VictorJuiz/thesis huggingface dataset:
Conservation planning in Europe: ecological, financial, and political challenges

Conservation of biodiversity and sustainable resource use are central aims within ecology. This thesis focuses on the current data and environmental frameworks used to support these aims across different states in Europe. In particular, it examines the impact of geo-political boundaries on data-use, funding and planning for temporal movement of species in response to climate change. It also examines the current environmental framework agreements in Europe and their capacity to deal with trans-boundary aspects of biodiversity change.
Through examination of European biodiversity datasets, undertaking species distribution modelling of forest taxa, examining economic data, palaeo-ecological data, and assessing international environmental framework agreements, this thesis identifies a number of important knowledge gaps. Probably unsurprisingly, the distribution of biodiversity in Europe mostly does not match political entities, all of which have individual aims, financial resources, and biodiversity management regimes in place. All have a significant impact on biodiversity conservation planning because i) the use of geo-politically truncated data influences modelling predictions, ii) financial commitment to biodiversity conservation varies between countries influencing success outcomes, iii) biodiversity persistence in current and future climate change does not recognise geo-political boundaries, and iv) many of the key environmental frameworks are implemented within countries and do not considering trans-boundary issues.
Overall these findings significantly improve the understanding of conservation and resource management in Europe and fill a number of important knowledge gaps. They highlight the importance of appropriate trans-boundary ecological datasets and the need for more consistency across Europe in financial resources for biodiversity conservation. They also highlight the need for appreciation of areas of high-persistent biodiversity regardless of geo-political boundaries and environmental framework agreements that support cross-border conservation measures.

Keywords: Species Distribution Modelling
Conservation
Europe
Biodiversity
Environmental framework agreements
Advisor: Macias-Fauria, M
Willis, K
Systems within systems – free and open source software licences under German and United States law

Free and Open Source Software (FOSS) licences channel the exclusionary and individualising force of copyright to establish a qualitatively different, somewhat subversive, system for the exploitation of software. This thesis examines how it is that FOSS licences establish this 'system within a system' under both German and United States law. The inquiry begins with a detailed examination of FOSS licence templates as the instruments which transform code from its default position as the 'res' of proprietary relations to its status as 'open' or 'free'. The thesis then considers whether FOSS licence templates, as the legal basis for this subversive move, are valid and enforceable under domestic law. In addressing this question, the thesis undertakes a critical analysis of the leading case law in each jurisdiction. Going beyond the immediate case law, the thesis considers the broader systemic effects of FOSS licence enforcement. It highlights how building a system within a system foments certain tensions and contradictions within the law, in turn giving rise to unintended consequences and legal uncertainty. By highlighting these tensions, the thesis argues that the questions of FOSS licence enforcement in Germany and the United States may not be as settled as some may think.

Keywords: Open Source Software
FOSS
United States Law
FOSS Licensing
Free Software
German Law
Advisor: Dinwoodie, G
iASPP in the balance between tolerance and autoimmunity

Maintenance of immunological homeostasis between tolerance and autoimmunity is essential for the prevention of human diseases ranging from autoimmune disease to cancer. Adaptive immune responses require both antigenicity and adjuvanticity, and cell death can critically influence immunological homeostasis by modulating the adjuvanticity it elicits. Accumulating evidence suggests that in addition to inducing apoptosis, p53 mitigates phagocytosis-induced adjuvanticity thereby promoting tolerance following physiologic tissue turnover. Here I identify Inhibitor of Apoptosis Stimulating p53 Protein (iASPP), a negative regulator of p53 transcriptional activity widely considered to be oncogenic, as a novel master regulator of immunological tolerance. Surprisingly, iASPP deficiency promoted oncogenic K-ras driven lung adenocarcinoma and pancreatic cancer tumorigenesis, while iASPP deficient mice were less susceptible to autoimmune disease. Furthermore, immune responses to iASPP-deficient tumors exhibited hallmarks of immunosuppression, including activated regulatory T cells and exhausted CD8+ T cells, and iASPP-deficient CD4+ T cells were less responsive to TCR engagement in vitro. Interestingly, iASPP-deficient tumor cells, myeloid cells, CD4+, and γδ T cells expressed elevated levels of PD-1H, a recently identified transcriptional target of p53 that promotes tolerogenic phagocytosis. These findings suggest that iASPP can inhibit p53-mediated immunosuppressive PD-1H cross-talk between malignant cells, phagocytes, and responding immune cells, thereby promoting adjuvanticity following phagocytosis. Identification of a novel iASPP/p53 axis of immune homeostasis provides an exciting therapeutic opportunity for both autoimmune disease and cancer.

