VictorJuiz/thesis huggingface dataset:
Evolution and function of long noncoding RNAs in Drosophila
Keywords: Drosophila
evolution
long intergenic noncoding RNAs

Not all transcribed DNA encodes protein, and some of these noncoding RNAs (ncRNAs), such as roX1 and roX2, may play important roles in the cell. The functional roles of the majority of these, however, remain largely unknown. In this thesis, I first used EST and mRNA evidence to define 2,788 lincRNA loci within the Drosophila melanogaster genome. I suggest that up to 1,652 of these are functional, as 1,411 show evidence for significant evolutionary constraint while 241 fast-evolving loci are enriched in short RNA species. A distinct set of 1,119 lincRNA loci were defined by RNA-seq, the vast majority of which show clear primary sequence constraint. Their expression profiles and enrichment in particular chromatin domains indicate that these lincRNAs are likely involved in developmental regulation. I also identified 42 potential analogous lincRNAs with shared genomic locations between Drosophila and mouse. Constrained, non-embryonic lincRNAs defined by ESTs are transcribed preferentially in the vicinity of protein-coding genes encoding transcription factors and I demonstrated that one of these, which I name dEvf-2, positively regulates the expression of its genomically adjacent transcription factor, Dll, in cell culture. Finally, I used a reverse genetics approach to search for lincRNA promoter mutations and examined the effect of these on lincRNA expression. My findings suggest that many, previously unknown, functional lincRNAs exist within the Drosophila genome and are worthy of further in-depth experimental investigation.
Political economy of local and participatory governance
Keywords: auctions
local government
participation

Chapter 2 compares government consultation via an opinion poll and a citizens' jury". In a jury, about fiffteen volunteers spend several days learning about a policy choice before voting. If the public is ill-informed, the government trades-off "information" against participation". Jurors have better information than poll respondents, but constitute a smaller sample. More- over, participation costs may bias the jury sample. Indeed, the literature suggests that costs might induce "neutrality": over-representation of the minority to the extent that the result is uninformative. I show that although the minority will often be over-represented, "neutrality" is a knife-edge result here so juries may be worthwhile. Extensions consider compensating jurors and excluding "special interests".
Chapter 3 uses evidence from the allocation of regeneration funding to motivate a model in which central government may ask councils to compile apparently pointless dossiers to ap- ply for money, because the dossiers provide information about councils' competence. I then consider when the government might prefer a simpler but less flexible auction-type process.
The UK government's ability to "ring-fence" money, obliging councils to spend it on its priority, is central to chapter 3. Chapter 4 develops the analysis of auctions in this context. With variations in competence, ring-fencing effectively imposes type-specific minimum bids. I characterise equilibrium bidding and show that the ring-fencing constraint may not only increase bids, but actually induce councils to contribute resources.
Continuing the themes of participation and competence in the policy process, chapter 5 examines parish councils' use of a general spending power. I find parishes with more well-educated and older citizens (groups with generally higher political participation) are more likely to use their powers. Further investigation suggests that these citizens matter because they are involved in governance, rather than because they exert democratic pressure. This has impli- cations for wider neighbourhood governance policy.
Molecular modelling of beta-barrel outer membrane proteins
Keywords: computer simulations

In Gram-negative bacteria, the Outer membrane (OM) acts as a first barrier to screen unwanted compounds whilst enabling ions and very small solutes to diffuse into the cell. Most of nutrients and essential ions are effectively transported across a membrane via the outer membrane proteins (OMPs). The water-filled β- barrel OMPs are called porins. These pores are classified into two groups, non- specific and substrate-specific porins. Each of them has different mechanisms to facilitate its substrate translocation. To reveal the process of substrate permeation and selectivity in microscopic detail, molecular dynamics (MD) simulations and applications were performed in this thesis.
The studies in this thesis focus on a series of classical porins. These proteins share similar feature where extracellular loop(s) (generally loop 3 (L3)) is folded into the middle of the pore and act as a constriction site which is important for substrate specificity and selectivity. The studies firstly concentrate on the structural properties and dynamics of the general trimeric porins, OmpC and OmpF whose sequences share 60% identity. OmpC and OmpF are found to have similar mechanism of latching loop (L2) to maintain trimeric stability. The smaller pore size allows OmpC to be more cation-selective than OmpF. Additionally, the major driving force for cation permeation in both porins is not from electrostatic properties. This differs from the phosphate-selective porin, trimeric OprP, where a phosphate diffusion depends on electrostatic interactions with positively charged pore-lining residues. The charge brush-like behavior of interior Arg and Lys residues plays a major role in phosphate selectivity. Also, the free energy profiles (PMF) reveal two key regions that are important for differentiating phosphate from other anions. The brush-like mechanism of OprP were also implanted to the simplified model pores in order to determine the possibility of transferring phosphate-selective properties of OprP to a model which may be useful for future design of nanopores. It is found that the duplication of functional residues and pore cavity can turn a model into the highly phosphate-selective pore. Importantly, the phosphate-binding affinity is dependent on the ability of the pore to interfere and occupy the hydration shell of a translocating phosphate where such ability can be maximized by an increase in sidechain flexibility. In case of uptake of more complex substrates, OpdK also employs a constriction site to select its substrate, aromatic vanillate (VNL) with total charge of -1. Unlike ion-specific porins, the free VNL is attracted by polar and aromatic interactions and sequentially directed through the periplasmic vestibule by charged residues insides the pore. The correct orientation of VNL on arrival is crucial for OpdK to recognize and enable the permeation process.
A functional and structural study of HLA-­B*2705 restricted CTL responses associated with delayed HIV-­1 disease progression
Keywords: B*27
long-term non-progressor
KK10
HLA

