VictorJuiz/thesis huggingface dataset:
Émile Durkheim

Durkheim's background is described: born into a rabbinical family in Alsace-Lorraine, he grew up in an environment of defensive social cohesiveness, austerity and moral severity. On the third attempt, he was admitted to the Ecole Normale Superieure in 1879.
His reaction to the Ecole's largely classical and literary curriculum was unfavourable, but he excelled in philosophical and political discussions with his contemporaries (he was strongly republican) and, though critical of most of his teachers, he is shown to have been influenced by Boutroux and Fustel de Coulanges, as well as by the work of Renouvier. After his agregation, he became a lycee teacher of philosophy.
His early ideas about sociology are traced: in particular, his move from social philosophy to sociology, the formative influence of Comte, his qualified sympathy for Taine, his hostility to Renan, his adherence to scientific rationalism and strong opposition to all forms of dilettantism and mysticism, his early ideas about the practical implications of social science (and his hesitations in this regard), the development of his so-called "social realism" and the influence upon it of Comte, Spencer and Espinas respectively. Wishing to see social science at work, he visited Germany during 1835-6.
His reactions to this visit are considered: his admiration of German university life, his attitude to German philosophy and the implications he drew concerning philosophy teaching in France, his approval of the Germans 1 organic conception of society, arid, in particular, of the work of the social econo­ mists, the jurists and Wundt. Their influence on his thought is assessed. In 1887 he was appointed to teach social science and education at Bordeaux.
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Viscous fingering and liquid crystals in confinement

This thesis focuses on two problems lying within the field of soft condensed matter: the viscous fingering or Saffman-Taylor instability and nematic liquid crystals in confinement.
Whenever a low viscosity fluid displaces a high viscosity fluid in a porous medium, for example water pushing oil out of oil reservoirs, the interface between the two fluids is rendered unstable. Viscous fingers develop, grow and compete until a single finger spans all the way from inlet to outlet. Here, using a free energy lattice Boltzmann algorithm, we examine the Saffman-Taylor instability for two different wetting situations: (a) when neither of the two fluids wet the walls of the channel and (b) when the displacing fluids completely wets the walls. We demonstrate that curvature effects in the third dimension, which arise because of the wetting boundary conditions, can lead to a novel suppression of the instability. Recent experiments in microchannels using colloid-polymer mixtures support our findings.
In the second part of the thesis we examine nematic liquid crystals confined in wedge-structured geometries. In these systems the final stable configuration of the liquid crystal system is controlled by the complex interplay between confinement, elasticity and surface anchoring. Varying the wedge opening angle this competition leads to a splay to bend transition mediated by a defect in the bulk of the wedge. Using a hybrid lattice Boltzmann algorithm we study the splay-bend transition and compare to recent experiments on {em fd} virus particles in microchannels. Our numerical results, in quantitative agreement with the experiments, enable us to predict the position of the defect as a function of opening angle, and elucidate its role in the change of director structure. This has relevance to novel energy saving, liquid crystal devices which rely on defect motion and pinning to create bistable director configurations.

Keywords: viscous fingering
Lattice Boltzmann method
complex fluids
Saffman-Taylor instability
multi-phase flow
liquid crystals
Advisor: Ard, L
Yeomans, J
Aarts, D
Synthetic aspects of organosulphur chemistry

