VictorJuiz/thesis huggingface dataset:
The origins and development of professional legal attorneys by reference to thirteenth-century eyre proceedings
Keywords: history of the English legal profession

In exploring the origins and development of professional legal attorneys by reference to thirteenth-century eyre proceedings, it is firstly argued that attorneyship, as it existed circa 1200, originated in the coalescence of three separate traditions based, respectively, on putting in place, attornment and procuration. Evidence for this proposition lies in the remarkably diverse vocabulary employed by contemporary scribes, clerks and commentators in describing the activity of attorneyship.
Simple attorneyship, the basic core function of which was physical substitution, is then shown to have accommodated over the course of some 60 years legal attorneyship with its numerous duties and capacity for professionalisation. This process is charted by reference to the activities of attorneys at eight selected eyres held between 1218-19 and 1281. Themes and issues discussed include the circumstances surrounding the recorded presence of attorneys in court; outcomes achieved; the several motivations of litigants in appointing attorneys in increasing numbers; and the emergence of men displaying lawyerly qualities and characteristics including those of competence, articulacy, literacy, administrative skill and legal expertise.
The activities of professional legal attorneys at a series of eyres in the 1280s are next examined. Issues addressed include how many of them there were; their identities; where they practised; for whom they acted; what they did; how they organised themselves; and the extent to which they associated.
Finally, it is argued that the reason for professionalisation and the means of its emergence lie in the concept of supply and demand. The respective contributions of secular men and women, husbands and wives litigating together, and of ecclesiasts in the creation, firstly, of a critical mass of attorneys able to accommodate a minority of legal professionals and, secondly, of a demand for expert services supplied by those professionals, are analysed, as are the sources of the expertise demanded.
A corpus study of formulaic variation and linguistic productivity in early Greek epic
Keywords: distributional semantics
hexameter poetry
quantitative linguistics
construction grammar
early Greek epic poetry
formulaic language
formulae

This thesis addresses the general issue of formulaic variation in early Greek epic – not formulaic change, in that I do not adopt a diachronic perspective or seek to restore the original form of any formulae, but simply to describe how different variants of the same formulae coexist, and what their patterns of variation can tell us about formulaic language. I introduce the concepts of formula and formulaic variation in part I, which is functionally a two-part introduction (chapters I and II). Part II addresses the issue of syntactic variation, focusing on formulae composed by an adjective and a (common) noun; the behaviour of these formulae is analysed in a corpus made of Homer, Hesiod, and the major Homeric Hymns, and compared to the behaviour of similar structures in a non-formulaic 5th-century baseline corpus. The final chapter in part II (chapter V) analyses the behaviour of the same Adj + N pairs in a Hellenistic poem, the Argonautica of Apollonius of Rhodes. Part III focuses on semantic variation, and applies Distributional Semantics in order to study the range of meaning that objects of transitive verbs can take in Homer and Hesiod. Both Parts II and III have an introductory chapter of their own (chapters III and VI, respectively), in which the linguistic framework that will be used in the whole section is introduced and applied to a smaller-scale study.
The impact of cytomegalovirus infection and viral vector vaccination on human and mouse immune systems
Keywords: NK cells
viral vector
ChAdOx1
vaccines
SARS-CoV-2
Cytomegalovirus
immunology

