VictorJuiz/thesis huggingface dataset:
Studies of Dº→Kºsh+h'- decays at the LHCb experiment

This thesis documents two studies of the neutral charm meson system using the LHCb detector, and gives an overview of the numerous changes made to the LHCb software trigger in advance of Run 2 of the LHC.
In the first analysis, amplitude models are applied to studies of the resonance structure in D0 → K0SK−π+ and D0 → K0SK+π− decays using proton-proton collision data, corresponding to an integrated luminosity of 3.0 fb−1, collected during Run 1 of the LHC. Relative magnitude and phase information is determined, and coherence factors and related observables are computed for both the whole phase space and a restricted region of 100 MeV/c2 around the K&ast;(892)± resonance. Two formulations for the Kπ S-wave are used, both of which give a good description of the data. The ratio of branching fractions B (D0→ K0SK+π−) /B (D0→ K0SK−π+) is measured to be 0.655 ± 0.004 (stat) ± 0.006 (syst) over the full phase space and 0.370 ± 0.003 (stat) ± 0.012 (syst) in the restricted region. A search for CP violation is performed using the amplitude models and no significant effect is found. Predictions from SU(3) flavour symmetry for K&ast;(892)K amplitudes of different charges are compared with the amplitude model results, and marginal agreement is found.
The second study estimates the sensitivity to D0–D̄0 mixing and indirect CP violation parameters that can be achieved using a model-independent technique and the samples of D0→ K0SK+K− decays recorded by LHCb in Run 1 and Run 2 of the LHC. These studies show that constraints on these parameters could be significantly improved by an analysis of the anticipated Run 2 dataset.

Keywords: Particle Physics
Amplitude Analysis
Charm Physics
High Energy Physics
Flavour Physics
Advisor: Wilkinson, G
Methods for phasing and imputation of very low coverage sequencing data

The introduction of massively parallel short-read sequencing has facilitated rapidly dropping costs of DNA sequencing. This has led to substantial growth in the size of human sequencing projects, with consortia of low coverage sequencing data containing tens of thousands of samples. However, current statistical methods for genotype calling from this data scale poorly with sample size, and are infeasible to use on the largest of current projects. This thesis explores the problem of genotype calling and phasing of large sample sizes of low-coverage sequencing data.
Current methods are applied to call and phase genotypes of the CONVERGE consortium, a data set consisting of very low coverage next-generation sequencing data collected from around 12,000 Chinese women. A genotyping accuracy of 92% as measured by squared Pearson correlation (R2) against a SNP geno-typing chip is achieved for minor allele frequencies &GT;5%, demonstrating that very low coverage sequencing can be used instead of SNP genotyping chips to genotype a study of this size.
A new statistical model is described that allows genotype calling and phasing of low coverage sequencing data in N(logN) time complexity, where N is sample size, which greatly improves run time compared to current methods. Other adaptations of the model, including a GPU implementation, are also presented.
The new statistical model is used to call and phase genotypes from the largest collection of low coverage sequencing data in the world (about 32,000 Europeans), the Haplotype Reference Consortium (HRC). At a non-reference allele frequency of 0.1% the HRC haplotypes provide a downstream imputation accuracy of up to 64% R2, compared to an R2 of 36% when using 1000 Genomes Phase 3 haplotypes, the largest publicly available collection of haplotypes derived from low coverage sequencing.
Finally, a web server has been written to allow small numbers of high coverage whole genome sequenced samples to be phased using the HRC panel. The HRC panel is only available to HRC consortium members, but this web server allows the academic community to gain access to the HRC panel for phasing their own samples.

Keywords: Genome-wide association study
GLPhase
CONVERGE
Haplotype Reference Consortium
Advisor: Marchini, J
Online optimisation of the CLIC drive beam bunch train recombination at CTF3

The Compact Linear Collider (CLIC) design is the leading alternative for a future multi-TeV e+e− linear collider. One of the key aspects of the design is the use of a Drive Beam as power source for the acceleration of the colliding beams. This work is focused on the optimisation of the set-up and the operations of the CLIC Drive Beam recombination at the CLIC Test Facility (CTF3) at CERN.
The main effects that may affect the beam quality during the recombination are studied, with emphasis on orbit, transverse dynamics and beam energy effects. A custom methodol- ogy is used to analyse the problem, both from a theoretical and a numerical point of view. The aim is to provide first-order orbit and transverse optics constraints, which can be used as guidelines during the set-up of the beam recombination process. The developed techniques are applied at the CTF3, and the results are reported. The non-linear beam energy effects have been investigated by means of MAD-X simulations. The results show that these effects might be critical for the quality of the recombined beam. A proper non-linear correction turns out to be necessary, especially in the Delay Loop (DL). An alternative DL optics is proposed to mitigate the non-linear energy effects using only linear elements, in contrast with the original design, which relies on sextupoles.
A set of tools for the online control and optimisation of the beam orbit and dispersion has been implemented, deployed and used for the optimisation of the Drive Beam produc- tion at CTF3. Particular effort was put into the development of a generic linear feedback application, which is presented in this work. Thanks to the generality of the problem and its implementation, the feedback has been successfully used for a series of optimisations of the beam at CTF3. A collection of experimental results, focused on the Drive Beam recombination process, is presented and discussed.