The thesis is concerned with approaches to substituted 2-phenyl- 1,3-oxathiolans and their cycloreversion to olefins.
2-(α-Methoxybenzylthio)acetophenone (l) was prepared by in situ alkylation of the thiolate generated by aminolysis of 0-ethyl-S-phenacyldithiocarbonate with α-chlorobenzyl methyl ether. Reduction of (l) with lithium aluminium hydride gave 2-(α-methoxybenzylthio)—1— phenylethanol which cyclised in the presence of p-toluenesulphonic acid to give 2,5-diphenyl-l,3-oxathiolan. α-(α'-Methoxybenzylthio)acetone (2), was prepared by a similar route to that used for (l). Compounds (1) and (2) and various other a-thiosubstituted ketones were investigated as potential starting materials for the synthesis of substituted β—(α-methoxybenzylthio)alcohols but the transformations attempted were unsuccessful.
A reasonably flexible synthesis of substituted oxathiolans and hence the corresponding olefins was developed starting from α—(benzylthio)ketones. The olefins prepared were 2-methyl—3—phenyl—2— butene, 1,2-dimethylcyclohexene and the Z-(3) and E-(4) 3,4—dimethylhex— 3—enes. Alkylation of the a-(benzylthio)ketones proceeded regio— specifically α- to the thio and keto groups. Subsequent reaction with organometallic reagents gave β-benzylthioalcohols. Generally alkyllithiums gave the best yields and higher stereoselectivities in these additions. The benzylthio group was cleaved with sodium/ ammonia to give β-mercaptoalcohols which were condensed with benzaldehyde to give 2-phenyl-l,3-oxathiolans. Treatment of the oxathiolans with lithium diisopropylamide resulted in cycloreversion to olefins in high yields (75-100%).
Stereochemical integrity was maintained throughout the reactions used to convert the β-benzylthioalcohols into olefins and consequently the stereoselectivity was determined at the β-benzylthioalcohol forming step. Thus the ratio found for (3) to (4) synthesised from a 3-benzylthioalcohol prepared by reaction of methyllithium with 3-benzylthio-3- methyl-4—hexanone was 3:7, whereas when the β-benzylthioalcohol was prepared from 3-benzylthio-3-methyl-2-pentanone by an ethyllithium reaction the ratio of (3) to (4) subsequently obtained was 6:4.

Advisor: Whitham, G
Spatio-temporal dynamics of neotropical high-altitude mixed oak forests in western Mexico

This thesis contributes to the understanding of two of the most intriguing questions that forest ecologists have faced over recent decades: 1) how high diversity is maintained in species-rich ecosystems; and 2) what is the role of spatio-temporal environmental variation in structuring forest communities. The aims of the research were to ascertain how species composition varies both spatially and temporally and how changes in the vegetation can be understood in the context of species coexistence theories (niche versus neutral). A group of 38 sympatric species, including 9 species of Quercus, on which little ecological research has been undertaken, were used in this study.
The data used in this project include eleven years of periodic remeasurements of permanent plots established in high-altitude oak forests in Mexico. Adult, sapling and seedling trees were studied as well as their environmental surrounding. Spatial and temporal variations in forest composition were analysed using multivariate statistical approaches.
The results show that there are discrete communities in these mixed oak forests that correspond to specific environments. At a broad scale the study area can be classified into two floristic zones, a mesic zone characterised by associations that include Quercus candicans, Q. laurina and Q. castanea and; a xeric zone dominated by Q. crassipes. However of a finer scale of analysis important variation in composition was associated with different life stages of the trees, with adult trees showing much stronger environmental associations than seedlings and saplings.
Successional pathways and rates vary at relatively fine scales. This may be as a result of dominance alternation between dominant canopy species.
Micro-niche zonation processes caused by a high degree of environmental heterogeneity combined with individual species traits explain the coexistence of phylogenetically similar sympatric Quercus species. A hierarchy of processes, each acting at a different spatial and temporal scale, determines species diversity and coexistence. The overall findings support the idea that niche differentiation rather than chance events such as dispersal limitation, are more important in permitting species coexistence.

