VictorJuiz/thesis huggingface dataset:
Investigating the genetic basis of sleep using forward genetics

The alternation between waking and sleep is regulated by the internal circadian clock and sleep-wake history, and is also influenced by the external environment. Although our understanding of the circadian aspect of sleep regulation has increased, the mechanisms underlying sleep homeostasis are still largely unknown. Independent of the circadian clock, only a limited number of genes have been associated with specific sleep-wake properties. Forward genetics provides an unbiased approach, which seeks to identify genes involved in specific biological processes. This project has focused on the Sleepy6 mouse line which was obtained via a forward genetics sleep screen. This model has a mutation in synaptobrevin 2, which results in a decreased sleep duration. We aimed to further characterise the sleep phenotype of this line, at a molecular and behavioural level, to gain novel insights into the regulation of sleep. Using molecular techniques to evaluate neurotransmitter levels and gene expression, we found no significant differences in the neurotransmitter pathways investigated. Behavioural assays highlighted hyperactivity, with a mild learning deficit. Electrophysiology recordings from the motor (M1) and visual (V1) cortical areas revealed that Sleepy6 homozygous mice have reduced amounts of rapid-eye movement sleep (REMS) and a strong decrease in the amplitude of electroencephalography (EEG) and local field potential (LFP) signals, especially during non-REMS when traces are reminiscent of the burst suppression patterns often observed during anaesthesia, rather than natural sleep. At a local level, neuronal firing in Sleepy6 homozygotes ceased for seconds at a time during non-REMS, coinciding with very low-amplitude EEG and LFP traces. Sleepy6 homozygous mice also displayed a longer latency to switch between vigilance states. Finally, the successful adaption of an elaborated version of the “two-process” model of sleep regulation to recordings performed in mice suggests that sleep pressure decreases at a slower rate in Sleepy6 homozygotes. This result should be interpreted in light of the above findings, as the model relies on power in the slow-wave (0.5-4 Hz) range during non-REMS, which is affected by the very low-amplitude oscillations observed in this state in Sleepy6 homozygotes. This combination of in vivo and computational work using the Sleepy6 line provides new insights into the mechanisms that underlie sleep architecture and the alternation between vigilance states. It also has the potential to further our understanding of the mechanisms underpinning the generation of slow-waves and anaesthesia.

Keywords: Neurosciences
Mouse mutant
Sleep
Forward genetics
Advisor: Peirson, S
Vyazovskiy, V
Bacterial infection in children hospitalised with diarrhoea in the South of Vietnam

Paediatric diarrhoeal disease is major global health problem. The aetiological diagnosis of diarrhoeal disease is often complex due to the wide array of potential infectious agents, available diagnostic techniques and local resources. Bacterial associated diarrhoeal diseases are an increasing issue due to high burden of antimicrobial resistance (AMR). As a consequence of standard treatments for diarrhoea (i.e. ORS), diarrhoea mortality has been decreased globally. However, the use of antimicrobial therapy for infectious diarrhoea has become controversial as the disease is often self-limited and the epidemiology of AMR pathogens. Here, I estimated the prevalence of bacterial infection among children hospitalised with bloody/mucoid diarrhoea using routine standard methodology (microbial culture) and multiplex real-time PCR. Information regarding antimicrobial usage and the proxy outcome of the patient were recorded. Novel diagnostics and methods (Luminex xTAG GPP and whole genome sequencing) were used in comparison to routine standard methodology and to investigate the infecting agents in more detail. In this setting non-typhoidal Salmonella (NTS) has become the most common bacterial cause of diarrhoea in children; followed by Campylobacter and Shigella with a substantial rate of AMR observed among these three major enteric pathogens. In a high usage setting, antimicrobial treatment for children with diarrhoea contradicted the antimicrobial susceptibility profiles and appeared to prolong the duration of hospitalisation. Diarrhoeagenic E. coli (DEC) were commonly detected; however, most pathotypes were found in stool samples from both diarrhoeal and non-diarrhoeal children. Only enteroinvavise E. coli (EIEC)/Shigella infections were significantly associated with diarrhoea. The xTAG GPP assay provided high sensitivity and specificity and was valuable for detecting other enteric pathogens which were not diagnosed by routine laboratory. S. Typhimurium was determined the most frequent NTS serovar via genoserotyping and were associated with an array of AMR genes; especially blaTEM-95, qnrS1. In conclusion, future studies in Vietnam should focus on a more streamlined approach to the diagnosis of diarrhoeal disease, to provide greater clinical evidence for supporting better clinical decision making to reduce or stop empirical antimicrobial usage for paediatric diarrhoea.

