VictorJuiz/thesis huggingface dataset:
Assessment of obstetric ultrasound images using machine learning
Keywords: fetal ultrasound
image analysis
machine learning

Ultrasound-based fetal biometry is used to derive important clinical information for identifying IUGR (intra-uterine growth restriction) and managing risk in pregnancy. Accurate and reproducible biometric measurement relies heavily on a good standard image plane. However, qualitative visual assessment, which includes the visual identification of certain anatomical landmarks in the image is prone to inter- and intra-reviewer variability and is also time-consuming to perform. Automated anatomical structure detection is the first step towards the development of a fast and reproducible quality assessment of fetal biometry images. This thesis deals specifically with abdominal scans in the development and evaluation of methods to automatically detect the stomach and the umbilical vein within them.
First, an original method for detecting the stomach and the umbilical vein in fetal abdominal scans was developed using a machine learning framework. A classifier solution was designed with AdaBoost learning algorithm with Haar features extracted from the intensity image. The performance of the new method was compared on different clinically relevant gestational age groups.
Speckle and the low contrast nature of ultrasound images motivated the idea of introducing features extracted from local phase images. Local phase is contrast invariant and has proven to be useful in other ultrasound image analysis application compared with intensity. Nevertheless, it has never been implemented in a machine learning environment before. In our second experiment, local phase features were proven to have higher discriminative power than intensity features which enabled them to be selected as the first weak classifiers with large classifier weight.
Third, a novel approach to improving the speed of the detection was developed using a global feature symmetry map based on local phase to select the candidate locations for the stomach and the umbilical vein. It was coupled with a local intensity-based classifier to form a “hybrid” detector. A nine-fold increase in the average computational speed was recorded along with higher accuracy in the detection of both the anatomical structures.
Quantitative and qualitative evaluations of all the algorithms were presented using 2384 fetal abdominal images retrieved from the image database study of the Oxford Ultrasound Quality Control Unit of the INTERGROWTH-21st project.
Finally, the “hybrid” detection method was evaluated in two potential application scenarios. The first application was clinical scoring in which both the computer algorithm and four experts were asked to record presence or absence of the stomach and the umbilical vein in 400 ultrasound images. The computer-experts agreement was found to be comparable with the inter-expert agreement. The second application concerned selecting the standard image plane from 3D abdominal ultrasound volume. The algorithm was successful in selecting 93.36% of the images plane defined by the expert in 30 ultrasound volumes.
Simulations of shock-induced phase transitions in silicon
Keywords: pressure
physics
SIlicon
material
laser
Phase Transition
shock
density functional theory
molecular dynamics
Crystal

An understanding of the fundamental mechanism behind the relief of shear stress in single-crystal silicon subject to loading by shock-waves has to this day remained elusive. What is known is that this material undergoes a first-order pressure-induced polymorphic phase transition from its ambient pressure cubic-diamond (cd) crystal structure to its first stable high-pressure phase, known as β-Sn, at a pressure of about 120 kbar under hydrostatic compression. By investigating the evolution of the transition parameters for this phase transition as a function of increasing uniaxial shear stress representative of the effects of shock-compression via ab-initio Density Functional Theory computational techniques, we predict a significant lowering of the stress at which the phase transition occurs. This raises the question as to whether the onset of plastic response at the material's Hugoniot Elastic Limit (HEL) reported in experiments corresponds in fact to the phase transition itself, a very plausible possibility which has never been considered before. Furthermore, we present molecular dynamics simulations using a Tersoff-like potential of shock-compressed single crystals of silicon. We find an elastic response up to a critical stress, above which the shear stress is relieved by an inelastic response associated with a partial transformation to a new high-pressure phase, where both the new phase (Imma) and the original cubic diamond phase are under close to hydrostatic conditions. We note that these simulations are also consistent with shear stress relief provided directly by the shock-induced phase transition itself, without an intermediate state of plastic deformation of the cubic diamond phase.
Multilocus approaches to the detection of disease susceptibility regions: methods and applications
Keywords: genetic interaction
statistical genetics
prostate cancer
multilocus analysis

