VictorJuiz/thesis huggingface dataset:
Scalable reasoning for description logics
Keywords: automated reasoning
classification
description logics

Description logics (DLs) are knowledge representation formalisms with well-understood model-theoretic semantics and computational properties. The DL SROIQ provides the logical underpinning for the semantic web language OWL 2, which is quickly becoming the standard for knowledge representation on the web.
A central component of most DL applications is an efficient and scalable reasoner, which provides services such as consistency testing and classification. Despite major advances in DL reasoning algorithms over the last decade, however, ontologies are still encountered in practice that cannot be handled by existing DL reasoners.
We present a novel reasoning calculus for the description logic SROIQ which addresses two of the major sources of inefficiency present in the tableau-based reasoning calculi used in state-of-the-art reasoners: unnecessary nondeterminism and unnecessarily large model sizes. Further, we describe a new approach to classification which exploits partial information about the subsumption relation between concept names to reduce both the number of individual subsumption tests performed and the cost of working with large ontologies; our algorithm is applicable to the general problem of deducing a quasi-ordering from a sequence of binary comparisons. We also present techniques for extracting partial information about the subsumption relation from the models generated by constructive DL reasoning methods, such as our hypertableau calculus.
Empirical results from a prototypical implementation demonstrate substantial performance improvements compared to existing algorithms and implementations.
The syntax of adverbs: an LFG approach
Keywords: General Linguistics
Phonetics
Comparative Philology

This article proposes an LFG treatment of predicational adverbs in English. We argue that each adverb contains in its lexical entry a typological designation, or disjunction of multiple typological designations, which interact with lexical entries to produce c- and f-structures. ADVPs are adjoined to either I' or VP, depending on this typological designation, and provide all necessary readings from these two adjunction sites. Functional precedence is used to resolve ordering restrictions in cases of multiple adverb occurrence within a sentence.
Towards a small molecule inhibitor of Lactate Dehydrogenase-A
Keywords: synthesis
Warburg effect
tumour metabolism
rational drug design
breast cancer

Lactate Dehydrogenase-A (LDH-A) is up-regulated in a broad array of cancers and is associated with poor prognosis. Involved in the hypoxic response, LDH-A is a HIF-1 target and is responsible for the enzymatic reduction of pyruvate to lactate. This is important for several reasons, chiefly (1) the regeneration of NAD+ which feeds back into earlier glycolytic stages and (2) the depletion of intracellular pyruvate concentrations. High intracellular pyruvate is known to inhibit HDACs and is associated with increased apoptosis. LDH-A is also known to be controlled by oncogenes such as c-Myc suggesting an oncogenic role. Studies have shown that the knock-out of LDH-A reduces proliferation and tumourgenicity, and stimulates the mitochondria. This thesis therefore had three aims: firstly, to validate LDH-A inhibition and elucidate its full nature in terms of the implications for tumour survival; secondly, to ascertain the role of LDH-B in order to determine whether selectivity towards LDH-A would be a necessary feature of any small molecule; lastly, to recapitulate siRNA mediated LDH-A inhibition with small molecule inhibitors that had the potential for clinical application. The thesis examined both clinical data and a broad panel of cultured cancer cell types in order to select appropriate model in which to validate siRNA mediated inhibition of LDH-A and LDH-B. After it was demonstrated that LDH-A inhibition reduced the growth of cultured cells, a range of techniques were used to quantify this reduced growth in terms of cell death and changes in metabolism. Further to this, literature studies had proposed a role for LDH-B in maintaining lactate fuelled tumour growth; however, this thesis shows that in the cell lines studied, lactate-fuelled tumour growth was an LDH-A dependent phenomenon. Finally, a high throughput assay system was designed and validated and a library of small molecules was selected, synthesized, and screened in order to identify selective inhibitors of LDH-A.
Developing evidence-based strategic plans for malaria control and elimination in Indonesia
Keywords: Elimination
Indonesia
GIS
Malaria