The HIV-1 Gag p24 protein contains the HLA class-1 B*2705 restricted epitope KK10, responses to which are associated with delayed progression. Data from in vitro proteasomal digestion studies from our group has shown the production of a number of C-terminally extended and truncated epitopes containing KK10, produced in far higher quantities during proteasomal digestion than this “optimal epitope” and that the amount of antigen made in proteasomal digestion is instrumental in determining the development of immunodominance. This work aims to characterise the contribution of these naturally processed epitope forms to the cellular immune response to this region.
Further proteasomal digestion studies have shown that the common KK10 intra-epitope escape mutant sequences R132K and L136M have major effects on epitope production by the proteasome and that a range of short peptides containing the N-terminal of the KK10 sequence are produced in large quantities by the proteasome. Recognition of the KK10 epitope forms by HLA B*2705 HIV-1 patients were characterised ex vivo and show recognition of KK10 epitope forms somewhat independent of the presence of KK10 recognition, we also show cross-recognition between KK10 epitope forms by CD8+ T cells, as well as recognition by CD4+ T-cells. TCR from CD8+ T-cells specific for KK10 epitope forms were found to share common features in the HLA binding CDR hyper-variable loops.
Structural studies of the HLA B*2705 molecules in complex with the KK10 epitope forms show a shared binding motif at the N-terminus, and to a lesser extent, the C-terminus of the binding groove which may facilitate cross-recognition of complexes. In addition these studies show a potentially novel binding mode for a 14mer peptide, and refolding of truncated KK10 peptides as short as a 4mer with the HLA B*2705 molecule (crystallisation with a 6mer peptide shown). This demonstrates previously unrecognised flexibility of the HLA class-1 to bind and present peptides of different lengths to T-cells.
We show that these HLA B*2705 binding-capable truncated peptides do not induce a CD8+ T-cell response in HLA B*2705 HIV-1 patients and may be able to block CD8+ T-cell responses to the KK10 epitope. This might represent a novel form of viral CTL escape. In addition we observe the presence of KK10 flanking mutations in patient sequences and significant associations between the presence of intra-epitope escape mutations, KK10 recognition and patterns of escape in flanking sequences.
Finally we note the reduction in binding of KIR3DL1 to KK10 epitope forms relative to the KK10 epitope-HLA B*2705 complex. The presence of HLA B*2705 and KIR3DL1 associate with improved disease course in HIV-1 though the mechanism through which this occurs has yet to be defined.
Investigation of the potential of PorA and FetA as meningococcal vaccine components
Keywords: vaccine
Neisseria meningitidis
meningococcus

In the search for a vaccine providing comprehensive protection against meningococcal disease, one vaccine currently under development contains the immunogenic proteins PorA and FetA in meningococcal outer membrane vesicles (OMVs). To achieve high levels of coverage against disease-causing isolates, the antigenic variability of these proteins could be overcome using knowledge of meningococcal epidemiology and population structure. In this study, the possible implications of variable expression levels of PorA and FetA on vaccine efficacy were investigated. Producing OMVs containing consistent amounts of FetA is difficult due to iron-repressed expression; therefore, meningococcal strains were constructed which constitutively expressed FetA at increased levels for OMV vaccine production and analysis. In mice, OMVs from modified strains induced antibodies against both PorA and FetA. These antibodies acted synergistically in a serum bactericidal assay; however, antibodies against FetA were weakly bactericidal alone. The potential to increase levels of PorA- and FetA-specific bactericidal antibodies with a prime-boost strategy, using OMV and protein inoculums, was also tested. While successful for a weakly-immunogenic PorA variant, a similar strategy did not increase bactericidal activity against FetA. Although antibodies against FetA can be induced following OMV immunisation, sufficient antigen expression in target bacteria is also required for bactericidal killing; therefore, the variability and regulation of porA and fetA transcription was investigated in a range of isolates. Despite differences in regulation among clonal complexes, variable expression is unlikely to be an issue for vaccine coverage. In particular, regulation of fetA by iron is reduced in many isolates due to a deletion in the sequence bound by the regulatory protein, Fur. Therefore, a vaccine targeting PorA and FetA may provide high levels of protection against meningococcal disease; however, an alternative formulation or immunisation strategy is required to improve coverage against FetA.
Differential games of exhaustible resource extraction
Keywords: Stackelberg
dynamic game
Cournot
Hotelling
resource extraction

