VictorJuiz/thesis huggingface dataset:
Modelling the impact of cyclic hypoxia on cell-cycle regulation in cancer cells
Keywords: cancer
delay-differential equations
structured population models
cyclic hypoxia

In vivo observations show that oxygen levels in tumours can fluctuate on fast timescales. As a result, cancer cells can be periodically exposed to pathologically low oxygen levels; a phenomenon known as cyclic hypoxia. Even though in vitro models of cyclic hypoxia exist, they fail to capture the complex and heterogeneous oxygenation dynamics of real tumours. Mathematical models can help to overcome current experimental limitations and, by doing so, offer new insights into the biology of cyclic hypoxia by predicting cell responses to a wide range of cyclic dynamics. Recent experimental evidence suggests that cyclic hypoxia alters the progression of cancer cells along the cell-cycle. In this thesis, we use a range of mathematical approaches to study cell-cycle dysregulation in cyclic hypoxia and its impact on the growth and survival of cell cultures.
Accordingly, we develop and analyse a series of mathematical models that can be used, alongside in vitro experiments, to increase understanding of cell responses to cyclic hypoxia. First, we present a deterministic cell-cycle model to describe the dynamics of a population of cells growing in different oxygen environments, in the absence of competition for space. Our model comprises a system of 6 linear differential equations with two time delays and describes the evolution of the number of cells in different cell-cycle states. The impact of hypoxia on cell-cycle progression is captured by introducing arrest (or checkpoint compartments) and allowing the rates at which cells transition between different cell-cycle states to depend on the oxygen environment they experience. We then develop a corresponding individual-based model to study the impact of cyclic hypoxia on cell survival in the presence and absence of treatment.
We apply the models we develop in two different ways. On the one hand, we use a combination of analytical and numerical approaches to identify cell-cycle control strategies that favour proliferation and/or cell survival in different oxygen environments. Specifically, we identify environmental regimes in which cells may, or may not, benefit from having defective cell-cycle checkpoints. Furthermore, we illustrate how our models can be used as a tool to complement and design in vitro experiment to uncover the biological mechanisms that drive cell responses to constant and cyclic hypoxia.
Assumption violations in instrumental variables regression: weak 
instruments in subvector testing under heteroskedasticity and 
assessing the exclusion restriction
Keywords: Endogeneity
Instrumental variables
Subvector testing
Weak instruments
Heteroskedasticity
Exclusion restriction

Instrumental variables (IV) is a commonly used regression technique to estimate treatment parameters when the treatment is not random, i.e., it is endogenous. It relies on key assumptions and this dissertation explores strategies to deploy when those assumptions may not hold. Chapter 1 deals with the case of testing a subset of non-random treatment parameters when both the assumptions of strong instrument relevance and homoskedasticity fail. We recommend bootstrapping the Kleibergen-Paap Test or a 2-step LIML-based J-test in this situation. Chapter 2 considers a different assumption of IV regression: the exclusion restriction. We prove that the test devised by Kiviet (2020) does not function as a true test of the exclusion restriction and recommend reformulating it as a test of the endogeneity of the treatment variable, a test that is only valid when the exclusion restriction holds. Thus while the problems considered in Chapter 1 - weak instruments and heteroskedasticity - can be addressed by using the tests we recommend in the subvector case, the exclusion restriction, considered in Chapter 2, is not easy to relax or test. It is a foundational assumption of IV regression without a simple workaround, although past work offers adjustments if a certain type of subsample is available (van Kippersluis and Rietveld, 2018) and our endogeneity test can provide limited information in assessing whether the exclusion restriction holds for a particular instrument, even though a true test of endogeneity remains impossible.
Advanced cracking catalysts for the conversion of naphtha into light olefins
Keywords: ZSM-5
light olefin
catalytic cracking of naphtha
kaolin
Cr2O3

