VictorJuiz/thesis huggingface dataset:
Synthesis and properties of nucleic acid analogues containing artificial backbones
Keywords: Antisense
modified nucleic acids
Gene synthesis

Nucleic acid analogues are very attractive molecules for therapeutic applications as in principle they can specifically inhibit the expression of virtually any gene through antisense or RNA interference pathways. For this purpose, nucleic acid analogues with modified backbones have advantageous properties compared to their natural counterparts. In particular they can provide better resistance to nucleases as well as improving cellular uptake. However, radically changing the nucleic acid backbone while maintaining a good affinity for a mRNA or DNA target remains challenging. Developing synthetic strategies to conveniently access new modified backbones that could be used in antisense oligonucleotides is therefore essential. With this in mind a new solid-phase method to efficiently functionalise an amine-modified DNA backbone has been developed. Using this approach, three new oligonucleotide modified backbones have been synthesised, and their hybridisation properties have been investigated.
Modified DNA backbones are also potentially useful in the development of new methods for chemical-ligation of oligonucleotides. This approach could allow the large-scale de novo synthesis of genes containing site-specific chemical modifications including epigenetic signals. Such constructs represent challenging targets in medicinal and biotechnology applications. An important class of modified DNA linkages containing a triazole ring developed in our research group has been further investigated through the synthesis of two new triazole modified backbones. The synthesis of a DNA amide backbone with favourable duplex stability was also performed. A detailed study of the biophysical properties of the above modified backbones including their performance as templates for various DNA polymerases has been carried out.
Danegeld: the land tax In England, 991-1162
Keywords: government
heregeld
tenth-century England
Harthacnut
William the Conqueror
Anglo-Saxon Chronicle
twelfth-century England
Henry I
William II
treasury
fiscal history
danegeld
economic history
Edward the Confessor
Domesday
William I
King Stephen
tax
land tax
finance
Pipe Roll
geld
Norman Conquest
land taxation
Aethelred Unready
taxation
Rufus
Henry II
gafol
Cnut
coins
eleventh-century England
land-tax

This thesis examines the genesis and development of the English land tax, commonly known as geld or Danegeld, from 991 until 1162. The thesis begins with an analysis of tribute money (gafol) paid by King Æthelred to Viking invaders, and the evolution of that tax into heregeld, an annual tax paid to maintain a standing Scandinavian fleet. It examines the feasibility of paying large tributes, given the size of the English economy and availability of silver coin. The thesis then moves on to show how, although Edward the Confessor abolished heregeld in 1051, land taxation continued right up until 1066 to serve other purposes.
One of William the Conqueror’s first acts as king was to levy geld, and he probably continued to do so in every year of his reign. The thesis extensively examines some of the rich sources of his reign, most especially Domesday Book and its ‘satellite’ texts. William Rufus and Henry I followed in their father’s footsteps, probably levying gelds of 2s per hide in most years, helping finance numerous wars against their brother Duke Robert of Normandy. The Pipe Roll of Henry I is our single most detailed source about the tax on a national basis; this receives a close examination especially regarding the nature of exemption. King Stephen appears to have continued levying Danegeld, as it was invariably called by this point, in the areas in which he had control during the Anarchy. Henry II only levied Danegeld twice, as other taxes and feudal sources of income gradually became more important as the twelfth century progressed. After aborted attempts to revive and reform the land tax system in the reigns of Richard, John and Henry III, the land tax was abandoned for good.
Civic identity in the digital age: an investigation into the civic experiences of American young people
Keywords: Technology and civic engagement
Civic education
Civic engagement and social media
Youth political engagement
Civic identity
Civic engagement

Contemporary society is characterized by digitally mediated interactions and activities, especially through social media. As young people discover their identities, they make decisions about how to present themselves to others, and they develop an understanding of how they fit into society, what it means to be a citizen and to be civically engaged, and how to effectively engage in the political world. Literature reveals the lack of an adequate framework for understanding how young people come to develop their civic identity in contemporary times. This study therefore explores three research questions: 1) In what ways do young people, ages 14 through 17, present themselves to others in contemporary society? 2) What are the mechanisms through which young people form their civic identity in this era, and how do young people understand citizenship and civic engagement? 3) What are the means through which young people engage in the political world, and what factors contribute to this engagement?
Using in-depth interviews with 46 participants of diverse backgrounds, this study investigated how young people in the United States aged 14 through 17 conceptualize their civic identities in today’s world. In the United States, the tradition of education for democratic citizenship has declined in recent decades due to a focus on science, technology, engineering, and mathematics (STEM) subjects. Young people have thus not received adequate civic education, and the public has consequently perceived them as disengaged from the political world. Despite this public perception, a growing body of research indicates that young people are civically engaged in non-traditional ways, and there is an assumption that the use of technology among young people will elevate their voices and civic actions. This study finds that while young people are civically engaged, and despite the multitude of digital media that could be used to amplify their voices and causes, they still feel their voices are unheard. These findings highlight certain areas where educators, parents, and policymakers can improve their support for young people’s civic identity formation and feeling that their voices will make a difference. This thesis therefore proposes a new framework for civic identity to reflect the experiences of young people in the digital era, and recommends a reinvigoration of civic education to foster young people’s civic efficacy in contemporary society.
The role of Shaikh Sidiyya and the Qadiriyya in southern Mauritania
Keywords: Mauritania
Qadiriyya
Shaikh
Sidiyy
Islam