This thesis is concerned with game-theoretic models of oligopoly resource markets. They revolve around an open market, on which a number of firms sell a common resource. The market price-demand relationship means that the price (demand) that results from the firm’s production (pricing) decisions is a function of the decisions of all firms selling to that market. This means that firms must generally anticipate the actions of competing firms when determining their own strategies, which means that these models often need to be analysed using game theory.
We focus on games in which the resource is exhaustible, with the exception of Chapter 5, in which the majority of the analysis is carried out in an inexhaustible resources setting. Exhaustibility introduces an additional complication into these games; that of allocating the extraction and sale of a limited resource pool over time. We consider several separate areas of extension, which we outline below.
In Chapter 2, we consider a dynamic Stackelberg game. Stackelberg competition is an asymmetric form of competition in which one player (the leader) has the ability to pre-commit to and announce a strategy in advance. The ability to pre-commit to a strategy is almost always highly valuable, and in this case allows the leader to drive down the follower’s production by pre-committing to drive up their own. We follow the framework used in [62] to analyse Cournot competition to derive our results.
In Chapter 3, we compare the two settings in which resource extraction models are usually formulated: Open-Loop, in which the players determine their strategies as functions of time and the initial resource levels of the players only; and Feedback-Loop, in which the players determine their strategies at each point in time as a function of the current resource levels at that time. Our focus is on the investigation of the relationship between the difference in the production or value of a firm under these two models, and the distribution of resources across the firms.
In Chapter 4, we consider a common property resource game. These involve multiple firms which can extract from a common resource pool. We study a widely-used Open- viii Loop model, as formulated in [79]. We examine the result that analysis of the problem by standard methods results in two candidate equilibria, and argue that one of these equilibria can be ruled out by construction of a superior response.
In Chapter 5, we analyse joint constraints on production, namely constraints which are met when the total production is above or below a certain level. It is a well- established result that these constraints can result in multiple equilibria. We provide several brief extensions to existing uniqueness results. We also demonstrate methods by which these results can be utilised to analyse games with piecewise-linear windfall taxes or congestion charges. Finally, we discuss the problems of extending these results to games with resource exhaustibility.
Partly exchangeable fragmentations
Keywords: exchangeability
continuum random tree
Markov branching model
Poisson-Dirichlet distribution
alpha-gamma tree
self-similar fragmentation
R-tree
dislocation measure
splitting rule
sampling consistency
part exchangeability

We introduce a simple tree growth process that gives rise to a new two-parameter family of discrete fragmentation trees that extends Ford's alpha model to multifurcating trees and includes the trees obtained by uniform sampling from Duquesne and Le Gall's stable continuum random tree. We call these new trees the alpha-gamma trees. In this thesis, we obtain their splitting rules, dislocation measures both in ranked order and in sized-biased order, and we study their limiting behaviour. We further extend the underlying exchangeable fragmentation processes of such trees into partly exchangeable fragmentation processes by weakening the exchangeability. We obtain the integral representations for the measures associated with partly exchangeable fragmentation processes and subordinator of the tagged fragments. We also embed the trees associated with such processes into continuum random trees and study their limiting behaviour. In the end, we generate a three-parameter family of partly exchangeable trees which contains the family of the alpha-gamma trees and another important two-parameter family based on Poisson-Dirichlet distributions.
Dams of Damocles
Keywords: Syr Darya
dams
Nile
geopolitics
transboundary water politics