To meet the current global warming limit of 1.5℃ above pre-industrial levels, an urgent requirement is to develop advanced technologies fully- able to decarbonise the energy industry and other sectors. It is also expected that the demand for fossil of derived fuels will start declining in the coming years. Thereby, a significant fraction of the still vast resources of fossil hydrocarbons will be targeted towards the production of petrochemicals, notably to the production of light olefins, especially propene, and aromatics within an environmentally–friendly, climate-conscious perspective. The main scope of the project is to design and develop highly selective solid based catalysts and also to optimize the reaction conditions for converting the relatively high molecular weight hydrocarbons present in naphtha into the desired compounds.
ZSM-5 is the most efficient catalyst for naphtha cracking to light olefins. Our initial studies reveal that, for these catalytic processes, the SiO2/Al2O3 ratio is not perhaps the primary criterion for the assessment of the performance of the zeolite catalyst.
When compared to the catalyst formulation that was created by the impregnation approach, Cr2O3 loading on HZSM-5 (SiO2/Al2O3 = 80) zeolite using the mechanical mixing (MM) method results in a better n-heptane conversion (i.e., 95 wt.%) than the impregnation method (IMP). The inclusion of Cr had an effect on the physicochemical parameters of the catalysts, as well as their catalytic activity and selectivity. The optimum amount of Cr loading, which was 10% by weight, resulted in an increase in selectivity toward olefins, especially ethylene. In order to gain an understanding of the interaction mechanisms of the catalyst components and the role of support in the catalytic cracking of n-heptane over a hybrid of zeolite-matrix catalysts, it was investigated the effect of different matrix over ZSM-5 zeolite.
The advance made in this thesis is based on the designed combination of HZSM-5 with kaolin, the latter being a highly versatile catalyst and support matrix. This inert, inexpensive and earth-abundant material significantly improves the catalyst's sustainable features alongside the effective production of light olefins from n-heptane (a model compound) and naphtha (the actual petrochemical feedstock). The matrix alters the texture, morphology, surface density and strength of acid sites of HZSM-5 zeolite hence, enhancing the production of light olefins, particularly propene, followed by ethene and in minor extension C4H8 compound.
This work highlights the favourable impact of carefully tuning the strength and surface density of acid sites in HZSM-5 by combining it with a natural clay! This strategy enhances the production of light alkenes, particularly propene, and even aromatics via the catalytic cracking of naphtha.
Hydrogen production from crude oil using microwave-initiated catalytic technology
Keywords: fossil fuel
microwave
activated carbon
syngas
hydrogen
iron

The current target of limiting global warming to 2 °C above pre-industrial levels is recognised as a demanding task. Should renewable technologies, for example, wind and solar, be not able to decarbonise the energy industry sufficiently in the near future, other approaches are needed to generate energy without the emission massive amounts of CO2.
Hydrogen as an energy vector or fuel of the future has many advantageous properties compared to the current fuels. At the present, hydrogen production relies on fossil fuels and this trend will continue in the foreseeable future. As a result, hydrogen plants are and will remain a major source of CO2 emissions to the atmosphere. Decarbonisation is rapidly becoming a pressing but attractive challenge for worldwide fossil fuel utilization.
Here, we present an application of this new approach to the deep-dehydrogenation of Saudi Arabian light crude oil (LCO) - a liquid petroleum that has a low density and flows freely-. Hydrogen from fossil LCO - without significant CO2 production - is realized through microwave-initiated catalysis on activated-carbon-supported inexpensive Fe catalysts. Further optimisation can make the new process potentially competitive with current H2 production technologies, typically involving the steam reforming of methane, which invariably involves the release of significant amounts of CO2 to the atmosphere.
This environmentally - acceptable approach - to clean hydrogen production directly from fossil fuels and having near - to - zero CO2 production can make this new process potentially competitive with the current hydrogen production technologies, particularly through the portal of a carbon tax on energy producers. It, therefore, ushers in a new era …. The decarbonization of fossil fuels.
Of triggers, supersymmetry and photons: triggers for dark matter and a search for gauge-mediated supersymmetry breaking with the ATLAS detector at the LHC
Keywords: gravitino
GMSB
particle physics
trigger
supersymmetry
new physics

