VictorJuiz/thesis huggingface dataset:
Non-parametric probability density function estimation for medical images
Keywords: probability density function
automated image analysis
Non-parametric
colorectal cancer
mixture model
level sets

The estimation of probability density functions (PDF) of intensity values plays an important role in medical image analysis. Non-parametric PDF estimation methods have the advantage of generality in their application. The two most popular estimators in image analysis methods to perform the non-parametric PDF estimation task are the histogram and the kernel density estimator. But these popular estimators crucially need to be ‘tuned’ by setting a number of parameters and may be either computationally inefficient or need a large amount of training data. In this thesis, we critically analyse and further develop a recently proposed non-parametric PDF estimation method for signals, called the NP windows method. We propose three new algorithms to compute PDF estimates using the NP windows method. One of these algorithms, called the log-basis algorithm, provides an easier and faster way to compute the NP windows estimate, and allows us to compare the NP windows method with the two existing popular estimators. Results show that the NP windows method is fast and can estimate PDFs with a significantly smaller amount of training data. Moreover, it does not require any additional parameter settings. To demonstrate utility of the NP windows method in image analysis we consider its application to image segmentation. To do this, we first describe the distribution of intensity values in the image with a mixture of non-parametric distributions. We estimate these distributions using the NP windows method. We then use this novel mixture model to evolve curves with the well-known level set framework for image segmentation. We also take into account the partial volume effect that assumes importance in medical image analysis methods. In the final part of the thesis, we apply our non-parametric mixture model (NPMM) based level set segmentation framework to segment colorectal MR images. The segmentation of colorectal MR images is made challenging due to sparsity and ambiguity of features, presence of various artifacts, and complex anatomy of the region. We propose to use the monogenic signal (local energy, phase, and orientation) to overcome the first difficulty, and the NPMM to overcome the remaining two. Results are improved substantially on those that have been reported previously. We also present various ways to visualise clinically useful information obtained with our segmentations in a 3-dimensional manner.
The application of optimal estimation retrieval to lidar observations
Keywords: aerosol
Raman lidar
Optimal estimation

Optimal estimation retrieval is a nonlinear regression scheme to determine the conditions statistically most-likely to produce a given measurement, weighted against any a priori knowledge. The technique is applied to three problems within the field of lidar data analysis.
A retrieval of the aerosol backscatter and either the extinction or lidar ratio from two-channel Raman lidar data is developed using the lidar equations as a forward model. It produces profiles consistent with existing techniques at a resolution of 10-1000 m and uncertainty of 5-20%, dependent on the quality of data. It is effective even when applied to noisy, daytime data but performs poorly in the presence of cloud.
Two of the most significant sources of uncertainty in that retrieval are the nonlinearity of the detectors and the instrument's calibration (known as the dead time and overlap function). Attempts to retrieve a nonlinear correction from a pair of lidar profiles, one attenuated by a neutral density filter, are not successful as uncertainties in the forward model eliminate any information content in the measurements. The technique of Whiteman et al. [1992] is found to be the most accurate.
More successful is a retrieval of the overlap function of a Raman channel using a forward model combining an idealised extinction profile and an adaptation of the equations presented in Halldórsson and Langerholc [1978]. After refinement, the retrieval is shown to be at least as accurate, and often superior to, existing methods of calibration from routine measurements, presenting uncertainties of 5-15%.
These techniques are then applied to observations of ash over southern England from the Eyjafjallajökull eruption of April 2010. Lidar ratios of 50-60 sr were observed when the plume first appeared, which reduced to 20-30 sr after several days within the planetary boundary layer, indicating an alteration of the particles over time.
A primary care-based intervention to improve participation in the NHS bowel cancer screening programme
Keywords: Primary Care
mass screening
faecal occult blood test
randomised trial
colorectal cancer
questionnaires

