VictorJuiz/thesis huggingface dataset:
Factors affecting the commercialization of cellular based therapeutics

Introduction
Cell based therapeutics represent a commercially and clinically important treatment modality that offers a transformative approach to managing untreatable diseases. However, despite promising global demand and mounting investor appetite, the translation of cellular based therapeutics from “bench-to-bedside” remains challenging. This research systematically delineates the commercialization pathway and offers viable solutions to expedite clinical translation.
Methods
A systematic review was conducted to establish principal factors in the commercialization pathway. Two independent reviewers examined the retrieved publications, performed data extraction and desegregated barriers into a proprietary scorecard to assess impact utility and factor prioritization. The findings were used to inform a clinical trial and manufacturing landscape analysis of CAR-T therapeutics, alongside proprietary scorecards to identify critical bottlenecks. A model manufacturing protocol was developed and biomanufacturing modeling software was used to determine key inflection points for cell therapy manufacturing campaigns.
Results
The systematic review identified n=3374 unique publications. N=138 manuscripts qualified for full assessment and n=83 were selected for data extraction and final meta-analysis. Major barriers included cell therapy clinical trials and manufacturing. Clinical trial searches yielded n=2597 records. N=20 published trials were fully analyzed, alongside ClinicalTrials.gov data (n=113 active study protocols involving 8000 patients). Variation was seen with trial design, outcome reporting and patient populations. A mixed-methods analysis of global manufacturing identified n=19 studies with insufficient protocol evidence relating to unit operations and procedural steps. Modelling demonstrated a cut-off vessel volume of 20L as a cost-effective point for scale-up.
Conclusion
Ongoing translational challenges include CAR-T development, manufacturing practicalities and clinical trial approaches. Investigators should focus on accumulating harmonized data sets that can be aggregated to formulate evidence-based manufacturing protocols and treatment strategies. This will enable stakeholders to streamline the pathway to market for high-value candidate therapeutics, proficiently assess viable clinical trial and manufacturing options and contribute to prompter patient access.

Keywords: CAR-T
immunotherapy
stem cell
commercialization
Advisor: Holländer, G
Brindley, D
Languages and language use in classical Greek historiography and the Alexander tradition

This thesis examines six ancient historians and one biographer who wrote about Greek contact with the Persian Empire. It explores how these writers explicitly discuss the Greek language in its varying dialects (Chapter One), minor bilingual figures like interpreters and envoys (Chapter Two), and major bilingual individuals who adopted foreign tongues in their own interest (Chapter Three). Previous work in this area has largely been historical in focus, seeking the ‘reality’ behind the text whilst underappreciating any literary aims of the historians. Some scholarship has attempted to move beyond this, at least for certain ancient historians (e.g. Herodotus), but no single study yet exists examining this phenomenon in Greek historiography more broadly, incorporating works at the permeable frontiers of and across the genre to arrive at a more integrated description and analysis.
The three thematic chapters are each divided into two sections: one on classical Greek historiography (Herodotus, Thucydides, and Xenophon’s Anabasis); the other on the main surviving historians and biographers of Alexander (Diodorus, Curtius Rufus, Plutarch, Arrian – all from the Roman period). Throughout, I place language in its context by considering it alongside other, cultural, aspects of identity (e.g. nomoi). More generally, I seek to situate details of language and language use in their wider contexts: on a narrative level (why do such details occur where they do?), and on a historical level (how do such details fit into a broader contemporary cultural picture?).
Influenced by recent work on ancient identities as well as the ‘literary turn’ in ancient historiographical scholarship – that is, the appreciation that historians were writers crafting their own cultural products, not just chroniclers of events – this thesis employs the insights of narratology and philology to attempt to evaluate the historians’ approaches to language and identity on their own terms and in their own contemporary cultural, political, and literary contexts.

Keywords: Thucydides
Diodorus Siculus
Xenophon
Curtius Rufus
Alexander the Great
language
Plutarch
Herodotus
Arrian
Bilingualism
ethnicity
Multilingualism
Greek historiography
identity
Advisor: Thomas, R
Kallet, L
Towards an appropriate pedagogy for the development of the Muslim-background Church of Algeria