This thesis summarises research using the ATLAS experiment to search for Dark Matter. A performance study of the ATLAS Run 2 E
miss
T
trigger is presented, introducing relevant performance metrics and the algorithms that have lead to the successful operation of the trigger during LHC Run 2. The \texttt{trktc} algorithm, a candidate algorithm for the Run 3 E
miss
T
trigger, and its performance are discussed in detail, motivating the combination of a tracking-based algorithm with a Run 2 algorithm in constructing the Run 3 primary trigger. A search for new physics in hh
+invisible in 139fb−1
of pp
data collected at
√
s
=13TeV
with the ATLAS experiment is presented. Searches are performed for events in which one Higgs boson decays to γγ
and the other to b
ˉ
b
. The final state of γγb
ˉ
b
+E
miss
T
was previously unexplored by the ATLAS experiment. No evidence for physics beyond the Standard Model has been found. Results are interpreted in the context of Gauge-Mediated Supersymmetry Breaking models. Limits are presented assuming a pure Higgsino neutralino, which decays via
˜
χ
0
1
→h
˜
G
or
˜
χ
0
1
→Z
˜
G
. Assuming BF(
˜
χ
0
1
→h
˜
G
)=100%
, models with m(
˜
χ
0
1
)≤300GeV
are excluded. For lower branching fractions of BF(
˜
χ
0
1
→h
˜
G
)=75%
, models with neutralino masses of up to ∼250GeV
are excluded. Models with m(
˜
χ
0
1
)=130GeV
are excluded for branching fractions as low as 40%
. The presented search almost completely closes a gap in the ATLAS experiment's sensitivity to Dark Matter models.
The shiftiness dilemma applied to telling and its norms
Keywords: Telling
Invariantism
Epistemic Contextualism
Contextualism

This thesis represents an attempt to argue that there is an invariant epistemic standard that governs the assertability of knowledge attributions, and that any context variability with practical stakes is owed to the interpersonal norm that constitutes the speech act of telling. The way I reach my conclusions is by arguing that the subject matter of epistemic contextualism has been analysed in a sub-optimal way, and that this has led to a significant omission of an important aspect of knowledge attributions and denials, namely their interpersonal normativity. The literature on this issue has been universally analysing all of the examples that have motivated arguments between epistemic contextualists, classical invariantists, and subject-sensitive invariantists as cases of assertions of knowledge attributions and denials. I propose that there is a more precise way in which we can analyse the same examples, namely as cases of telling, which will require contextualists and invariantists alike to make room in their analyses for interpersonal normativity.
These two proposals, of analysing examples of knowledge attributions and denials more precisely, and of accepting that telling, as a speech act, involves an interpersonal norm, are not too controversial independently. However, I will use their combination to argue that the context-sensitivity exhibited by uses of knowledge ascriptions and denials owes to the interpersonal norm that constitutes telling, which stipulates that in telling their audience that p, the speaker takes responsibility for the truth of p. I finally argue that the practical stakes involved in a situation determine the amount of epistemic warrant that one needs to have in order to be warranted in taking responsibility for the truth of p.
If all of the arguments presented above are right, I manage to provide a way of evading the context shiftiness dilemma, which is an argument made by the contextualist against the classical invariantist. Moreover, a strong invariantist case has been built.
The Christian life and the disclosure of being : Karl Barth's Christology and Martin Heidegger's Question of being
Keywords: Christology
being
Heidegger
Christian life
Martin Heidegger
Question of being
Karl Barth
Barth
disclosure of being
Christ
ontology
Über die Linie
Jesus Christ

The aim of this thesis is to explore the ethical dimensions of both Barth’s and Heidegger’s works, and to present them as the unifying element of their diverse publications. This ethical dimension can be best described as their concern that human beings conceal ultimate reality by way of their existence, and thus as the imperative to exist in a way that allows reality to reveal itself, unhindered by the projections of human worldviews.
For Barth, the proper way of existence, through which we disclose our present situation under God’s Lordship, consists in prayer. Yet prayer involves, for Barth, both anticipation and remembrance of the history of the covenant. The exposition of the meaning of prayer therefore leads to a consideration of the history of the covenant, according to its biblical witnesses. The thesis therefore explores Barth’s exegetical interpretation of the two main perspectives of the history of the covenant in the New Testament, and reconstructs Barth’s understanding of the covenant-history as the hermeneutical framework of the disclosure of our present situation under the Lordship of God. Next follows the exposition of our concrete ethical obligations within the hermeneutical framework of the covenant-history. This exposition proceeds via a comparative study of Barth’s Minster ethics-lectures and his Church Dogmatics. Given that, for Barth, our concrete ethical obligations involve allowing ourselves to be challenged by a different perspective of reality, this thesis introduces Heidegger as a dialogue partner. The presented reading of Heidegger’s major works and lecture-circles focuses on his understanding of the interrelation between human existence and the self-manifestation of being as the final paradigm of meaning and horizon of this existence.
The thesis concludes with a dialogue between Barth and Heidegger, which aims to create the space for a new self manifestation of reality through the experience of a conflict between different perspectives of reality, and to translate Heidegger’s perspective of reality into Barth’s, in order to reconstruct Barth’s perspective in a process in which reality can reveal itself anew.
Development of a diverter piloted switched vortex valve for secondary flow modulation
Keywords: coolant flow
switched vortex valve
fluidics
flow modulation
aeronautic
jet engine
diverter
active control
staged fluidic

