VictorJuiz/thesis huggingface dataset:
The constitution of the gold-cadmium system

The constitution of the gold-rich region of the gold—cadmium diagram has been etudied by means of thermal analysis, optical microscopy and Debye-Scherrer X-ray films of high-temperature and quenched specimens. Five phases have been identified, α face-centred cubic, α2 close-packed hexagonal, β' ordered body-centred cubic as well as two phases at low temperatures, α1 face-centred tetragonal and α' face-centred cubic.
The liquidus and solidus relationships have been found for the α, α2 and β-phases by thermal analysis, the results being in good agreement with the X-ray and microscopical results. A eutectic horizontal representing the reaction α2 + β' ⇌ liquid is found at 626.5°C. The β'-phase maximum is only just detectable, rising to 629°C. From the X-ray evidence a peritectic horizontal, corresponding to the reaction α + liquid ⇌ α2, is believed to exist between 633°C and the eutectic temperature; the thermal arrests place it at 627°C.
The α2(α2 + β') and (α2 + β')β boundaries have been determined microscopically. Only a few experimental points have been obtained for the α + α2 boundaries but the high-temperature X-ray films indicate that the boundaries of previous workers are in need of revision. The maximum solid solubility of cadmium in gold is 34 atomic % at 620°C to 630°C.
The β'-phase narrows in composition range as temperature falls. The high-temperature X-ray films showed superlattice lines up to 624°C and an estimate of the degree of ordering at 620°C suggests the β-phase to be about 90% ordered at this temperature.
The α1-phase at 23 atomic % cadmium is disordered face- centred tetragonal when photographed at elevated temperatures. The absence of superlattice lines is contrary to previous work which describes the unit cell in quenched α1, specimens as ordered (an anti-phase domain structure based on four fundamental tetragonal cells). It is conjectured that quenched α1 specimens may be ordered but as temperature is increased the long-range order is broken down, producing small domains each highly ordered.
At about 25 atomic % cadmium the structure is face- centred cubic. A new phase α' is proposed at this composition. A tentative diagram of the Au3Cd region, linking the four phases α, α1, α' and α2 is suggested with peritectoid horizontals at 412°C and 407°C.
Factors affecting the behaviour of the liquidus and solidus of the gold-cadmium system are revealed by comparing with other systems of copper, silver and gold. The comparisons show the influence of the electron concentration, modified by lattice distortions and the electrochemical factor.
The α2-phase (close-packed hexagonal) is shown to contain numerous stacking faults; this may be a consequence of the α(face-centred cubic) and α2-phases having nearly equal free energies. The occurrence of the 3/2 electron compounds in gold is discussed and suggestions are given for their bearing on maximum solid solubilities in gold.
Investigating the pathogenic effects of antibodies against the VGKC-complex and N-methyl-D-aspartate receptor in CNS disorders

