VictorJuiz/thesis huggingface dataset:
PAGOdA: Pay-as-you-go ontology query answering using a datalog reasoner
Keywords: query
knowledge representation
description logic

Answering conjunctive queries over ontology-enriched datasets is a core reasoning task for many applications of semantic technologies. Conjunctive query answering is, however, computationally very expensive, which has led to the development of query answering procedures that sacrifice either the expressive power of ontology languages, or the completeness of query answers in order to improve scalability. This thesis describes a hybrid approach to query answering over OWL 2 ontologies that combines a datalog reasoner with a fully-fledged OWL 2 reasoner in order to provide scalable "pay-as-you-go" performance. The key feature of this hybrid approach is that it delegates the bulk of the computation to the datalog reasoner and resorts to expensive OWL 2 reasoning only as necessary to fully answer the query. Although the main goal of this thesis is to efficiently answer queries over OWL 2 ontologies, the technical results are more general and the approach is applicable to first-order knowledge representation languages that can be captured by rules allowing for existential quantification and disjunction in the head; the only assumption is the availability of a datalog reasoner and a fully-fledged reasoner for the language of interest, both of which are used as "black boxes". All techniques proposed in this thesis are implemented in the PAGOdA system, which combines the datalog reasoner RDFox and the OWL 2 reasoner HermiT. An extensive evaluation shows that PAGOdA succeeds in providing scalable pay-as-you-go query answering for a wide range of OWL 2 ontologies, datasets and queries.
RNA-based therapeutics for Alzheimer's disease
Keywords: neurodegenerative disease
Alzheimer's disease
exosomes

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterised pathologically by the accumulation of amyloid-β plaques and neurofibrillary tangles within the brain. Currently, there are no disease-modifying therapeutic interventions available. This thesis describes the development and delivery of novel RNA-based therapeutics for AD.
Recently, significant advances have occurred in the field of RNA interference (RNAi)-based therapeutics, allowing targeted silencing of disease-relevant genes through the use of short interfering RNAs (siRNAs) or microRNAs (miRNAs). However, development has been impeded by poor penetrance of the blood-brain-barrier (BBB) in vivo. Exosomes, as secreted extracellular vesicles (EVs), may overcome this problem as they naturally deliver RNA between cells and cross the BBB. Furthermore, recent evidence suggests that they may be loaded with exogenous RNA and preferentially targeted to neuronal tissue. Thus, this study investigated EV-mediated delivery of RNAi-based therapeutics shown to regulate AD-relevant genes. A comparison of EV-loading methods revealed that electroporation was confounded by the formation of large siRNA aggregates and indicated that endogenous loading strategies may be preferable. Endogenous loading of RNAi molecules was shown to be enhanced by co-expression with RNA-binding proteins, particularly following inclusion of an acylation domain. These findings highlight the potential for EV-mediated delivery of RNAi-based therapeutics.
A combinatorial therapeutic approach is increasingly recognised to hold the most promise for the future of AD. Thus, this study also focused upon the development of novel multi-gene targeting locked nucleic acid-modified antisense oligonucleotides (LNA-ASOs) as a combinatorial approach towards AD therapy. Two multi-gene LNA-ASOs each produced potent silencing of two separate target genes simultaneously, resulting in a significant reduction in amyloid-β production in vitro. A murine-specific multi-gene LNA-ASO was also identified, paving the way for future in vivo studies. These findings suggest that multi-gene targeting LNA-ASOs may represent a promising novel therapeutic strategy for AD.
In summary, this thesis has investigated novel strategies for both RNA delivery and multi-gene targeting, demonstrating the potential of RNA-based therapeutics for the treatment of AD.
Electrochemistry of silver nanoparticles
Keywords: Silver Nanoparticles
Nano-impacts