Keywords: P53
iASPP
Apoptosis
Advisor: Lu, X
RNA-based engineering of inducible CRISPR-Cas9 transcription factors for de novo assembly of eukaryotic gene circuits

Synthetic biology in mammalian cells holds great promise for reverse engineering biological processes and rewiring cellular behaviors for therapeutic purpose. An essential aspect in our ability to reprogram the cellular code is the availability of highly orthogonal, inducible transcriptional regulators. CRISPR-based strategies employing effector-domain tethering to the single guide RNA (sgRNA)-dCas9 complex have greatly advanced this field by allowing for precise activation or repression of any gene via simple sgRNA reprograming. However, the implementation of inducible CRISPR-based transcriptional regulators (CRISPR-TRs) has so far been restricted to dCas9 protein engineering and conditional effector tethering. Although elegant, these approaches are limited by dCas9 promiscuous loading of sgRNAs, which hinders their use for the creation of independent multi-gene transcriptional programs.
To address this limitation, I have developed a modular framework for the rational design of inducible CRISPR-TR, based on simple and reversible modifications of the sgRNA sequence. At the core of this conceptual framework lies the ability to inactivate native sgRNAs by appending on their 5’-end a short RNA segment, which folds to form a spacer-blocking hairpin (SBH). Base-pairing between the extension and the sgRNA spacer prevents docking of the CRISPR-TR on-target, fully abrogating its activity. Subsequently, I have created inducible SBH variants (iSBH) by replacing the hairpin loop with conditional RNA cleaving units. Using a variety of sensing-loops, I was able to engineer a panel of switchable iSBH-sgRNAs, designed to activate specifically in the presence of protein, oligonucleotide, and small molecule inducers. Leveraging the versatility of this method, I demonstrate that iSBH-sgRNAs expression can be multiplexed to assemble synthetic gene circuits implementing parallel and orthogonal regulation of multiple endogenous gene targets. Finally, I have distilled the design principles derived throughout this project to develop a web tool that automates the creation of iSBH- sgRNAs. Already a valuable addition to the synthetic biology toolkit, iSBH-based inducibility should in theory also be applicate to all CRISPR-Cas9 derivatives (genome editing, epigenetic alteration, DNA labelling, etc.) as well as other newly characterized RNA-guide nucleases from the CRISPR family.

Keywords: RNA engineering
CRISPR
synthetic biology
transcription factor
genome engineering
Advisor: Fulga, T
Synthesis of the EFG-ring system of pectenotoxin-4

The EFG-ring system of pectenotoxin-4 was synthesised via a novel pathway which ultilised a cobalt-mediated oxidative cyclisation to access the trans F-ring, and an osmium-mediated oxidative cyclisation to form the cis E-ring.
Subsequent union of these fragments, under modified Julia-Kocienski olefination conditions, facilitated the synthesis of the EFG-ring system of pectenotoxin-4.
Introduction
This chapter reports the previous total syntheses of pectenotoxin molecules, along with completed syntheses of pectenotoxin fragments, including the Donohoe group’s synthesis of the ABC-ring system of pectenotoxin-4.
Results and Discussion
The synthesis of the FG-ring system and subsequent coupling to the E-ring fragment are detailed in this chapter. The final steps from the Julia adduct to the EFG-ring system conclude this chapter.

