VictorJuiz/thesis huggingface dataset:
Volcanic history and magmatic evolution of Mocho-Choshuenco Volcano, Southern Chile
Keywords: Volcano
Mocho-Choshuenco
Arc volcano
SVZ
Geology
Glacial
Geochemistry
Chile
Earth Sciences

Active volcanoes pose a significant natural hazard. In order to evaluate the hazard it is important to reconstruct the history of such volcanoes to understand the frequency, style of eruption and the areas typically affected by the explosive eruptions.
This thesis focuses on deciphering the volcanic and magmatic record for one of the most productive volcanoes in southern Chile, Volcán Mocho-Choshuenco. Work presented in the thesis establishes a detailed record of the explosive activity during the last 18 kyrs, constructed using field observations and geochemical analyses of the eruption deposits. Using a multi-technique approach Mocho-Choshuenco is shown to be one of the most explosive, frequently active and hence hazardous volcanoes in Chile.
This high-resolution eruptive record provides new constraints on the underlying causes of spatial and temporal variability in arc volcanism. Temporally, the record gives new understanding into the response of arc volcanoes to deglaciation; clear temporal variation in eruption flux, eruption size and magma composition are observed. This time-varying behaviour is hypothesised to reflect changes in the crustal plumbing system, and magma storage timescales in response to removal of an ice-load. It demonstrates that deglaciation can drive changes in eruption behaviour at arc volcanoes; however the response is more complex and subtle than settings where decompression melting dominates.
Spatially, Mocho-Choshuenco has a high number and density of scoria cones that have erupted relatively primitive magmas but nonetheless with a wide range of magma compositions. For some of the 'classical' slab and mantle geochemical tracers the erupted magmas span the complete range seen in this part of the arc. The tight temporal and spatial constraints provided by the analysed samples, coupled with recent advances in numerical modelling of magma transport through subduction zones, enable new hypotheses for interpreting the signatures of mafic arc magmas to be defined.
A study of CP violation in B∓→Dh∓ (h=K,π) with the modes D→K∓π±π0, D→π+π−π0 and D→K+K−π0
Keywords: CP violation
LHC
CERN
B physics
LHCb

One of the objectives of the LHCb experiment at CERN is a precision determination of the angle γ from the CKM Unitarity Triangle, a CP-violating parameter of the Standard Model. Sensitivity to γ can be obtained by exploiting the interference effects in B∓→Dh∓ (h=K,π) decays, which can lead to measurable charge asymmetries.
This thesis presents an analysis of the decays B∓→DK∓ and B∓→Dπ∓ where the D meson is reconstructed in the three-body final states of K∓ π± π0, π+π−π0 and K+K−π0. The analysis is performed using 3.0 fb−1 of pp collision data collected by LHCb in 2011 and 2012. It represents the first time that these particular decay modes are studied at the LHCb experiment.
Several CP observables are measured using a simultaneous fit to the invariant B∓ mass distributions of the decay channels of interest. A first observation is obtained of the decays B∓→[π∓K±π0]Dπ∓ and B∓→[K+K−π0]Dπ∓ at 5.3σ and greater than 10σ significance levels, respectively. In addition, first evidence of the decay B∓→[K+K−π0]DK∓ is obtained at a significance of 4.5σ. The results are interpreted in the context of γ and related parameters.
Joint criminal enterprise in English and German law
Keywords: Accessory Liability
Participation in Crime
Joint Enterprise

This thesis explores the English doctrine of joint criminal enterprise by way of a comparative study. Joint enterprise allows for the conviction of an accomplice (S) of an offence (crime B) committed by his associate-in-crime (P) on the basis of S's foresight of its commission by P as a possible incident to their joint criminal venture (crime A).
While it is generally accepted that this common law principle needs reforming, successive governments have declined to take on the task. Against this backdrop, this thesis explores whether the contentious features of joint enterprise liability might be reformed by way of common law development. To this end, the thesis examines the doctrine’s constituent elements, its function, underlying rationale and place within the structure of primary and secondary liability. Particular emphasis is put on the specific problems associated with the application of joint enterprise liability in the context of murder. Looking at the functional equivalents of joint enterprise in German law, the thesis challenges the orthodox view that joint enterprise is a head of liability available to the prosecution alongside co-perpetration and aiding and abetting. Indeed, it argues that an inculpatory function of the principle is difficult to justify and suggests that, both historically and as a matter of principle, it is better seen as an exculpatory device aimed at delineating the scope of co-perpetration and aiding and abetting. The thesis concludes that the current law does not serve this function very well, as its mens rea threshold (some form of recklessness, when proof of intention is needed to convict the principal offender) sets the hurdle for conviction of secondary parties indefensibly low. Informed by ideas taken from German law – especially an extended concept of intention known as dolus eventualis – the thesis's principal contention is that English law would do better defining joint enterprise liability in terms of foresight plus endorsement. Indeed, the thesis aims to show that English law was very close to such a conception, and that the common law took a wrong turn in Powell. It concludes that it is still open to the Supreme Court to adopt an endorsement-focussed approach to joint enterprise liability, thereby alleviating concerns that the law in this area is too harsh and over-inclusive, and bringing it closer to the threshold of liability for principal offenders which requires proof of intention. Such an approach would also make the law of complicity more principled and coherent.
Application of next-generation sequencing to analysis of the genetic basis of complex traits in plants, with particular focus on nickel hyperaccumulation in the Alyssum serpyllifolium species complex
Keywords: nickel hyperaccumulators
Evolution
hyperaccumulation
Alyssum

