VictorJuiz/thesis huggingface dataset:
Rotating instability on steam turbine blades at part-load conditions
Keywords: steam turbine; LP; rotating instability

A computational study aimed at improving the understanding of rotating instability in the LP steam turbine last stage working under low flow rate conditions is described in this thesis. A numerical simulation framework has been developed to investigate into the instability flow field. Two LP model turbine stages are studied under various flow rate conditions. By using the 2D simulations as reference and comparing the results to those of the 3D simulations, the basic physical mechanism of rotating instability is analysed. The pressure ratio characteristics across the rotor row tip are found to be crucial to the inception of rotating instability. The captured instability demonstrates a 2D mechanism based on the circumferential variation of unsteady separation flow in the rotor row. The 3D tip clearance flow is found not a necessary cause of the instability onset. Several influential parameters on the instability flow are also investigated by a set of detailed studies on different turbine configurations. The results show that the instability flow pattern and characteristics can be altered by the gap distance between the stator and rotor row, the rotor blading and the stator row stagger angle. Some flow control approaches are proposed based on the observations, which may also serve as design reference.
The tip region 3D vortex flow upstream to the rotor row is also captured by the simulations under low flow rate conditions. Its appearance is found to be able to suppress the inception of rotating instability by disrupting the interaction between the rotor separation flow and the incoming flow. Finally, some recommendations for further work are proposed.
Evolutionary theory and normative realism in epistemology
Keywords: epistemology
metaethics
realism
evolution
evolutionary debunking arguments
normativity
evolutionary psychology
epistemic reasons

In this thesis I discuss one way in which evolutionary theory has been brought to bear on the evaluation of competing meta-normative views in epistemology. More specifically, I investigate whether normative realism in epistemology (epistemic realism) is compatible with the view that we are justified in holding many of the epistemic beliefs we hold, on the assumption that those beliefs can be explained in evolutionary terms.
In Part I I discuss normativity in epistemology and meta-epistemology. I begin by drawing attention to the fact that there are very different ways of understanding which concepts in epistemology are normative and what their normativity consists in. I focus on the concept of an epistemic reason to illustrate this point. I then discuss, in some detail, how different interpretations of epistemic-normativity will affect the form which normative-realist views in epistemology can take. I conclude by drawing a taxonomy of epistemic-realist views which is mindful of the different interpretations of epistemic normativity which I distinguished.
In Part II I turn to discuss the topic of Darwinian arguments against normative-realist views in epistemology. I begin by considering the form which Darwinian arguments have taken in recent metaethical literature. I argue that Darwinian arguments of a kind which is meant to raise a distinctively epistemological challenge for normative-realist views – I call those 'Darwinian-epistemological' arguments – represent a more interesting object of philosophical investigation than Darwinian arguments of a different 'metaphysical' kind. I then formulate a Darwinian-epistemological argument which targets normative-realist views in epistemology (DEA), explain how it works, and spend some time discussing its key premises.
In Part III I engage with the Darwinian-epistemological challenge against realism about epistemic normativity that Sharon Street presents in her paper 'Evolution and the Normativity of Epistemic Reasons' (2009). I argue that Street’s epistemological challenge is best viewed as an instance of a Darwinian-epistemological argument of the kind I formulated (DEA). I then go on to reply to Street’s argument on behalf of the epistemic realist. I conclude that arguments with the form of DEA do not represent a serious threat for normative realist views in epistemology.
A graph theoretic approach to matrix functions and quantum dynamics
Keywords: Matrix exponential
Spin system
Path-sum
Digraph
Many-body physics
Unique factorisation
Dynamical localisation
Matrix inverse
Quantum dynamics
Matrix logarithm
Rydberg atom
Matrix power
Resolvent
Matrix function
Anderson localisation
Prime