Advisor: Donohoe, T
Cultural appropriation in Messiaen’s rhythmic language

Bruhn (2008) and Griffiths (1978) have referred in passing to Messiaen’s use of non-Western content as an appropriation, but a consideration of its potential moral and aesthetic failings within the scope of modern literature on artistic cultural appropriation is an underexplored topic. Messiaen’s first encounter with India came during his student years, by way of a Sanskrit version of Saṅgītaratnākara (c. 1240 CE) written by the thirteenth-century Hindu musicologist Śārṅgadeva. I examine Messiaen’s use of Indian deśītālas within a cultural appropriation context. Non-Western music provided a safe space for him to explore the familiar, and served as validation for previously held creative interests, prompting the expansion and development of rhythmic techniques from the unfamiliar.
Chapter 1 examines the different forms of artistic cultural appropriation, drawing on the ideas of James O. Young and Conrad G. Brunk (2012) and Bruce H. Ziff and Pratima V. Rao (1997). I consider the impact of power dynamic inequality between ‘insider’ and ‘outsider’ cultures. I evaluate the relation between aesthetic errors and authenticity. Chapter 2 considers the internal and external factors and that prompted Messiaen to draw on non-Western rhythm. I examine Messiaen’s appropriation of Indian rhythm in relation to Bloomian poetic misreading, and whether his appropriation of Indian rhythm reveals an authentic intention. Chapter 3 analyses Messiaen’s interpretation of Śārṅgadeva’s 120 deśītālas and its underlying Hindu symbolism. Chapter 4 contextualises Messiaen’s Japanese poem Sept haïkaï (1962) in relation to other European Orientalist artworks of the late-nineteenth and early-twentieth centuries, and also in relation to Michael Sullivan’s (1987: 209) three-tiered definitions of japonism.
.

Keywords: Traité de rythme, de couleur, et d'ornithologie
Sarangadeva
Hindu symbolism
Saṅgītaratnākara
Sept Haïkaï
Śārṅgadeva
Turangalîla-Symphony
Encyclopédie de la musique et dictionnaire du Conservatoire
decitalas
Messiaen, Olivier, 1908-1992
Technique de mon langage musical
Turangalîla-Symphonie
Non-retrogradable rhythms
Sangita Ratnakara
Greek meter
Sept Haikai
Animal symbolism
Deśītālas
Indian rhythm
Cultural Appropriation
Le Tombeau resplendissant
Harold Bloom
Les Offrandes oubliées
Advisor: Saxton, R
Stanyek, J
Finite element limit analysis of offshore foundations on clay

Capacity analysis is a common preliminary step in the design of offshore foundations. Inaccuracies in traditional capacity analysis methods, and the advancement of numerical modelling capabilities, have increasingly led designers to optimise foundations using more complex methods. In this thesis, the ultimate limit state capacity of a range of foundation types is investigated using finite element limit analysis.
Novel three-dimensional finite element limit analysis software is benchmarked against analytical solutions and conventional displacement finite element analysis. It is then used to find lower and upper bounds of foundation capacity, with adaptive mesh refinement used to reduce the bound gap over successive iterations of the solution. Rigid foundations subjected to short term loading on clay soil are analysed. The undrained soil is modelled as a rigid--plastic von Mises material, and attention is given to modelling any normal and/or shear stress limits at the foundation/soil interface.
Shallow foundations, suction anchor foundations, and hybrid mudmat/pile foundations are considered. Realistic six degree-of-freedom load combinations are applied and results are reported in the form of normalised design charts, and tables, that are suitable for use in preliminary design. Relationships between loading combinations and failure mechanisms are also explored. A number of case studies based on authentic foundation designs are analysed. The results suggest that finite element limit analysis could provide an attractive alternative to displacement finite element analysis for preliminary foundation design calculations.

Keywords: geotechnics
finite element analysis
finite element limit analysis
caisson
cohesive soil
limit analysis
adaptive mesh refinement
capacity analysis
mudmat
undrained clay
offshore foundations
plastic capacity
Advisor: Martin, C
Aspects of frustrated magnetism