Viral vectors are a next-generation vaccine platform that elicit a robust response from the humoral and cellular arms of the immune system. The importance of this vaccine platform was demonstrated during this PhD with the emergence of SARS-CoV-2 and the development of the chimpanzee adenovirus-vectored vaccine ChAdOx1 nCoV-19. Although this vaccine is immunogenic, pre-existing infections such as cytomegalovirus have been shown to reduce antigen-specific vaccine immunogenicity in other vaccines. Cytomegalovirus is a chronic herpesvirus that is prevalent in ~40-100% adults worldwide, and although infection is often asymptomatic it can increase the frequency of terminally differentiated immune cells in healthy young adults.
This thesis aims to characterise the effect of viral vectored vaccines including ChAdOx1 on immune populations not traditionally studied in vaccinology, including NK cells. It also investigates how cytomegalovirus impacts the immune phenotype and vaccine immunogenicity in humans and mice. This thesis demonstrates that viral vector vaccination activates NK cells and induces robust cytokine secretion in both mouse and human studies, although can affect NK cell phenotype following vaccination with MVA. Furthermore, CMV seropositivity elicits a terminally differentiated phenotype on the immune system, but does not affect viral vector vaccine immunogenicity following a single dose or homologous boost of ChAdOx1. Overall, these findings which are especially important for the ongoing vaccination regimen against SARS-CoV-2, and provide further insight into the interplay of viral vectored vaccines and viral infection on the immune system.
Targeting the 5' untranslated region of SMN2 as a therapeutic strategy for spinal muscular atrophy
Keywords: antisense oligonucleotides
SMN2
5′ UTR
spinal muscular atrophy

Nucleic acid therapeutics allow sequence-based targeting of disease genes, such as the genes involved in spinal muscular atrophy (SMA) pathogenesis. SMA is a neuromuscular disorder caused by mutations in the survival motor neuron 1 gene (SMN1). All patients have at least one copy of a paralog, SMN2, but a C-to-T transition in this gene results in exon 7 skipping in a majority of transcripts. As a result, only 10 to 20 percent of SMN2 transcripts encode the fully functional SMN protein. Nusinersen, an FDA-approved therapeutic for SMA, is an antisense oligonucleotide (ASO) that promotes exon 7 inclusion in the SMN2 transcript. The ceiling effect associated with splice-switching approaches makes complementary therapeutic strategies necessary. Increasing the total pool of SMN2 transcripts and increasing the translational efficiency of these transcripts are strategies that can be used in combination with splice correction. I sought to determine whether the 5’ untranslated region (5’UTR) of SMN2 contains an element that reduces its expression that can be targeted as a means of increasing SMN levels. I found that ASOs targeting the 5’ end of SMN2 increase SMN mRNA and protein levels, and that this effect is due to ASO-mediated inhibition of SMN2 mRNA decay. Moreover, using the 5’UTR ASO in combination with a splice-switching oligonucleotide (SSO) increases SMN levels above those attained with the SSO alone. I show that the effect of this 5’UTR ASO is human-specific. These results add to the current understanding of SMN regulation and point toward a new therapeutic target for SMA.
A medicine of constitutions: Sasang medicine in contemporary South Korea
Keywords: East Asian medicine
chejil
Sasang medicine
Constitutional medicine
(post-)modernity
habitus
Korean medicine
constitution

This thesis investigates the process of standardisation, scientisation, and diversification of Sasang medicine in contemporary South Korea, through the lens of its central concept ch’ejil (constitution 體質). Sasang medicine (sasang ŭihak 四象醫學) is a current of medical tradition which emerged from the scholarly physician Yi Chema (李濟馬) in late 19th century Chosŏn. Sasang medicine is known as ch'ejil ŭihak (constitutional medicine 體質醫學) because it assumes that human beings have different constitutions with different physiologies and pathologies as well as different psychological traits. Sasang medicine is a unique example in [traditional] Korean medicine because it has constantly been practiced for over a century and is ingrained into health practices of modern Koreans as well as the contemporary health care system in South Korea.
Based on multi-sited ethnographic fieldwork in a school of Korean medicine and its teaching hospital, in a national research institute, and in private clinics, this thesis meticulously explores how an established form of Sasang medicine has been situated in the institutionalised system of Korean medicine. Ethnographies from different field sites provide microscopic details which are interspersed with various issues of collaboration, confrontation, and negotiation of different values and epistemologies. Furthermore, this thesis scrutinizes ‘how practitioners of Sasang medicine know what they know’ in such different social settings. These attempts are fulfilled by exploring how the central concept of Sasang medicine, ch’ejil, is understood in each field site. In so doing, this thesis aims to elucidate to what extent the practice of Sasang medicine in historical and social formation diversifies concepts of ch’ejil, which have played a role as a fluid medium to raise legitimacy or “efficacy” of Sasang medicine.
Pulsed squeezed light: characterization and applications
Keywords: femtosecond lasers
quantum optics
squeezed light