Reliable, high-throughput and low-cost next-generation sequencing technologies have invigorated genetic research into non-model organisms over the last decade. In this work, RNA-Seq was employed to obtain the first-ever transcriptomes of two groups of closely related plant taxa possessing distinctive complex physiological traits, namely metal hyperaccumulation and C4 photosynthesis.
Metal hyperaccumulator plants possess an extraordinary ability to take up trace elements from the soil and accumulate them to high concentrations in their shoots, probably to serve as a type of elemental defence against natural enemies. Taxonomically, the most common form of metal hyperaccumulation, nickel hyperaccumulation, is encountered on nickel-rich ultramafic (serpentine) soils, and is found with the highest frequency (ca. 51 species) in the genus Alyssum (family Brassicaceae). Here, the genetic basis and evolutionary history of nickel tolerance and hyperaccumulation was investigated in the Alyssum serpyllifolium Desf. species complex, which contains both serpentine and non-serpentine populations of unresolved phylogenetic relationships on the Iberian Peninsula. Genome scans for outlier loci and differential expression analyses identified a number of candidate hyperaccumulator genes common to two serpentine populations found in Portugal and Spain, but the majority of adaptive variation was of local origin. Phylogenetic and population-genetic inferences based on neutral and putatively adaptive loci suggested that the key genes for the nickel hyperaccumulation trait evolved once and spread across serpentine populations early in the history of this species, with no genetic isolation but continued recent gene flow between serpentine and non-serpentine populations.
To test the power of next-generation sequencing for analysing the genetic basis of a separate complex trait, a cross-species comparison was performed using RNA-Seq of two congeneric tropical species, the C4 plant Alternanthera pungens Kunth and the C3 plant Alternanthera philoxeroides (Mart.) Griseb. f. angustifolia Suess. (family Amaranthaceae). These species were cultivated at two different temperatures and showed significant differences in levels of overall gene expression plasticity and isoform switching in certain photosynthesis genes, which it is proposed may explain the observed difference in the ability of these two species to acclimate to low and high growth temperatures.
Novel embolic particles for cancer therapy
Keywords: Nanotechnology
Tantalum
Titania
Silica
Embolization
Ophiobolin A

The aim of this thesis was to develop novel embolic particles for cancer therapy using a combination of nano and microparticles. The particles have been designed and synthesised to have a polystyrene core, be radiopaque, act as a radiosensitiser and have a high capacity for loading of chemotherapy drugs.
The polystyrene core has been designed so it effectively blocks the tumour vasculature thereby limiting oxygen and nutrient delivery to the tumour thus causing tumour necrosis. The core of the polystyrene particle incorporates tantalum oxide nanoparticles to provide X-ray contrast to the embolic microparticles.
The surface of the polystyrene particle has been coated with rare earth doped titanium dioxide (TiO2) nanoparticles which produce reactive oxygen species upon X-ray activation. This allows the embolic particle to act as a radiosensitising agent and has been shown to reduce cell proliferation in the presence of X-rays.
The surface of the polystyrene particles has also been coated with mesoporous SiO2 nanoparticles which allow for the high loading capacity of chemotherapeutic drugs. This permits chemotherapy to be delivered directly to the tumour location, thereby reducing the toxic side effects of systemic treatment. As a proof of concept, the chemoembolization particles have been loaded with a novel fungal derived chemotherapeutic Ophiobolin A and the controlled release has been demonstrated. The OphA chemoembolization particles reduced cell viability by approximately 70% compared to the blank chemoembolization particles.
The mechanism of cell death of OphA on eight cancer cell lines and one control cell line has also been studied and its effect on cellular organelles elucidated. OphA shows great promise as a novel chemotherapeutic which could be taken forward to animal trials.
Computational modelling of hand-centred visual representations in the primate brain
Keywords: Reference frames
VisNet
Hand-centred
Neural networks