Many problems in applied mathematics and physics are formulated most naturally in terms of matrices, and can be solved by computing functions of these matrices. For example, in quantum mechanics, the coherent dynamics of physical systems is described by the matrix exponential of their Hamiltonian. In state of the art experiments, one can now observe such unitary evolution of many-body systems, which is of fundamental interest in the study of many-body quantum phenomena. On the other hand the theoretical simulation of such non-equilibrium many-body dynamics is very challenging. In this thesis, we develop a symbolic approach to matrix functions and quantum dynamics based on a novel algebraic structure we identify for sets of walks on graphs.
We begin by establishing the graph theoretic equivalent to the fundamental theorem of arithmetic: all the walks on any finite digraph uniquely factorise into products of prime elements. These are the simple paths and simple cycles, walks forbidden from visiting any vertex more than once. We give an algorithm that efficiently factorises individual walks and obtain a recursive formula to factorise sets of walks. This yields a universal continued fraction representation for the formal series of all walks on digraphs. It only involves simple paths and simple cycles and is thus called a path-sum.
In the second part, we recast matrix functions into path-sums. We present explicit results for a matrix raised to a complex power, the matrix exponential, matrix inverse, and matrix logarithm. We introduce generalised matrix powers which extend desirable properties of the Drazin inverse to all powers of a matrix.
In the third part, we derive an intermediary form of path-sum, called walk-sum, relying solely on physical considerations. Walk-sum describes the dynamics of a quantum system as resulting from the coherent superposition of its histories, a discrete analogue to the Feynman path-integrals. Using walk-sum we simulate the dynamics of quantum random walks and of Rydberg-excited Mott insulators. Using path-sum, we demonstrate many-body Anderson localisation in an interacting disordered spin system. We give two observable signatures of this phenomenon: localisation of the system magnetisation and of the linear magnetic response function.
Lastly we return to the study of sets of walks. We show that one can construct as many representations of series of walks as there are ways to define a walk product such that the factorisation of a walk always exist and is unique. Illustrating this result we briefly present three further methods to evaluate functions of matrices. Regardless of the method used, we show that graphs are uniquely characterised, up to an isomorphism, by the prime walks they sustain.
Genetics and pathophysiology of coronal craniosynostosis revealed by next-generation DNA sequencing
Keywords: coronal synostosis
TWIST1
genetics
craniosynostosis
craniofacial biology
Saethre-Chotzen syndrome
TCF12-related craniosynostosis
diagnostic outcomes
TCF12
exome sequencing
high-throughput DNA sequencing

This thesis further delineates the molecular genetic basis of a relatively common craniofacial condition, coronal craniosynostosis. It used whole-exome sequencing to identify novel disease genes in patients with non-syndromic coronal synostosis and negative genetic testing.
Initially, 2 patients were identified with damaging, frameshift mutations in a gene not previously linked with craniosynostosis – Transcription Factor 12 (TCF12). A further intronic mutation was identified in a third patient. This gene encodes a transcription factor that dimerises with TWIST1, mutations of which cause Saethre-Chotzen syndrome, also associated with coronal synostosis. Screening 344 undiagnosed patients identified 35 further mutations, all with coronal synostosis with 14 cases arising de novo. This work was published and testing for TCF12-related craniosynostosis was translated clinically.
Significant non-penetrance (60%) was identified in mutation-positive relatives and the genetic background was investigated. Firstly, analysis of parental origins of de novo mutations identified 6 of paternal origin and helped refine haplotype assignment. Secondly, haplotype analysis of TCF12-mutation carriers revealed modest correlation with phenotypic status, but this was insufficient to be useful in clinical testing. Thirdly, TCF12 haplotypes were analysed for association with non-syndromic coronal synostosis, but no significant association was found.
Further exome sequencing revealed a de novo frameshift mutation in Transcription Factor 20 (TCF20) in a patient with coronal synostosis and autism, although the mutation only correlated with the latter phenotype. Analysis of 5 trios revealed a novel variant in myosin heavy chain 4 (MYH4) in 1 family, although its role in suture development is uncertain. Reviewing pooled exome data from 19 mutation-negative patients revealed no further disease genes.
In summary, this thesis describes novel gene discovery, defines a new clinical entity and investigates genetic background of penetrant and non-penetrant individuals. Further exome sequencing identified another disease gene, a de novo mutation and compiled lists of damaging variants to allow future work.
Acute upper gastrointestinal bleeding in the United Kingdom: improving outcomes
Keywords: coagulopathy
endoscopy
transfusion
gastrointestinal bleeding
liver cirrhosis
weekend effect