Squeezed light is expected to enable new quantum metrology and quantum computation applications, but the very high degree of experimental control required in practice places severe demands on the physical devices used to generate it. As ultrafast squeezed light sources are reaching an unprecedented degree of brightness and modal control, there is a strong interest in developing methods for their experimental characterization and theoretical understanding. In this thesis, we demonstrate both a new application and a new characterization technique for pulsed squeezed light.
In the first part of the thesis, we present a new metrological application of pulsed squeezed light: quantum-enhanced label-free nonlinear microscopy. Stimulated emission microscopy (SEM) is a state-of-the-art pump-probe microscopy technique whose sensitivity is ultimately limited by shot noise in the probe beam. We propose to overcome this fundamental limitation by using a sub-Poissonian probe generated via optical parametric amplification. We demonstrate an intensity-squeezed sub-picosecond pulsed probe, and a simple stimulated emission microscope. Using this squeezed probe, sub-Poissonian statistics are observed in the SEM signal. After this proof-of-principle experiment, we aim to provide an improved design for a source of intensity-squeezed light. First, we develop a theoretical framework to simulate the photon statistics of a general sub-Poissonian source, considering pulsed and focused pump and seed fields in a unified spatio-temporal description. Next, we use this framework to suggest possible improvements to our previous squeezed probe.
In the second part of this thesis, we provide new theoretical and experimental tools to analyze the high gain regime of pulsed spontaneous parametric down-conversion (SPDC). We study a waveguided source capable of generating twin-beams with tens of photons in a single spatio-temporal mode. We develop a framework to efficiently simulate SPDC for an arbitrary nonlinear gain, including the effect of parasitic nonlinearities such as self-phase modulation (SPM) of the pump and cross-phase modulation (XPM) between pump and twin-beams. We experimentally characterize our source using a new technique based on stimulated difference-frequency generation (DFG). In a type-II down-conversion process, we measure the frequency generation produced not only in the orthogonal polarization to the seeding beam, but also in its same polarization, which we interpret as cascaded difference-frequency generation. We argue that the additional information obtained in this measurement allows for a self-referenced estimation of the squeezing gain. Using these measurements, we accurately fit our theoretical model, revealing that, in the high gain regime, parasitic nonlinearities strongly affect the spectral structure of the twin-beams. We propose a simple strategy to reduce the impact of these nonlinearities on the modal structure of SPDC.
Characterisation of endometrial B cells and lymphocytes in the peri-implantation window
Keywords: flow cytometry
recurrent implantation failure
recurrent pregnancy loss
T follicular helper cells
RNA-seq
B cells
endometrium

Immunological regulation at the implantation site is a complex process, dysfunction may contribute to infertility, recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL). Apart from endometrial NK and T cells, whose phenotypic profile and functional involvement have been recognised, evidence suggests that endometrial B cells may also have a potential role in reproductive pathologies. This thesis aimed to investigate endometrial immune profiles during human implantation, with a specific focus on the role of endometrial B cells.
Both healthy women and infertility, RIF or RPL patients were recruited for endometrial immune profiling, focusing on cell proportions (NK, T and B cells) and activation status. Additionally, peripheral blood samples were collected and analysed in parallel. Significant differences were observed between peripheral and endometrial immune profiles, in minor cell populations like CD56bright CD16dim NK cells and CD4 CD8 double positive T cells, such differences were not previously reported. A standard operating protocol (SOP) was established so that comparison between controls and infertility, RIF or RPL patients could be made with more patients being enrolled in the near future.
The role of B cells in the human endometrium was investigated. A systematic review was performed to understand the B cell involvement in reproductive pathologies. A number of immunohistochemistry studies were retrieved that identified endometrial B cells in association with T cells in ‘lymphoid aggregates (LAs)’, however, neither have been extensively characterised. RNA-sequencing and flow cytometric analysis were performed on CD19+ endometrial B cells. B cells comprised 1-5% of endometrial immune cells, the majority were naïve or memory B cells, with few plasma cells. Compared with circulating B cells, endometrial B cells had an activated phenotype, with increased expression of CD69, HLA-DR, CD74 and CD83, and IL-10 production capacities. PD1+CXCR5+ICOS+ T follicular helper-like cells and FAS+IgD􀀀 germinal centre-like B cells were present in the endometrium. Together with previously reported LAs, endometrial B cells may be an active player in shaping the endometrial immune environment.
Establishing an antibody mimetic applicable to targeting in the gastrointestinal tract
Keywords: synthetic biology
phage display
gastroenterology
nutrition
protein engineering