Keywords: non-linear dispersion
Optics optimisation
Dispersion correction
Orbit correction
Advisor: Burrows, P
Measurements of the CKM angle γ at the LHCb experiment

Two measurements of the Cabibbo-Kobayashi-Maskawa angle γ using B → DK and B0 → DK&ast;0 decays are presented in this thesis. The subsequent D meson decays to the KS0π+π− and KS0K+K− final states are studied using a binned Dalitz plot analysis. The D strong-phase variation over the Dalitz plot is taken from measurements performed at the CLEO-c experiment, making the analysis independent of a model to describe the D decay amplitude. Both measurements are performed using proton-proton collision data collected by the Large Hadron Collider beauty (LHCb) experiment in 2011 and 2012, corresponding to an integrated luminosity of 3 fb−1 at centre-of-mass energies √s = 7 TeV and 8 TeV. The value γ= (62 +15−14)° is measured using B0 → DK&ast;0 decays and γ = (71 ± 20)° is measured using B0 → DK&ast;0 decays, with a second solution for each value corresponding to γ + 180°. The measurements are consistent with the world average value of γ.

Keywords: B physics
Large Hadron Collider
CKM matrix
CP violation
Advisor: Harnew, N
Malde, S
Magneto-inductive wave data communications systems

Metamaterials display unusual electromagnetic properties, such as, a negative effective permeability and negative effective permittivity. This has sparked much interest due to possibility of negative refraction which was later confirmed by experiments.
The ability of magnetically coupled resonant circuits to display an effective permeability lead to the discovery of magneto-inductive waves. These waves are only supported on arrays of magnetically coupled resonant circuits. Research into magneto-inductive waves has been largely concentrated on their use in filters and their potential use in magnetic resonance imaging.
However, some work has proposed the use of magneto-inductive waveguides as a data transfer medium. This report builds on previous work which found that an optimum existed for terminal-waveguide coupling, and aims to investigate the application of magneto-inductive waves in data transfer systems.
A brief overview of the topic is given along with a description of the underlying characteristics. Factors that affect the capacity of magneto-inductive wave data transfer systems, such as inter element coupling, were identified. Two novel structures, both with the intent of increasing the bandwidth via different methods, are studied. One, by making a pseudo one-dimensional channel from a two-dimensional structure, and the other by using a dual-layer design to increase the coupling between adjacent elements. Both systems are modelled, using simple circuit theory and the impedance matrix method, and a comparison between simulated behaviour and experimental observation was made. There is discussion about the differences between experiment and simulation as well as their limitations.
Magneto-inductive wave data transfer systems are eventually expected to support multiple terminals and as previous research only considered two-terminal systems, an investigation into the response of a one- and two-dimensional system with a blocking terminal was undertaken. The system was modelled, again using simple circuit theory and the impedance matrix method, and simulation and experiment were compared. As a whole, the simulations showed good agreement with experiments, after some initial adjustments. Both one- and two-dimensional systems showed that their performance was not severely effected by a blocking terminal. This suggests that magneto-inductive waveguides could support more terminals.

Keywords: Magneto-inductive waves
Advisor: Stevens, C
Structure and inhibition of novel cyclin-dependent kinases

Protein phosphorylation by members of the cyclin-dependent kinase (CDK) family determines the cell cycle and regulates gene transcription. CDK12 and CDK16 are relatively poorly characterised family members containing atypical domain extensions and represent novel targets for structural studies, as well as cancer drug discovery. In this thesis, I developed protocols to express and purify the human CDK12 kinase domain in complex with its obligate partner, CycK. I solved three distinct crystal structures of the complex providing insights into the structural mechanisms determining CycK assembly and kinase activation. These structures revealed a C-terminal kinase extension that folded flexibly across the active site of CDK12 to potentially gate the binding of the substrate ATP. My structures also identified Cys1039 in the C-terminal extension as the binding site for the first selective covalent inhibitor of CDK12, which has enormous potential as a pharmacological probe to investigate the functions of CDK12 in the DNA damage response and cancer. I also identified rebastinib and dabrafenib as potent, clinically-relevant inhibitors of CDK16 and solved a co-crystal structure that defined the extended type II binding mode of rebastinib. Preliminary trials using these relatively non-selective compounds to inhibit CDK16 in melanoma and medulloblastoma cancer cell lines revealed rebastinib as the more efficacious drug causing loss of cell proliferation in the 1-2 micromolar range. Use of the co-crystal structure to design more selective derivatives would be advantageous to further explore the specific role of CDK16. Finally, I identified a D-type viral cyclin from Kaposi’s sarcoma-associated herpesvirus that could bind to the CDK16 kinase domain and interfere with its functional complex with human CycY causing loss of CDK16 activity. These studies provide novel insights into the structural and regulatory mechanisms of two underexplored CDK family subgroups and establish new opportunities for cancer drug development.