Over the last few years, antibody-mediated disorders of the central nervous system (CNS) have been a rapidly expanding field in neurology. The antibodies bind to extracellular domains of proteins expressed in the CNS and impair neuronal function. Patients with limbic encephalitis, Morvan’s syndrome have antibodies that bind to the voltage gated potassium channel (VGKC)-complex proteins, LGI1 and CASPR2, while patients with antibodies to the NMDAR have more complex encephalopathies. Clinical evidence suggests that these antibodies are pathogenic as immunotherapy reduces antibody levels, which correlate closely with clinical improvement. Antibodies can be detected in patient sera using human embryonic kidney (HEK) cells transfected with CASPR2, LGI1 and NMDAR subunits, or by binding to rodent brain sections and primary neuronal cultures. In vitro NMDAR-antibodies have been shown to cross-link synaptic NMDARs and cause their subsequent internalisation from the cell membrane. It is not known if passive transfer of NMDAR-antibodies can recapitulate features of disease or if these pathogenic mechanisms occur with VGKC-complex antibodies.
The characteristics of LGI1 and CASPR2 antibodies were explored in vitro. IgG1 and IgG4 were identified as the predominant antibody subclasses, with all CASPR2 sera containing IgG1 antibodies and all LGI1 sera containing IgG4. On transfected cells both LGI1 and CASPR2 antibodies activated the classical pathway of the complement cascade. Furthermore CASPR2 antibody binding to transfected HEK cells showed a reduction in intensity over time which was most likely a result of internalisation of the CASPR2-antibody bound complex. Both CASPR2 and LGI1 antibodies bound strongly to the surface of live hippocampal neurons in culture, and this staining was reduced 24 hours after the removal of IgG, corresponding to a loss of antigen expressed at the cell surface.
Patients with NMDAR-encephalitis present with a psychotic disturbance, memory loss and seizures, usually progressing to a reduced level of consciousness and a marked movement disorder. A single injection of IgG, purified from patients with NMDAR-encephalitis was administered into the lateral ventricle of mice. Animals were observed for 40 days and showed significant behavioural changes, including a deficit in spontaneous alternation, dyskinetic hind-limb clasping and visual signs of spontaneous seizures, which are reminiscent to features of the disease. Behavioural changes were not observed in animals injected with IgG from healthy individuals. These behavioural alterations appeared to be reversible and were no longer present at day 40, which was supported by protein analysis showing equivalent levels of the NMDAR expressed in the hippocampus in animals receiving patient and control IgG.
In summary, these findings provide further evidence that supports a direct role of autoantibodies in NMDAR-encephalitis, limbic encephalitis and Morvan’s syndrome.

Keywords: Neurology
Immunology
Advisor: Vincent, A
External actors and the evolution of Latvian nationality policy, 1991-1999

Since regaining independence in 1991, Latvian nationality policy has developed from an exclusive, almost restitutionist, policy seeking to identity the Latvian state with the Latvian nation into a more inclusive civic definition of Latvian citizenship. This thesis aims to explain why this has occurred by examining the role of domestic, regional, and systemic level actors. Analysis of the external actors has been divided into states and institutions grouped into circles of Latvian interest. The inner circle includes Latvian domestic political actors, the next Latvia's principal bilateral relationship with the Russian Federation, followed by the Baltic States, then by Baltic Sea regional cooperation. The EU and OSCE, NATO, UN, and United States lie in the outer circles. Questions are asked about what the actors wanted in terms of Latvian nationality policy, which tools were at their disposal, and the results, if any, they were able to achieve.
Although not a theoretical study, the thesis touches on theoretical and methods issues, querying the extent to which external rather than internal factors determine policy outcomes in small states and arguing that Latvia's desire to join the EU was critical in the reform of Latvian citizenship legislation. It is the author's view that the evolution in nationality policy cannot be accounted for through a single level analysis. Domestic, regional, and international bilateral contexts are all necessary aspects of an explanation, although they might not fully account for the liberalisation of the citizenship legislation. After rejection from EU accession talks and a marked deterioration in relations with the Russian Federation, the Latvian Saeima and electorate amended the Citizenship Law to conform to OSCE HCNM recommendations. This suggests that the membership conditions of the EU are a powerful force in persuading applicant countries to alter their legislation to comply with a civic concept of citizenship.

Advisor: McFarlane, N
Simultaneous estimation of population size changes and splits times using importance sampling

The genome is a treasure trove of information about the history of an individual, his population, and his species. For as long as genomic data have been available, methods have been developed to retrieve this information and learn about population history. Over the last decade, large international genomic projects (e.g. the HapMap Project and the 1000 Genomes Project) have offered access to high quality data collected from thousands of individuals from a vast number of populations. Freely available to all, these databases offer the possibility to develop new methods to uncover the history of the peopling of the world by modern humans. Due to the complexity of the problem and the large amount of available data, all developed methods either simplify the model with strong assumptions or use an approximation; they also dramatically down-sample their data by either using fewer individuals or only portions of the genome.
In this thesis, we present a novel method to jointly estimate the time of divergence of a pair of populations and their variable sizes, a previously unsolved problem. The method uses multiple regions of the genome with low recombination rate. For each region, we use an importance sampler to build a large number of possible genealogies, and from those we estimate the likelihood function of parameters of interest. By modelling the population sizes as piecewise constant within fixed time intervals, we aim to capture population size variation through time. We show via simulation studies that the method performs well in many situations, even when the model assumptions are not totally met. We apply the method to five populations from the 1000 Genomes Project, obtaining estimates of split times between European groups and among Europe, Africa and Asia. We also infer shared and non-shared bottlenecks in out-of- Africa groups, expansions following population separations, and the sizes of ancestral populations further back in time.

