VictorJuiz/thesis huggingface dataset:
Computational studies of ligand-water mediated interactions in ionotropic glutamate receptors
Keywords: computational
drug-design
Density Functional Theory
Ionotropic glutamate receptor
ligand binding
ab initio
X-ray crystallography
conserved waters

Careful treatment of water molecules in ligand-protein interactions is required in many cases if the correct binding pose is to be identified for molecular docking. Water can form complex bridging networks and can play a critical role in dictating the binding mode of ligands. A particularly striking example of this can be found in the ionotropic glutamate receptors (iGluRs), a family of ligand gated ion channels that are responsible for a majority of the fast synaptic neurotransmission in the central nervous system that are thought to be essential in memory and learning. Thus, pharmacological intervention at these neuronal receptors is a valuable therapeutic strategy. This thesis relies on various computational studies and X-ray crystallography to investigate the role of ligand-water mediated interactions in iGluRs bound to glutamate and α-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA).
Comparative molecular dynamics (MD) simulations of each subtype of iGluRs bound to glutamate revealed that crystal water positions were reproduced and that all but one water molecule, W5, in the binding site can be rearranged or replaced with water molecules from the bulk. Further density functional theory calculations (DFT) have been used to confirm the MD results and characterize the energetics of W5 and another water molecule implicated in influencing the dynamics of a proposed switch in these receptors. Additional comparative studies on the AMPA subtypes of iGluRs show that each step of the calculation must be considered carefully if the results are to be meaningful.
Crystal structures of two ligands, glutamate and AMPA revealed two distinct modes of binding when bound to an AMPA subtype of iGluRs, GluA2. The difference is related to the position of water molecules within the binding pocket. DFT calculations investigated the interaction energies and polarisation effects resulting in a prediction of the correct binding mode for glutamate. For AMPA alternative modes of binding have similar interaction energies as a result of a higher internal energy than glutamate.
A combined MD and X-ray crystallographic study investigated the binding of the ligand AMPA in the AMPA receptor subtypes. Analysis of the binding pocket show that AMPA is not preserved in the crystal bound mode and can instead adopt an alternative mode of binding. This involves a displacement of a key water molecule followed by AMPA adopting the pose seen by glutamate.
Thus, this thesis makes use of various studies to assess the energetics and dynamics of water molecules in iGluRs. The resulting data provides additional information on the importance of water molecules in mediating ligand interactions as well as identifying key water molecules that can be useful in the de novo design of new selective drugs against iGluRs.
Southeast Asia in the ancient Indian Ocean world: 
Keywords: historical linguistics
Southeast Asia
archaeology
cultural contact
India

This thesis casts a new light on the role of Southeast Asia in the ancient Indian Ocean World. It brings together data and approaches from archaeology and historical linguistics to examine cultural and language contact between Southeast Asia and South Asia, East Africa and the Middle East. The interdisciplinary approach employed in this study reveals that insular Southeast Asian seafarers, traders and settlers had impacted on these parts of the world in pre-modern times through the transmission of numerous biological and cultural items. It is further demonstrated that the words used for these commodities often contain clues about the precise ethno-linguistic communities involved in their transoceanic dispersal.
The Methodology chapter introduces some common linguistic strategies to examine language contact and lexical borrowing, to determine the directionality of loanwords and to circumvent the main caveats of such an approach. The study then proceeds to delve deeper into the socio-cultural background of interethnic contact in the Bay of Bengal and the Indian Ocean as a whole, focusing on the oft-neglected Southeast Asian contributions to the cultural landscape of this region and addressing the nature of pre-modern contact between Southeast Asia and the different parts of the Indian Ocean Word. Following from that, the last three chapters look in-depth at the dispersal of respectively Southeast Asian plants, spices and maritime technology into the wider Indian Ocean World. Although concepts and their names do not always neatly travel together across ethno-linguistic boundaries, these chapters demonstrate how a closer examination of lexical data offers supportive evidence and new perspectives on events of cultural contact not otherwise documented.
Cumulatively, this study underlines that the analysis of lexical data is a strong tool to examine interethnic contact, particularly in pre-literate societies. Throughout the Indian Ocean World, Southeast Asian products and concepts were mainly dispersed by Malay-speaking communities, although others played a role as well.
Numerical linear approximation involving radial basis functions
Keywords: numerical linear algebra
radial basis functions