Advisor: Baker, S
The synthesis of hybridised tetramic acids for antibacterial activity

Tetramic acids are a naturally occurring class of antibacterial compounds which have been widely assessed in the literature. Hybridised tetramic acids are those which contain the tetramic acid bonded to another antibacterially active compound with the aim of possessing dual-inhibition functionality. This thesis describes the synthesis and biological evaluation of hybridised tetramic acids.
Chapter I reviews the methods by which drug discovery is employed in the search for novel antibiotics and the need for the discovery of antibiotics possessing novel modes of action. Previously employed tetramic acid syntheses and points of structural manipulation have been reviewed. A discussion of hybrids and a review of hybrids found in the literature has been produced.
Chapter II discusses the synthesis of tetramic acids conjugated to other antibacterial compounds through various linkers. Tetramic acids were successfully conjugated with coumarins, imidazoles, and imidazolines and attempts at synthesising various other conjugates were made. Chapter II also discusses the structural features of the tetramic acids which were troublesome when attempted to purify the hybrid compounds.
Chapter III investigates the synthesis of tetramic acid hybrids by fused hybridisation strategy. To achieve this, attempts were made at synthesising various spirocyclic tetramic acids however, isomerisation rendered the ability to characterise and biologically evaluate these compounds difficult.
The synthesised compounds were evaluated for their antibacterial activity against multidrug resistant pathogens and disappointingly, all but one showed no antibacterial activity.

Advisor: Moloney, M
Genesis of natural fracture systems in mudrocks (Upper Cretaceous-Eocene), Jordan

Organic-rich mudrocks are of great importance to the petroleum industry, potentially acting as source rocks, cap rocks or unconventional reservoirs. The analysis of natural fractures in mudrocks is crucial for the evaluation of their impact on fluid storage and flow. This research focuses on the investigation of natural fractures in organic-rich mudrocks, using integrated core, borehole image, field, petrographic, and geochemical techniques. The aim is to obtain a better understanding of the development of natural fracture systems in mudrocks, regarding their stratigraphic distribution, timing and formation mechanism. Natural fractures are abundant in the Upper Cretaceous-Eocene Belqa Group of Jordan. Distribution analyses of fractures resulted in an informal division of the stratigraphic section into three units; upper and lower highly fractured units and a middle weakly fractured unit. The host lithology represents an important factor influencing fracture distribution and formation; calcite-filled veins were observed in calcareous mudstone and carbonate intervals, and silica-filled veins were observed in chert intervals. Bitumen is present within natural fractures, either as macroscopic deposits, or as inclusions in the fracture cement, suggesting that hydrocarbons were present throughout and after the opening of fractures. Fractures are commonly associated with concretions in the Upper Cretaceous strata, implying that fracturing is sensitive to diagenesis. Open fractures in the succession are often confined to specific beds minimizing the potential leakage risk due to the high fracture intensities within the upper and lower caps which can be posed where fracture networks are connected. Mechanical stratigraphic controls on fracture distribution, relationship to compaction and early cementation, as well as the presence of bitumen within fractures, suggest that fracturing was affected by different processes and has different timings. Fracture formation mechanisms can be summarized as fluid pressuring (bedding-parallel veins), early diagenesis (folded calcite veins and silica veins) and late tectonic processes (planar calcite veins and joints, and gypsum veins). Petrographic and geochemical analyses show that fractures have developed at two main stages; (1) early diagenesis (calcite veins, ~40-30 Ma, were folded by sediment compaction), followed by fracturing during burial diagenesis, and (2) late fractures (~25-20 Ma) formed during uplift and extension, or fault reactivations.