Advisor: Brown, N
Savill, P
The electronic spectrum of selenium dioxide

The C͂¹B₂ ←　X͂¹A₁ electronic transition of SeO₂ has been investigated under high resolution, at a rotational temperature of around 10 K, using the technique of Laser Excitation Spectroscopy. The vibrationally-resolved survey spectrum contained around 100 new bands in addition to the bands which had been reported in a previous study of the same region (G.W. King and P.R. McLean, J. Mol. Spec. 51, 1974). In the light of this new spectrum a number of bands have been reassigned, most significantly the O⁰₀ band, and a number of progressions have been extended. This led to a revised determination of the vibrational constants of the excited state, and a more acceptable estimate of v'₃ than was suggested in the previous work. These reassignments and extensions of existing assignments accounted for only a small fraction of the newly observed bands; those remaining are thought to be due to a different electronic transition which lies in the same region as the C͂¹B₂ ←　X͂¹A₁ transition. The 1³₀, 1²₀ and 1¹₀ bands of the C͂¹B₂ ←　X͂¹A₁ transition were also recorded at rotational resolution and analysed using the method of ground state combination differences. The 1³₀ band was found to be perturbed, which was one of the major factors which prompted the survey study described above. From the analysis of these bands the rotational constants of the excited state were determined and hence the geometry of the SeO₂ molecule in the given vibrational levels of the ¹B₂ excited state was calculated. This in turn enabled the rotational constants and the geometry of the (00) vibrational level of the excited state to be estimated. This work confirms that the symmetry of the excited state is ¹B₂ and the transition studied is C͂¹B₂ ←　X͂¹A₁. An additional band around 31957 cm⁻¹ was also recorded at rotational resolution, which was initially though to be the O⁰₀ band, on the basis of King and McLean's assignments. However in the light of the reassignments the nature of this band is not known, and attempts to assign it as vibrationally cold band of the C͂¹B₂ ←　X͂¹A₁ transition were unsuccessful, implying that it is probably either a hot band of the C͂¹B₂ ←　X͂¹A₁ transition or a band belonging to different electronic transition.

Keywords: selenium dioxide
electronic spectrum
Advisor: Brown, J
Tet2 and relevant potential intervention in cancer

5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxycytosine (5caC) are products of TET enzyme activity, which initiates at 5-methylcytosine (5mC) in DNA. 5hmC has been found to be globally depleted in cancer, while TET2 is highly mutated. The first objective of this work was the investigation of the fate of the associated nucleosides in the context of nucleotide metabolism. Moreover, since many nucleoside analogs are used in cancer therapy to induce replication arrest and DNA demethylation, the effects on proliferation induced by the administration of nucleosides with bases, which are implicated in DNA demethylation, were evaluated. Finally, the TET2 protein interaction network was investigated to elucidate its lost function in cancer and shed light on possible means of intervention. It is demonstrated that DNA polymerase is capable of accepting modified cytidine triphosphates for polymerization. However triphosphate generation is impaired by substrate selectivity of CMPK1. 5hmdC and 5fdC given as media supplements to a number of cancer cell lines caused selective inhibition of proliferation without obvious defects in DNA methylation. By analyzing gene expression datasets, cytidine deaminase (CDA) overexpression was identified in sensitive cell lines. Overexpression and knockdown experiments demonstrated that CDA is necessary and sufficient to confer sensitivity to 5hmdC. Furthermore, CDA was able to deaminate in vitro 5hmdC and 5fdC, but not 5cadC, and a deaminated version (5hmU) was detected in the DNA of treated cells. 5hmU and 5fU in the DNA correlated with S/G2 phase arrest and increased levels of γH2AX at 72 h, suggesting that defects in proliferation relate to DNA damage. 5hmdC and 5fdC administration to mice (IP route) resulted in no overt toxicity and some degree of antitumor activity. Furthermore, TET2 was found to interact with WDR61, a member of the PAF complex (involved in transcriptional elongation), possibly explaining its role in 5hmC deposition over gene bodies and in oncogenesis, given the documented role of PAF in leukaemia. In conclusion, this study identifies the salvage route of new biological cytidine variants, a new avenue with which to target CDA overexpressing cancers, and a possible mechanism to explain the role of TET2 in leukemogenesis.

