing an insight into the nature of ultra-stable noncovalent interactions.
Palaeomagnetic and geochemical characterisation of geomagnetic excursions in the quaternary
Keywords: geomagnetic excursions
geomagnetic reversals
ODP
uranium-series
sedimentation rate

Geomagnetic excursions, brief deviations in geomagnetic field behaviour from that expected during 'normal' secular variation, remain some of the most enigmatic features of geomagnetic field behaviour. This thesis presents high-resolution records of geomagnetic excursions recorded at the Blake-Bahama Outer Ridge in the Western North Atlantic. The highest resolution record yet of the Blake geomagnetic excursion (~125 ka) is measured in three cores from Ocean Drilling Program Site 1062 (ODP Leg 172). These cores have sufficiently high sedimentation rates (>10 cm ka-1) to allow detailed reconstruction of the field behaviour at these sites during the excursions. Previous reconstructions of geomagnetic field behaviour during excursions from marine cores have been limited by low-resolution age models. This thesis discusses a new approach, whereby measurements of excess 230Th (230Thxs) are used to constrain relative variations in sedimentation rate. Modifications are suggested to the methods previously used to calculate the concentration of 230Thxs and a new MATLAB® program is developed and described that allows rapid and flexible calculation of 230Thxs. Using this new approach, the duration (6.5±1.3 kyr) and age (129-122 ka) of the Blake excursion are accurately constrained. A palaeomagnetic study is also conducted on two ODP Sites, 1061 and 1062 on the Blake-Bahama Outer Ridge to obtain a high-resolution record of the Laschamp geomagnetic excursion (~41 ka). The Blake excursion is found to be of 'long' duration (6.5±1.3 kyr) whilst the Laschamp excursion is relatively short (<400 years) showing that excursions do not have a characteristic duration, linked to the conductivity of the inner core, but instead occupy a continuous range of durations. The records of both the Blake excursion and the Laschamp excursion from the Blake-Bahama Ridge sites also show rapid transitions to excursional geomagnetic pole positions (less than 500 years), much faster than often quoted for full geomagnetic reversals. Based on current estimates for reversal durations, this would imply that excursions and reversals are controlled by different processes.
Tissue expression and functional insights into HIF prolyl hydroxylase domain enzymes
Keywords: hypoxia inducible factor (HIF)
prolyl hydroxylase domain proteins (PHD)

This research programme investigated the expression of prolyl hydroxylase (PHD) proteins in rodent tissues. The importance of PHD enzymes lies in their ability to render oxygen sensitivity to Hypoxia inducible factor (HIF), the principal mediator of intracellular oxygen homeostasis. The first part of this study focused on developing and validating anti-sera capable of detecting PHD proteins in rodent tissues. With these reagents, it was possible to assess the relative expression of each PHD protein in a number of different rat tissues. PHD2 was the most abundant isoform in all tissues studied. In contrast, an abundance of PHD1 was observed only in testis and skeletal muscle. A number of different tissue species of PHD3 were identified and their abundance was found to vary between different tissues.
These observations provide further evidence of the principal role of PHD2 in regulating HIF in vivo, but also point towards additional roles for PHD1 and PHD3 in selected tissues. They highlight the potential for there being a complex interplay between different PHD enzymes which could, in the future, prove potential targets for therapeutic manipulation. This study also provides additional insights into the mechanisms underlying the phenotypes observed in PHD deletional mouse models which appear, in many cases, to be directly related to the abundance of a given PHD isoform.
The emerging role of PHD3 as a promoter of sympathetic lineage apoptosis prompted further study of PHD3 expression in rat neuronal tissues. An abundance of PHD3 was demonstrated throughout the rat sympathetic nervous system, a finding which appeared at odds with its known role as a promoter of neuronal apoptosis and resulted in a series of collaborative studies which demonstrated a sympatho-adrenal phenotype in wild type compared to PHD3-/- mice. Further collaborative studies utilising wild type mice and those deleted of specific PHD isoforms, were carried out to assess the significance of the abundance of PHD3 and PHD1 noted here in rat hippocampus and testis respectively. While neither study demonstrated statistically significant phenotypes, these observations remain of interest and areas for future research.