VictorJuiz/thesis huggingface dataset:
Coral reefs and climate change in the Indian ocean: a case study of Watamu Marine National Park, Kenya and other Indian Ocean locations

Coral reefs are arguably the most threatened marine habitat because of multiple anthropogenic stressors degrading the health and resilience of these systems. In the past 20 years there have been increasing observations of mass coral bleaching and mortality associated with increasing water temperatures in the tropics. Reefs provide ecosystem services worth billions of dollars to people living in tropical coastal areas and are the architects of one of the most beautiful structures found on earth. Conserving these habitats is paramount, and conservation planning must contend with climate change along with local and regional stressors. In this thesis Watamu Marine National Park in Kenya is used as a case study of the current challenges facing the conservation of reefs in a warming world. The Western Indian Ocean suffered dramatic bleaching during 1998, which caused the mortality of 70% of Watamu's corals. Using datasets from the 1980s to present the historical trajectory of Watamu's reef community is presented. The current ecosystem resilience is assessed to suggest how this reef will respond to future climate stress. It appears that Watamu's coral community has remained in an altered state post-1998, which, based on its past thermal stress and current coral community, should be resistant to future bleaching. Watamu's resilience and reef health is compared with other locations in the Indian Ocean, including reefs in Kenya and the Maldives that bleached in 1998 and examples from Mozambique and Sumatra of reefs with little evidence of historical thermal stress. Resilience is a multi-faceted process with different major components and numerous interacting factors, which act synergistically on the reef community. Conservation options and opportunities are discussed for the 6 locations examined, using current resilience models and theory as a framework for identifying priority actions. Local and regional-scale human impacts on shallow marine habitats during the last 50 years has been dramatic, and with global-scale climate change as an additional major threat, the next 50 years will be critical for the future of reefs. The locations visited during this study showed encouraging signs of resilience to past thermal stress, with evidence to suggest that corals are acclimatising and/or adapting to increasing water temperatures. The future of reefs in locations like Watamu is uncertain. Better understanding of reef ecology, appropriate conservation techniques and ultimately greater public concern for reefs is required to ensure that there is a future for these ecosystems in the Indian Ocean.

Keywords: Coral bleaching
Climate change
Kenya
Marine ecology
Advisor: Rogers, A
Taylor, M
Obura, D
Sluka, R
Ordering geniculate input into primary visual cortex

Precise point-to-point connectivity is the basis of ordered maps of the visual field in the brain. One point in the visual field is represented at one locus in the dLGN and one locus in primary visual cortex. A fundamental problem in the development of most sensory systems is the creation of the topographic projections which underlie these maps. Mechanisms ranging from ordered ingrowth of fibres, through chemical guidance of axons to sculpting of the map from an early exuberant input have been proposed. However, we know little about how ordered maps are created beyond the first relay. What we do know is that a topological mismatch requires the exchange of neighbours in the geniculo-cortical projection and that manipulating the input to the primary relay can affect the geniculo-cortical topography. Taking advantage of the immaturity of the newborn hamster’s visual system, I studied the generation of an ordered map in primary visual cortex during the time of target innervation in normal and manipulated animals. I also investigated the patterning of neuronal activity prior to natural eye-opening.
Paired injections of retrograde fluorescent tracers into visual cortex reveal that geniculate fibres are highly disordered at the time of invasion of the cortical plate. Topography in the geniculo-cortical projection emerges out of an unordered projection to area 17 in the first postnatal week. Furthermore, I show that manipulating the peripheral input can alter the topographic map which arises out of the early scatter. Removal of one eye at birth appears to slow the process of geniculo-cortical map formation ipsilateral to the remaining eye and at the end of the second postnatal week, a double projection between thalamus and cortex has formed. If retinal activity is blocked during this time, this double projection does not emerge. The results implicate retinal activity as the signal that induces the development of a different topographic order in the geniculo-cortical projection.
It is generally believed that visual experience can influence development only after eye-opening. However, the final part of my thesis shows that neurons in the developing visual cortex of the ferret can not only be visually driven at least 10 days before natural eye-opening, but are also selective for differently oriented gratings presented through the closed eye-lid. Thus, visually-driven neuronal activity could influence development much earlier than previously assumed in many developmental studies.