Keywords: epigenetic
drug
cancer
Tet2
nucelotides
Paf
metabolism
Advisor: Skirmantas, K
Random finite sets for multitarget tracking with applications

Multitarget tracking is the process of jointly determining the number of targets present and their states from noisy sets of measurements. The difficulty of the multitarget tracking problem is that the number of targets present can change as targets appear and disappear while the sets of measurements may contain false alarms and measurements of true targets may be missed. The theory of random finite sets was proposed as a systematic, Bayesian approach to solving the multitarget tracking problem. The conceptual solution is given by Bayes filtering for the probability distribution of the set of target states, conditioned on the sets of measurements received, known as the multitarget Bayes filter. A first-moment approximation to this filter, the probability hypothesis density (PHD) filter, provides a more computationally practical, but theoretically sound, solution.
The central thesis of this work is that the random finite set framework is theoretically sound, compatible with the Bayesian methodology and amenable to immediate implementation in a wide range of contexts. In advancing this thesis, new links between the PHD filter and existing Bayesian approaches for manoeuvre handling and incorporation of target amplitude information are presented. A new multitarget metric which permits incorporation of target confidence information is derived and new algorithms are developed which facilitate sequential Monte Carlo implementations of the PHD filter.
Several applications of the PHD filter are presented, with a focus on applications for tracking in sonar data. Good results are presented for implementations on real active and passive sonar data. The PHD filter is also deployed in order to extract bacterial trajectories from microscopic visual data in order to aid ongoing work in understanding bacterial chemotaxis. A performance comparison between the PHD filter and conventional multitarget tracking methods using simulated data is also presented, showing favourable results for the PHD filter.

Keywords: Bayesian statistics
random finite set theory
mathematics
Advisor: Moroz, I
Allwright, D
Bond, P
Benton, R
Davidson, G
Investigation of the role of ASPP2 in tumourigenesis

The skin is the site where two of the most common types of epithelial cancer, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), arise. In this work, we have investigated how ASPP2, a member of a family of proteins that interact with the p53 family, can affect skin tumourigenesis. ASPP2 is expressed in the squamous epithelia of various organs, localising exclusively in the upper and most differentiated layers. We show here that Balb/c ASPP2-null and heterozygous mice develop spontaneous SCCs. To investigate how the absence of ASPP2 from the epithelial compartment could lead to tumour formation, we analysed ASPP2’s relationship with pathways involved in the normal homeostasis of the epithelium, such as p63 and Notch. ΔNp63 is the main p63 isoform expressed in the adult epidermis, and its function is to drive the proliferation of the basal keratinocytes. Aberrant or misplaced activation of ΔNp63 in the epithelium is a known initiating cause for SCC. Consistent with this, ΔNp63 was found to be highly expressed in tumours derived from ASPP2-deficient mice. Our results indicate that ASPP2 is important in limiting ΔNp63 expression in the differentiated epithelium, preventing cell proliferation in the upper layers of the skin. This is achieved by antagonising ΔNp63 transcript and protein expression, resulting in a mutually exclusive expression pattern during differentiation of keratinocytes, as well as in epithelial cancer. ASPP2 expression was found reduced or lost in human SCC cell lines and during head and neck cancer progression, reflecting what was observed in ASPP2-deficient mice. Overall, our results indicate a possible mechanism by which p63 expression can be regulated in the skin, and provide a new model for the spontaneous formation of SCC in vivo. Additionally, we found that ASPP2 can cooperate with and enhance the activity of skin pro-differentiation pathways, such as Notch. In contrast to p63, ASPP2 and Notch1 are co-expressed in the differentiated layers of the squamous epithelium. Moreover, ASPP2 can interact with components of Notch nuclear transcriptional machinery, and it is shuttled into the nuclear compartment upon activation of Notch pathway. This recruitment results in modulation of Notch transcriptional activity on specific target genes with a differential pattern of binding sites, providing new insights into the understanding of Notch transcriptional regulation.

