VictorJuiz/thesis huggingface dataset:
An intellectual history of the inheritance of acquired characteristics before Darwin: readers and ideas

In the 19th century, debates over heredity were fuelled by anecdotal evidence and special, unusual cases. Farmers, animal and plant breeders, medical writers and natural historians all took part in wider efforts to compile and arrange this production of evidence in order to tell different stories about nature, and the laws of inheritance. While many historians have claimed that 'the inheritance of acquired characteristics', an important theory about the laws of inheritance, was a widespread belief during this period, the means by which this idea became widespread have been overlooked by other historians. Recently, Bernard Lightman and Sally Shuttleworth have both argued that early-19th century efforts to create community-led scientific periodicals and publications were more constitutive of scientific practice than earlier historians have considered, while Pietro Corsi has argued that the industry of 'contributors' to periodicals, encyclopaedias and dictionaries during this period provides a means by which we can better understand readership and reception of popular scientific ideas. In this thesis, I argue that the evidence produced by practitioners and amateurs in support of the inheritance of acquired characteristics is an important means by which we can come to understand how the idea became a widespread belief, and an important part of how many people understood the workings and laws of nature. This thesis draws on a range of practical agriculture and gardening magazines, popular encyclopaedias, as well as from phrenological journals and temperance writings, many of which have not previously been included in the history of the inheritance of acquired characteristics. One important aspect of this increasing popularity came via the fact that many of the proponents of the inheritance of acquired characteristics found the idea provided a means by which familiar, religious understandings of the family, sin, and reproduction, were preserved. In an era of scientific activity that Adrian Desmond has depicted as materialist and radical, the 1820s and 1830s saw medical and scientific writers from different religious backgrounds, discovering immediate and significant biblical value in the idea that sinful habits and virtues acquired in life are transmitted to offspring.

Advisor: Corsi, P
Mahone, S
Essays in household finance

This dissertation presents three empirical analyses on individual investment decisions with risky financial markets. Each chapter investigates a distinct aspect of individual financial behaviour with risky financial markets, but provide evidence on one important aspect of household finance: Individual behaviour is systematically different from normative views of what they ought to do. The first paper, Endowment effects in the field: Evidence from India’s IPO lotteries presents large-scale field evidence to a suite of laboratory studies call into question the fundamental neoclassical assumption that preferences and beliefs are independent of fownership. It documents that winners of randomly assigned initial public offering (IPO) lottery shares are significantly more likely to hold these shares than lottery losers, 1, 6 and even 24 months after the random allocation. This finding persists in samples of highly active investors, suggesting along with additional evidence that this "endowment effect" is not driven by inertia alone. This evidence is consistent with the laboratory literature that documents endowment effects for risky gambles. The second paper, The effect of experience on investor behaviour: Evidence from India’s IPO lotteries exploits the randomized allocation of stocks in Indian IPO lotteries to provide new estimates of the causal effect of investment experiences on future investment behaviour. It shows that investors experiencing exogenous gains in IPO stocks (the treatment) are more likely to apply for future IPOs, increase trading in their portfolios, exhibit a stronger disposition effect, and tilt their portfolios towards the sector of the treatment IPO. These effects vary with the size, variability and salience of the gain, and are stronger for smaller and younger investors. However, these effects persist for larger and older investors, suggesting that experiencing gains exerts a powerful force even on sophisticated players in financial markets. The third paper, The effect of subjective life expectancy on financial decisions investigates one potential mechanism by which experiences affect individual financial decisions. It investigates whether exposure to natural disasters and mass shootings influences subjective life expectancy and affect financial decisions. Using data from the United States, the paper shows that being exposed to natural disasters and mass shootings significantly decreases an individual’s subjective life expectancy. Further, it shows that such experiences monotonically reduce the share of financial assets in equities and non-government bonds for increasing levels of lifespan optimism. These findings provide evidence for the existence of an expectations channel for personal experiences to affect financial decisions. Taken together, these three studies contribute to the growing body of work on household finance and open the door to further theoretical and empirical research in the field.