This thesis presents findings realising two main objectives. The first aim is to investigate the electrochemical detection of nanomaterials with an emphasis on silver nanoparticles. The second goal is to employ silver nanoparticles in electroanalysis to aid in the detection of other analytes.
First, the detection of silver nanoparticles was demostrated through two different electrochemical methods, stripping voltammetry and 'nano-impacts'. For stripping voltammetry, the potential of metallic nanoparticles oxidation was quantified by various new analytical expressions for peak potential. For the novel method of 'nano-impacts', individual silver nanoparticles were successfully detected in an optically opaque suspension. Then, a comparison between the two techniques was achieved via the oxidation of silver nanoparticles with different capping agents. Strong capping agent effects was found for stripping voltammetry and one may markedly underestimate the amount of silver nanoparticle present on the electrode surface. The electrochemical sizing of nanoparticles via 'nano-impacts' remained unaffected by the capping agent effect. Amidst the study on the various types of capping agent, it was discovered that cetyltrimethylammonium bromide (CTAB) is electroactive due to the oxidation of its bromide content. This inspired the use of 'nano-impacts' to detect the presence of large CTAB micelles which self-assembled at concentrations above the critical micelle concentration.
Next, various types of silver nanoparticles were applied to different electroanalytical systems to aid in the measurement of other analytes. (a) Small silver nuclei, remaining after the oxidative stripping of an electrode modified by silver nanoparticle suspension drop casting, allowed subsequent signal enhancement (at least a factor of three) in anodic stripping voltammetry of silver ions. (b) The thermodynamic favourable formation of silver halide complexes allowed the silver nanoparticle modified electrode to analyse the halide content of a solution. Hence, a proof-of-concept for an electrochemical sensor based on silver nanoparticle modified electrode for chloride ions was established. This might be applied to the pre-screening of cystic fibrosis, a genetic disease detrimental to many infants' lives. (c) Another key halide in human body, iodide ions, was also measured using a related concept. The level of iodide ions in synthetic human urine was determined.
Last, the strong affinity of silver to thiol groups also warranted a study devoted to their interaction through electrochemical and spectroscopic measurements. It was found that there is no general mechanism for silver-thiol interaction and each thiol must be treated as a separate entity.
Flow boiling near the critical heat flux
Keywords: heat
water
flux
ebullition
transmission
thermography
boiling
flow

An experimental investigation of the flow boiling of water at atmospheric pressure was undertaken, including a high—speed cine photographic study of the flow structure near the Critical Heat Flux (CHF). Experimental tests from single-phase forced convection to burnout were conducted at different flow velocities and inlet subcoolings for water flowing upwards through a vertical channel of rectangular cross—section electrically heated on one wall with a glass window forming the opposite wall. The test surfaces were stainless steel strips of constant dimensions, except that wall thickness ranged from 0.08 mm to 0.20 mm.
Quantitative measurements of the bubble parameters for the same heating surface under the same operating conditions with varying levels of heat flux (70% to 95% of CHF) were carried out. A nucleation site deactivation/reactivation process was observed with increasing heat flux. A proposed site deactivation mechanism explained this behaviour. A nucleate boiling heat transfer model was proposed for the fully— developed nucleate boiling region, with allowance made for the overlapping areas of bubble influence. It compared favourably with the experimental data.
The effect of wall thickness on CHF was investigated: increases in CHF as between the 0.08 mm and the 0.20 mm wall thickness ranging from 38% to 57% were observed. An empirical expression for CHF, including wall thickness as a parameter was developed, correlating the experimental data to within 15% and indicating a limiting value for wall thickness affecting CHF. The flow regimes near burnout were identified as bubbly and slug, these being independent of wall thickness.
Other models proposed for the CHF mechanism were tested against the detailed experimental observations at high subcoolings. They were found to be inconsistent with the experimental evidence. A possible alternative for the CHF mechanism points towards stabilisation/ growth of a vapour patch following bubble coalescence as a most likely cause for burnout.
Evaluating conjunctive and graph queries over the EL profile of OWL 2
Keywords: OWL 2
Query Answering
Description Logics
Ontologies