This thesis focuses on multilocus methods designed to detect single nucleotide polymorphisms (SNPs) that are associated with disease using case-control data. I study multilocus methods that allow for interaction in the regression model because epistasis is thought to be pervasive in the etiology of common human diseases. In contrast, the single-SNP models widely used in genome wide association studies (GWAS) are thought to oversimplify the underlying biology. I consider both pairwise interactions between individual SNPs and modular interactions between sets of biologically similar SNPs. Modular epistasis may be more representative of disease processes and its incorporation into regression analyses yields more parsimonious models. My methodological work focuses on strategies to increase power to detect susceptibility SNPs in the presence of genetic interaction. I emphasize the effect of gene-gene independence constraints and explore methods to relax them. I review several existing methods for interaction analyses and present their first empirical evaluation in a GWAS setting. I introduce the innovative retrospective Tukey score test (RTS) that investigates modular epistasis. Simulation studies suggest it offers a more powerful alternative to existing methods. I present diverse applications of these methods, using data from a multi-stage GWAS on prostate cancer (PRCA). My applied work is designed to generate hypotheses about the functionality of established susceptibility regions for PRCA by identifying SNPs that affect disease risk through interactions with them. Comparison of results across methods illustrates the impact of incorporating different forms of epistasis on inference about disease association. The top findings from these analyses are well supported by molecular studies. The results unite several susceptibility regions through overlapping biological pathways known to be disrupted in PRCA, motivating replication study.
Generation of a novel endogenously StrepII/FLAG tagged system for the identification of the vertebrate FANCJ associated proteins
Keywords: Fanconi anaemia
StrepII/FLAG tag
FANCJ
interstrand crosslink
helicase
DNA damage

Fanconi Anaemia (FA) is a rare inherited chromosomal instability disorder characterized by developmental abnormalities, bone marrow failure, increased risk of developing cancer and an increased cellular sensitivity to DNA interstrand crosslinking compounds, including the anticancer drugs, cisplatin, nitrogen mustard and mitomycin C. From a therapeutic point of view, it is important to understand how cells respond to and repair DNA damage caused by crosslinking compounds, used to treat cancer. To date, fifteen different proteins involved in a common pathway, known as the FA pathway have been identified and are known to respond to, and influence repair of interstrand crosslinks (ICLs). So far, the role of these proteins in ICL repair remains elusive. To gain insights into the molecular basis of ICL repair, we chose to study the FA-associated helicase FANCJ, as it is known to bind and metabolize a variety of DNA substrates, implicating it in maintenance of genomic stability. Here, I report a novel genetic-proteomic approach to study FANCJ. This system uses epitope tagged FANCJ expressed from its chromosomal locus, in chicken DT40 cells, kept under the control of its endogenous promoter. Tandem affinity purification is employed to purify and isolate the tagged protein and identify interacting partners of interest. To date, I have generated, characterized and validated epitope tagged FANCJ cell lines. Pilot immunoprecipitations were carried out to establish the efficiency and reproducibility of the immunoprecipitations (IPs). Analysis by mass spectrometry revealed the presence of epitope tagged FANCJ in scaled-up immunoprecipitations. In the future, these cell lines will be used to identify and characterize the FANCJ interactome.
The concept of community in the transformation of systems theory: Luhmann, Habermas and recent German writing
Keywords: Luhmann
systems theory
community

The concept of community is highly problematic in the German context. ‘Gemeinschaft’ plays only a minor role in post-1945 philosophical writing, arguably as a result of the abuse of the concept by the National Socialists (‘Volksgemeinschaft’). Two of the major contemporary social philosophies in the German language, those of Jürgen Habermas and Niklas Luhmann, are deeply critical of ‘community’. Habermas rejects ‘community’ that has not been purified by a rational filter (as opposed to what he conceives of as the ideal ‘Kommunikationsgemeinschaft’). Luhmann rejects the concept outright, arguing that it is simply ‘alteuropäisch’ (i.e. based on out-of-date philosophical assumptions), and that it has no place in the description of modern society. In contrast to these prominent dismissive positions, I argue that the concept of community is an underrated one. First, Habermas relies more heavily on the concept of community than his focus on the ‘Lebenswelt’ makes us believe. I characterise his conception as a ‘transformation’ of systems theory, because his social philosophy partly adopts systems theory, while complementing it with the aspect of ‘community’. Second, I argue that contemporary cultural theoreticians (for example, Peter Sloterdijk) take systems theory as a starting point for developing ultimately communitarian social philosophies. The concept of community proves crucial as supplementation and balancing of systems-theoretical elements in contemporary thinking. Once this transformative role is recognised, a purely historical treatment of the concept of community – one which, as in Luhmann’s systems theory, sees no place for it in present or future theory – begins to look premature.
Close together but a world apart: a comparative history of research practices during the formative years of Brazilian academic science (1934-1955)
Keywords: History of Science
Brazilian Studies
Comparative History