Models of magnetism show complex collective behaviour which arises from simple interactions among microscopic degrees of freedom. Upon cooling from high temperatures conventional magnets typically undergo a phase transition to a magnetically ordered phase due to microscopic interactions which favour an ordered state. In frustrated magnets however, competing microscopic interactions place non-trivial constraints on the allowed configurations at low temperature, without selecting a unique ordered state.
In this thesis, we investigate the collective behaviour of a paradigmatic frustrated magnet, the classical Heisenberg model on the pyrochlore lattice with antiferromagnetic nearest neighbour interactions. Within a self consistent Gaussian approximation, we derive analytic expressions for correlation functions which match Monte Carlo simulations extremely well at all temperatures. We study the precessional dynamics of the model and provide a comprehensive description of the dynamics by constructing an analytically tractable stochastic model by extending the self-consistent Gaussian approximation to include dynamics. We relate these results to other highly constrained models.
Real experimental systems often have features that go beyond the phenomenology afforded by the simplest models; we investigate the effects of further neighbour interactions on paramagnetic spin correlations, and propose further neighbour interactions as the mechanism underlying experimentally observed patterns of scattering in frustrated spinel compounds.
In the dynamics linearized around a ground-state, the macroscopic degeneracy of the classical model leads to modes with zero frequency. Small perturbations stabilize ordered states and lift such zero modes to finite frequency. The ordered state has two widely separated energy scales both of which affect the dynamics, the leading scale of nearest neighbour exchange coupling, and the much smaller scale of the perturbation which relieves the frustration. We investigate the interplay between these widely different energy scales in setting the mode frequencies in states ordered by weak interactions.

Keywords: frustrated magnetism
Advisor: Chalker, J
Characterization of Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Binding Proteins

Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent intracellular second messenger capable of inducing calcium release from acidic organelles and is responsible for many important physiological activities. It has been recognized that an intermediate protein is required for NAADP to mediate its calcium-mobilizing effect through two-pore channels (TPCs). However, the identity of the intermediate NAADP binding protein remains unknown. This thesis aims to identify the elusive NAADP binding proteins to further elucidate the molecular mechanism of NAADP signalling pathway.
The first part of this thesis describes the characterization of NAADP binding protein using a chemistry approach, which includes crosslinking study in mouse embryonic fibroblasts (MEFs) and affinity isolation of binding protein via a NAADP affinity column. Crosslinking introduced significant interference to NAADP binding in MEFs. Radioligand binding assays revealed that NAADP binding in MEFs were predominantly in the membrane fraction and no high affinity binding site was detected. Affinity isolation of binding proteins by NAADP affinity columns was carried out using mouse liver cytosol. However, no high-affinity binding protein was isolated through this approach.
The second part of this thesis describes the identification of NAADP binding proteins via a combination of techniques including protein chromatography, photoaffinity labelling, mass spectrometry, virtual screen and label-free ligand binding assays. A sequential chromatography was conceived and optimized, which achieved a more than 2300-fold enrichment of high-affinity binding proteins. Photoaffinity labelling of the enriched fractions by [32P]-5-azido-NAADP revealed a 27 kDa band in SDS-PAGE gel. Subsequent mass spectrometry analysis generated a list of 35 candidates. Virtual screening of candidates by AutoDock Vina and CLC Drug Discovery Workbench predicted Carbonyl Reductase 1 (CBR1), Thiopurine S-Methyltransferase (TPMT) and Cytochrome b5 Reductase 3 (CYB5R3) as promising NAADP binding protein candidates. Further experimental validation by bio-layer interferometry (BLI) and microscale thermophoresis (MST) confirmed that TPMT and CBR1 are NAADP binding proteins. CBR1 binds NAADP and NADP with similar affinities. On the other hand, TPMT showed higher affinity and high selectivity to NAADP as no binding of NADP was observed. The identification of NAADP binding protein suggests new possibility of NAADP functionality and may provide new insights into the mechanism of action of NAADP signalling pathways.

Advisor: Galione, A
Sequential Monte Carlo methods for demographic inference

Patterns of mutations in the DNA of modern-day individuals have been shaped by the demographic history of our ancestors. Inferring the demographic history from these patterns is a challenging problem due to complex dependencies along the genome. Several recent methods have adopted McVean's sequentially Markovian coalescent (SMC') to model these dependencies. However, these methods involve simplifying assumptions that preclude the inference of rates of migration between populations.
We have developed the first method to infer directional migration rates as a function of time. To do this, we employ sequential Monte Carlo (SMC) methods, also known as particle filters, to infer parameters in the SMC' model. To improve the sampling from the state space of SMC' we have developed a sophisticated sampling technique that shows better performance than the standard bootstrap filter. We apply our algorithm, SMC2, to Neanderthal data and are able to infer the time and extent of migration from the Vindija Neanderthal population into Europeans.
With the large volume of sequencing data being produced from diverse populations, both modern and ancient, there is high demand for methods to interrogate this data. SMC2 provides a flexible algorithm, which can be modified to suit many data applications. For instance, we show that our method performs well when the phasing of the samples is unknown, which is often the case in practice.
The long runtime of SMC2 is the main limiting factor in the adoption of the method. We have started to explore ways to improve the runtime, by developing an adaptive online expectation maximisation (EM) procedure.