Controlling and eliminating malaria in Indonesia is a challenging endeavour. Evidence-based strategic plans should be critically formulated to overcome a complex mosaic of infection risk across the 5000-km-long archipelago of thousand islands and distinctive habitats. This project aimed to thoroughly explore the challenges and opportunities for controlling/eliminating malaria and present the application of malaria cartographic tools to allow malaria control agencies and their partners to comprehensively assess the prospects for reaching pre-elimination, monitor and evaluate the effectiveness of future strategies against the baseline generated.
First, the historical context of malaria in Indonesia and important methods of control and their impact in the context of the political systems that supported them was comprehensively described. A series of distribution maps of twenty Anopheles malaria vector mosquitoes in Indonesia were also produced, supported by comprehensive reviews of each species’ bionomics and susceptibility to insecticides.
Then, the application of malaria cartographic tools for malaria control/elimination in Indonesia was explored. The first high spatial resolution (1 x 1 km) baseline endemicity maps of Plasmodium falciparum and P. vivax malaria were generated, together with corresponding estimates of population at risk and clinical burdens of each species in 2010. Low malaria prevalences of these parasites were predicted in western areas, with high prevalences in eastern Indonesia. Over 132 million people in Indonesia lived at risk of P. falciparum transmission with 70% of them in areas of unstable transmission and 30% in stable transmission. There were an estimated 7.7 million P. falciparum clinical cases across the populations at risk. Meanwhile, nearly 130 million people lived at risk of P. vivax malaria with 79% living in unstable and 21% in stable transmission areas. This infection caused 1.5 million estimated clinical cases in 2010. Both estimates were 30-fold and 6-fold higher than routinely reported numbers, respectively.
Finally, this project revealed the substantial multi-faced problems that impede current efforts towards the pre-elimination agenda. High rates of undiagnosed clinical cases, insufficient competence of malaria microscopy, inadequate primaquine dosing against P. vivax malaria infections, insufficient evidence of vector control interventions, wide diversities of vector mosquitoes and their bionomics, mosquito resistance against insecticides and inadequate malaria surveillance systems are challenging the task of controlling and eliminating malaria. A diverse range of strategies enabling locally-specific approaches must be implemented for controlling and eliminating malaria in Indonesia. Strategic recommendations are listed and future research priorities are proposed for further study.
The ecology of vascular epiphytes in the Peruvian Andes
Keywords: Peru
Bromeliaceae
Andes
vascular epiphytes
biomass

Little is known about the composition of tropical epiphytic communities and the influence of environmental variables on community composition. In this thesis I quantify the diversity and biomass of bromeliads, and other vascular epiphytes along an altitudinal transect on the eastern slope of the southeast Peruvian Andes and then look for species’ adaptations related to patterns of diversity and biomass. I compare patterns with those of woody species. Bromeliad species, like tree species, were found to form ecological zones related to climate. The lowest altitude ecological zone (below 1250 m) is the lowland rainforest (LRF), which has the warmest climate and highest evapotranspiration. In LRF vascular epiphytes are less prominent than other ecological zones, with the lowest bromeliad species richness and lowest vascular epiphyte biomass. However, low water-availability gives rise to most variable shoot morphology of bromeliads. The tropical montane forest (TMF), between 1250 m and 2250 m, is intermediate in climate between the LRF and the tropical montane cloud forest (TCF). The TMF has the highest α-diversity, but species richness is lower than the TCF. The shoot morphology of bromeliads is intermediate between TCF and LRF. The highest altitude ecological zone with forest is the TCF (above 2250 m). The TCF has the highest bromeliad species richness, and lowest diversity of shoot forms. The low diversity of shoot forms represents the need for a large phytotelm (water-impounding shoot) to intercept and store precipitation. The TCF has the highest vascular epiphyte biomass, although the biomass is variable as a consequence of the natural disturbance caused by landslides. Along the transect bromeliad species with CAM photosynthesis are only present in the LRF. Terrestrial bromeliad distribution records covering the Neotropics show CAM photosynthesis is more prevalent in drier environments showing that CAM photosynthesis is primarily an adaptation to drought. Epiphytic bromeliads, pre-adapted to a water-stressed environment show no differences in presence along rainfall gradients, but species with CAM photosynthesis occupy warmer environments.
Essays on the financial governance of firms
Keywords: firm entry
unions
CEO pay
firm exit
bankrupcy
professional partnerships
debt
capital structure

Four essays, or chapters, model the capital structure, governance, and investment decisions as part of a sequential game. Each chapter is separate in its context, assumptions, and conclusions. The titles of the chapters are below. Abstracts of each essay or chapter can be found at the beginning of each chapter. The titles of the chapters or essays are as follows: I. Managerial Ownership with Rent-Seeking Employees, II. Financing Professional Partnerships, III. Sunk Cost Efficiency with Identical Competitors, and IV. Business Stealing and Bankruptcy. With the exception of Chapter III, which is meant to complement Chapter IV, these essays argue that the structure of financial contracts can affect the real behavior of firms. The first chapter argues that financial governance policies affect the behavior of rank-and-file employees. In Chapter II, the governance and capital structure of professional service firms affects clients’ expectations of the firm’s quality. In Chapter IV, the enforcement of financial contracts by bankruptcy courts affects the number of firms that enter and exit the industry.
Investigating the role of the fat mass and obesity associated gene (Fto) in obesity
Keywords: fat mass and obesity gene
Obesity
Metabolism
GWAS
FTO
Genetics
Genome Wide Association