Keywords: Geochemistry
Unconventional
Jordan
Mudrocks
Natural Fractures
Oil Shale
Advisor: Cartwright, J
Hooker, J
Search for a low-energy excess of electron neutrinos in MicroBooNE

The Micro Booster Neutrino Experiment (MicroBooNE) is a Liquid Argon Time Projection Chamber (LArTPC) designed for short-baseline neutrino physics at the Fermi National Accelerator Laboratory. The main physics goal of MicroBooNE is to address the low-energy excess of electron-like events observed by the MiniBooNE experiment and, if confirmed, clarify its nature. The MiniBooNE experiment is a Cherenkov detector and this technology does not allow to distinguish between electrons and single photons in the final state. LArTPC detectors, instead, offer excellent granularity and powerful separation between electrons and photons. For this reason, they represent an ideal technology for the detection of electron neutrino interactions. This thesis presents the first fully-automated electron neutrino selection in a LArTPC. The selection looks for charged-current electron neutrino interactions with no pions and at least one proton in the final state. It is applied on a sub-sample of the data acquired by the detector in the Booster Neutrino Beam, corresponding to 4.34 x 1019 protons-on-target. A validation of the analysis is performed on two orthogonal side-bands, enriched with neutral-current and charged-current muon neutrino interactions, respectively. The uncertainties on the neutrino cross sections, flux, and detector simulation are evaluated. The MicroBooNE detector is placed off-axis with the Neutrinos at the Main Injector (NuMI) beam. An independent dataset of events acquired by triggering on the NuMI beam is employed to measure the significance of the detection of electron neutrinos in the beam using the selection presented here. The sensitivity of the MicroBooNE experiment to the MiniBooNE low-energy excess of electron-like events is evaluated. The efficiency and background-rejection power necessary to achieve 5σ sensitivity are also quantified.

Keywords: microboone
oscillations
neutrino
sterile neutrino
Advisor: Guenette, R
Weber, A
Z/2-equivariant Heegaard Floer cohomology and transverse knots

This thesis consists roughly of two parts. In the first part, we study various properties of Z2-equivariant Heegaard Floer cohomology. Then, in the second part, we apply the results of the first part to study transverse knot invariants in the standard contact S3.
When (L,p) is a based link in S3, the branched double cover Sigma(L) is a rational homology sphere which carries a natural Z2-action. Hendricks, Lipshitz, and Sarkar studied this action on the Heegaard Floer setting to define HFZ2(Sigma(L), p), the Z2-equivariant Heegaard Floer cohomology of Sigma(L), using bridge diagrams of L drawn on a sphere. They also proved that its isomorphism class as an F2[theta]-module is an isotopy invariant of (L,p), which also implies that we can drop p from its notation when L is a knot.
In this thesis, we prove that, when L=K is a knot, then HFZ2(Sigma(K)) satisfies naturality and admits cobordism maps for based knot cobordisms. Then we move on to show that HFZ2(Sigma(K)) can be calculated in terms of bridge diagrams of L, which are now drawn on any weakly admissible Heegaard diagrams representing S3. Based on this observation, we point out that, for knots K, we can consider HFZ2(Sigma(K)) as a weak Heegaard invariant, and prove that it is actually a strong Heegaard invariant. We also prove that the definition of HFZ2(Sigma(K)) in terms of bridge diagrams and its alternative definition as a strong Heegaard diagram are equivalent, by constructing an invertible natural transformation between the two TQFT functors induced by those two definitions. Using that fact, we construct Z2-equivariant knot Floer cohomology HFKZ2(Sigma(K)), and show that it is a refinement of both HFK(-S3,K) and HFZ2(Sigma(K)).
We then construct the Z2-equivariant contact class cZ2(xiK) of a transverse knot K inside the standard contact 3-sphere (S3,xistd) std, as a well-defined element of HFZ2(Sigma(K)), and prove that it is a transverse knot invariant which refines the contact class c(xiK) of the contact branched double cover (Sigma(K),xiK) of (S3,xistd) along K. We also construct the Z2-equivariant LOSS invariant TZ2(K) of a transverse knot K in (S3,xistd), as an element of HFKZ2(Sigma(K),K) and prove that it is also a transverse knot invariant which refines both cZ2(xiK) and the LOSS invariant T(K).
Lastly, we give an interesting topological application of cZ2(xiK), by showing that it can be used to prove the nonvanishing of c(xiK) when K achieves equality in a Bennequin-type inequality.