Advisor: Tufano, P
Ramadorai, T
Understanding the constraints on the operation of corporate insolvency law in the economic transition of developing countries: the case of China

This thesis seeks to contribute to our understanding of why creditors and debtors do not ordinarily use China’s reformed Enterprise Bankruptcy Law ('EBL'), whether the low use of the EBL is problematic, and if so, what can be done to ensure a more efficient resolution of corporate insolvencies and corporate financial distress in China. The EBL has been lauded – domestically and internationally – as a major legislative success. However, despite the rapidly growing number of companies, level of corporate indebtedness and non-performing loans – which should, one might expect, lead to an increase in the use of the EBL – the number of court-run insolvency cases has in fact been decreasing since the law was implemented in 2007. The thesis draws on newly collected insights from a series of interviews in China – to supplement the scarce and often incoherent data that is available – to determine what motivates debtors and creditors not to use the EBL. The findings are presented as four complementary constraints on a more effective and efficient operation of the EBL. First two constraints relate to the low payoffs under the EBL that debtors and creditors expect to receive due to (i) flaws in the EBL itself and (ii) problems in surrounding non-bankruptcy rules and practices that reduce or prevent recoveries under the EBL. A third constraint affects those debtors and creditors who wish to use the EBL despite the low expected payoffs – for example to avoid directors' liability for corporate insolvency – but are prevented from doing so due to (iii) potential enforcers' limitations and biases. A fourth and final constraint on the use of the EBL that reinforces debtors' and creditors' unwillingness to use the EBL is (iv) the parties' (often inaccurate) perception that alternative debt enforcement mechanisms may offer comparatively higher payoffs (v. the EBL).
Building on this discussion, the thesis then considers the desirability of, and options for, reform. It argues that reform and subsequent greater use of court-enforced insolvency law are desirable in China because the (reformed) EBL has the potential to contribute to economic development through more efficient resolution of complex financial distress; better control of bad debt; easier and cheaper corporate financing; more efficient allocation of resources; and more entrepreneurial activity. However, because the necessary changes to deliver this are likely to be slow in coming, it proposes a dual-track reform encompassing (i) substantive reform of the EBL and select non-bankruptcy laws and practices; accompanied by (ii) the introduction of a new speedy, independent and confidential mechanism for insolvency resolution, 'MedArb.'

Keywords: transition economy
China
insolvency law
law reform
Advisor: Armour, J
The molecular epidemiology and ecology of Neisseria species in the African meningitis belt

Neisseria meningitidis (Nm) is one of the major causes of bacterial meningitis in the African meningitis belt (AMB). This organism is part of the genus Neisseria, which includes ten human restricted species, mostly harmless commensals of the nasopharynx; however, Nm is capable of causing invasive meningococcal disease. The transition from carriage to pathogenic state remains perplexing, and strict virulece factors have yet to be identified.
It has been hypothesised that non-pathogenic Neisseria (NPN) carried asymptomatically in the oroopharynx could play a role in modulating carriage of Nm, and therefore, its likelihood of invasion. In chapter 3, the diversity of the genus was characterised within a collection of 46 034 nasopharyngeal samples obtained across the AMB: five different species were identified, with Nm and NPNs displaying inversely related risk factors fo carriage. Chapter 5 presents the whole genome sequence (WGS) analysis of 107 Neisseria isolates unclassified by other methods. This higher genetic resolution, complemented with the use of a novel speciation approach, revealed seven novel Neisseria species, mostly collected in African countries.
The invasive potential may also be due to the presence of particular genetic factors in the meningococcal genome. Chapter 4 presents the WGS comparison of 23 carried and invasive serogroup A Nm collected in Chad during the 2011 meningitis epidemic. Isolates from both phenotypic groups were found to be part of the same bacterial populations; however, discrete clusters were identified, associated with distinct age groups.
These results indicate that genomic analyses are essential to appropriately study Neisseria diversity, and that lower resolution methods have greatly underestimated the diversity of the genus in Africa. The identification of Nm clusters associated with certain niches and of the differences in carriage risk factors suggests that variation in the environment, including the presence of NPNs, may be key in modulating carriage of Nm.