Keywords: geniculate
primary
visual
cortex
Advisor: Thompson, I
Syntheses &amp; characterization of nanoZSM-5 &amp; MOR zeolites, characterization of ZNS in the pore network of MOR

This study was carried out on the synthesis of mordenite zeolite and ZSM-5 zeolite. In Chapter 3 reports the growth of ZnS nanoclusters in the pore channels of mordenite zeolite. ZnS as an important wide-band-gap (3.6 eV) semiconductor nanoclusters and have various technological applications such as photocatalysis, nonlinear optics, sensors, solar cells, injection lasers, flat panel displays, ultraviolet light emitting diodes (LED).
Zeolites have several different applications in industries, such as in catalysis, ion exchange adsorption and gas separation. Zeolites are mostly used as a catalyst in the petrochemical industry. ZSM-5 zeolite is widely used a heterogeneous catalyst in the petrochemical industry due to its unique porous structure. Special attention has been made to synthesize nano-ZSM-5 in order to improve its catalytic activity. Catalysis depends on the characteristics length scale of the active sites, while the rate depends on the accessible active sites. In order to improve the performance of ZSM-5 zeolite used as a catalyst in the petrochemical industry, the researchers amid to produce nanocrystalline of the ZSM-5 zeolite. That will help to reduce the path length for the reaction and hence will increase the rate of a reaction. Comparative synthesis nano-particles of ZSM-5 zeolite using two different methods of treatment i.e. pre-treatment and interrupted treatment with ultrasound and without ultrasound was studied, its effect on aging and crystal growth during the hydrothermal treatment.
In Chapter 4 the pre-treatment with ultrasound and without ultrasound (static) with an increasing time intervals have been reported. The resulting product the particle size is clearly decreased by using ultrasound pre-treatment. While in Chapter 5 using a different method of treatment called interrupted of the hydrothermal process. As in this method, we stopped the hydrothermal process for 20 minutes and treated the gel with ultrasound for 15 minutes. This treatment was repeated after every 2 hours of hydrothermal treatment. Similarly, the same method was applied to the experiment but without the use of ultrasound called a static method of aging.
A 3rd method was also applied to investigate the effect of ultrasound on the particle size distribution of the synthesized crystalline powder. All the results showed that the ultrasound not only effects on the particle size but it also affects the crystallinity too i.e. increased the crystallinity and the reduced in the particle size.

Advisor: Edwards, P
Sartbaeva, A
Metamaterial based superdirectivity

A model-supporting, simple, compact, robust and high efficiency two- element parasitic superdirective array comprising electrically small reso- nant metamaterial elements, namely singly split resonator rings (SSRRs), is predicted by an analytical model and is verified by CST simulation re- sults. The analytical model is built by combining a method of calculating a two-SSRR array's far fild radiated energy density and a well working equivalent circuit for a two-SSRR parasitic array. This model is capable of easily but accurately predicting the far field radiation behaviours of an electrically small parasitic array of two SSRRs (the two SSRRs are not necessarily standard and identical), based on certain information of the array, namely the SSRRs' dimensions, the SSRRs' electrical components (L, C and R), the SSRRs' rotating orientation angles (α1 and α2), the two SSRRs's separation (d) and the array's operation frequency. The impor- tance of this analytical model in designing parasitic superdirective arrays is discussed. Simulation results show that the model predicted two-SSRR parasitic superdirective structure (the `CC' structure) can achieve an end- fire directivity of 4.36, with an elements' separation d = 4mm working at 1:914GHz, and can maintain an efficiencyciency as high as 98:6%. After a short discussion of the design principle behind the ℂ′structure,improvedsu-perdirectivestructuresofareidentifiedandstudiedbasedonsiμlationrest̲s.Amongthesestructures,the′ℂLr′structurecanaχevethelar≥stdirectivityvalueof5.06(veryclose→5.25,thetheoreticallimitvalueofatwo-dipo≤array)withamoderateefficiencyof81:4%.Acom-parisonbetweenthesetwo-SSℝparasitic⊇rdirectivestructures(theCC' and its improved versions) and two commercial two-element Yagi an- tennas show that these two-SSRR structures achieve better directive per- formances than the commercial two-element Yagi antennas do. Through performing the study of near field energy ow for magnetic dipole based structures (analytical results) and SSRR based structures (simulation re- sults), with the help of the concept of causal surfaces, the physical reason behind the superdirectivity phenomenon is revealed.