In 2007, a genome wide association study identified a SNP in intron 1 of FTO with increased BMI. Homozygous risk allele carriers are on average three kg heavier than those homozygous for the protective allele. Mouse models have been made, including a conditional knockout, which is lean when globally expressed, as well as a conditional overexpression allele, which has increased body weight when globally expressed. The results from these and other studies suggest that the FTO SNPs lead to weight gain by increasing FTO activity and/or expression.
Adult inactivation of Fto using the tamoxifen inducible Cre demonstrated that removal of Fto may be as deleterious as overexpression, with the adult knockout mice having increased fat mass and decreased lean mass. It also supported the role FTO plays in development as adult inactivation of Fto did not increase mortality rates as seen in the global Fto-/- pups. This study also revealed the importance of effective energy expenditure analysis in the mouse.
I have confirmed a link between Fto-/- and increased mortality, which may be caused by alterations to developmental processes. Fto-/- reduces cilia formation in MEFs and results in dysregulated cilia formation in specific tissues in Fto-/- embryos. Levels of FTO also appear to affect adipogenic differentiation, which could be due to altered WNT/β-CATENIN signalling.
Pharmacological inhibition of FTO was a success in vitro and a compound screen identified FG2216, which could be used in vivo to inhibit FTO. The in vivo effects of FG2216 at 60 mg/kg/2days did not affect body weight or composition in the mouse.
My research suggests that there is dysregulation of gut hormones and neuronal signalling pathways in the FTO overexpression mice, which could cause the hyperphagia and increased body weight. These studies add to our current knowledge of FTO function, and suggest a role for FTO in control of body composition, development, and satiety signalling.
A comparative study of volunteering and giving
Keywords: pro-social behaviour
social context
quantitative methods
charitable giving
multilevel modelling
social capital
social cohesion
volunteering

The main research question in this thesis explores why some people volunteer and give money compared to those that do not. The thesis builds on existing research that explains volunteering and giving, but is primarily concerned with showing how the social environment – or the context – in which people live can explain individual decisions to volunteer and give. This thesis answers three main research questions with this central theme in mind. First, how do the background characteristics of people explain whether they volunteer or give? Second, net of background characteristics of people, how does the social environment (context) that people live in explain volunteering and giving? Third, how do background characteristics of people and the social environment in which they live interact to explain volunteering and giving? Each of the four empirical chapters focuses on research questions that have received limited attention in the literature, while also utilizing relatively unique data, in relatively unique contexts.
The main results of this study are as follows. Comparatively, the shared profile of a volunteer and charitable giver is someone who is middle aged, more educated, married, richer, healthier, and a religious service attendee. Contextual country characteristics also displayed an independent effect of these individual-level characteristics: religious diversity and belonging to a religious minority group was associated with a greater likelihood of volunteering, but are not associated with giving. Income inequality is associated with a decreased likelihood of volunteering and giving for respondents in developed countries, whereas the opposite is true for respondents in developing countries, supporting Wilkinson’s relative income hypothesis. A curvilinear relationship exists between national devoutness and volunteering, whereas a strong positive correlation exists between national devoutness and giving. Females are more likely to volunteer and give in societies that exhibit more gender equality; and the lower educated are more likely to volunteer in more educated societies, but that they are not more likely to give in these societies. There is no support for the idea that income disparities in volunteering and giving are exacerbated in more socially unequal societies.
In England, there was no support for the idea that a stable residential area promotes volunteering and giving among adults, while neighbourhood deprivation and ethnic diversity were strong negative predictors of both behaviours. Among the youth demographic in England, religious diversity of schools is not associated with any form of civic engagement. Ethnic diversity is positively related to school extra curricular activities, but negatively with youth club participation. Youths attending private schools were more likely to take part in school-based extra-curriculars, but less likely to take part in out of school clubs and groups.
Pathogenic mycobacteria achieve cellular persistence via lipid-mediated inhibition of the Niemann-Pick disease type C pathway
Keywords: NIEMANN-PICK DISEASE TYPE C
LYSOSOME
PHARMACOLOGY
TUBERCULOSIS
LYSOSOMAL STORAGE DISORDERS