Advisor: Juhasz, A
Gene expression and regulation in the yeast metabolic cycle

Biological oscillations such as the circadian rhythm are central to physiology of organisms ranging from humans to bacteria. By coupling cellular processes to a periodic oscillator or "clock", cells can pro-actively coordinate their behaviour with periodic changes in their environment such as cycles of the Earth and the Moon. Defects in these processes can lead to diseases ranging from diabetes to cancer and improving these processes has the potential to enhance yields from crops and bioreactors. As such, a thorough understanding of the mechanisms underlying biological rhythms is critical for medical, agricultural and industrial applications.
The yeast metabolic cycle is a model ultradian rhythm that can be induced in prototrophic S. cerevisiae cells under nutrient-limiting conditions. However, very little is known about either the role of post-transcriptional gene-regulation in maintenance of metabolic cycling or the extent to which protein levels cycle. In order to better understand these processes, this study examines the effects of disruption of RNA degradation pathways on transcript cycling and uses polysome profiling, RiboSeq & proteomics to assess the impact of cycling transcripts on the proteome of the yeast metabolic cycle. We find that low rates of protein turnover effectively suppress transcriptional cycling at the protein level and argue that the role of cycling mRNA levels in the yeast metabolic cycle is to control steady-state rather than dynamic protein levels, coupling gene expression to growth rate and nutrient availability.

Keywords: Metabolism
mRNA degradation
Protein turnover
S. cerevisiae
YMC
Translation
cell cycle
ultradian rhythm
UGRR
circadian rhythm
Gene Expression
Yeast Metabolic Cycle
Advisor: Mellor, J
Investigation of the effects of Anti-Müllerian Hormone on preventing Doxorubicin-induced primordial follicle loss

Survival rates from childhood cancer are improving, however chemotherapy can cause ovarian failure and infertility. Doxorubicin (DXR) is a gonadotoxic chemotherapy agent commonly used in childhood cancers. For pre-pubertal girls, ovarian tissue cryopreservation is the only fertility preservation option, however it is invasive and currently experimental. Therefore, non-invasive options need to be developed. A potential strategy utilizing Anti-Müllerian Hormone (AMH) to inhibit primordial follicle activation exists, but needs to be fully investigated.
To determine the effect of AMH on DXR-induced primordial follicle loss in vitro, pre-pubertal mouse ovaries were cultured with AMH, DXR or co-treated with AMH and DXR. To determine the effect of AMH on DXR-induced primordial follicle loss in vivo, pre-pubertal human ovarian tissue was xenotransplanted into adult female immunocompromised mice administered with AMH, DXR or co-treated with AMH and DXR. Mouse and human ovarian tissues were collected after experiments, fixed, embedded, sectioned and stained with Haematoxylin and Eosin. Primordial follicles (in vitro and in vivo studies) and growing follicles (in vivo studies) were counted.
In this thesis, we showed that DXR induced primordial follicle loss in pre-pubertal mouse ovarian tissue in vitro, in a dose-dependent manner. Follicular damage caused by DXR was also demonstrated in adult mouse ovaries in vivo but not in human pre-pubertal ovarian tissue xenotransplanted into mice. Although there were trends, there was no significant effect of AMH treatment alone on inhibiting primordial follicle activation in mouse ovarian tissue (in vitro and in vivo) or human ovarian tissue (xenotransplanted into mice). There was also no significant evidence of AMH acting to prevent DXR-induced primordial follicle loss in mouse ovaries. Therefore, more studies are warranted to further investigate the effect of AMH on DXR-induced primordial follicle loss.