The first half of the 19th century in West Africa was a period of rapid islamization, marked by the establishment of four Islamic states which were created immediately before or during this period by mujāhidūn, and numerous religious settlements or sawayya which were established in areas not touched by the jihāds. These several movements appear to have had two common denominators: the objective of legal reform and strict application of the sharī'a, and the practice of the Qadiriyya Islamic brotherhood. This study sets out to examine the role of the Qadiriyya in the islamization of West Africa, but in a relatively 'controlled' context so as to isolate as much as possible the ideas and practices with which it was associated. The case study which is the subject of this study is the career of a Mauritanian shaikh, Sidiyya al-Kabir (d. 1868). This particular case study has been selected because of the wealth of Arabic manuscript documentation which is available in the family papers of the Shaikh's descendants and the similarities between his career and the careers of his teachers from the Kunta confederation, who were the principal Qadiri shaikhs in West Africa from the mid-18th century until the end of the first quarter of the 19th century. Other reasons for selecting this case study are that Mauritanian history and the Moorish social structure of the study which terminates in 1868 pre—dates the competition which developed between the Qadiriyya and other ṭuruq in Mauritania. The main source of documentation for this study is the correspondence and literary works written by Shaikh Sidiyya al-Kabir, although French archival material, oral tradition and other Arabic texts have been used to supplement this manuscript source.
Continued in thesis ...
Yugoslavism, rebellion, and exile - a political and intellectual biography of Tin Ujević (1909-1919)
Keywords: politics
Augustin Ujević
Croatia
Yugoslavia

From 1909-1919, the young Croatian poet, essayist, and political revolutionary Augustin (Tin) Ujević (1891-1955) was passionately involved in Croatian politics. Today recognized as one of Croatia’s foremost poets, the fact that Ujević was one of the most prominent leaders of the Yugoslav youth during the lead-up to the First World War is almost unknown. Born in Dalmatia, Ujević spent his childhood in one of Austria-Hungary’s most neglected provinces, which was going through a profound economic and demographic crisis at the time. Dalmatian politicians, however, would set the pace for the process of Yugoslav national integration in the years to come. At Zagreb University, the young poet turned into a skilled political agitator, writing passionate polemics against the Habsburg Monarchy while taking part in demonstrations that led to multiple arrests by the police. Ujević, who had started out as a fervent Croatian nationalist, soon became one of the leaders of the Yugoslav Nationalistic Youth Movement, which aimed at establishing a South Slav state based on Serbo-Croat cultural and political unity. In the spring of 1912, he moved to Belgrade, where he intensified his political activity and established contact with the infamous ‘Black Hand’. After another short stay in Dalmatia, Ujević finally left the Balkans in the fall of 1913 to go to Paris, where he worked alongside the Serbian government and the newly established Yugoslav Committee. 1915 saw a turning point as the federalist Yugoslav state he worked for seemed to be slipping away in the hands of opportunistic politicians, which resulted in his ultimate break with politics. This dissertation examines Ujević’s life, alongside his works, to better understand a complex and important time in Croatian and Southeastern European history. It will use Ujević to explore the political thought of the region during the tumultuous time of the end of Austria-Hungary and the formation of the first Yugoslavia. Through his political evolution, the thesis will examine the way in which ideologies and nationalisms competed with each other through argument and action. The thesis will also shed light on the radicalisation process that the youth in Croatia, Dalmatia, Bosnia and Serbia underwent. Through his essays, Ujević contributed significantly to an ideological framework that encouraged revolutionary action which culminated in the assassination of Archduke Franz Ferdinand of Austria.
4D reconstruction of oncological dynamic PET data
Keywords: Image reconstruction
Computational modelling
Spline-residue
Tomographic reconstruction
Dynamic PET
PET
Monte-Carlo simulation
B-splines
Tomography
Mathematical modelling
Kinetic modelling