Theories of transboundary water politics have failed to explain the status quo in many river basins: fragile political relations between riparian states and nationalist domestic politics, as well as weak regional institutions and huge economic inefficiencies – but also an absence of wars over water. This is due to an uncritical approach to scale, power, and geopolitics. It is the purpose of this thesis to address these conceptual gaps by critically evaluating the multiple relationships between the logic of large dams and the politics of international rivers.
The meaning of dams, the politics of their operation and construction, and their impact on international relations are much more ambiguous, opaque and complex than existing explanations have suggested so far. In turn, their logic influences, competes with, and contradicts the logic of river basin governance. Dams produce alternative spaces of development, energy, and state power that complement or are superimposed on existing spaces of riparian cooperation. This thesis argues that the contradictions between these spaces explains the geopolitical limbo of many international rivers in the developing world.
Drawing from Foucault’s governmentality theory, the literature of critical geopolitics, and post-structural approaches to spatial scale the case-oriented research design of this thesis evaluates two geopolitical processes in contentious transboundary river basins: the construction of the Grand Ethiopian Renaissance Dam on the Nile and the operation of the Toktogul Dam in the Kyrgyz stretch of the Syr Darya River.
By unpacking these processes, this thesis makes three substantial contributions to existing scholarship. Firstly, it is argued that regional river basin management is essentially a geopolitical project that contradicts the geo-economic imperatives of the dam. Secondly, power and agency in water politics is diffused far beyond the nation-state and can be understood in terms of “network effects”. Thirdly, to marry the concerns of the geopolitical and the geo-economic, I propose that the contrasting logics give rise to “geopolitical entrepreneurs” – actors who use geopolitics for wealth accumulation, legitimacy, nation-building, and other ends. While dams may provide power, wealth, and authority an allegorical Sword of Damocles is let down on the riparians.
Efficient algorithms for compressed sensing and matrix completion
Keywords: hard thresholding
matrix completion
compressed sensing
low per iteration complexity
numerical algorithms
alternating minimization

Compressed sensing and matrix completion are two new data acquisition techniques whose efficiency is achieved by exploring low dimensional structures in high dimensional data. Despite the combinatorial nature of compressed sensing and matrix completion, there has been significant development of computationally efficient algorithms which can produce accurate desired solutions to these problems. In this thesis, we are concerned with the development of low per iteration computational complexity algorithms for compressed sensing and matrix completion.
First, we derive a locally optimal stepsize selection rule for the simplest iterative hard thresholding algorithm for matrix completion, and obtain a simple yet efficient algorithm. It is observed to have average case performance superior in some aspects to other matrix completion algorithms.
To balance the fast convergence rates of more sophisticated recovery algorithms with the low per iteration computational cost of simple line-search algorithms, we introduce a family of conjugate gradient iterative hard thresholding algorithms for both compressed sensing and matrix completion. The theoretical results establish recovery guarantees for the restarted and projected variants of the algorithms, while the empirical performance comparisons establish significant computational advantages of the proposed methods over other hard thresholding algorithms.
Finally, we introduce an alternating steepest descent method and a scaled variant especially designed for the matrix completion problem based on a simple factorization model of the low rank matrix. The computational efficacy of this method is achieved by reducing the high per iteration computational cost of the second order method and fully exploring the numerical linear algebra structure in the algorithm. Empirical evaluations establish the effectiveness of the proposed algorithms, compared with other state-of-the-art algorithms.
Through the eyes of justice: a comparative study of liberationist and women's readings of the Qur'an
Keywords: political Islam
Islam
liberation theology
religion
theology
radical Islam
feminism
Qur'an

The shari‘a, or the inherited legal tradition, has tended to dominate discussions of contemporary Islam. Relatively little attention has been given to the Qur’an, however, despite its importance both in terms of Muslim theology, in which it is understood as the actual Word of God, and of Islamic reformist thought. Far from being marginal, the Qur’an has emerged as a rich resource for theological reflection and sociopolitical action. Specifically, it has become a source of empowerment, speaking to contexts of oppression. This thesis examines the commentaries of four Muslim intellectuals who have expounded the Qur’an as a liberating text – namely, the South African Farid Esack (b. 1956), the Indian Asghar Ali Engineer (b. 1939), the American Amina Wadud (b. 1952) and the Pakistani Asma Barlas (b. 1950) – supplemented by in-depth interviews. In so doing, this study seeks (i) to fill a major gap in the literature by offering the first comprehensive survey and analysis of their readings and (ii) to challenge common portrayals of justice-based exegesis as being an obscure, fundamentalist scripturalism; as being rooted in North America; and as being focussed primarily, even exclusively, on gendered oppression. Indeed, the centring of the Qur’an in Islamic thought, I argue, is an increasingly mainstream practice – a global hermeneutic – as Muslims throughout the world seek answers in scripture to the pressing problems of the present. Furthermore, justice-based exegesis has been holistic, addressing (in addition to patriarchy) poverty and racism, communal violence and imperialism. Liberationist and women’s readings are significant, I conclude, for two reasons. Firstly, they shed new insights into the rise of ‘thematic commentary’ (tafsir mawdu‘i) in Qur’anic exegesis. Secondly, their expressly political character exposes the hegemony of Islamism over our understanding of ‘the political’ and ‘the radical’ in an Islamic context, thereby forcing us to redefine political and radical Islam.