This thesis aims to acquire, deepen and promote understanding of computing techniques for high dimensional scattered data approximation with radial basis functions. The main contributions of this thesis include sufficient conditions for the sovability of compactly supported radial basis functions with different shapes, near points preconditioning techniques for high dimensional interpolation systems with compactly supported radial basis functions, a heterogeneous hierarchical radial basis function interpolation scheme, which allows compactly supported radial basis functions of different shapes at the same level, an O(N) algorithm for constructing hierarchical scattered data set andan O(N) algorithm for sparse kernel summation on Cartesian grids. Besides the main contributions, we also investigate the eigenvalue distribution of interpolation matrices related to radial basis functions, and propose a concept of smoothness matching. We look at the problem from different perspectives, giving a systematic and concise description of other relevant theoretical results and numerical techniques. These results are interesting in themselves and become more interesting when placed in the context of the bigger picture. Finally, we solve several real-world problems. Presented applications include 3D implicit surface reconstruction, terrain modelling, high dimensional meteorological data approximation on the earth and scattered spatial environmental data approximation.
Placed deposits in early and middle Anglo-Saxon rural settlements
Keywords: Anglo-Saxons
offerings
votive deposits
archaeology
ritual
rural settlement
placed deposits
lifecycle
social life
liminality
rites
early medieval
boundaries
structured deposits
England

Placed deposits have received increasing attention over the past 30 years, particularly in prehistoric British archaeology. Although disagreement still exists over the definition, identification, and interpretation of placed deposits, significant advances have been made in theoretical and methodological approaches to placed deposits, as researchers have gradually moved away from relatively crude ‘ritual’ interpretations toward more nuanced considerations of how placed deposits may have related to daily lives, social networks, and settlement structure, as well as worldview. With the exception of comments on specific deposits and a recent preliminary survey, however, Anglo-Saxon placed deposits have remained largely unstudied.
This thesis represents the first systematic attempt to identify, characterize, analyse and interpret placed deposits in early to middle Anglo-Saxon settlements (5th–9th centuries). It begins by disentangling the various definitions of ‘placed’, ‘structured’, and ‘special’ deposits and their associated assumptions. Using formation process theory as a basis, it develops a definition of placed deposits as material that has been specially selected, treated, and/or arranged, in contrast with material from similar or surrounding contexts. This definition was applied to develop contextually specific criteria for identifying placed deposits in Anglo-Saxon settlements.
Examination of 141 settlements identified a total of 151 placed deposits from 67 settlements. These placed deposits were characterized and analysed for patterns in terms of material composition, context type, location within the settlement, and timing of deposition relative to the use-life of their contexts. Broader geographical and chronological trends have also been considered. In discussing these patterns, anthropological theories of action, agency, practice, and ritualization have been employed in order to begin to understand the roles placed deposits may have had in structuring space and time and expressing social identities in Anglo-Saxon settlements, and to consider how placed deposition may have articulated with Anglo-Saxon worldview and belief systems.
Two-photon dyes for biological application
Keywords: Photodynamic therapy
Photochemistry
Peptide synthesis
Non-linear optics
Organic synthesis

Two photon absorption (TPA) is the near simultaneous absorption of two photons of light to achieve an electronically excited state. It has led to huge advances in microscopy and microfabrication due to its quadratic dependence on the local light intensity. This thesis describes the design, synthesis and application of dyes with strong TPA properties, and as such is divided into three chapters. The first introduces the theory and measurement of TPA as well as structure-property relationships known to maximise the efficiency of TPA. The subsequent chapters present explorations of the application of these dyes in biological applications; namely two-photon uncaging and two-photon photodynamic therapy. A recurring theme in my research is the discussion and evaluation of strategies for improving the compatibility of organic macromolecules with biological systems.
Uncaging is the use of photolysis to achieve a rapid increase in the local concentration of a physiologically active species via a photoremovable protecting groups. Photoremovable protecting groups are covalently attached to the physiologically active species, thus rendering it inactive. At the desired time and location, a light dose releases the molecule in its active form. There are many compounds known to uncage following photoexcitation, but there are few examples of caging groups which exhibit both strong two-photon absorption properties and highly efficient uncaging. Chapter 2 discusses the rational design of such groups through the development of a new mechanism for uncaging, in which a photoinduced electron transfer (PeT) between a two-photon-excited electron donor and an electron acceptor/release group drives the uncaging event.
Photodynamic therapy (PDT) is a treatment for neoplastic disorders such as cancer in which localised cell death is induced through photoexcitation of a sensitiser. Following light absorption, the photosensitiser enters a relatively long-lived excited state which reacts with cellular oxygen to produce its highly cytotoxic singlet form. The main challenges of the field are to achieve deep penetration of light into tissue and to reduce coincident damage to unaffected tissue by light scattering during irradiation. In 2008, the Anderson group reported the development of PDT photosensitisers with highly efficient two-photon absorption as well as high singlet oxygen quantum yields. Chapter 3 discusses strategies for improving the pharmacokinetics and defining the sub-cellular localisation of these photosensitisers.
The long-term impact of the Italian colonial expenditures in the Horn of Africa
Keywords: Economic history
History of the Italian colonization
Development
History of Africa