Advisor: Lunter, G
The good infinite in early German romanticism

In this dissertation I challenge the 'standard' reading of early German romanticism, according to which the movement is most fundamentally characterized by unfulfilled longing, infinite approximation and nostalgic despair. Against this 'defeatist reading' I put forward a ‘conciliatory reading’ according to which the romantics advocate a harmonious relationship between ourselves and the world. The reading I offer is centred on the idea of 'good infinity', an idea long associated with Hegel but one which I argue the romantics (especially Schlegel) anticipated. A good infinity is united with, rather than opposed to, finitude. This dissertation sets out to show how this romantic conception of infinity underlies major aspects of romanticism such as 'incomprehensibility', 'irony', and the method of 'Wechselerweis'.
In chapter 1, I argue that the romantics are neither pre-critical idealists continuing the Spinozistic heritage (the view of Frederick Beiser), nor Kantian skeptics replacing the 'thing-in-itself' with the Absolute (the view of Manfred Frank). On the reading I advance, the romantics are forbears to the phenomenological tradition. In chapter 2, I argue that Schlegel's recurring references to 'incomprehensibility', or Novalis' appraisal of 'the night' in his Hymns, are intended as 'positive' contributions in that they ask us to acknowledge and accept, rather than commiserate and reject, an incomprehensible dimension to the world. In chapter 3, I argue that ‘good infinity’ is implied in the method of ‘Wechselerweis' because of its emphasis on a reciprocal relationship. I survey various philosophical attempts to classify romanticism and show how I take my reading to preserve the various truths contained in each. In chapter 4, I distinguish the romantics' version of 'good infinity' from that of Hegel. I use various examples to motivate and describe a first personal sense of commitment that romantic irony, understood as feeling at the same time 'finite and infinite', makes available.
Together these chapters support my claim that interpreting infinity to entail unreachability amounts to a limited and ultimately unfaithful reading of the early German romanticist project. With 'good infinity' I offer a way out of those limitations.

Advisor: Schear, J
Laser-based temperature pressure &amp; species concentration measurements in combusting and non-combusting flows

The development of Laser Induced Thermal Grating Spectroscopy (LITGS) and Degenerate Four-Wave Mixing (DFWM) techniques for measurements in combusting and non-combusting flows is presented. The two techniques are used simultaneously with nitric oxide (NO) as an absorbing species. Signals generated by degenerate and non-degenerate probes are studied for NO in N2 buffer gas up to 4 bar, using a pulsed laser system to excite the (0, 0)γ-bands of NO at 226.21 nm. Contributions to the signal from scattering off the coherent or population grating of DFWM are distinguished from the scattering off the thermal grating of LITGS.
A systematic study of LITGS in NO is presented as a means of thermometry in air-fed combustion. LITGS signals from combustion-generated NO in a laminar, pre-mixed CH4/O2/N2 flame on an in-house constructed slot burner are used to derive temperature values as a function of O2 concentration and position in the flame at 1 bar and 2.5 bar total pressure. Temperature values, consistent with the calculated adiabatic flame temperature, are derived from averaged LITGS signals over 50-100 single shots at 10 Hz repetition rate in the range of 1600 K - 2400 K with a pressure-dependent uncertainty of ±1.8% at 1 bar to ±1.4% at 2.5 bar. Based on observed signal-to-noise ratios the minimum detectable concentration of NO in the flame is estimated to be 80 ppm for a 5 second measurement time at 10 Hz repetition rate.
LITGS signal shape is used to simultaneously derive pressure and temperature. Pressures are found to match measured gauge pressure well at ambient conditions along the full range of pressures measured from 1 to 5 bar and an extension of the technique is discussed for use in a high pressure combustion environment.

Advisor: Gregori, G