Keywords: Rebastinib
CDK12
Cancer
Cyclin-dependent kinase
THZ531
CDK16 (PCTAIRE1/PCTK1)
Kinase
Transcriptional CDKs
Advisor: Bullock, A
Holistic image understanding with deep learning and dense random fields

One aim of holistic image understanding is not only to recognise the things and stuff in images but also to localise where they are exactly. Semantic image segmentation is set up to achieve this goal. The purpose of this task is to recognise and delineate the visual objects. The solution to this task provides detailed information to understand images and is central to applications such as content-based image search, autonomous vehicles, image-editing, and smart glasses for partially-sighted people. This task is challenging to address not only because the visual objects from the same category could have a variety of appearances but also because of the need to account for contextual information across images such as edges and appearance consistency. The objective of this thesis is to bridge the gap between the pixel-based image representation in computer devices and the meaning extracted by humans.
Our primary contributions are fourfold. Firstly, we propose a factorial fully-connected conditional random field that addresses the problem of jointly estimating the segmentation for both object class and visual attributes. Secondly, we embed the proposed factorial fully-connected conditional random fields framework in an interactive image segmentation system. This system allows users to refine the semantic image segmentation with verbal instructions. Thirdly, we formulate filter-based mean-field approximate inference for fully-connected conditional random fields with Gaussian pairwise potentials as a recurrent neural network. This formulation allows us to integrate fully convolutional neural networks and conditional random fields in an end-to-end trainable system. Fourthly, we show the relationship between fully-connected conditional random fields with Gaussian pairwise potentials and iterative Graph-cut: We found that fully-connected conditional random fields with Gaussian Pairwise potential implicitly model the unnormalised global colour models for foreground and background.

Keywords: Probabilistic Graphical Model
Deep Learning
Conditional Random Fields
Dense Random Fields
Advisor: Torr, P
Climate and biodiversity in the Andean Dry Puna

Arid mountain systems and their biological diversity are particularly vulnerable to changes in climate. The aim of this thesis was to evaluate climate variability and its impacts on ecological systems at different spatial and temporal scales, focusing on the Dry Puna ecoregion in the Central Andes, around the triple frontier of Argentina, Bolivia and Chile, and using a combination of climate data, data from remote sensors, and ecological surveys. I expanded on earlier generalized climatic trends by empirically assessing climate variability since 1980 with a larger set of weather stations at high elevation. I found no consistent temporal trends in temperature and rainfall, but high inter-annual variation in rainfall associated with El Niño Southern Oscillation (ENSO) effects. Climate and topography affected vegetation productivity (measured as the Normalized Difference Vegetation Index NDVI) in the Dry Puna in various ways. Primary productivity was overall low but higher in the High Plateau, under the humid influence of the Amazon. There was no significant temporal trend in productivity in the study area since 1980 and NDVI variability was chiefly driven by ENSO conditions (lower during El Niño years, with dry and hot summers). At a finer scale, vegetation types responded to low rainfall in different ways; tussock grasslands were the most affected by low rainfall; wetlands and scrublands the most resilient. The aridity of the Dry Puna also poses particular ecological limitations to animals. Using species distribution models and resource selection functions I showed that mesocarnivores coexist in this low productive ecosystem by selecting key resources at different degrees and scales, including free water, clusters of prey and refuge. The endangered Andean cat Leopardus jacobita, the most specialized, was also the most selective at finer scales and showed the larger spatial overlap with its preferred prey the southern mountain viscacha Lagidium viscacia. Using bioclimatic models at the continental level, I predicted that suitable habitats for Andean cats will decline under future scenarios of climate change by up to a third by 2080. Although 15% would still be represented within the current network of protected areas, there will be a dramatic decline in the northern reach of the species range. Given the dearth of earlier climatic and ecological studies in the Dry Puna, this thesis makes a substantial contribution to better understand the impact of climate on the productivity of this dry environment, and how threatened species may interact and respond to current and projected climate conditions.