Acute Upper Gastrointestinal Bleeding (AUGIB) accounts for 7000 deaths in the UK annually and is the single leading indication for transfusion of blood components. A large UK audit in 2007 reported high case fatality and rates of further bleeding. Since many deaths are determined by pre-existing co-morbidity, strategies to improve outcome should be targeted at preventable deaths and therefore focus upon improved control of haemorrhage and prevention of further bleeding, which are investigated in this thesis.
Data for the analyses presented originate from the UK national audit of AUGIB, a laboratory study and a cross sectional survey. Five broad themes were investigated including service provision and timing of endoscopy, the use of transcatheter arterial embolisation (TAE) or surgery for refractory bleeding, the impact of coagulopathy on outcome, management of acute variceal haemorrhage (AVH) and haemostatic derangements after AVH, and the use of red blood cells (RBCs).
Although there was no evidence of a “weekend effect” for mortality, earlier endoscopy (<12 hours) was associated with improved control of haemorrhage in higher risk patients compared to later endoscopy (>24 hours). TAE was an effective and safe modality for refractory bleeding, but the high post-surgical mortality (29%) raises questions about the appropriateness of case selection for surgery. Coagulopathy after non-variceal haemorrhage was associated with a 5-fold increase in risk-adjusted mortality. Further bleeding after AVH was strikingly high (26%) with notable deficiencies in the use of vasopressors, antibiotics and endotherapy. Global assessments of coagulation demonstrated that thrombin generation after AVH was normal, but clot strength was poor with excessive fibrinolysis. Platelets, fibrinogen and antifibrinolytics improved haemostasis ex vivo but coagulation factor transfusion had no effect. RBC transfusion practice is variable.
This work on AUGIB provides new data highlighting areas of sub-optimal care, and informs both current practice and research questions for new interventional trials.
Herodotos and Greek sanctuaries
Keywords: Sanctuaries
Delphi
Herodotus

This thesis argues that sanctuaries of the gods played a significant role in the political life of the Greek polis in the archaic and classical periods, and that the politics of the period cannot be understood fully without consideration of religion. It uses the text of Herodotos as a source of evidence about the history and perceptions of the period, but also makes use of other literary and archaeological evidence, so that the resulting models may be considered generally useful for the study of the period. Ch. 1 lays out the background to the subject; ch. 2 is an analysis of the activities related to sanctuaries described by Herodotos; ch. 3 examines sanctuaries as the meeting places of federations of Greek states, as well as investigating the nature of sanctuaries as areas of bounded space, showing that political meetings were frequently, if not always, held in sanctuaries, and that this was perceived as allowing some divine influence on decisions; ch. 4 investigates the dedications made at sanctuaries by foreigners, as part of a diplomatic process, showing that they provided a means of access to the polis as well as the god; ch. 5 compares the dedication of booty at sanctuaries with the construction of the battlefield trophy; ch. 6 argues that Herodotos portrays divine intervention as always happening through sanctuaries; ch. 7 argues that Herodotos' frequent mentions of Delphi are a sign of its importance in Greek history, not his own interest; ch. 8 draws some of these ideas together and suggests some general explanations for the importance of sanctuaries, as providing symbolic control of access to the polis, and bestowing authority on decisions taken by assemblies. Finally it suggests that Herodotos's inclusion of religious matters in his histories increases his importance as a source and an historian.
Global patterns and processes in avian diversification
Keywords: latitudinal gradients
ecology
sexual selection
birds
diversification
Speciation