A growing body of literature analyses the relationship between colonialism and long-term development, but largely overlooks the effect of colonial public investments on transportation infrastructure, schooling and sanitary facilities. In my research, I exploit the case study of Italian colonial investments in the Horn of Africa between 1934 and 1941, to unveil the relationship between such investments and present-day inequalities in terms of level of development and living standards and to explore the mechanisms that explain the persistence of colonial investments over time.
I create three geo-referenced (a grid dataset and two individual) datasets by matching historical data on colonial investments, collected from both archival and printed primary sources, with micro-level open-source contemporary data for development and modern surveys for living standards to perform OLS and probit regression analysis. Firstly, I regress proxies for level of development, such as population density and light density at night, on dummies for being within 20km from colonial roads. Secondly, I regress measures of living standards, such as female literacy, BMI and children holding a sanitary card, on binary variables for living less than 10km away from a colonial schools and hospitals. Several robustness checks are performed to address the possible endogenous placement of colonial facilities including IV estimation, placebo treatment and nearest neighbour score matching.
The data show a strong, positive and statistically significant relationship between proximity to colonial roads and economic development, on the one hand, and proximity to schooling, sanitary facilities and living standards, on the other. This demonstrates that areas endowed with more generous investments from the colonial period perform better in terms of economic development and living standards at present. The analysis also points out that the effect persisted mainly through phenomena of path-dependency and re-location.
Functions of conserved centriole proteins in African trypanosomes
Keywords: SAS-6
basal body
Trypanosoma brucei
centriole
SAS-4

Centriole and basal bodies are related nine-fold symmetric microtubule-based eukaryotic organelles central to the organisation of cilia/flagella and centrosomes. Mechanisms of eukaryotic centriole and basal body assembly are mainly based on studies in animal systems.
To understand which centriolar proteins are the universally important ones in the assembly across eukaryotes, a bioinformatic survey presented here investigates the distribution of centriolar and cilia-associated proteins across a diverse range of eukaryotes. This analysis showed also that the basal body function is ancestral to eukaryotes, whereas centrosomal components are specific to Holozoa (which include animals). It also suggested that the ancestor of all eukaryotes possessed a cilium/cilia not only with motility function but also with a sensory role. The most frequently conserved proteins in extant ciliated eukaryotes found in this analysis included SAS-6, SAS-4 and WDR16. To test whether these proteins are also important for basal body assembly in distantly-related species to metazoan and other model organisms where the proteins have been studied to date, the proteins were investigated in Trypanosoma brucei. I used a combination of genetic tools and microscopy techniques to demonstrate that SAS-6 but not SAS-4 is essential for basal body assembly in T. brucei. I showed that WDR16 is a stably integrated component of the transition zone and axoneme but not the basal body. Furthermore, I identified a novel SAS-6 like protein which localises to a position consistent with the basal plate and has the capacity to form into filaments.
This thesis provides new insights into the evolution of centrioles and basal bodies, and into the function of conserved centriole proteins in T. brucei, a distantly-related organism to animals.
Symmetries of free and right-angled Artin groups
Keywords: partially-commutative groups
Right-angled Artin groups
graph groups
automorphism groups of free groups

The objects of study in this thesis are automorphism groups of free and right-angled Artin groups. Right-angled Artin groups are defined by a presentation where the only relations are commutators of the generating elements. When there are no relations the right-angled-Artin group is a free group and if we take all possible relations we have a free abelian group.
We show that if no finite index subgroup of a group G
contains a normal subgroup that maps onto mathbbZ
, then every homomorphism from G
to the outer automorphism group of a free group has finite image. The above criterion is satisfied by SLm(mathbbZ)
for mgeq3
and, more generally, all irreducible lattices in higher-rank, semisimple Lie groups with finite centre.
Given a right-angled Artin group AGamma
we find an integer n
, which may be easily read off from the presentation of AG
, such that if mgeq3
then SLm(mathbbZ)
is a subgroup of the outer automorphism group of AGamma
if and only if mleqn
. More generally, we find criteria to prevent a group from having a homomorphism to the outer automorphism group of AGamma
with infinite image, and apply this to a large number of irreducible lattices as above.
We study the subgroup IA(AGamma)
of Aut(AGamma)
that acts trivially on the abelianisation of AGamma
. We show that IA(AGamma)
is residually torsion-free nilpotent and describe its abelianisation. This is complemented by a survey of previous results concerning the lower central series of AGamma
.
One of the commonly used generating sets of Aut(Fn)
is the set of Whitehead automorphisms. We describe a geometric method for decomposing an element of Aut(Fn)
as a product of Whitehead automorphisms via Stallings' folds. We finish with a brief discussion of the action of Out(Fn)
on Culler and Vogtmann's Outer Space. In particular we describe translation lengths of elements with regards to the `non-symmetric Lipschitz metric' on Outer Space.
Global cloud properties on Venus from orbital infrared spectroscopy
Keywords: VIRTIS
clouds
Venus
spectroscopy
Venus Express