Advisor: Shamonina, E
Stevens, C
A clinical and ethical evaluation of secondary findings in the era of clinical whole-genome sequencing

With transformative initiatives like the UK’s 100,000 Genomes Project underway, vast amounts of data from genome sequencing are being generated. Genomic results are being actively returned to participants, although policies around their management remain inconsistent and a subject of debate. Secondary findings (SF) have been of particular concern—variants associated with health conditions other than the indication for sequencing, which may or may not be medically actionable. I have conducted a mixed methods study to explore the current transitional period and the issue of secondary findings, and inform future management. Following a narrative review of the literature around SF in genome sequencing and a focused systematic review of primary studies on stakeholder views towards the subject (Part I), gaps in the current literature were identified. These were, chiefly: (1) the need for diverse stakeholder views based on experience making actual decisions around SF; and, (2) empirical data—phenotypic, psychological, behavioural—on actual returned SF. Thus, taking advantage of the local programme of translational genome sequencing, I conducted qualitative studies involving genomic healthcare professionals and genome sequencing participants, to explore their views towards genomic medicine and SF (Part II). Following this, I detail a case study illustrating the process and challenges of returning an SF, as well as outline a study designed to collect empirical data on actual returned SF and present preliminary data to this end (Part III). I illustrate that secondary findings will be a part of tomorrow’s genomic medicine: cautious optional screening of actionable SF (including treatable conditions and carrier status information) appears favourable. However, if SF are to be a part of the genomic medicine paradigm, several barriers must be considered: insufficient connectivity between specialties, variant interpretation, clinical interpretation and management, and overpromise and expectations (including recontact in light of new information). In order to overcome these challenges, individuals in unselected populations must be prospectively phenotyped to derive more accurate estimates of population-level penetrance and better understand the full phenotypic spectrum, and we must explore the downstream impact of disclosure. As genome sequencing is mainstreamed, clear evidence-based guidelines for SF in genome sequencing will be essential if harms are to be minimised and benefits are to be maximised, both for participants and the healthcare system at large. At this point, albeit cautiously, we must 'learn by doing'.

Keywords: Stakeholder views
Clinical genetics
Qualitative research
Ethical, legal and social implications
Genome sequencing
Advisor: Watkins, H
Parker, M
Ormondroyd, E
Application of multi-resolution partitioning of interaction networks to the study of complex disease