Keywords: coalescent theory
methodology
Statistics
genetics
population history
Advisor: Marchini, J
Myers, S
Analysis of the quasicontinuum method and its application

The present thesis is on the error estimates of different energy based quasicontinuum (QC) methods, which are a class of computational methods for the coupling of atomistic and continuum models for micro- or nano-scale materials.
The thesis consists of two parts. The first part considers the a priori error estimates of three energy based QC methods. The second part deals with the a posteriori error estimates of a specific energy based QC method which was recently developed.
In the first part, we develop a unified framework for the a priori error estimates and present a new and simpler proof based on negative-norm estimates, which essentially extends previous results.
In the second part, we establish the a posteriori error estimates for the newly developed energy based QC method for an energy norm and for the total energy. The analysis is based on a posteriori residual and stability estimates. Adaptive mesh refinement algorithms based on these error estimators are formulated.
In both parts, numerical experiments are presented to illustrate the results of our analysis and indicate the optimal convergence rates.
The thesis is accompanied by a thorough introduction to the development of the QC methods and its numerical analysis, as well as an outlook of the future work in the conclusion.

Keywords: Quasicontinuum method; atomistic/continuum coupling; coarse-graining; a priori error analysis; a posteriori error analysis
Advisor: Suli, E
Ortner, C
The Chinese revolutionary army in the reform era, 1985-2010

This thesis studies the way that the single-party state has renovated the political identity of the armed forces in the reform era of the People’s Republic of China (PRC). It argues that the Chinese Communist Party succeeded in doing so and therefore was able to use the national military as a prop of continued single-party rule.
Engaging with theories of civil-military relations, this study challenges the dominant view of military professionalism according to which an armed force must be separate from politics to become truly professional. I show that the People’s Liberation Army (PLA) professionalization process, triggered by the establishment of the National Defense University in 1985, was completed by 2010, when the National Mobilization Law was issued. It provided the PLA with clear responsibility, esprit de corps, and area of expertise, these three core components of professionalism being put under firm regulatory control. This process, however, was not isolated from the political developments under way in the PRC during the same period. Instead, the ruling party turned the military into an active agent of its ‘spiritual civilization’ policy by tying it more closely to local governments, by giving it the duty to teach civic education to university students and the wider population, and by committing an increasing number of troops and other PLA resources to the United Nations peacekeeping program.
This work is based on an extensive reading of the untranslated literature published, mainly, by the PLA itself, to account for the way that it adapted its tradition of ‘political work’ (the system of indoctrination and human resource management linking it to the ruling party) to the requirements of military professionalism. I completed this account with about 60 interviews with Chinese serving and retired military personnel, foreign military attachés, and students with experience of military training in Chinese universities.

Keywords: China
Advisor: Shue, V
Time trends in childhood cancer: Britain 1966-2005