4D reconstruction of dynamic positron emission tomography (dPET) data suppresses noise in both the reconstructed image sequences and kinetic parameter estimates by fitting smooth temporal functions to the voxel time-activity-curves (TACs) during the reconstruction. Cancer imaging studies often have many tissues within the scanner field of view, leading to a wide range of TAC shapes to be fitted. The development of flexible temporal functions for use in such situations is an ongoing area of research, and forms the primary focus of this thesis.
Two commonly used models for 4D-PET reconstruction in situations with diverse kinetics are the spectral model, which models TACs as weighted sums of convolutions of the arterial input function (AIF) with exponential decays, and spline functions. In a digital phantom study comparing the performance of 4D-PET reconstruction based on adaptive-knot cubic B-splines and the spectral model, the spline-based reconstruction produced the least biased images overall, though the spectral model based reconstruction provided a better bias-noise trade-off in the early time-frames.
A spline-residue model describing TACs as weighted sums of convolutions of the AIF with cubic B-spline functions is then proposed. As with the spectral model, convolution with the AIF constrains the spline-residue model at early time-points, potentially enhancing noise suppression in early time-frames, while still allowing a wide range of TAC descriptions over the entire imaged time-course, thus limiting bias. In a digital phantom study comparing 4D-reconstructions based on the spline-residue model, adaptive-knot cubic B-splines, the spectral model and an irreversible two-tissue compartment model, spline-residue based 4D reconstruction produced the highest quality (lowest bias and noise) parametric maps of radiotracer uptake kinetics and was particularly effective at suppressing noise in the early time-frames.
To investigate whether the proposed spline-reside model gives physiologically meaningful kinetic parameters, fits of the spline-residue model to FDG-dPET tumour TACs obtained from a dataset comprising 41 primary breast cancer patients, who also underwent tumour biopsies, are compared to fits of irreversible two- and three-tissue compartment models. These TACs were obtained from analytically reconstructed dPET images. Using goodness-of-fit measures, the spline-residue model was found to give the best description of the patient TACs, and after accounting for multiple hypothesis testing the flux constant from the spline-residue model produced the strongest correlations with gene expression data derived from the tumour biopsies.
Das Engelhusvokabular. Lexikographie, Diktat und Lateinunterricht im Spätmittelalter
Keywords: Cod. Guelf. 956 Helmst.
Dietrich Engelhus
Herzog August Bibliothek Wolfenbüttel
Cod. Guelf. 720 Helmst.

How was Latin taught and learned in the late Middle Ages? This thesis provides an evidence-based answer by contrasting the intended purpose and actual use of a dictated dictionary. The two manuscripts on which the analysis is based transmit the so-called Engelhusvokabular, a fifteenth-century alphabetical list of rare Latin and Greek terms and their Middle Low German equivalents. The thesis both utilises and facilitates interdisciplinary research on late-medieval (school-)lexicography, palaeography, codicology, digital editing, and the history of learning and women’s education. It could thus become the basis for future studies in the history of education as well as linguistic studies of dictionaries.
The political press in southern Ghana and southern Nigeria: nationalism, visuality and professionalisation, c. 1937 – 1966
Keywords: West Africa
transnational
media history
history
Ghana
visuality
print cultures
Nigeria
information circulation
photography
nationalism,
newspapers

The present study of pictorial journalism in West Africa offers a pioneering analysis of the circulation and interpretation of newspaper photographs published in Ghana and Nigeria, during the period of anticolonial struggle and interparty competition, between 1937 and 1966. More specifically, this thesis examines how journalists and politicians adapted and appropriated newspaper photographs to their needs by captioning, selecting and aligning them with articles. While these images had travelled across numerous transnational and intraimperial information networks, their frequent use by editors and journalists in Ghana and Nigeria highlights the relationships between global connections and local adaptations. Such photographs have previously been overlooked by historians focusing on West Africa during this period, yet, as this study aims to demonstrate, they serve as invaluable sources, shedding light on the processes of elite self-understanding and identification in this context. A historical analysis of the development of pictorial journalism advances the understanding of material and ideological processes in the use of newspaper photographs, which are essential to the understanding of the emergence of an anticolonial public sphere and counter-culture in these countries.
Inhibition and mechanistic studies of FTO
Keywords: enzymatic assays
FTO
formaldehyde