OWL 2 EL is a popular ontology language that is based on the EL family of description logics and supports regular role inclusions,axioms that can capture compositional properties of roles such as role transitivity and reflexivity. In this thesis, we present several novel complexity results and algorithms for answering expressive queries over OWL 2 EL knowledge bases (KBs) with regular role inclusions.
We first focus on the complexity of conjunctive query (CQ) answering in OWL 2 EL and show that the problem is PSpace-complete in combined complexity, the complexity measured in the total size of the input. All the previously known approaches encode the regular role inclusions using finite automata that can be worst-case exponential in size, and thus are not optimal. In our PSpace procedure, we address this problem by using a novel, succinct encoding of regular role inclusions based on pushdown automata with a bounded stack. Moreover, we strengthen the known PSpace lower complexity bound and show that the problem is PSpace-hard even if we consider only the regular role inclusions as part of the input and the query is acyclic; thus, our algorithm is optimal in knowledge base complexity, the complexity measured in the size of the KB, as well as for acyclic queries.
We then study graph queries for OWL 2 EL and show that answering positive, converse- free conjunctive graph queries is PSpace-complete. Thus, from a theoretical perspective, we can add navigational features to CQs over OWL 2 EL without an increase in complexity.
Finally, we present a practicable algorithm for answering CQs over OWL 2 EL KBs with only transitive and reflexive composite roles. None of the previously known approaches target transitive and reflexive roles specifically, and so they all run in PSpace and do not provide a tight upper complexity bound. In contrast, our algorithm is optimal: it runs in NP in combined complexity and in PTime in KB complexity. We also show that answering CQs is NP-hard in combined complexity if the query is acyclic and the KB contains one transitive role, one reflexive role, or nominals—concepts containing precisely one individual.
The aesthetics of videogame music
Keywords: aesthetics
videogame music
ludomusicology

The videogame now occupies a unique territory in contemporary culture that offers a new perspective on conceptions of high and low art. While the fear that the majority of videogames 'pacify' their audience in an Adornian "culture industry" is not without justification, its reductionism can be countered by a recognition of the diversity and aesthetic potential of the medium. This has been proposed by sociologist, Graeme Kirkpatrick, although without close attention to the role of music. Videogame music often operates in similar ways to music in other mixed-media scenarios, such as film, or opera. In the same way that film music cannot be completely divorced from film, videogame music is contingent on and a crucial part of the videogame aesthetic. However, the interactive nature of the medium—its différance—has naturally led to the development of nonlinear musical systems that tailor music in real time to the game's dynamically changing dramatic action. Musical non-linearity points beyond both music and videogames (and their respective discourses) toward broader issues pertinent to contemporary musicology and critical thinking, not least to matters concerning high modernism (traditionally conceived of as resistant to mass culture). Such issues include Barthes's "death of the author", the significance of order/disorder as a formal spectrum, and postmodern conceptions and experiences of temporality. I argue that in this sense the videogame medium—and its music—warrants attention as a unique but not sui generis aesthetic experience. Precedent can be found for many of the formal ideas employed in such systems in certain aspects of avant-garde art, and especially in the aleatoric music prevalent in the 1950s and 60s. This thesis explores this paradox by considering videogames as both high and low, and, more significantly, I argue that the aesthetics of videogame music draw attention to the centrality of "play" in all cultural objects.
Assessment of anti-merozoite antibody function in the context of blood-stage malaria vaccine development
Keywords: Neutrophil
Antibody
Vaccine
Malaria