Proteins are a valuable class of therapeutics because proteins, like antibodies or non-antibody scaffolds, can bind their targets with high selectivity and affinity. The upper gastrointestinal tract, however, rapidly inactivates protein-based targeting reagents. Compared to injections, oral administration of protein therapies is favourable for treating gastrointestinal disease. In this thesis, I have developed a protein scaffold termed a gastrobody, that is suited to applications in the gastrointestinal tract. Gastrobodies are derived from Kunitz-type soybean trypsin inhibitor (SBTI). SBTI is resilient to digestion with stomach-like concentrations of pepsin and pH 2. Furthermore, SBTI is stable in the presence of intestinal proteases and bile acids, as well as being resilient to high temperatures. I used the protein modelling software Rosetta to assist design of a binding surface on SBTI. I also established phage display of SBTI to enable directed evolution. As proof of concept, gastrobody binders to domains of two toxins of the enteric pathogen Clostridium difficile were developed. After optimisation of the binding surface and affinity maturation, I identified gastrobodies that bound their target with nanomolar affinity. Gastrobodies bind their target after incubation with physiological concentrations of gastrointestinal proteases, including pepsin at pH 2. Lastly, I explored alternative gastrobody backbones using structural homologues of SBTI. The work presented in this thesis may provide a foundation for generating binding reagents for therapeutic and diagnostic use in the gastrointestinal tract.
Nowhere to hide: investigating the use of unilateral alternatives to extradition in United States prosecutions of transnational cybercrime
Keywords: transnational crime
alternatives to extradition
cyberespionage
transnational criminal law
Budapest Convention on Cybercrime
international cooperation
extradition
lure operations
computer crimes
international law
United States Department of Justice
cybercrime
hacking

Transnational cybercrime is an increasing public menace, and prosecuting countries must often turn to extradition and its alternatives to bring perpetrators to justice. These alternatives include quasi-extradition (informal cooperation with the host country) and unilateral action (capture or lure operations). I posit that pursuing countries are more likely to employ unilateral alternatives over extradition and quasi-extradition in prosecutions of cybercrime as compared to other transnational crimes. I predict this is due to the remote nature of cybercrime; legal barriers; and political considerations in the host country.
The United States is a leader in prosecuting cross-border cybercrime, so I focus my analysis there. Interviews with 81 US officials and case studies suggest that unilateral alternatives are applied more frequently for cybercrime. I uncover that the need for such tools does not stem from legal barriers. Rather, it stems from the remote and anonymous nature of cybercrime, a lack of political will in host countries, and state sponsorship.
I then compare the trajectory of transnational cybercrime prosecutions to those of terrorism; drug trafficking; fraud and foreign corruption; and export control and sanctions violations. Unlike these other offenses, I conclude that cybercrime prosecutions cannot be expected to rely, even in the long-term, on cooperation with the host country or the perpetrators traveling as part of the conspiracy. This foreshadows that cybercrime prosecutions will likely require a sustained reliance on unilateralism.
Building on existing scholarship related to the use of unilateral alternatives in war crimes, terrorism, and drug trafficking prosecutions, I thus propose a pragmatic framework to guide pursuing countries when the use of lures may be prudent in cybercrime cases. This framework seeks to mitigate any infringements on the sovereignty of the host country and human rights of the accused while still enabling the pursuing country to end ongoing cybercrimes, recognize victims’ injuries, and deter future attacks.
The Jacobian of solutions to the conductivity equation and problems arising from EIT
Keywords: Numerical Analysis
Inverse Problems
Partial Differential Equations
Sigma Harmonic Mappings