Keywords: Neisseria
bacterial genomics
African meningitis belt
Advisor: Maiden, M
Robust lifelong visual navigation and mapping

The ability to precisely determine one’s location in within the world (localisation) is a key requirement for any robot wishing to navigate through the world. For long-term operation, such a localisation system must be robust to changes in the environment, both short term (eg. traffic, weather) and long term (eg. seasons).
This thesis presents two methods for performing such localisation using cameras — small, cheap, lightweight sensors that are universally available. Whilst many image-based localisation systems have been proposed in the past, they generally rely on either feature matching, which fails under many degradations such as motion blur, or on photometric consistency, which fails under changing illumination.
The methods we propose here directly align images with a dense prior map. The first method uses maps synthesised from a combination of LIDAR scanners to generate geometry and cameras to generate appearance, whilst the second uses vision for both mapping and localisation. Both make use of an information-theoretic metric, Normalised Information Distance (NID), for image alignment, relaxing the appearance constancy assumption inherent in photometric methods. Our methods require significant computational resources, but through the use of commodity GPUs, we are able to run them at a rate of 8-10Hz. Our GPU implementations make use of low level OpenGL, enabling compatibility across almost any GPU hardware.
We also present a method for calibrating multi-sensor systems, enabling the joint use of cameras and LIDAR for mapping.
Through experiments on both synthetic data and real-world data from over 100km of driving outdoors, we demonstrate the robustness of our localisation system to large variations in appearance. Comparisons with state-of-the-art feature-based and direct methods show that ours is significantly more robust, whilst maintaining similar precision.

Keywords: Localisation
SLAM
Advisor: Newman, P
Maddern, W
Identification and characterisation of the genetic determinants of variable response to antigens from infectious agents

Despite the success of vaccines in routine use worldwide, there are substantial challenges hampering our ability to develop vaccines against extant diseases including malaria and tuberculosis. Novel approaches are urgently required to help us understand immunological correlates of protection against disease and facilitate our understanding of the impact of human genetic variation on the success of diverse vaccines.
To identify host genetic factors responsible for variation in antibody responses against vaccine antigens delivered routinely to infants worldwide I performed a genome-wide association study (GWAS) involving 2,499 infants recruited from three diverse sites across Africa. I identified strong genetic associations between variants in the class II major histocompatibility complex (MHC) locus and responses against five antigens: pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin; diphtheria toxin (DT); and hepatitis B surface antigen.
To characterise these associations at the gene and allelic level I developed a large, high-resolution (6-digit ‘G’) population-specific human leukocyte antigen (HLA) imputation reference panel including 697 individuals from the vaccine GWAS typed at 11 genes, highlighting the diversity of HLA across the African continent. Using this panel I imputed HLA into the remaining GWAS dataset to fine-map the associations to specific HLA alleles, amino acid and single nucleotide polymorphism sites; some of which were found to be African specific.
I then used these HLA association findings observed with PT response to correlate, through genetics, this trait with susceptibility to whooping cough in an independently recruited and analysed set of cohorts from the UK. I further used these genetic correlations to demonstrate the relevance of levels of PT-specific circulating follicular helper T-cells and TRBV29-1 T-cell receptor gene expression levels in the development of this protective immune response against PT. By using HLA-peptide binding studies I also demonstrate the diversity of mechanisms that are involved in HLA-disease association, showing that the breadth and affinity of DT-peptide binding are increased with HLA-DRB1 alleles associated with increased DT antibody responses.
Taken together, these data represent the first comprehensive genetic association study of multiple vaccine responses undertaken in African infants. These results highlight the importance of human genetics in modulating protective responses against vaccine antigens and demonstrate how such associations can be harnessed to understand biological mechanisms of protective efficacy in greater detail that may in turn facilitate future vaccine development.

Keywords: Antibody
Genome-wide association study
Human leukocyte antigen
Pertussis
Africa
Advisor: Hill, A
Hollander, G
Production optimization and value chain analysis for decellularized skin

Due to rapidly advancing developments in tissue engineering, and the depth of its potential for application in the health sector, its involvement in medical therapy have become the focus of pharmaceutical and clinical studies across both academia and industry. Nevertheless, there remains a significant gap between the commercial availability of biomedical technology products and their demand – with high costs and low manufacturing efficiency acting as key contributing factors towards this discrepancy. For this project, a simple sequential decellularised skin production process was designed based on the available information in the literature. In aiming to minimise the total cost of production, the size and quantity of components – as well as the time-sensitive scheduling of production stages – were optimised. Furthermore, the feasibility of eliminating freeze-drying to reduce the total cost of production was analysed, taking into account the difference between the reduction of operational costs and the additional costs that are incurred due to increased wastage from its reduced shelf life. Finally, this product is examined on a larger scale where all activities – from manufacturing to application – and the total costs incurred throughout the decellularised skin product lifetime is evaluated via the framework of value chain analysis proposed by Porter.