Keywords: p63
epithelium
ASPP2
notch
squamous cell carcinoma
Advisor: Lu, X
The effects of exercise on the chemical control of breathing in man

This thesis is concerned with the chemical control of breathing during exercise in humans.
Chapter 1 reviews some of the relevant studies in animals and humans.
Chapter 2 describes the experimental apparatus and the technique of dynamic end-tidal forcing performed using a computer-controlled gas-mixing system.
Chapter 3 describes a study of the effects of sustained hypoxia on ventilation during steady exercise. The acute ventilatory response to hypoxia (AHR) was increased during exercise as compared with rest, but the magnitude of the subsequent decline in ventilation (HVD), expressed as a fraction of the AHR, was reduced. A simple model of the hypoxic peripheral chemoreflex is proposed, in which the mechanisms underlying AHR and HVD are functionally separate and can be independently modulated by external factors.
Chapter 4 assesses changes in peripheral chemoreflex sensitivity to hypoxia in terms of the degree of decline in AHR measured in the resting periods shortly after prior conditioning periods of hypoxia and/or exercise. At rest, a second AHR measured 6 min after a period of sustained hypoxia had declined by 30% as compared with the initial AHR. In contrast, the AHR measured in the resting period after a period of sustained hypoxic exercise was only 11% smaller in magnitude than the AHR measured after a period of euoxic exercise. The results suggest that the degree to which hypoxic sensitivity declines during sustained hypoxia is genuinely attenuated, rather than masked, by exercise.
Chapter 5 describes the changes in respiration during prolonged exercise breathing air with and without added CO2. During prolonged poikilocapnic exercise, ventilation remained constant, but metabolic CO2 production, respiratory quotient and end-tidal PCO2 declined; a result which suggests that in man, ventilation can be dissociated from the CO2 flux. During hypercapnic exercise, ventilation progressively increased; this was interpreted as being due to a correction by end-tidal forcing of the natural tendency for end-tidal CO2 to decline, together with an independent effect of CO2 per se on the ventilation.
Chapter 6. Electrical muscle stimulation was used as means of inducing non-volitional exercise. Electrically-induced exercise increased the AHR as compared with rest, and with voluntary exercise at matched external work rate. The AHRs during electrical stimulation and voluntary exercise matched to the internal work rate were similar.
Chapter 7. Electrical muscle stimulation was used in paraplegic subjects in whom there would be no neural control of exercise. Electrically-induced exercise increased the AHR as compared with rest. When compared with the data from Chapter 6, the results suggest that the observed increase in AHR during normal voluntary exercise can be wholly accounted for by the increase in metabolic CO2 production, or closely related factors.
Chapter 8 presents a brief summary of the findings in this thesis.

Advisor: Robbins, P
Expression and functional characterisation of the collagen receptor glycoprotein VI

This thesis is concerned with the study of the collagen receptor glycoprotein VI (GPVI). GPVI has been studied in a number of human haematopoietic cell lines and found to be expressed only in those showing mekaryocytic features. Moreover, differentiation of the human cell lines HEL and CMK to a megakaryocytic lineage using the phorbol ester PMA revealed upregulation of GPVI together with the associated FcR γ-chain. Further, primary cultures of mouse marrow cells demonstrated up-regulation of GPVI towards the end of differentiation, therefore confirming data obtained with cell lines and pointing to GPVI as a possible marker of megakaryocytic differentiation.
Structure/function studies of GPVI were carried out by means of transient and stable transfection of the receptor into COS-7 or K562 cells. These studies demonstrated the necessity of the transmembrane argine and the cytoplasmic tail of GPVI for association to the FcR γ-chain. Lack of association or absence of FcR γ-chain rendered GPVI unable to signal, despite binding to convulxin, a GPVI-specific ligand which causes activation of the receptor.
K562 cells expressing GPVI and the FcR γ-chain were able to reconstitute the proximal but not distal events in GPVI signaling. A detailed analysis demonstrated impairment in phosphorylation and translocation of SLP-76 to the membrane, despite the presence and activation of others proteins known to be necessary for this phosphorylation/translocation to occur.
Stable expression of GPVI in K562 cells, which display low levels of expression of the collagen receptors α2βl and CD36, does not confer signaling properties in response to collagen. However, the cells respond to a collagen related peptide (CRP) which is specific for GPVI and to the snake venoms convulxin, alborhagin and alboaggregin-A, demonstrating that GPVI is one important component through which these venoms are acting.

Advisor: Watson, S