This study is based on qualitative research in the field of practical theology. It is a theological reflection on the practices of teaching and learning in the Muslim-background Church of Algeria. It reflects on the development of this Church with a view to ensuring its critically faithful participation in the continuing mission of the triune God. It seeks to explain and evaluate appropriate pedagogy for the development of the Church in the local and universal context of national Algerian identity and World Christianity. The journey of this thesis explores what it might look like to have a nuanced understanding of the indigenous Church as it develops in the cultural, religious and educational context of Algeria. It observes that in multiple ways, the experience of the Algerian Church is liminal. It also identifies the way in which a negative experience of liminality has been an impediment to the development of a coherent Algerian Christian identity, to the Church’s progress and development in Algeria, and to its place in the movement of World Christianity. However, it then moves on to argue how and why this context may be viewed positively, suggesting that the paradox of liminality can be viewed as a positive ‘state’ pregnant with potential for Algerian Christians. It concludes with a proposal for a framework of liberating liminal pedagogy, which is an invitation for the Algerian Church to engage in Christian education and theological training in the context of the Church’s Theo-dramatic performance of God’s mission. This leads to an overall attitude and commitment to continual praxis, which integrates local identity and Christian maturity through a multidimensional cognitive, affective and behavioural training process.

Keywords: Liminality
BMB
Liberating Liminality
Advisor: Wood, N
Willis, M
Characterization of barefoot and shod running

Barefoot (BF) and shod (SD) running mark relevant mechanical boundary conditions for affecting running biomechanics. This thesis studies the variation in foot-strike strategy (FSS), and whilst accounting for this variation provides a description of BF and SD running at different aerobic training velocities in uninjured, highly trained competitive (1500 m personal best: mean (standard deviation) = 3:59.8 (10.0)) male distance runners (n = 19). At one velocity, BF running for nine uninjured competitive female runners is also studied. Three dimensional (3D) gait analysis was used to measure lower-limb joint angles during treadmill running, and surface electromyography (EMG) was used to measure lower-leg muscle activity. Generalized linear mixed models (GLMMs) were used to account for and quantify between-subject variation and stride-specific foot-strike angle (FSA).
This thesis provides evidence to discourage the general practice of classifying runners in the present population within a FSS group for BF running. Also, a subset of individuals exhibited high FSA variability for BF running, possibly because of discomfort.
The hypothesis that FSA correlates with changes in running kinematics was supported. A larger hip width to femur length ratio found in females was associated with more hip adduction, corroborating previous research.
More plantarflexed FSA was hypothesized for higher velocities, and flatter foot placement was anticipated for BF versus SD running. Flatter foot placement was observed for BF running, but FSA was independent of velocity for BF running and more foot dorsiflexion at foot-strike (FS) was observed for fast velocity for SD running. These adjustments may be motivated by maximal or sub-maximal deformation of the heel pad and the novelty of BF running. Coupled with the observed increase in gastrocnemius muscle activity for BF versus SD running, these observations may be cause for caution for the novice BF runner. A different coordinative structure for tibia and rearfoot coupling emerged as velocity increased, possibly in response to an increased functional demand of the talocrural and subtalar joints for BF running as velocity increases.
The hypothesis that coordinative variability changes with FSA during impact phase, to reflect the underlying elevated injury risk for rearfoot-strike runners, was not supported. Coordinative variability was independent of FSA. In addition, coordination was more robust to changes in velocity and differences in FSA for SD running, possibly reflecting habituation.
Running BF may have potential as a diagnostic tool for studying injury etiology, because the limit of no external cushioning may place mechanical demands on the runner sufficient to elicit anomalous running kinematics, which may manifest as high kinematic variability.

Keywords: electromyography
Dynamical systems theory
foot-strike
barefoot
foot strike
running
Mixed effects models
Variability
Advisor: Zavatsky, A
Stebbins, J
“What do you want to be when you grow up?” and other tales: an ethnography of children in Greater London

Aspiration has become a political buzzword, and the rhetoric surrounding ‘raising aspirations’ to improve futures has filtered down to primary school level. Some researchers have critiqued the rhetoric as vacuous without material investment, and at worst, detrimental to disadvantaged groups. Whilst engaging with these ideas, this research offers a radical rethink. Firstly, rather than approaching the issue from a policy-driven perspective, it presents an emic view of children’s aspirations. Instead of applying a categorisation of aspirations as ‘high’ or 'low’ (and therefore able to be ‘raised’), it examines both the content and context of aspirational statements. Secondly, and more crucially, it does not just examine children’s elicited representations of their futures (or presents), but engages with children’s spontaneous practices occurring in time. This kind of engagement is rare, but is one of the possibilities and benefits of ethnography.
My fieldwork involved almost total immersion into children’s life-worlds. Using a method of ‘full participation’ with children, I took part in my participants’ practices for the greater part of each day over 15 to 18 months. In documenting both their everyday practices and their ‘in time’ narratives spontaneously embarked upon, I am able to reconcile the real-time ‘flow’ of life with the ‘fixings’ of meaning people everywhere construct in order to make meaning in and of their lives. In telling futures, my participants employed the flexibility of narrative in optimistic expressions of ideal competence, ownership and autonomy that asserted the teller’s personhood in the present – as able to act; effectual; recognisable by others; and worth knowing. In their telling, aspirations were not so much individually motivational, as they were an inter-subjective action in the world with productive power that could and did have ‘future’ effects.