Background: Currently, participation in the NHS Bowel Cancer Screening Programme (NHSBCSP) is poor, with around half of all people invited returning their (FOBT) kits. The research programme aimed to investigate whether a general practitioner’s (GP) letter encouraging participation and a detailed leaflet explaining how to complete the (FOBT) included with the invitation materials would improve uptake.
Methods: The research programme was divided into three phases which were designed to sequentially develop and evaluate the two interventions. The initial and second phases developed and refined the two interventions and the trial outcome measures with previous participants and stakeholder representatives. The final phase was a randomised 2x2 factorial trial conducted with people invited to screening in October 2009. Participants were randomised to either a GP’s endorsement letter and/or a detailed procedural leaflet with their FOBT kit. The primary outcome was verified participation in the NHSBCSP. Questionnaires were also used to evaluate participant perceptions of CRC screening and GPs views on involvement with the NHSBCSP.
Results: The factorial trial demonstrated both the GP’s endorsement letter and the detailed procedural leaflet increased participation in the NHSBCSP. In the intention-to-treat analysis, participation improved by 6% for the detailed procedural leaflet and 5.8% for the GP endorsement letter 20 weeks after receipt of the FOBT kit. The random effects logistic regression model confirmed that there was no important interaction between the two interventions, and estimated an adjusted rate ratio of 1.11 (P=0.038) for the GP’s letter and 1.12 (P=0.029) for the leaflet. The per protocol analysis indicated that the insertion of an electronic GP’s signature on the endorsement letter was associated with increased participation (P=0.039).
Conclusions: Including both an endorsement letter from each patient’s GP and a detailed procedural leaflet could increase participation in the NHSBCSP by around 10%, a relative improvement of 20% on the current participation rate. Both interventions were well-received by participants and there was minimal impact on GP workload.
The role of type I interferons in regulating intestinal inflammation
Keywords: type i interferons
mucosal immunology
colitis
inflammatory bowel disease

Intestinal homeostasis is a delicate balance between suppression of immune responses against innocuous antigens and stimulation of immune responses against pathogens. Type I interferon (IFN-1) cytokines have both immunostimulatory and immunomodulatory effects. Colon mononuclear phagocytes (MP) constitutively produced IFN-1 in a TRIFdependent manner. We explored the function of endogenous IFN-1 in the colon using the T cell adoptive transfer model of colitis. Transfer of CD4+CD45RBhi naïve T cells from wild type (WT) or IFNAR subunit 1 knockout (IFNAR1-/-) mice into RAG-/- hosts resulted in similar onset and severity of colitis. In contrast, RAG-/- x IFNAR1-/- double knockout (DKO) mice developed accelerated severe colitis compared to RAG-/- hosts when transferred WT CD4+CD45RBhi T cells. Although WT or IFNAR1-/- regulatory T (Treg) cells equally prevented disease caused by CD45RBhi naïve T cells, WT Treg cells co-transferred with naïve CD4+ T cells into DKO recipients failed to expand or maintain Foxp3 expression and gained effector functions in the colon. IFNAR signaling on host hematopoietic cells inhibited T cell-mediated colitis, but not innate colitis. MPs isolated from the colon lamina propria (cLP) required IFNAR signaling for the production of the anti-inflammatory cytokines, IL-10, IL-27, and IL-1RA, but not for the production of classic pro-inflammatory cytokines. IFN-1-dependent secretion of IL-1RA was particularly important in inhibiting the migration of inflammatory DCs with potent T cell proliferative capacity from the cLP to the mesenteric lymph nodes. Finally, preliminary results suggested that IFN-1 may shape the commensal microbiota, but is not essential for controlling specific colitis-inducing bacteria.
Varieties of regulation: how states pursue and set international financial standards
Keywords: Resolution
Globalization
Regulation
Banking law
Insurance
International finance
Securities

What explains the form and substance of international financial standards? Form refers to the legal or non-legal bindingness of an international standard. Substance refers to how significantly the standard changes the international status quo. The form and substance of international standards on bank capital adequacy, hedge funds, “bail-in” resolution, and insurance capital adequacy challenge the predictions of major rationalist, realist, and two-level perspectives. I propose a novel theory and present original evidence to test two central claims. First, the structure of domestic institutions and strategic interaction within a state incentivizes an actor from that state to prefer and pursue a certain form of international standard: legally or non-legally binding. The state actor, as a first mover, aims to propose a standard at an appropriate international institution which produces standards of its preferred form. Second, the state actor must bargain with representatives of other states according to certain decision-making rules at the international standard-setting institution. The type of decision-making rule used in bargaining—not the market power or other characteristics of key players—explains the substance of the final standard. More restrictive decision-making rules, which use majority or supermajority voting, lead to greater change than open rules, which are based on consensus or unanimity voting.
My empirical findings remove the veneer of technocratic legitimacy associated with international standard-setting to reveal intense distributional battles. In pursuing the Basel capital standards, the US Federal Reserve has been motivated more by turf wars with other US bank regulators than by its publicly stated desire to create a “level playing field” for internationally active banks. Supported by domestic collaboration between regulators and industry, French officials set a legally binding and deep de facto international standard for hedge fund managers over the vigorous objections of the City of London. By pursuing a soft standard on bail-in, the Bank of England has sought not only to protect taxpayers from costly bailouts, but also to keep Her Majesty’s Treasury at arm’s length. The lack of international insurance regulation is due not to the lack of effort by the UK Financial Services Authority and its European partners, but to open decision-making rules that allow US state regulators, albeit fragmented and under-resourced, to protect the international status quo. In each of these cases, I specify how domestic and international institutional settings provide enduring opportunities and constraints for key players in global finance.
Armies, politics and revolution. Chile, 1780-1826
Keywords: Chile
revolution
military
independence