This thesis compares the ways in which the nationalisation process impacted the research practices of academics from two universities, the University of Rio Grande do Sul and the University of Parana. Systematic comparisons of both institutions located in the South of Brazil has shown that the differences between them were, indeed, significant during pre-nationalisation years. In Brazilian terms, they are ‘close’ together since only seven hundred kilometres separate them. However, the necessity for regionalised studies on the development of academic science is demonstrated in this thesis through a focus on specific faculties that achieved remarkably different research results, despite their geographical proximity. The comparative analysis carried out in this thesis reveals that significant differences existed, such as institutional arrangements, disciplinary boundaries and networks, despite the fact that they were often found under similar academic arrangements. The nationalisation project carried out in 1950 did not alter these differences overnight, but introduced a new element in both settings that would shape their scientific capabilities to this day. Substantial new evidence presented here indicates that in the early 1950s President Dutra, perhaps inadvertently, forced research-minded academics in both universities to consider the possibility of adapting their research projects to their nationalised institutions. Because of the chain of events enabled by this initiative, in later years, these universities became some of the most prominent institutional settings for scientific research in Brazil. A comparative study of the differences and similarities between ongoing practices in these academic settings at the moment of nationalisation indicates that nationalisation did not occur in an historical vacuum; rather, it enhanced and legitimised deeply rooted academic traditions that came to shape local research cultures over the following decades. When this context is explored it becomes clear that an understanding of nationalisation actually lends greater coherence to traditional chronologies of Brazilian academic science.
The globalisation of universal human rights and the Middle East
Keywords: Arab Charter of Human Rights
United Arab Emirates
MENA
Globalisation
Dubai
Islam
Gulf Cooperation Council
Transnational Activist Networks
Regionalism
UN Human Rights Council
Arab League
Middle East
North Africa
Egypt
Arab Awakening
Women's Rights
Human Rights
Arab Spring
Norm Diffusion
Iran
Cultural Relativism
Universalism

The goal of this study is to generate a more holistic picture of the diffusion and assimilation of universal human rights norms in diverse cultural and political settings such as the Middle East and North Africa (MENA). The overarching question to be investigated in this thesis is the relationship between the evolving international human rights regime and the emerging human rights normative and legal culture in the Middle East. This question will be investigated in detail with reference to regional human rights schemes such as the Arab Charter of Human Rights, as well as local human rights developments in three Middle Eastern states, Egypt, the United Arab Emirates, and the Islamic Republic of Iran. Having gauged the take-up of human rights norms on the ground at the local and regional levels, the thesis examines in full the extent of socialisation and internalisation of human rights norms across the Middle East region at large.
Transcriptional brain networks and their key regulators across the human lifespan
Keywords: gene expression
transcriptional network
ageing
neuroscience

The human brain’s transcriptome undergoes substantial changes over the lifespan and shows characteristic patterns that reflect anatomical regions and cellular compositions. In this thesis, I applied combinations of network algorithms and tools from computational biology to analyse transcriptional networks and their key regulators in the human brain across space (brain regions) and time (the human life course). First, I identified an age-dependent transcriptional network enriched for microglial markers. The microglia network recapitulated haematopoietic master regulators that are crucial for early microglia development using data from the ageing human brain only. In the second project, I demonstrated that gene clusters linked to neurogenesis during fetal life show moderate to strong preservation in the human adult brain. In addition to temporal development, I analysed transcriptional network dynamics across the spatial axis and detected a network of ion channel/transporter genes that express their longest 3’ untranslated regions (3’UTRs) exclusively in the brain. Enrichment for predicted miRNA response elements that are often shared among the ion channel/transporter genes, along with increased co-expression of this gene set, indicated that the extended 3’UTRs could serve as a hub for an endogenous competitive RNA network. I extended the analysis to differentiate between brain regions and additional regulatory RNA elements, namely long noncoding (lnc) RNAs. I found that genes in the hypothalamus express a region-specific network to which are also associated co-expressed lncRNAs. Finally, I added global metrics to the analysis of local networks. The dynamics of global network metrics indicated strong coordination of expression across the lifespan compared to similar variance within age groups. This work shows that the transcriptome of human post-mortem brains at least partially preserves the network structure of cell types and functionally related genes, and how it may be dissected using suitable combinations of bioinformatic algorithms.
Bayesian and frequentist methods and analyses of genome-wide association studies
Keywords: case-control
GWAS
Bayes factor
Genome-wide association study
linkage disequilibrium
complex human diseases
g-prior
Bayesian
frequentist