Advisor: Yang, A
Cui, Z
The power to shape the internal market: constitutional implications of the case law of the Court of Justice of the European Union

This thesis aims to determine the constitutional implications of the exclusive authority granted to the CJEU to interpret the Treaties in the context of the internal market. In particular, it examines how the Court’s interpretation of the free movement and competition rules – the two principal components of the internal market law – has shaped the constitutional division of competences between the EU and the Member States (the vertical dimension) and between the EU’s legislative institutions and the Court (the horizontal dimension). The argument to be advanced in this thesis is based on a comparative analysis of the Court’s reasoning in cases involving conflicts between, on the one hand, the free movement and competition rules and, on the other, domestic regulatory measures that embody various social policy considerations. The policy areas selected as case studies for the inquiry are healthcare, education, collective labour law, and gambling. None of these areas has been harmonised at EU level, save for the legislation essentially codifying the case law, and therefore come within the purview of EU law mainly through the judgments of the Court adopted in the context of the internal market. The comparative analysis – both among the selected policy areas and between the Court’s free movement and competition case law – reveals the inconsistencies in the Court’s exercise of its interpretative authority in light of the principles that govern the division of competences and powers in the EU. The thesis ultimately argues that, unlike its competition case law, the Court’s free movement case law involving the areas of healthcare, education and collective labour law, but not gambling, has encroached on national regulatory autonomy to an extent incompatible with the principles of conferral, subsidiarity and proportionality, and has reduced the scope of EU legislative action to the point of upsetting the institutional balance of powers between the EU’s judiciary and legislature.

Advisor: Weatherill, S
Davies, A
Probing environmental effects on gas-phase protein structure

Growth in the use of mass spectrometry as an analytical tool for studying protein structure and functionality has posed questions regarding correlation of native structures and observed gas-phase conformations for proteins. This thesis explores the relationship between the solution-phase and gas-phase structures of soluble proteins, and investigates the effect of the lipid environment on membrane proteins.
To assess gas-phase structure, ion-mobility mass spectrometry was used to measure directly the collision cross-sections of soluble proteins across a broad mass range. These collision cross-sections values were then compared with those derived from solution-phase data, calculated from dynamic light scattering experiments. Using computational methods collision cross-sections were calculated from structures reported in the protein data bank using a variety of techniques. Differing physical environments in solution and gas phases are not shown to affect protein structure by the dynamic light scattering and ion-mobility measurements. Contrastingly the computational calculations demonstrate that there is less correspondence between x-ray structures and their gas-phase counterparts.
Despite the effect that lipid environment has on membrane protein structure, capturing this native environment has been challenging. Lipodisqs look to overcome this problem by removing the portion of the membrane surrounding the embedded protein. Lipodisqs were investigated as potential vehicles for membrane protein mass spectrometry and compared with conventional detergent based approaches. Lower charge states are observed for proteins released from lipodisqs, compared to those released from detergent micelles, increasing the probability of native features being retained including native-like protein-lipid interactions. Lipodisqs therefore demonstrate significant potential as a tool for membrane protein mass spectrometry.
In summary, through this body of experimental work relationships have been established between gas-phase and solution-phase structures as well as computational methods. The use of Lipodisqs to eject membrane proteins from regions of the native membrane has been investigated.

Advisor: Robsinson, C
Translational control of autophagy rejuvenates immune responses

As our body's guardian, the immune system maintains systemic health through removal of pathogens, damage and cancer. Ageing of the immune system is associated with compromised immune responses as well as decreased tumour surveillance and is therefore a key risk factor for major diseases in the elderly. Adaptive immune responses are mediated by T and B lymphocytes, and failure in adaptive immunity is a particular hallmark of the ageing organism. Here we show that autophagy is impaired in aged murine B lymphocytes, and loss of autophagy causes severely reduced B cell responses. Our data demonstrate that B cell senescence can be reversed in an autophagy-dependent manner by spermidine, a naturally occurring polyamine metabolite. Mechanistically, our study reveals that the translation factor eIF5A, that requires spermidine for its activation, regulates the expression of the master autophagy/lysosomal transcription factor TFEB. Importantly, we show in humans that spermidine, eIF5A and TFEB levels decrease with age and may serve as ageing biomarkers. Taken together our results indicate that the translational control of autophagy by eIF5A is dysregulated with ageing, and identify a novel pathway with therapeutic implications.

Keywords: Ageing
Spermidine
Immunity
TFEB
eIF5A
Translation
Autophagy
Advisor: Simon, K