This thesis describes the derivation of Venusian global cloud properties from infrared remote sensing data obtained by the Visible and Infrared Thermal Imaging Spectrometer (VIRTIS) on the European Space Agency Venus Express satellite. A computationally-efficient retrieval method is designed to exploit the dataset, which provides coverage of the entire nightside southern hemisphere of Venus. Spatially-resolved near-infrared spectra have been used to derive improved models of the vertical structure and global distribution of cloud properties in the southern hemisphere. Wavelengths within transparency windows in the 1.0 - 2.6 micron range covered by VIRTIS are sensitive on the nightside to absorption by the lower and middle sulphuric acid cloud layers, which are back-lit by thermally-emitted radiation from the hot lower atmosphere (Taylor et al. 1997).
The cloud model used to interpret the spectra builds on work by Crisp (1986), Pollack et al. (1993) and Grinspoon et al. (1993). Retrieved parameters are the acid concentration in the cloud droplets, the average size of the particles in the lower cloud and the altitude of the cloud base in the model. Values are estimated initially using wavelength pairs selected for their unique sensitivity to each parameter, and then validated using model spectra generated using the NEMESIS radiative transfer and retrieval code (Irwin et al. 2008) as developed for Venus (Tsang et al. 2008a).
The spatial variation of sulphuric acid concentration in the cloud particles is estimated ; the concentration is found to be higher in regions of optically thick cloud. The retrieved cloud base altitude varies with latitude, reaching a maximum height near -50 degreees before falling by several km towards the pole. An increase in average particle size near the pole (Wilson et al. 2008) and the finding of latitudinally-variable CO abundance at 35 - 40 km altitude (Tsang et al. 2008) are both confirmed. A decrease in tropospheric H₂O abundance at high latitudes is observed, and provides evidence for strong downwelling between +/-60 and +/-75 degrees latitude, which marks the poleward extent of the Hadley cell circulation. Long-term secular change is also observed over a period of two Earth years. The measurements presented here provide a reference dataset for microphysical and dynamical modelling of the cloud deck, and the role of the cloud as a dynamical and chemical tracer means that such observations are of considerable value for increased understanding of the Venusian atmosphere.
Studying the altered reactivity of electrochemical systems in room temperature ionic liquids
Keywords: electrosynthesis
kinetics
simulation
electrochemistry
cyclic voltammetry
mechanistics
reactivity
thermodynamics
microelectrodes
chronoamperometry
room temperature ionic liquids

The work presented in this thesis examines the electrochemical behaviour of a number of species, both surface-bound and in the solution phase, in various room-temperature ionic liquids (RTILs), in order to identify systems which show altered reactivities in room-temperature ionic liquids, compared to that in conventional, molecular, aprotic solvents. The fundamentals of electrochemistry are outlined and an introduction to room-temperature ionic liquids is given, after which the results of six original investigations are presented, as follows;
The electrochemical response of surface-bound anthraquinonyl films was investigated as a function of RTIL cation size.
The reduction of oxygen to superoxide in the [C2mim][NTf2] RTIL was studied at different carbon electrodes.
The mechanisms of electrodeposition and stripping of Zn(II) onto bulk zinc deposits, on glassy carbon electrodes, in the [C4mPyrr][NTf2] RTIL were investigated.
A novel and successful method for the fabrication of zinc microdisk electrodes was developed and the electrochemical behaviour of these electrodes was investigated.
The mechanisms for the electrochemical reductions of some bromo- and nitrobenzenes at platinum microelectrodes were determined in the [C4mPyrr][NTf2] ionic liquid, in order to identify systems which displayed changed reactivities in RTILs compared to those in molecular aprotic solvents.
The altered reactivity of 1-bromo-4-nitrobenzene in the [C4mPyrr][NTf2] ionic liquid was utilised via electrochemical reduction at zinc microelectrodes in order to form arylzinc compounds.
The work presented in this thesis shows that the oft-taken view that the reactivity of a given species in an ionic liquid will mimic that in conventional aprotic solvents is not always the case. Reactivities can be markedly different between RTILs and aprotic solvents and can also be highly dependent on the specific ionic liquid employed.