Recent technological advances and remarkable successes have led to genome-wide association studies (GWAS) becoming a tool of choice for investigating the genetic basis of common complex human diseases. These studies typically involve samples from thousands of individuals, scanning their DNA at up to a million loci along the genome to discover genetic variants that affect disease risk. Hundreds of such variants are now known for common diseases, nearly all discovered by GWAS over the last three years. As a result, many new studies are planned for the future or are already underway. In this thesis, I present analysis results from actual studies and some developments in theory and methodology. The Wellcome Trust Case Control Consortium (WTCCC) published one of the first large-scale GWAS in 2007. I describe my contribution to this study and present the results from some of my follow-up analyses. I also present results from a GWAS of a bipolar disorder sub-phenotype, and a recent and on-going fine mapping experiment. Building on methods developed as part of the WTCCC, I describe a Bayesian approach to GWAS analysis and compare it to widely used frequentist approaches. I do so both theoretically, by interpreting each approach from the perspective of the other, and empirically, by comparing their performance in the context of replicated GWAS findings. I discuss the implications of these comparisons on the interpretation and analysis of GWAS generally, highlighting the advantages of the Bayesian approach. Finally, I examine the effect of linkage disequilibrium on the detection and estimation of various types of genetic effects, particularly non-additive effects. I derive a theoretical result showing how the power to detect a departure from an additive model at a marker locus decays faster than the power to detect an association.
The role of glutamate in rotator cuff tendinopathy
Keywords: rotator cuff
shoulder
tendon
pain
tendinopathy
glutamate

Thesis questions:
Is the glutaminergic system altered in rotator cuff tendinopathy?
Is the glutaminergic system altered by common treatments?
Are glutaminergic changes related to pain symptoms?
What are the effects of glutamate and glutamate receptor modulation on tendon derived cells?
Summary answers:
The glutaminergic system is altered in rotator cuff tendinopathy
Changes within this system are seen after common treatments
Specific glutaminergic changes are associated with the resolution of pain following shoulder surgery but do not predict the severity of pain symptoms
Glutamate has significant effects on tendon derived cells
What is known: It is known that extracellular glutamate concentrations are increased in both Achilles and patellar tendinopathy. It has also been previously shown that the glutamate receptors NMDAR1 and mGluR5 are upregulated in patellar tendinopathy.
What this thesis adds: This thesis has shown for the first time that glutamate and NMDAR1 are increased in rotator cuff tendinopathy. Increases in cell proliferation, vascularity and HIF1α are seen after surgical rotator cuff repair and these features are not seen after glucocorticoid injection. There are significant differences between painful and pain-free rotator cuff tendons in terms of glutamate receptor expression (KA1, mGluR7 and mGluR2) and inflammatory cell numbers (CD45 and CD206). Exposure to 1.875mM glutamate for 72 hours results in reduced cell viability, decreased collagen (COL1A1 and COL3A1) and increased aggrecan gene expression; NMDAR antagonism with MK-801 attenuates the deleterious effect on cell viability but had no effect on the changes in matrix gene expression.
Bias, confounding and other reasons for caution: The observational histological work was limited by the control tissue. Some control tissue was not age matched, while some of the pain-free control tendons were post-surgical intervention. Confounding factors include tendon structure, length of symptoms and previous treatments. Caution must be applied when discussing the in vivo implications of the in vitro work.
Study funding/potential competing interests: This thesis was funded by the Jean Shanks Foundation and Orthopaedic Research UK.
Multiscale modelling of fluid and drug transport in vascular tumours
Keywords: tumour biology
homogenization
vascular networks

Understanding the perfusion of blood and drugs in tumours is fundamental to foreseeing the efficacy of treatment regimes and predicting tumour growth. In particular, the dependence of these processes on the tumour vascular structure is poorly established. The objective of this thesis is to derive effective equations describing blood, and drug perfusion in vascular tumours, and specifically to determine the dependence of these on the tumour vascular structure. This dependence occurs through the interaction between two different length scales - that which characterizes the structure of the vascular network, and that which characterizes the tumour as a whole. Our method throughout is to use homogenization as a tool to evaluate this interaction. In Chapter 1 we introduce the problem. In Chapter 2 we develop a theoretical model to describe fluid flow in solid tumours through both the vasculature and the interstitium, at a number of length scales. Ultimately we homogenize over a network of capillaries to form a coupled porous medium model in terms of a vascular density. Whereas in Chapter 2 it is necessary to specify the vascular structure to derive the effective equations, in Chapter 3 we employ asymptotic homogenization through multiple scales to derive the coupled equations for an arbitrary periodic vascular network. In Chapter 4, we extend this analysis to account for advective and diffusive transport of anticancer drugs delivered intravenously; we consider a range of reaction properties in the interstitium and boundary conditions on the vascular wall. The models derived in Chapters 2–4 could be applied to any drug type and treatment regime; to demonstrate their potential, we simulate the delivery of vinblastine in dorsal skinfold chambers in Chapter 5 and make quantitative predictions regarding the optimal treatment regime. In the final Chapter we summarize the main results and indicate directions for further work.