Advisor: Sillero-Zubiri, C
Marino, J
Optimisation of vessel-selective magnetic resonance perfusion imaging and angiography

The diagnosis and treatment of cerebrovascular disease, such as stroke and vascular lesions in the brain, requires knowledge of the status of brain tissue and cerebral arteries. Perfusion imaging and angiography offer information on blood flow to the tissue and through the brain-feeding arteries. A variety of imaging modalities exist to assess brain haemodynamics, including measures of cerebral blood flow and other parameters, however many of these are invasive and/or involve the use of contrast agents toxic to certain patient populations.
One non-invasive magnetic resonance imaging alternative for perfusion imaging and angiography, which also provides vessel specific blood flow information, is vessel-encoded pseudocontinuous arterial spin labelling (VEPCASL). VEPCASL uses the blood as an endogenous tracer and can magnetically label the blood from different arteries of interest. The combination of VEPCASL with different imaging strategies can provide a map of the vascular perfusion territories in the brain, or dynamic information on blood flow through the cerebral arteries.
The work in this thesis seeks to optimise and develop the encoding process of VEPCASL and accompanying angiographic readouts. Firstly, a rapid and automated method for calculating a minimal number of signal-to-noise ratio (SNR) efficient encodings, for any number and arrangement of vessels, was developed. Its use resulted in improved SNR in perfusion territories fed by more complicated vessel arrangements in the labelling plane. The labelling efficiency of VEPCASL, and its non-vessel-selective equivalent, PCASL, is affected by the presence of magnetic field inhomogeneities in the labelling plane. Consequently, a correction for phase offsets was introduced into the calculation of the optimised encodings. These encodings enabled the recovery of SNR in perfusion territories for PCASL and VEPCASL when phase offsets were present at the labelled arteries.
As current VEPCASL angiography methods are relatively slow to acquire, an accelerated readout was developed to acquire two-dimensional vessel-selective dynamic angiograms in approximately one minute. A radial k-space trajectory was found to offer the best vessel definition and SNR. Three-dimensional (3D) angiograms provide the most detailed view of the cerebral vasculature for use in diagnosis and treatment of cerebrovascular disease. A 3D radial readout was optimised to acquire vessel-selective dynamic angiograms. These angiograms offer information on the structure of the vascular tree and how it is fed by the major arteries in the neck.
The techniques developed here aim to increase the clinical viability and applicability of VEPCASL perfusion imaging and angiography. It is hoped that the techniques herein could be used in patient populations to add to and improve the diagnostic information available.

Keywords: Perfusion imaging
Angiography
Advisor: Okell, T
Jezzard, P
Probing the cohesin loading reaction using forward genetics and quantitative ChIP-sequencing

Cohesion between sister chromatids that are newly formed in S-phase is crucial to ensure the fidelity of chromosome segregation. The cohesin complex mediates cohesion and is comprised of two SMC proteins, Smc1 and Smc3, with a kleisin subunit, Scc1. The SMCs interact via their hinge domains to form a v-shaped heterodimer, with Scc1 forming a bridge between their head domains to produce a ring structure that topologically entraps sister chromatids. In order to confer cohesion, cohesin needs to be loaded onto DNA, a process that is poorly understood. It is known that cohesin loading depends on a loading complex comprised of Scc2 and Scc4, ATP hydrolysis and presumably opening of at least one of the interfaces of the cohesin ring.
Using the recently developed technique, quantitative ChIP-seq, we show that Pds5, a cohesin-associated protein, is displaced at centromeres from the cohesin ring during the loading reaction. This event is accompanied by the engagement of SMC ATPase heads in the presence of ATP. Upon ATP hydrolysis, the loading reaction completes with DNA entrapment, translocation to the pericentromeric sequences and the displacement of Scc2 by Pds5.
We also describe mutations in Scc2, Smc1 and histone proteins H2A and H2B that enable loading in the absence of Scc4. The mutations in Scc2 alter the dynamics of the association between the loading complex and cohesin, reducing dissociation during the translocation step. All of the mutations are able to restore loading along chromosome arms but not at centromeres where Scc4 has a particular role. However, the Smc1 mutation hinders loading at the centromere, even in the presence of Scc4, due to a defect in the second step of the loading reaction, namely translocation driven by ATP hydrolysis. We suggest that this discrepancy in functionality at the arms and centromere is due to changes in the hinge accompanying both the first and second steps. The rate limiting reaction is the first step at arms and the second at the centromeres. The histone mutants show that nucleosome occupancy plays an important role, at least on chromosome arms, but we find no evidence that this involves the RSC complex.

Keywords: Calibrated ChIP-seq
Smc1
RSC complex
Scc2
Advisor: Nasmyth, K