The Fat Mass and Obesity Associated protein (FTO) is a nucleic acid demethylase that belongs to the 2-oxoglutarate dependent oxygenase superfamily (2OG oxygenases). Like other 2OG oxygenases, FTO uses Fe(II), 2-oxoglutarate (2OG) and molecular oxygen (O2) to catalyse oxidation of its substrates. Mutation of the gene encoding for FTO have been linked to obesity, type II diabetes, cancer, and Alzheimer’s disease. One aspect of the work described in this thesis aimed at developing small molecule inhibitors of FTO. An NMR binding assay was developed using 2OG as a reporter ligand. The inhibitors developed in this thesis exhibit high potency and selectivity for FTO (the lead inhibitor has an IC50 value of 1.32 μM).
The work also aimed at the synthesis of N6-methyladenosine (m6A) phosphoramidite with the aim of synthesising single stranded RNA (ss-RNA) oligonucleotide containing m6A. Apart from the literature reported substrates, work also focussed on the investigations of other nucleosides as natural and unnatural substrates of FTO. During the study, new synthetic routes to the m6A phosphoramidite, ethanoadenosine, ethylethanoadenosine and methylethanoadenosine were developed. The iodouridine phosphoramidite was also synthesised with the future aim of synthesising a ss-RNA substrate crosslinked to FTO.
The reaction of formaldehyde (the FTO co-product) with canonical and non-canonical nucleotides was then investigated using NMR. Various nucleotide/HCHO adducts were identified, including multiple novel species. Among the canonical nucleosides, TMP and UMP reacted the fastest followed by dCMP, dGMP and lastly dAMP. However, dAMP was observed to form the most stable adduct with formaldehyde, while the adducts of TMP and UMP were dynamically favoured. Comparing cytidine, 5-methyldeoxycytidine (5mdC) and 5-hydroxymethyldeoxycytidine (5hmdC) revealed that 5mdC reacts the fastest. Among m6A, N1-methyladenosine (m1A) and adenosine, the initial rate of reaction with formaldehyde was fastest with adenosine.
Finally, the FTO and AlkB catalysed oxidative demethylation of substrates was investigated by NMR using [13C] labelled substrates (e.g., N6-[13C]-methyladenosine ([13C]-m6A), N3-[13C]-methythymidine ([13C]-m3T) or N1-methyladenosine ([13C]-m1A)) as probes. The studies reveal the first direct evidence, using NMR, for the formation of N6-hydroxymethyladenosine as an intermediate of FTO- catalysed oxidative demethylation of m6A. The results also confirmed the formation of formaldehyde. The observation of formaldehyde in AlkB-catalysed oxidative demethylation of m1A led to the invalidation of the previously reported hypothesis that a phosphate group attached to a nucleoside is the minimum requirement for AlkB substrates.
Overall, the work described in this thesis suggests new approaches to the inhibition of FTO, helps to define the range of substrates for FTO, reassign the requirement for AlkB-catalysed oxidative demethylation, and informs on the reaction of the FTO-catalysed reaction co-product, HCHO, with nucleosides.
Self-supervised learning using motion and visualizing convolutional neural networks
Keywords: Convolutional Neural Networks
Deep Learning

We propose a novel method for learning convolutional image representations without manual supervision. We use motion in the form of optical-flow, to supervise representations of static images. Training a network to predict flow from a single image can be needlessly difficult due to intrinsic ambiguities in this prediction task. We instead propose two simpler learning goals: (a) embed pixels such that the similarity between their embeddings matches that between their optical-flow vectors (CPFS), or (b) segment the image such that optical-flow within segments constitutes coherent motion (S3-CNN). At test time, the learned deep network can be used without access to video or flow information and transferred to various computer vision tasks such as image classification, detection, and segmentation. Our CPFS model achieves state-of-the-art results in self-supervision using motion cues, as demonstrated on standard transfer learning benchmarks.
Despite high transfer learning performance, we feel the need to visualize the representation learned by our self-supervised CPFS model. With that motivation we develop a suite of visualization methods and study several landmark representations, both shallow and deep. These visualizations are based on the concept of “natural pre-image”, that is a natural-looking image whose representation has some notable property. We study three such visualizations: inversion, in which the aim is to reconstruct an image from its representation, activation maximization, in which we search for patterns that maximally stimulate a representation component, and caricaturization, in which the visual patterns that a representation detects in an image are exaggerated. We formulate these into a regularized energy-minimization framework and demonstrate its effectiveness. We show that our method can invert HOG features more accurately than recent alternatives while being applicable to CNNs too. We apply these visualization techniques to our self-supervised CPFS model and contrast it with visualizations of a fully supervised AlexNet and a randomly initialized one.