Neurons have been found in various areas of the primate brain that respond to the location of objects with respect to the hand. In this thesis we present a number of self-organising theories of how these hand-centred visual receptive fields could develop during visually guided learning in unsupervised neural network models. Experimental chapters 3 and 4 show the development of hand-centred representations under two different learning hypotheses Continuous Transformation learning and Trace learning, using a neural network model of the primate visual system, VisNet. In Chapter 5 the trace learning hypothesis is advanced by gradually increasing the realism in the visual training conditions. Results are shown using realistic visual scenes consisting of multiple targets presented at the same time around the hand. In Chapter 6 this learning hypothesis was further explored using natural eye and head movements recorded from human participants. This required a new time accurate differential formulation of the VisNet model to faithfully represent the temporal dynamics of the recorded gaze changes. These results provide an important step in showing how localised, hand-centred receptive fields could emerge under more ecologically realistic training conditions. In Chapter 7 we present a new self-organising model of how hand-centred representations may develop using a proprioceptive signal representing the position of the hand. In these simulations we first develop a body-centred representation of the location of the visual targets by trace learning. I then showed how these body-centred representations of the visual targets can be combined with a proprioceptive representation of the location of the hand in order to develop hand-centred representations. This thesis concludes with a discussion of the main findings and some suggestions for future work.
Biochemical studies on muscarinic cholinergic receptors
Keywords: biochemical
cholinergic
receptors
muscarinic

A novel solubilising agent (0.l% sodium cholate—lM NaCl) has been developed which will solubilise 10—30% of muscarinic cholinergic receptors from bovine caudate nucleus. Using the muscarinic antagonist quinuclidinyl benzilate (QNB), a single saturable binding component was found with an equilibrium constant of ZOOpM, approximately 10—fold higher than the membrane receptor and 4—fold higher than the ratio k-l/kl determined kinetically in the soluble material. This latter difference may indicate that the binding of QNB to the solubilised receptor is not a simple second—order process. Inhibition constants for a variety of muscarinic agonists and antagonists were 10 to 20—fold higher than in the membrane state and non-muscarinic ligands were without effect. The decrease in affinity was shown to be due to the presence of high salt.
Evidence was presented that the apparent increase in Hill coefficient for muscarinic agonist binding to soluble material was not due to a differential solubilisation of muscarinic receptors or to a conformational change of high to low affinity agonist sites during the solubilisation. Instead the Hill coefficient of the soluble material decreased as the percentage of total binding sites solubilised increased. The stability of receptor binding at different temperatures was shown to be dependent on the protein: cholate (w/w) ratio. Results from gel filtration, affinity chromotography and immunization studies are also reported. The results of this thesis are discussed in the light of the possible importance of phospholipids for receptor activity.
Optical Bloch equations for simulating trapped-ion qubits
Keywords: Efficient atomic simulation
Fitting fluorescence scans
Doppler cooling
Atomic clock transitions
Multi-level resonance dynamics
Optical Bloch equations

This thesis describes work on numerical modelling of the 43Ca+ ion in a Paul trap using the optical Bloch equations. This is a challenging system to study, with many states involved in the internal dynamics. A major outcome is the development of a cooling scheme for the 146.09 gauss atomic clock transitions which makes use of a dark resonance. It is much more effective than methods that avoid coherent effects. The scheme is realised in experiment. Complicated fluorescence data is modelled very well, and predictions for the ion's motional temperature show good agreement with measured values. Data and fits for an ion that has been Doppler cooled below the Doppler limit are presented.
I describe GLOBES, a set of routines that simulates an arbitrary ion in the presence of an arbitrary system of laser beams using the optical Bloch equations. Techniques used to efficiently calculate the steady state, analyse fluorescence scans and solve time-dependent problems for small and large times are discussed. A new routine SILVER IMPER that leapfrogs over the initial dynamics to model the approach to the steady state is introduced.
Doppler cooling in 40Ca+ is analysed and two extensions made to the basic theory. The ‘excursion method’ of calculation takes account of the non-linear variation with velocity of the scattering rate. The ‘dynamic method’ allows for the fact that the ion may not be in equilibrium with the incident radiation during its oscillations, a necessity as the timescale of the external motion is of order the characteristic timescale of the internal motion for standard secular frequencies. This 'dynamic effect' is a general property of trapped ion systems and is also observed in a two-state system.
A two-variable fluorescence scan taken from a four-laser, five-level system in 40Ca+ is analysed. Techniques to fit large data sets and automatically resolve resonant features are demonstrated. A general treatment of resonant behaviour in three, four and five level pump/probe systems is used to describe the data. This is verified by a second, tailor-made set of scans.
Alpha-synuclein in Parkinson's disease: molecular pathogenesis and development of genome engineering-based silencing approaches
Keywords: Parkinson's disease
Induced pluripotent stem cells
Alpha-synuclein
CRISPR/Cas9
Unfolded protein response
Genome Engineering
Endoplasmic reticulum stress