This thesis studies the political role of the Chilean military during the years 1780-1826. Beginning with the last decades of the eighteenth century and ending immediately after the last royalist contingents were expelled from the island of Chiloé, this thesis does not seek to give a full picture of the participation of military men on the battlefield but rather to interpret their involvement in local politics. The main categories deployed in this study are 1) armies, 2) politics and 3) revolution, and the three are presented with the purpose of demonstrating that, as Peggy K. Liss has claimed, after 1810 Spanish American public life ‘became militarized; and the military, privileged’. I argue that, notwithstanding the sometimes tense relationship between civilians and the armed forces, the Chilean military became privileged because the demise of the Spanish monarchy in 1808 made them protagonists of the decision-making process. In so doing, this thesis aims to make a contribution to the understanding of Chile’s revolution of independence, as well as to discuss some recent historiographical contributions on the role of the military in the creation of the Chilean republican system. Although the focus has been placed on the career and participation of Chilean revolutionary officers, this thesis also seeks to provide an overview of both the role of royalist armies and the influence of international events in Chile.
Bioinformatical and experimental analysis of gene expression regulation through RNAi and alternative polyadenylation
Keywords: Human Nuclear Dicer
RNAi
Alternative Polyadenylation
Schizosaccharomyces pombe
microRNA
Cohesin
Poly(A) Signal

Polyadenylation signals in yeast are not very well defined and are believed to be largely degenerate. Here, we present a computational and experimental genome-wide analysis of polyadenylation signals in Schizosaccharomyces pombe (S. pombe), identifying the canonical AATAAA motif as the most frequent and functional signal. RNA-Seq data from cells grown under various physiological conditions were used to map 3’UTRs, which classify as commonly heterogenic. We have shown that many genes have alternative 3’UTRs. Our results are summarised and can be accessed in a user-friendly online database Pomb(A).
It has been shown that convergent genes require trans elements, like Cohesin, for efficient transcription termination. We demonstrate that convergent genes lacking Cohesin are generally associated with longer overlapping transcripts. Furthermore, we analysed ChIP-chip data of Rad21 and Mis4 as well as other Cohesin and loading complex subunits and show that regions of Rad21/Mis4 co-localisation are generally associated with highly transcribed genes. They are also cohesive, while sites with Rad21 only are less cohesive. Rad21/Mis4 co-localisation sites are in close proximity to annotated origins of replication, suggesting that cohesive sites may facilitate replication.
microRNAs (miRNAs) are well studies in higher eukaryotes and participate on post-transcriptional gene silencing by degrading target mRNA or blocking translation. It is believed that miRNAs do not exist in yeast. We reanalyzed miRNA presence in yeast using recently available small RNA data sets. Potential miRNA genes and targets in S. pombe were computationally predicted based on the described alternative 3’UTR data and further experimentally tested.
Dicer is an enzyme, which recognizes long dsRNA substrates and cleaves them into siRNA e↵ector molecules, essential for gene silencing. Dicer has been thought to be a purely cytoplasmic protein. However, we employed ChIP-Seq and dsRNA RNA-Seq data to show that Dicer localises in the nucleus of mammalian cells and associates with the chromatin on numerous loci. Furthermore, we present evidence that Dicer processes long dsRNA into siRNA in the nucleus and the lack of Dicer causes the accumulation of long dsRNA. This consequently induces the interferon response pathway, which ultimately leads to apoptosis and cell death.
Late Holocene archaeology in Namaqualand, South Africa: hunter-gatherers and herders in a semi-arid environment.
Keywords: Namaqualand
Hunter-gatherers
herders