In regions endemic for malaria, natural exposure results in an acquired immunity which protects individuals from severe disease. However, no vaccine against the blood-stage of malaria, against which naturally-acquired immunity is targeted, currently exists that is capable of emulating, or out-performing, natural protection. To rationally direct the next generation of blood-stage malaria vaccine development, a greater understanding of the immunological mechanisms involved in clinical protection is required.
To date, the assessment of naturally-acquired and vaccine-induced immunity to the blood-stage of malaria has suffered from a paucity of in vitro immunological assays that are both robust and reproducible, whilst allowing for assessment of anti-parasitic activity induced by antibodies, either alone, or in conjunction with immune cells. Thus this Thesis describes the development of the antibody-dependent respiratory burst (ADRB) assay, for assessment of blood-stage immunity against Plasmodium falciparum, as well as the Duffy antigen receptor for chemokines (DARC) – Duffy binding protein (DBP) binding inhibition assay, for assessing antibody mediated immunity to P. vivax. A reproducible and standardised assay of ADRB activity was developed here and applied to studies of immunity in both mice and humans. ADRB activity, which assesses antibodies' ability to activate oxidative burst in neutrophils via Fc receptor (FcR)-dependent pathways, was shown to associate with clinical protection in a cohort from Mali where FcR-independent immunological assays, such as the assay of growth inhibition activity, did not. This work thus elucidates the importance of FcR-dependent immunity to P. falciparum malaria and establishes the ADRB assay as a useful tool for future vaccine development. In addition, the DARC-DBP binding inhibition assay was established and utilised to assess inhibitory activity of antibodies induced in the first Phase I clinical trial of this antigen. Results identify the need for significant improvements in vaccine design, and show the utility of the assay as a tool for assessing future blood-stage vaccine development efforts against this neglected parasite.
The impact of disjunction on reasoning under existential rules
Keywords: Description Logics
Tuple-Generating Dependencies
Disjunction
Complexity
Existential Rules

Ontological database management systems are a powerful tool that combine traditional database techniques with ontological reasoning methods. In this setting, a classical extensional database is enriched with an ontology, or a set of logical assertions, that describe how new, intensional knowledge can be derived from the extensional data. Conjunctive queries are therefore answered against this combined knowledge base of extensional and intensional data.
Many languages that represent ontologies have been introduced in the literature. In this thesis we will focus on existential rules (also called tuple-generating dependencies or Datalog± rules), and three established languages in this area, namely guarded-based rules, sticky rules and weakly-acyclic rules. The main goal of the thesis is to enrich these languages with non-deterministic constructs (i.e. disjunctions) and investigate the complexity of the answering conjunctive queries under these extended languages. As is common in the literature, we will distinguish between combined complexity, where the database, the ontology and the query are considered as input, and data complexity, where only the database is considered as input. The latter case is relevant in practice, as usually the ontology and the query can be considered as fixed, and are usually much smaller than the database itself.
After giving appropriate definitions to extend the considered languages to disjunctive existential rules, we establish a series of complexity results, completing the complexity picture for each of the above languages, and four different query languages: arbitrary conjunctive queries, bounded (hyper-)treewidth queries, acyclic queries and atomic queries. For the guarded-based languages, we show a strong 2EXPTIME lower bound for general queries that holds even for fixed ontologies, and establishes 2EXPTIME-completeness of the query answering problem in this case. For acyclic queries, the complexity can be reduced to EXPTIME, if the predicate arity is bounded, and the problem even becomes tractable for certain restricted languages, if only atomic queries are used. For ontologies represented by sticky disjunctive rules, we show that the problem becomes undecidable, even in the case of data complexity and atomic queries. Finally, for weakly-acyclic rules, we show that the complexity increases from 2EXPTIME to coN2EXPTIME in general, and from tractable to coNP in case of the data complexity, independent of which query language is used.
After answering the open complexity questions, we investigate applications and relevant consequences of our results for description logics and give two generic complexity statements, respectively, for acyclic and general conjunctive query answering over description logic knowledge bases. These generic results allow for an easy determination of the complexity of this reasoning task, based on the expressivity of the considered description logic.
A fundamental perspective on the effects of sulfur modification for transition metal nanocatalysts
Keywords: Geometric modification
Sulfur poisoning
Catalyst deactivation
Catalytic hydrogenation
Electronic modification
Heterogeneous catalysis