Advisor: Williams, S
Lane, S
'I'm classic now': Byron's engagement with antiquity

Against the background of current debate within the academy about a less rigid demarcation between British Neoclassical and Romantic writing generally, and about the place of Rome among the Romantics specifically, this thesis examines Byron’s engagement with antiquity.
It reveals Byron as a sophisticated reader and inventive re-imaginer of classical texts and approaches. A significant component of his literary aesthetic was the extensive, and often highly creative, substratum of classical intertextuality in his writings throughout his life. By contrast, his exploitation of ancient texts as formal models fell largely into two periods, with an intense engagement in his apprentice years until 1812 and again in his artistic maturity from 1818, but a comparative hiatus during his ‘Years of Fame’ when he published Childe Harold’s Pilgrimage and the Oriental tales. His instincts in this regard were not academic or antiquarian. The value of the classical to Byron was not primarily to recover the past, but to illuminate the present and to enrich the reading experience.
A key contention of this thesis is that, notwithstanding Byron’s libertarian support of Greek independence from Turkey and a Hellenophilic culture in Britain in the early nineteenth century, his Hellenism—in the sense of being influenced by ancient Greek culture—and his expertise in ancient Greek have in general been over-emphasised. Conversely, the influential role of Latin texts and the Roman world in his self-construction and literary development has been under-appreciated. There is a preponderance of Latin source material in Byron’s classical translations and ‘imitations’, forms largely confined to his early years. Moreover, Roman writers emerge as central to the great works of his maturity in satire, epic and even tragedy, where the thesis argues that the principal classical dramaturgical influences on Byron’s three, professedly Greek, closet dramas of 1820–21—Marino Faliero, Sardanapalus and The Two Foscari—were in fact the tragedies of the contemporaneously unfashionable Roman writer, Seneca.
As revealed by his poetry and letters, what is most striking about Byron’s engagement with classical literature, once he left behind the enforced requirements of school and university, is his predominant Latinity.

Keywords: Byron's  classical translations and compositions
Byron's Latinity
Advisor: Macintosh, F
Harrison, S
Macroevolutionary history of Neotropical vegetation during the Cenozoic: a palynological perspective from Colombia

The Neotropics are the most plant species-rich realm of the Earth. This surprising megadiversity has been studied since times of Darwin and Humboldt, with different mechanisms proposed, not only to explain how such great diversity was produced but also how it is maintained. This system is not completely understood, and will continue being matter of study for a long time. Knowledge of the deep time patterns of diversity and diversification are central to testing hypothesised mechanisms. But the patterns have received much less attention than have the mechanisms proposed to explain them. In this thesis I used an extensive palynological record of Colombia to study the macroevolutionary history of Neotropical vegetation and its relationship with regional and global process occurring during the Cenozoic. The results show a strong correlation between fluctuations in palynological diversity and global changes in temperature. Contrasting responses of vegetation to temperature between the Palaeocene to Eocene and the Oligocene to Present suggest that different mechanisms operated during greenhouse and icehouse intervals. Throughout the Cenozoic, periods of elevated extinction are followed by periods of high origination. This relationship suggests that in the Neotropics when a species become extinct, it is replaced very fast. In contrast, the lack of correlation between origination and extinction suggest that extinction is not controlled by origination. The examination of the taxonomic rates and the global climatic curve indicate a good correspondence between episodes of global climate change and turnover, suggesting that extinction is exacerbated by these episodes. Finally, the palynological record also indicates that the Neotropics experienced several floods during the Cenozoic. These episodes include marine incursions, the development of extensive lacustrine systems and the establishment of mangrove forests. The relationship between floods and the evolution of Neotropical vegetation is challenging due to the uncertainty related to the temporal and geographic range of the floods. The evidence suggest that the floods had a local rather that a regional effect on the evolution of Neotropical vegetation.

Keywords: Macroevolution
Neotropics
Palynology
Colombia
Advisor: Benson, R