This study examines mid- to late Holocene Later Stone Age archaeological residues – specifically flaked stone artefacts, ostrich eggshell beads and pottery – from Namaqualand, north-western South Africa. Through its implication in all models so far proposed, Namaqualand is crucial to understanding the introduction of herding to the southern African subcontinent. Despite numerous publications on early herding, many key debates remain unresolved.
The study focuses on the northern and central Namaqualand coastline, but sites from other parts of Namaqualand are also described. The stone assemblages are grouped according to variation in materials and retouch and then, along with data from ostrich eggshell beads and pottery, analysed graphically for temporal and other patterning. A cultural sequence is then presented.
Using this sequence, key debates on early herding are explored and a hypothesis on its origins is constructed. Indigenous hunter-gatherers occupied the region throughout the Holocene and made Group 1 lithic assemblages from quartz and cryptocrystalline silica with frequent retouched tools primarily in cryptocrystalline silica. A new population – likely Proto-Khoekhoe-speaking hunter-gatherers with limited numbers of livestock – entered the landscape approximately 2000 years ago. They made Group 3 assemblages from clear quartz focusing on backed bladelets. Diffusion of stock and pottery among the local population occurred during this period. Later, c. AD 500, a new wave of migrants appeared. These last were the ancestors of the historically observed Khoekhoe pastoralists; they made Group 2 lithic assemblages on milky quartz without retouched tools. Bead diameter generally increases with time and contributes nothing to the debate. The pottery sequence is still too patchy for meaningful interpretation but differs from that elsewhere. Overall, the differing cultural signatures in western South Africa suggest that, although many questions will likely remain unanswered, a better understanding of southern African early herding will only be possible with a study addressing all regions simultaneously.
Mathematical modelling of cell population dynamics in the colonic crypt with application to colorectal cancer
Keywords: cancer
crypt
mathematical modelling

Colorectal cancer has the third highest mortality and incidence rates of all cancers worldwide, but the prognosis for long-term survival is good if diagnosed early. It is a well-characterised disease, and is initiated in colonic crypts which line the colon wall. The aim of this thesis is to use mathematical modelling to describe the heavily regulated cell renewal cycle in the crypt to determine the key features of the system kinetics, and help to explain the initiation of tumourigenesis. The dynamics of a single colorectal crypt is considered using a compartmental approach, which accounts for populations of stem, transit-amplifying and fullydifferentiated cells. A number of different model formulations are derived, and their validity and suitability are discussed. Two mechanisms are presented that could regulate the growth of cell numbers and maintain homeostasis (equilibrium), and it is illustrated how a model can describe both regulated and unregulated growth, with cancer-driving cells deriving from stem and/or transit cells. This model is used to explain the long lag phases observed in carcinogenesis, which occur between periods of rapid tumour expansion, before unlimited growth in cell numbers ensues. Significantly, it is found that, contrary to general belief, the proportion of cancer-driving cells in the exponential growth phase of a tumour may vary depending on tumour type. The process of cells accumulating mutations is also examined by considering both a stochastic individual cell-based model and an analytic approach. Finally, an ordinary differential equation model is shown to be valid by considering a simplified description of a one-dimensional spatial model, and the latter is used to consider the effect of changing the crypt shape. The suitability of this modelling approach to tracking stem cells in a niche, as well as mutant cell clones as they propagate in the crypt, is also discussed.
Carbon fixation in eukaryotic marine algae: Evolution of photosynthetic machinery and isotopic footprints
Keywords: Carbon fixation
Climate
Photosynthesis
Marine algae

Photosynthesis in the world's oceans by marine algae is responsible for approximately 50% of CO2 fixed into organic carbon. Aquatic primary producers are intricately linked to the climate system due to their reliance on CO2 as a substrate for photosynthesis and role in the removal and export of carbon from the surface ocean to marine sediments. The evolutionary history of marine algae was shaped by changes in the climate system. As a result, fossilized marine algae and modern representatives of ancient groups have the potential to unlock information about the Earth’s climatic past. To use this information and fully understand the role of marine algae in the carbon cycle, however, it is essential to develop an in-depth understanding of CO2 fixation in these organisms. In this thesis I look at carbon fixation in biomineralizing marine algae from a geological and a biological perspective. First I apply a carbon isotope proxy for CO2 to organic material preserved in marine diatom frustules from an extremely transformative period in geological history, the Eocene-Oligocene boundary. Subsequently, this thesis aims to address gaps in our understanding of carbon fixation in eukaryotic marine algae. I present a novel dataset of kinetics of the carbon fixing enzyme, Rubisco, in eukaryotic algae, investigate the role of a pyrenoid-based carbon concentrating mechanism, and identify plastic changes in carbon fixing machinery in response to changing CO2. The findings from this thesis refine our understanding of primary production in the oceans and how we apply algae-based CO2 proxies to understand ancient climates.