M.tuberculosis, the causative agent of human tuberculosis, is able to achieve long-term persistence within host organism macrophages. This persistence is achieved via the ability of the mycobacterium to prevent phagosomal-lysosomal fusion. The mechanisms by which fusion is inhibited remain incompletely understood. Here we provide evidence supporting a mechanistic link between infection with pathogenic mycobacteria and the cellular pathway defective in the rare lysosomal storage disorder Niemann-Pick disease type C (NPC). We observed that NPC phenotypes, including lipid storage and reduced lysosomal calcium release, can be induced in wild-type murine and human macrophages by infection with pathogenic mycobacteria. This phenotype induction did not occur following infection with the non-pathogenic M.smegmatis. Phenotype induction could be achieved in the absence of the mycobacteria using lipids from the mycobacterial cell walls. The importance of mycobacterial cell wall lipids to mycobacterial virulence has been well-documented. This lipid-mediated inhibition likely occurs through the NPC1 protein. Susceptibility to phenotype induction was inversely proportional to levels of functional NPC1, whilst a pre-existing dysfunction in the NPC pathway (either stemming from mutation or pharmacological inhibition) rendered cells less able to clear non-pathogenic mycobacteria. Finally, we demonstrate that therapies for NPC, particularly curcumin, are able to promote clearance of mycobacteria from infected macrophages. NPC therapies may hold promise for a new approach to the treatment of tuberculosis.
The functional consequences of autoimmune variants in the tyrosine kinase 2 gene region
Keywords: genetics
Autoimmunity

The tyrosine kinase 2 (TYK2) gene was first implicated in autoimmune disease in 2009 when a nonsynonymous single nucleotide polymorphism (nsSNP) in TYK2 was reported to be associated with multiple sclerosis (MS). The immunological function of TYK2, as a kinase involved in signal transduction downstream of numerous different cytokine receptors, further strengthened the candidacy of the gene as an MS-relevant risk factor. More recently, this nsSNP has been associated with several other autoimmune conditions. In addition, another three different SNPs in the region have been found to be associated with a number of autoimmune diseases, sometimes in opposing directions. Considering the complex genetic association pattern that is emerging for the TYK2 region across autoimmune conditions, it was hypothesised that this complexity reflects shared but also distinct pathogenic mechanisms, with the consequences of disease-associated SNPs being unlikely to all be restricted to genotype-dependent effects influencing TYK2. Therefore, the main aim of the work presented in this thesis has been to address this hypothesis by investigating the functional consequences of the disease-associated SNPs in the TYK2 gene region.
Using an in vitro cell line system and primary human immune cells, obtained from a genotype-selectable donor cohort, protection at the MS-associated nsSNP was found to correlate with reduced TYK2-mediated signalling downstream of the type I interferon receptor. However, other cytokine signalling pathways were not affected, indicating a greater specificity to the function of TYK2 than has previously been appreciated. For the other SNPs in the region, substantial effects on TYK2 were not observed but immune cell subset-specific correlations with RNA-level expression of other genes in the region were identified. Thus, this is the first study to support the concept that a careful cross-comparative analysis of SNP association patterns in a single genomic region across multiple autoimmune diseases can have significant implications for enabling the delineation of pathways common or specific to different conditions, and this is of particular importance for drug repositioning strategies.
A search for H -&gt; WW using a matrix element discriminant and a WW cross section measurement at ATLAS
Keywords: Electroweak
Particle physics
Higgs

One of the main motivating factors for the construction of the Large Hadron Collider (LHC) was the search for the Higgs boson, postulated to explain the origin of fundamental gauge boson masses. This thesis presents the results of the first search for the Higgs boson at the LHC, using 35 pb^−1 of proton-proton collision data with a centre of mass energy of 7 TeV collected by the ATLAS experiment throughout 2010.
The search is performed in the H -> WW channel, since the branching ratio for Higgs boson decays to W bosons is large for a wide range of Higgs boson masses. Two different search methods are presented: a straightforward cut-based method and a method using a matrix-element-based discriminant to provide additional separation between signal and background. The matrix element method is shown to give better expected sensitivity at all Higgs boson masses. Using these methods, a SM-like Higgs boson with a mass of 160 GeV with a production rate of 1.2 times the SM rate is excluded at 95% Confidence Level and limits are placed on the production rate of the SM Higgs boson in the range of masses from 120 < mH < 200 GeV.
In addition, a measurement of the SM WW cross section is performed. It is essential to understand this channel since it is the major background to the H -> WW search. SM WW production is also sensitive to new physics processes, which would enhance its cross section. The SM WW cross section is measured to be σ(WW) = 40+20−16(stat.)±7(syst.) pb, which is consistent with the NLO SM expectation of 46 ± 3 pb.