The natural world consists of a vast array of forms, some more plentiful than others, yet our understanding of the processes responsible the production of biological diversity remains surprisingly limited. Here I combine novel datasets with powerful phylogenetic modeling techniques and computer simulations to test the effects of both biotic and abiotic factors on the dynamics of species radiations and the evolution of organism traits in birds.
In the first part of this thesis, I develop our understanding of the importance of abiotic factors for diversification by showing that in the early stages of lineage diversification at least, rapid adaptation to novel climatic conditions is likely to represent a prominent driver of avian diversification. In the second part I concentrate on the role of biotic factors, in particular that of sexual selection. I show that not only is sexual selection associated with accelerated rates of speciation and secondary sympatry—as well as faster rates of net diversification across the entire avian tree of life—but also that across-species variation in rates of phenotypic evolution is best understood with reference to the focus and intensity of sexual selection. Finally, given that the relative importance of such processes appears to vary predictably across latitudes, in the final part of the thesis I argue that latitudinal differences in the speciation process offers a potentially powerful explanation for conflicting viewpoints regarding the contribution of speciation to high tropical diversity. Overall, this work provides fresh insight into the processes governing broad-scale patterns in biodiversity.
Lithiated azetidine and azetine chemistry
Keywords: Aztedine
lithiation
substituted
azetine
synthesis

This work describes developments in new azetidine and azetine chemistry; specifically, methods developed for the introduction of functionality α- to nitrogen in both ring systems, with additionally in situ formation of the latter system, from azetidine substrates.
Chapter 1 discusses the growing importance of azetidines, and the current methods available for making substituted azetidines by ring formation. Further discussion comprises of current sp3 C–H activation approaches α- to nitrogen in heterocyclic compounds as potential methods for sp3 C–H activation on azetidines to give substituted azetidines. Previous work by the Hodgson group in this area is detailed.
Chapter 2 describes the advance made towards 2,3-disubstituted azetidines using the thiopivaloyl protecting/activating group, where the latter plays a key role. Optimisation, scope, selectivity and mechanistic insight into the α-deprotonation–electrophile trapping of a 3-hydroxy azetidine system is discussed, which successfully gives access to a range of 3-hydroxy-2-substituted azetidines. Preliminary investigations with 3-alkyl-2-substituted azetidines are also described.
Chapter 3 describes the development of a straightforward protocol to make 2-substituted-2- azetines, a rarely studied and difficult to access 4-membered azacycle subclass, from readily accessible azetidine starting materials using α-deprotonation–in situ elimination followed by further α-lithiation–electrophile trapping. Extension of this methodology by transmetallation from the intermediate organolithium to the organocuprate, resulting in greater electrophile scope, is also described.
William Cobbett's correspondence, 1800-1835
Keywords: Radicalism
Journalism
Letters
William Cobbett

The vast majority of William Cobbett’s personal letters have never been published. This thesis examines these manuscripts alongside the ‘open letter’ form that dominated his published writings, using correspondence to illuminate the hybrid and highly idiosyncratic form of Cobbett’s radicalism. It shows how he responded to continued persecution from the government through a series of innovative epistolary strategies, creating a popular journalism that incorporated many of the tropes usually associated with letter writing, including familiarity, authenticity, the spontaneity of speech and the domestic scene of reception. These became inseparable from the idealized presentation of Cobbett’s own radical and agrarian domestic life, and this thesis represents the first critical study to address the significance of Cobbett’s family in the physical production and imaginative world of his writings, drawing on many of the letters written by his seven children. Individual chapters concentrate on a series of episodes in Cobbett’s post-1800 career, including his friendship with William Windham, imprisonment in Newgate, exile in America, support for Queen Caroline and writings on the Captain Swing uprising. During these years, Cobbett’s correspondence helped to establish the modern newspaper leading article as an open letter to readers, although Cobbett’s are stamped with his own personal authority. However, while correspondence invested Cobbett’s journalism with a sense of situatedness unmatched in radical writing of the period, it also highlights some of the tensions within his political and pedagogical practice. By the 1820s, Cobbett’s correspondence bristles with the contradictions of wanting to recognize the individuality and difference of his readers’ lives, and at the same time pull them within the orbit of a very paternal political vision.
Moral enhancement and moral disagreement
Keywords: reasoning
Mill
disagreement
moral enhancement