The first contribution of this thesis is an extension of the work originally done in [12]. We derive a general asymptotic expansion for the solution un to the conductivity equation in the presence of perturbative inclusions of very conductive or very insulating material. We study the perturbative regime, that is the case when this solution un converges to a limiting “background” potential u0, in which, the convergence may be described at first order volume expansion by a limiting Radon measure μ and a polarisation tensor M ∈ L2(Ω,Rd×d; dμ) which describes the variations of ∇un when a material is present in the conducting domain. The convergence result here is general for any inclusion set Qn which is Lebesgue measurable and has Lebesgue measure |Qn| converging to 0. From a numerical point of view, an asymptotic formula in terms of volume expansion is useful as it may be used to tackle a problem posed on very “small” sets which may be difficult to simulate by traditional finite elements methods due to the small mesh sizes.
The second focus of this thesis is on the behaviour of the solution to the conductivity system in Rd(d ≥ 3), where the solution satisfies a certain Jacobian determinant constraint. Namely, we demonstrate the failure of univalent γ−harmonic mappings in dimension d ≥ 3 by constructing a class of materials Q , and boundary conditions φ ∈ H1/2 (∂Ω) such that the Jacobian determinant of the γ−harmonic extension of φ in Ω changes sign in some open neighbourhoods of Ω. Our focus here is on quantifying the measure of the sets where the Jacobian determinant is positive and simillarly negative. We provide a general rule of thumb to obtain these estimates by a constructive approach.
The results obtained in this thesis would find itself useful in several problems in the field of elliptic inverse problems, homogenization and electrical impedance tomography. In particular, the sign changing Jacobian determinant property is applicable to the mathematical theory of cloaking whereas the asymptotic formula for the conductivity equation may be applied to a wide array of applications in the detection of inhomogeneity sets of small volume fraction such as cancer cells detection and mine detection for example.
Responding to emerging viral pathogens: Characterization of neutralizing epitopes on the Nipah virus glycoproteins and the humoral immune response against SARS-CoV-2
Keywords: viral glycoproteins
henipavirus
SARS-CoV-2
antibody response
Nipah
monoclonal antibody

The emergence of zoonotic viral pathogens into the human population represents a continuous threat to global health. Emergent human pathogens of significance include the henipaviruses, Hendra (HeV) and Nipah (NiV), and the coronaviruses, SARS-CoV, MERS-CoV, and SARS-CoV-2. Virion surface displayed viral glycoproteins mediate the critical processes of cellular attachment and membrane fusion that are required for infection. These glycoproteins are also major targets for host antibodies and are therefore important vaccine immunogens. Furthermore, characterization of antibody epitopes and mechanisms of neutralization can guide the selection and improvement of such immunogens as well as expand the basic understanding of the host immune response against these pathogens.
This thesis first aims to characterize the antibody response to NiV. Structural analysis identified neutralizing monoclonal antibody epitopes on the NiV attachment and fusion glycoproteins (NiV-G and NiV-F). The membrane distal apex of NiV-F was identified as a conserved, common site of vulnerability. Additionally, one anti-NiV-F monoclonal protected hamsters from lethal NiV challenge. Characterization of additional epitopes, such as the putative dimerization interface on NiV-G, to reveal additional sites of vulnerability can provide a blueprint for the structure guided design of vaccines and therapeutics.
The emergence of SARS-CoV-2 highlighted the need to quickly respond to outbreaks. Serology assays were optimized to study the antibody response to SARS-CoV-2. These assays were also used as part of a case study evaluating long-term SARS-CoV-2 shedding in an immunocompromised patient wherein replication competent virus was successfully cultured from the samples up to 70 days after diagnosis, demonstrating a longer infectious period than previously observed, as well as significant within-host virus evolution.
Taken together, the studies herein demonstrate the utility of structural approaches in defining sites of vulnerability on the viral surface. Additionally, future work to classify the immune components of reservoir host species, such as bats, is warranted to understand the risk of future spillover events and understand the infection dynamics of emerging viral pathogens.