Increasing time trends in the recorded incidence of childhood cancer have been reported in many different settings. The extent to which these trends reflect real changes in incidence, rather than improvements in methods for diagnosis and registration, is controversial. Using data from the National Registry of Childhood Tumours (NRCT), this thesis investigates time trends in cancer diagnosed under age 15 in residents of Britain during 1966-2005 (54650 cases), and considers potential sources of artefact in detail.
Several different methods are used to estimate completeness of NRCT registration. The history of methods for diagnosis and registration of childhood cancers in Britain is described, and predictions are made for effects on recorded incidence.
For each of the 12 main diagnostic groups, Poisson regression is used to fit continuous time trends and ‘step’ models to the annual age-sex-standardised rates by year of birth and year of diagnosis. Age-specific rates by period, and quinquennial standardised rates for diagnostic subgroups, are shown graphically. For three broad groups (leukaemia, CNS tumours and other cancer), geographical variation is compared by period of diagnosis. The results of these analyses are discussed in relation to the predicted artefacts.
The evidence for a positive association between affluence and recorded incidence of childhood leukaemia is briefly reviewed. A special form of diagnostic artefact, the ‘fatal infection’ hypothesis, is proposed as an explanation of both this association and the leukaemia time trend. This hypothesis is examined in a novel test based on clinical data.
The recorded incidence of childhood cancer in Britain increased in each of 12 diagnostic groups during 1966-2005 (from 0.5% per year for bone cancer to 2.5% for hepatic cancer, with 0.7% for leukaemia). Evidence presented here suggests that these increases are probably artefacts of diagnosis and registration. The potential implications for epidemiological studies of childhood cancer should be considered.

Keywords: childhood cancer
under-diagnosis
Poisson regression
deprivation
UK
CNS tumours
standardised rates
leukaemia
imaging
acute lymphoblastic leukaemia
epidemiology
affluence
fatal infection hypothesis
incidence
capture-recapture
completeness
time trend
paediatric
cancer registration
socioeconomic status
hospital episode statistics
temporal trends
international classification of childhood cancers
delayed diagnosis
Britain
National Registry of Childhood Tumours
childhood
flow method
artefact
cancer diagnosis
geographical variation
birth cohort
cancer
Advisor: Carpenter, L
Stiller, C
Characterisation of the human two-pore channels

The Ca²⁺-mobilising messenger NAADP has been shown to play a key role in the regulation of mammalian physiology. Recently, the two-pore channels (TPCs) have been proposed as an NAADP-gated Ca²⁺ channel.
Chapter 1 introduces the TPCs as the major candidates in governing NAADP-mediated Ca²⁺-release from acidic stores. Chapter 2 explains the methodologies developed and used.
Chapter 3 demonstrates the successful immunopurification of HsTPC2 and its incorporation into an artificial lipid bilayer. K⁺ and Ca²⁺ currents were seen in reponse to nM - μM concentrations of NAADP; with the open probability (P₀) fitting a bell-shaped concentration-response curve. Ligand sensitivity was shown to be regulated by luminal [Ca²⁺], whereby a 20-fold increase in [Ca²⁺] lumen (10 μM to 200 μM) caused a 100-fold reduction in the EC50 from ≈ 500 nM to 5 nM. Furthermore, a reduction in luminal pH from 7.2 to 4.8 reduced the P₀ but 1 μM Ned-19 inhibiting all channel activity.
Chapter 4 investigates the in situ properties of HsTPC2 by the purification and patch clamp of intact lysosomes from cells overexpressing HsTPC2. Three methods of purification were compared: differential centrifugation, whole lysosome immunoprecipitation and magnetic chromatography. Techniques involving lysosomal swelling and whole cell homogenisation were also optimised to ensure minimal contamination by non-lysosomal proteins. Whole lysosome patch clamping revealed NAADP-induced, Ca²⁺-specific currents in response to NAADP, but not cADPR, IP₃ or Ned-19. High concentrations of NAADP (mM) and Ned-19 (μM) showed prolonged ≈ 5 minutes) inhibition of channel activity.
Chapter 5 explores the protein-protein interactions of the purified HsTPC2 and identifies a heterodimeric interaction between HsTPC1 and HsTPC2 was further dissected by coimmunoprecipitation, colocalisation and FRET studies. Despite clear evidence that both isoforms independently form homodimers, it is likely that heterodimerisation is a dynamic interaction only seen in a subset of the channel population.
Chapter 6 discusses the results obtained in the wider context of cell physiology.