Large-scale gene expression studies are widely used to identify genes that are differentially expressed between phenotypes relevant to disease. Often thousands of differentially expressed genes (DEGs) are found using this type of analysis, which complicates the interpretation of the data. In this project we treat DEGs as windows into the biological processes that underlie disease. In order to find these processes, we put DEGs into the context in which they perform their functions – through the interactions of their protein products.
Protein-protein interactions can provide biological context to DEGs in the form of functional modules. These modules are groups of proteins that together perform cellular functions. In this thesis we have refined a functional module detection process that consists of two steps. Firstly, community detection methods are applied to protein interaction networks (PINs) to detect groups of interacting proteins, and secondly, the biological coherence of the proteins grouped together is evaluated to select communities that represent potential functional modules.
Two features that are central to this work are the detection of modules at different scales of network organization, and CommWalker, a module evaluation method that we developed which is able to detect signals of poorly-studied functions. By integrating these methods into our functional module detection process, we were able to obtain a good coverage of potential functional modules. Testing for enrichment of DEGs on these functional modules can uncover biological processes that are involved in the contrasted phenotypes and merit further investigation.
We have applied our pipeline to find differentially regulated functions between hypoxic and normoxic breast cancer cell lines, and between M1 and M2 macrophages. Our results generate biological hypotheses of cellular functions that are differentially regulated in the investigated phenotypes, and proteins that are involved in these functions. We were able to validate several proteins in enriched modules which did not correspond to DEGs that were input into the pipeline, which suggests our methodology can reveal new biological insight.

Keywords: Biological Network Analysis
Advisor: Deane, C
Reinert, G
Page, M
Voltaire et ses amis d'après la correspondance de Mme de Graffigny

Préface
Introduction
i. De Luneville à Cirey
ii. Cirey et l'abbé Desfontaines
iii. Paris
iv. Voltaire et Mme Du Châtelet à Paris
v. Départ de Voltaire et de Mme Du Châtelet; scandales et brouilles
Extraits de la correspondance de Mme de Graffigny concernant Voltaire
1. Lettres de Cirey (septembre 1738-février 1739)
Notes aux lettres de Cirey
2. Lettres de Paris (février 1739-décembre 1739)
Bibliographie
Health and economic burden of human Streptococcus suis infection in Viet Nam and the contribution of undercooked pig product consumption practices: implications for prevention and control

Streptococcus suis is a zoonotic bacterium capable of causing severe systemic infection in humans, including central nervous system infection (meningitis) which can lead to long-term sequelae including deafness and vestibular dysfunction. Despite a growing body of literature on the epidemiology, microbiology and molecular aspects of the disease, there has been little progress on the prevention and control of this disease in Asia. This thesis aimed to examine the long-term consequences of the disease in patients, quantify the health and economic impact, and investigate the local practice of consuming raw pig blood, one of the main risk factors for S. suis infection in Viet Nam.
A systematic review and meta-analysis conducted in this thesis showed that hearing loss and vestibular dysfunction were the most common health sequelae in patients surviving S. suis infection. In a patient follow-up study at a referral hospital in Ha Noi, I found that severe hearing loss and vestibular dysfunction both occurred, and persisted over a long period in 40% of patients. Morbidity caused by these two conditions accounted for about half of the disability adjusted life years lost due to the infection. The analysis of disease impact showed that S. suis infection caused a considerable impact on the patients and their family. The direct cost of hospitalization was estimated to be 35 million VND per episode (~ 1600 USD), which was greater than the average annual per-capita income in Viet Nam. The total annual cost of the disease was 54-70 billion VND (2.5-3.3 million USD), more than 80% of which was attributed to productivity loss due to premature deaths and long-term disability.
A mixed-methods community-based study, consisting of both quantitative survey and focus group discussion, showed that raw pig blood consumption was common in Viet Nam (reported in 35% of rural and 8.6% of urban participants). Many misperceptions about food safety and risk of disease transmission existed in the community; most importantly was the belief that apparently healthy or free-ranging pigs did not pose health risks to consumers. Data from this thesis can be used by public health and policy makers to prioritise and justify resource allocation and to identify options for disease prevention and control.

Advisor: Wertheim, H
Horby, P
Ngo, H
Total syntheses of (–)-gephyrotoxin and (±)-morphine

The aim of this DPhil research project is to apply cascade reactions to the total syntheses of gephyrotoxin and morphine.
This thesis describes a novel approach towards gephyrotoxin in which the key disconnection is a nucleophilic cascade reaction that constructs the core structure bearing three rings and five stereocentres. This cascade approach enables the total synthesis of gephyrotoxin in nine steps with 14% overall yield.
In addition, a new approach towards morphine, involving an ene-yne-ene cascade ring closing metathesis and 1,6-addition to efficiently construct the B/C/D ring systems in a single operation, shortening the synthesis to nine steps with 6.6% overall yield is discussed.
The cascade shortcuts enable rapid approaches to these natural products, which results in the most concise total syntheses of gephyrotoxin and morphine described to date.