The application of heterogeneous catalysts to industrial processes is a key factor in the synthesis of nearly all chemicals currently produced, however billions of pounds are lost every year due to unplanned reactor shutdowns and catalyst replacement as a result of catalytic deactivation processes. Poisoning of heterogeneous catalysts by sulfur compounds is a particularly prominent class of deactivation processes, affecting a wide range of catalytic materials and catalytic reactions, including the industrially-prominent Haber-Bosch process for the synthesis of ammonia and steam reforming of methane for the synthesis of hydrogen. However, while the effects of sulfur adsorption on catalytic behaviour are often unmistakably apparent, the fundamental interactions leading to these effects are not yet well understood.
The work presented in this thesis uses a combination of models systems, novel and traditional characterization techniques, and methods of modifying catalyst geometric and electronic structure to approach the topic of sulfur poisoning from a fundamental perspective. Particular focus is placed on using selective decoration of active sites to develop a system of model hydrogenation reactions to relate changes in catalytic behaviour to changes in geometric and electronic structure. Application of these model reactions to investigate the sensitivities of palladium- and ruthenium-based catalytic systems to modification by sulfur shows contrasting effects for the two metals. While both systems exhibit similar geometric effects of modification, the palladium-based catalysts are far more sensitive than the ruthenium-based catalysts to modification of electronic structure. Additionally, controlled variation in particle size for the palladium-based catalysts demonstrates that catalytic behaviour is dominated by electronic structure for small nanoparticles and geometric structure for large nanoparticles. This leads small nanoparticles to show increased sensitivity to electronic modification effects resulting from sulfur adsorption.
Ultimately, the research presented within this thesis provides a basis for the intelligent design of heterogeneous catalysts for improving tolerance for sulfur poisoning, and for utilizing the effects of sulfur modification to optimize catalytic activity and selectivity for the synthesis of fine chemicals.
Verification of message passing concurrent systems
Keywords: Concurrency

This dissertation is concerned with the development of fully-automatic methods of verification, for message-passing based concurrent systems.
In the first part of the thesis we focus on Erlang, a dynamically typed, higher-order functional language with pattern-matching algebraic data types extended with asynchronous message-passing. We define a sound parametric control-flow analysis for Erlang, which we use to bootstrap the construction of an abstract model that we call Actor Communicating System (ACS). ACS are given semantics by means of Vector Addition Systems (VAS), which have rich decidable properties. We exploit VAS model checking algorithms to prove properties of Erlang programs such as unreachability of error states, mutual exclusion, or bounds on mailboxes. To assess the approach empirically, we constructed Soter, a prototype implementation of the verification method, thereby obtaining the first fully-automatic, infinite-state model checker for a core concurrent fragment of Erlang.
The second part of the thesis addresses one of the major sources of imprecision in the ACS abstraction: process identities. To study the problem of algorithmically verifying models where process identities are accurately represented we turn to the π-calculus, a process algebra based around the notion of name and mobility. The full π-calculus is Turing-powerful so we focus on the depth-bounded fragment introduced by Roland Meyer, which enjoys decidability of some verification problems. The main obstacle in using depth-bounded terms as a target abstract model, is that depth-boundedness of arbitrary π-terms is undecidable. We therefore consider the problem of identifying a fragment of depth-bounded π-calculus for which membership is decidable. We define the first such fragment by means of a novel type system for the π-calculus. Typable terms are ensured to be depth-bounded. Both type-checking and type inference are shown to be decidable. The constructions are based on the novel notion of Τ-compatibility, which imposes a hierarchy between names. The type system's main goal is proving that this hierarchy is preserved under reduction, even in the presence of unbounded name creation and mobility.