Keywords: Contemporary
Ethnography
Fieldwork
Time
Participant-observation
Aspiration
Practice
Children
Childhood
Future
London
Advisor: Daniels, I
Temporal regularity in audition

Sound, by its very nature, is a temporal phenomenon. Everything from the perception of pitch to the sense of closure at the end of a symphony, relies on the brain's ability to integrate information over time. Ultimately it is perception that enables the richness of our interactions with the world around us, and it is a remarkable feat that the brain can quickly and accurately sift through the flood of information entering the ears to construct a coherent yet dynamic internal representation of the external world. Underlying this feat in part is the brain's ability to rapidly detect temporal patterns over timescales that span orders of magnitude, from sub-milliseconds to tens of seconds. Of particular interest is the ability to detect rhythms, or sound patterns in the range of hundreds of milliseconds to seconds. This timescale is particularly fascinating because it is critical to the perception of rhythm and beat in music, an ability that comes surprisingly naturally to us despite its neural underpinnings being far from understood. It is not just musical beat perception that remains mysterious; even the brain's mechanisms for detecting simple temporal patterns at this timescale are still not known. The work in this thesis therefore explores two broad questions that are key to understanding temporal processing at the rhythm timescale: 1- what are the perceptual consequences of rhythmic temporal regularity in sound? and 2- how does the brain detect temporal regularities at the rhythm timescale? I combine human psychoacoustics, rodent electrophysiology, and computational modelling to demonstrate that rhythmic sound patterns are easier to detect than arrhythmic ones, that adaptation in the auditory system may be a mechanism by which information about temporal structure at the rhythm timescale is encoded and made available to higher structures, and that low-level auditory processing may play a substantial part in shaping complex percepts such as where and how clearly we feel the beat in music.

Keywords: psychoacoustics
auditory cortex
temporal processing
psychophysics
rhythm
electrophysiology
temporal predictability
auditory midbrain
noise learning
pattern detection
beat perception
auditory system
Advisor: Schnupp, J
King, A
Willmore, B
Classification of partially labelled data using "mixture  of expert" models

In this thesis, we are concerned with the classification of partially labeled data. By partially labeled data we mean data where measurements are available from experimental units which are known to belong to one of a set of known classes but whose individual membership to subclasses within the known class is not known. Examples of these applications include fisheries research where fish lengths are available but sexual identities are not, sedimentology where information is available about the grain size distribution of a sample of sand but not its mineral composition and medical diagnosis
where the symptoms of the patients are known but not disease classifications.
A popular way of handling such partially labelled data is to use a mixture of Gaussian densities. Relying on the assumption of Gaussian densities (more information), results in an more efficient (less variance) discrimination procedure if the modelling assumptions are satisfied. However in practice, these assumptions rarely hold and often some of the features are qualitative variables, and hence it is generally of the view that logistic discrimination is a more robust bet as it relies on fewer assumptions. We chose to use a mixture of logistic regressions, embedded within a hierarchical mixture of experts to classify our data.
We compared its use in the plug-in-approach (frequentist approach) versus the predictive approach (Bayesian approach) in classification. The density of parameters required for the predictive approach was obtained using Markov Chain Monte Carlo simulation.

Advisor: Ripley, B
The civic virtue of philotimia: rhetoric, ideology, and politics in democratic Athens