Advisor: Smith, M
The human leukocyte antigen associations of survival in an acquired immunodeficiency syndrome

An understanding of the molecular basis of immune recognition in human disease is essential for the development of antigen specific immunotherapy. Here, a new method for unambiguous human leukocyte antigen typing (HLA) is assessed and followed by an immunogenetic study exploring the association of HLA with disease outcomes in a group of adolescents who have survived with untreated, perinatal human immunodeficiency virus type-1 (HIV-1) infection.
The new method for high-resolution, unambiguous, mono-allelic genotyping of HLA-B and C alleles was tested on a subset of samples from a cohort of Zimbabwean Shona adolesents. Three novel HLA-C alleles were described and named by the World Health Organisation Nomenclature Committee for Factors of the HLA System.
Next, the association of HLA in HIV-1 disease progression was assessed in the Shona adolescents perinatally infected with the virus. Previous reports have shown that African infants with vertically-acquired HIV-1 infection progress rapidly, with only 50% surviving beyond two years in the absence of treatment. Recent reports, however, have described a substantial burden of older children living with untreated vertically-acquired HIV-1 infection in Southern Africa. The immunological and genetic factors associated with long-term survival following vertical infection are poorly understood. Medium-tohigh resolution HLA typing was performed on DNA samples obtained from a cohort of presumed vertically HIV-1 infected children and age-matched uninfected controls in Harare, Zimbabwe. Overall, 93 HLA class I alleles were detected in the study population with a significant enrichment of HLA-C*08:02 and -C*08:04 in the HIV-1 infected longterm survivor group. Conversely, HLA-A*02:01, -A*34:02 and -B*58:02 were overrepresented in the uninfected control group.
Together, these preliminary studies serve as a common starting point to identify pathways of immune recognition inherent in disease susceptibility and survival.

Advisor: Rowland-Jones, S
Synthetic biology engineering to catalyse unbreakable linkage between peptide building blocks

Protein conjugation is an important tool for research and the development of novel therapeutics. Peptide tags are ideal handles for bioconjugation, as they are minimally disruptive to protein structure and function and are weakly immunogenic. In this thesis, I have developed SnoopLigase, a protein which is able to covalently link the two peptide tags SnoopTagJr and DogTag by site-specific transamidation. The three modules were obtained by splitting an isopeptide bond-containing domain of the Streptococcus pneumoniae adhesin RrgA. Using rational and computational protein design, rate and yield of the reaction were improved, while allowing efficient reaction in different buffers and temperatures.
The separation of conjugated proteins from unreacted substrate can be challenging when using established bioconjugation techniques. SnoopLigase bound strongly to its reaction product, which enabled the purification of conjugated SnoopTagJr-DogTag by SnoopLigase solid-phase immobilisation and subsequent product elution. Hence, SnoopLigase could be useful to produce high quality bioconjugate therapeutics.
Vaccines are important medical interventions, saving millions of lives each year. Recombinantly produced antigens are cost-effective and have an unmatched safety profile, yet often show poor immunogenicity. Protein multimerisation can strongly enhance the immune response against the antigen. Based on the SnoopLigase system and the heptameric protein IMX313, I developed a highly stable, modular vaccine platform. Covalent conjugation of SnoopTagJr-linked proteins to the platform nanoparticle IMX313-DogTag allowed simple, efficient and modular protein multimerisation. The efficient coupling by SnoopLigase and the small size of the tags provide potential to accelerate development of modular vaccines against malaria and other diseases.

Advisor: Howarth, M