Keywords: calcium
NAADP
two-pore channels
Advisor: Galione, A
Why and how is silk spun? : integrating rheology with advanced spectroscopic techniques

This thesis investigates the mechanisms behind natural silk spinning by integrating rheology, spectroscopy and small angle scattering to better understand this process and to guide our efforts towards mimicking Nature’s ways of producing high performance fibres.
As a result of natural selection, arthropods such as spiders and moths have evolved the ability to excrete silk proteins in a highly controlled manner. Spun from liquid feedstocks, silk fibres are used ex vivo to build structures with mechanical properties currently unmatched by industrial filaments. As yet, relatively little attention has been directed to the investigation of spinning under biologically relevant conditions. To better understand how and why silk is spun, this thesis bridges the gap between liquid silk flow properties and structure development.
To directly connect the two, I have developed and deployed novel experimental platforms that combine infrared spectroscopy and small angle scattering with rheology. This approach has clarified long-standing ambiguities on the structural root of silk’s apparently complex flow properties. Small angle scattering revealed the length scales involved in the flow induced solidification under a range of spinning conditions. Mo reover, infrared spectroscopy offered a unique perspective into silk’s formation process immediately after excretion.
In a similar manner to the post-extrusion tuning of the properties of partly solidified spider silk filaments, this thesis has revealed that silkworm silk fibres are far from completely formed once excreted. One might describe the filaments of mulberry silkworm as seeded molten polymers that form its hydrogen bonding network and crystallises slowly on site. Consequently, it enlightens that post-spinning conditions are equally paramount for silkworm silk, giving an explanation for the relatively poorer mechanical properties. The comparison of silks from a range of species, allowed this hypothesis to be extended to wild silkworm silk. My insights into spinning had the fortuitous repercussion of facilitating silk fibre solubilisation leading to the development of better artificial silk feedstocks flowing like native silks. With these findings, I believe we are now in an improved position to conceive artificial fibres with properties rivalling those of Nature.

Keywords: small angle scattering
Spinning
Cocoon
Bombyx mori
Silk
Rheology
infrared spectroscopy
Advisor: Vollrath, F
Holland, C
Terry, A
Selective permeabilisation of the blood-brain barrier at sites of metastasis.

Over one in five cancer patients will develop brain metastases and prognosis remains poor. Effective chemotherapeutics for primary systemic tumours have limited access to brain metastases owing to the blood-brain barrier (BBB). The aim of this study was to develop a strategy for specifically permeabilising the BBB at sites of cerebral metastases.
Tumour necrosis factor was injected intravenously into mouse models of haematogenously induced brain metastasis. BBB permeability was assessed through histology and in vivo MRI and SPECT. Tumour burden and neuroinflammation were assessed after injection of TNF with Caelyx or a novel therapeutic. Mechanism of permeabilisation was investigated through histology and receptor-specific agonist antibodies.
Administration of TNF dose-dependently permeabilised the BBB to exogenous tracers selectively at sites of brain metastasis, with peak effect after six hours. Metastasis-specific uptake of radiolabelled trastuzumab was also demonstrated following systemic cytokine administration. Administration of liposomal doxorubicin formulations in conjunction with TNF reduced tumour burden and mean metastasis size. Localised expression of TNFR1 was evident on the vascular endothelium associated with brain metastases. Human brain metastases displayed a similar TNF receptor profile compared to the mouse model.
These findings describe a new approach to selectively permeabilise the BBB at sites of brain metastases, thereby enabling detection of currently invisible micrometastases and facilitating tumour-specific access of chemotherapeutic agents. We hypothesize that this permeabilisation works primarily though TNFR1 activation and, owing to the similar TNFR1 expression profiles in mouse models and human condition, the strategy has the potential for clinical translation.

Keywords: metastasis
imaging
SPECT
Cancer
drug delivery
doxorubicin
MRI
chemotherapy
Advisor: Sibson, N
Anthony, D
Seymour, L