At first glance, the project of moral enhancement (making people more moral) may appear uncontroversial and obviously worth supporting; surely it is a good idea to make people better. However, as the recent literature on moral enhancement demonstrates, the situation is not so simple – there is significant disagreement over the content of moral norms as well as appropriate means by which to manipulate them. This disagreement seriously threatens many proposals to improve society via moral enhancement. In my dissertation, I develop an understanding of how, exactly, disagreement poses problems for moral enhancement. However, I also argue that there is a way forward. It is possible to bring about moral improvement without commitment to particular and controversial moral norms, but instead relying on relatively uncontroversial ideas concerning morally reliable processes. The upshot is that, while attempting to directly manipulate people’s moral ideas is objectionable, it is relatively unproblematic to focus on helping people reason better and avoid akrasia, with the justified expectation that this will generally lead to moral improvement.
We should, therefore, focus not on how to bring people in line with what we take to be the right ideas, motives or behaviors. Rather, we should look to helping people determine for themselves what being moral consists in, as well as help ensure that they act on those judgments. Traditional, non-moral education, it turns out, is actually one of the best moral enhancers we have. In fact, the tools of philosophy (which is, in many aspects, concerned with proper reasoning) are central to the project of indirect moral enhancement. Ultimately, one of the best ways to make people morally better may well be to make them better philosophers.
Measurement and characterisation of microvesicles and nanovesicles in pregnancy and pre-eclampsia
Keywords: pregnancy
microvesicles
nanovesicles
pre-eclampsia

Excessive release of syncytiotrophoblast vesicles (STBM) from the placenta into the maternal circulation may cause the inflammatory response, endothelial dysfunction and activation of the coagulation system characteristic of pre-eclampsia (PE). Consequently, other cell types including platelets, leukocytes, red blood cells (RBC) and endothelium may be activated to release cellular vesicles which exacerbate the disease. This thesis aimed to develop methodology for enumerating and phenotyping STBM and the other vesicle types to determine whether they could be used as biomarkers for PE.
In vitro derived STBM and vesicles from the other cells of the vascular compartment were examined to select a suitable panel of antibodies to analyse these same vesicle types in plasma samples from non-pregnant (NonP), normal pregnant (NormP) and PE women.
Our flow cytometer was shown to detect microvesicles ≥290nm, hence smaller nanovesicles and exosomes could not be detected by this method. Therefore, a novel technique for analysing both microvesicles and nanovesicles, Nanoparticle Tracking Analysis (NTA), was explored and was found to be able to detect vesicles as small as 70nm.
The origins of the vesicles that change in pregnancy are not yet known. Flow cytometry and NTA were used in parallel to determine the size, number and phenotype of STBM and other cellular vesicles in NonP, NormP and PE women. Flow cytometry showed that majority of vesicles were derived from platelets, followed by RBC vesicles, leukocyte vesicles and STBM. NTA showed that the total number of vesicles in plasma was significantly elevated in NormP and late-onset PE women compared to NonP controls, and the vesicles were smaller in size. Similarly, flow cytometry showed differences in the composition of vesicles between pregnant and non-pregnant women, demonstrating that pregnancy affects vesicle release. However, no differences were found between NormP and PE women. This was probably due to the majority of samples studied being from late rather than early-onset PE. Thus, although this is the most comprehensive analysis of circulating vesicles in pregnancy to date, their use as biomarkers for PE remains an open question.