This thesis explores the place that philotimia held in the value system and ideology of democratic Athens in the period between 430 and 320 BCE by examining the rhetoric of philotimia in instances of public speech, especially in the courtrooms and the Assembly.
Chapter 1 explores the relation between philotimia and metriotēs in courtroom rhetoric of Demosthenes’ time. Section 1 shows that being philotimos and being metrios could be presented as belonging to the same mentality, that of prioritizing public interest without ignoring appropriate personal ambitions and goals. Section 2 takes Against Meidias as a case study. In the rhetoric of Against Meidias, we find an account of what it means to be an exemplary elite philotimos citizens and what it means to be a rich hybristēs in democratic Athens.
Chapter 2 starts off by showing that the idea of civic-oriented philotimia that we find in Against Meidias is systematically found in courtroom speeches and honorific inscriptions from the mid-fourth century onwards. Section 2 moves backwards in time and explores the rhetoric of philotimia in the time of Lysias. In the last years of the fifth century and beginning of the fourth, I identify a greater need to warn the dikasts against bad or dangerous philotimoi rather than present oneself as a good philotimos. At the same time, the rhetoric of civicoriented philotimia can be traced as far back as 403/402, which indicates that it was not a novelty of the mid-fourth century. Section 3 explores cases of philotimoi that took action outside the democratic city as depicted in the speeches of Lysias and Demosthenes.
Chapter 3 explores the rhetoric of philotimia in political discussions. The rhetoric of philotimia is very limited when a speaker is discussing his contributions to policy-making, either directly in the Assembly or when discussions of politics are transferred in the courtroom. Section 1 discusses assembly scenes in Thucydides and Aristophanes. Section 2 focuses on representations of political competition in the time of Demosthenes. Section 3 discusses the rhetoric of charis in the deliberative speeches of Demosthenes. Section 4 explores Demosthenes’ self-presentation and collective philotimia in his trial battles with Aeschines.
This study does not argue for a semantic shift in the meaning of philotimia from a negative into a positive value, but shows that philotimia was an ambivalent concept throughout the period examined. The closely regulated and selective promotion of philotimia that is evidenced in the rhetoric of the courtroom and the Assembly reflects the duality of philotimia as a concept and the fact that the Athenians were very much alert to it.

Keywords: democracy
orators
classical Athens
Advisor: Thomas, R
Rood, T
Moduli spaces of unstable curves and sheaves via non-reductive geometric invariant theory

Many moduli problems in algebraic geometry can be posed using Geometric Invariant Theory (GIT). However, as with all such tools, if we are to have any hope of obtaining a well-behaved moduli space, certain objects, which are in whatever sense degenerate, must be ruled ‘unstable’ and left out of the classification. The goal of this thesis is to show how new results in non-reductive GIT may be used to construct moduli spaces that parameterise these unstable objects. Once a moduli problem is posed using GIT, this is done by studying the associated instability stratification and using non-reductive GIT to take quotients of the unstable strata, effectively splitting the moduli problem up into manageable pieces. We apply this method in two examples.
First, we consider moduli spaces of coherent sheaves over a projective scheme. The instability stratification in this case is closely related to the stratification by Harder-Narasimhan type. However, in order to apply the relevant theorems in non-reductive GIT, in fact one must perform a blow-up process analogous to partial desingularisation in the reductive case. This corresponds to refining the stratification by Harder-Narasimhan type. We give a sheaf-theoretic interpretation of this refinement, and use it to construct moduli spaces of such sheaves, in the case of Harder-Narasimhan length 2. We also include some results towards the length 3 case, and some remarks on generalisation to arbitrary lengh.
Our second application is moduli of projective algebraic curves. Here it is not clear a priori what the instability stratification should mean intrinsically, which leads us to define the notion of Rosenlicht-Serre type for curves. We show that in the case of a curve with only unibranch singularities this data essentially coincides with the semigroup of the singularities, and give a construction of moduli spaces of unibranch curves of fixed Rosenlicht-Serre type.

Keywords: Geometric Invariant Theory
Advisor: Kirwan, F
Bérczi, G
Reconciling content-externalism and self-knowledge: two frameworks considered

In this thesis, I assess the prospects for reconciling content-externalism and crucial guiding intuitions about self-knowledge within two different frameworks, respectively. The first framework belongs to the prominent contemporary externalist, Tyler Burge. The second framework is built from central strands of thought in Ludwig Wittgenstein’s later work.
I argue that a tension between the basic externalist intuition and crucial guiding intuitions about self-knowledge arises within a Burgean framework which does not arise within a Wittgensteinian framework. I show that given Burge’s views about the individuation of mental content, switching a subject slowly between two relevantly dissimilar contexts can undermine knowledgeability of her epistemic reasons. I argue that this is a troubling result, given Burge’s views about the sorts of things that epistemic reasons are. On Burge’s view, epistemic reasons are rational relations between mental states. If slow-switching can undermine knowledgeability of one’s epistemic reasons, then it can undermine knowledgeability of the rational relations between mental states. But the thought that the knowledgeability of the rational relations between mental states might be sensitive to changes in one’s context in this way seems at odds with our intuitive picture of self-knowledge.
I argue that this tension does not arise within a Wittgensteinian framework because there is evidence that Wittgenstein rejects certain of the claims about the individuation of mental content which generate the tension in Burge’s case.
The thesis examines the substantive similarities and differences between the Burgean and Wittgensteinian frameworks more generally. In doing so, it maps two contrasting ways in which the basic content-externalist intuition might be elaborated.

Advisor: Child, B