The ability to reprogram adult somatic cells into induced pluripotent stem cells (iPSCs) and subsequent development of protocols for their differentiation into disease-relevant cell types have enabled in-depth molecular analyses of multiple disease states as hitherto impossible. Parkinson’s disease (PD) is one such example, in which the dopaminergic neurons that manifest pathology are embedded in an inaccessible region of the midbrain, the substantia nigra pars compacta, making it unfeasible to obtain samples of the affected region from living patients. Overabundance of alpha-synuclein, encoded by the SNCA gene, has long been implicated in the pathogenesis of PD. However, the precise mechanism by which overexpression of alpha-synuclein leads to the demise of dopaminergic neurons remains elusive. Neurons differentiated from PD patient-specific iPSCs carrying multiplications of the SNCA gene may provide a means to recapitulate molecular phenotypes of the disease in vitro. The application of CRISPR/Cas9 to mammalian systems is likewise revolutionizing the utilization of genome editing in the study of molecular contributors to the pathogenesis of numerous diseases, including PD. In this body of work, I have utilized the double-nicking CRISPR/Cas9 system to mediate site-specific mutagenesis of SNCA in PD patient-specific iPSCs harboring a triplication of the SNCA gene locus, resulting in isogenic cells which can be used to phenocopy normal alpha-synuclein expression from two alleles. I have further demonstrated the utility of nuclease null or "dead" Cas9, for transcriptional silencing of alpha-synuclein expression. Finally, I have used these systems to interrogate phenotypic outcomes of SNCA triplication, demonstrating that alpha-synuclein induces endoplasmic reticulum stress and aberrant activation of a highly conserved arm of the unfolded protein response. The tools generated in these studies can be applied in future efforts to dissect the contributions of alpha-synuclein overexpression to PD pathogenesis and as a platform for the discovery of disease-modifying therapeutic approaches for PD.
Reversible myocardial depression in critical illness
Keywords: critical illness
Intensive Care
Critical care
Takotsubo
neurogenic myocardium
cardiomyopathy
sepsis cardiomyopathy
myocardial depression
critical therapy
sepsis

Introduction: Reversible myocardial depression (RMD) is a transient impairment of left ventricular systolic function. This has been described in sub populations of patients experiencing critical illness, but it is unclear if the epidemiological features are generalisable to the broader populations of critically ill adults. Previous work has identified that RMD is not benign and has been associated with a range of adverse sequelae such as arrhythmia, left ventricular outflow tract obstruction, and intra-ventricular thrombus. Consequently, studies were designed to determine the incidence, time course, and associated risk factors for the development of myocardial depression in the general population of adults experiencing critical illness.
Methods: Myocardial depression was defined as a decrease in left ventricular ejection fraction ≥5% from AICU baseline and was assessed using serial transthoracic echocardiography. Three studies were conducted - two prospective observational cohort studies and a retrospective analysis. The incidence, absolute decrease in ejection fraction, and time course of myocardial depression was described. Routinely available demographic and clinical variables were collected. These were then rationalised and trialled as candidate explanatory variables in a logistic regression model to predict the development of myocardial depression.
Results: The incidence of myocardial depression was between 16.3 – 34%, which occurred around day four of AICU admission. The median decline in LVEF at the onset of myocardial depression was between 6.5 – 14.7%, which progressed to between 10 – 17.5% at the nadir. Myocardial depression was not entirely reversible, with between 43.7 – 71.4% of participants demonstrating some degree of recovery, with LVEF improving between 13.3 – 20.2% across the studies. The probability of development of myocardial depression can be determined using five routinely collected variables, expressed as a factor; heart rate, systolic blood pressure, the presence of severe sepsis, cardiovascular organ dysfunction and sinus rhythm. Increasing systolic blood pressure, the presence of severe sepsis, and cardiovascular organ dysfunction were associated with increased risk. Increasing heart rate and the presence of sinus rhythm were associated with decreased risk. Model diagnostics indicated that the model was a good fit of the data. The model had a modest discriminating ability, with the area under the receiver operating characteristic curve = 0.69.
Conclusion: The incidence of myocardial depression was between 16.3 – 34% of participants, and usually developed around day four of AICU admission. The decreases in left ventricular ejection fraction were considerable and were not always reversible. Myocardial depression can be predicted using routinely collected haemodynamic and clinical variables that are available within the first 24 hours of AICU admission.