Active modulation of coolant flow rates would improve cycle efficiencies for jet engines. This thesis presents a proof of concept multistage fluidic device, the staged switched vortex valve (staged SVV), which modulates flow rates by switching between high and low flow impedance states. It is shown that the device can be actively switched between states using conventional mass flow injection and, with minimal modifications, 200 Hz acoustic tones.
A grey-box model of the staged switched vortex valve is developed as part of the investigation. This model encapsulates the complex fluid interactions associated with the vortex chamber and the diverter switch sections within black-box objects tuned with steady-state and transient characteristics. The model convincingly reproduces pressures and mass flow rates associated with steady conditions, switching events and self-excited oscillatory instabilities. Furthermore, the model can predict the conditions that will trigger switching and oscillatory instabilities.
The model is used in conjunction with the physical device to investigate the effects inter-stage duct impedances and sub-switching control signals can have on the stability and performance of the staged SVV. It is discovered that an appropriately sized inter-stage impedance can be used to improve the steady-state performance, with a localised constriction area ratio of 0.25 in one of the ducts affecting a 3.8% increase in the device’s turn-down ratio (TDR). However, the resulting increase in inter-stage pressure losses also makes the device more susceptible to self-excited oscillations. Sub-switching acoustic signals can also be used to improve steady-state performance. A 5.6% increase in the TDR is achieved by applying a 640 Hz acoustic tone to the unattached side of the pilot diverter section. Moreover, sub-acoustic tones can also be used to stabilise the staged SVV and suppress self-excited oscillations.
Exploring new paths towards biological anion recognition by lanthanide complexes
Keywords: chelation
chloride
sialic acid
host-guest chemistry
lanthanides
luminescence
photoinduced electron transfer
f-block chemistry
X-ray crystallography
anion recognition

Anions are ubiquitous in nature. In order to understand them in their natural setting, this thesis focusses on developing lanthanide complexes as hosts for the recognition of biologically relevant anions, particularly chloride and sialic acid. Chapter-I introduces lanthanide chemistry encompassing macrocyclic complexes, luminescence, and MRI. An account of anion recognition and lanthanide complexes used as hosts for biologically relevant anions are reviewed.
Chapter-II focuses on developing receptors for chloride recognition. The concept of binuclear lanthanide complexes, bridged by flexible ethane/propane spacer, for chloride recognition is envisioned. The proposed complexes are synthesised, and their anion binding properties are studied by luminescence, NMR spectroscopy, and X-ray crystallography. The study demonstrates the versatility of these binuclear complexes as the strongest chloride binding receptor to function in water and buffers to date. Thus, the work described here, hits a new milestone in anion coordination chemistry, ameliorating detailed exploration. Chapter-III builds on the drawbacks from these neutral complexes towards anion binding, and proposes tryptophan-conjugated cationic binuclear complexes for halide recognition. Initial studies show promising results towards halide recognition in water from this cationic coordination complex.
Chapter-IV revisits a ditopic approach of arylboronate-conjugated lanthanide chelates for sialic acid recognition, a tumour biomarker. However, the complexes suffer from protodeboronation, leading to the cleavage of boronic acid which is reported for the first time with structural evidence. The resulting boron free complex binds to L-lactate and D-gluconate. Chapter-V employs the ditopic approach, but with the incorporation of rigid anthracene and dansyl spacers between them, to improve the stability of the arylboronate during complexation. However, the anthracene-based receptor proved synthetically challenging. The success in making the dansyl-functionalised ligand extents the possibility of investigating sialic acid binding.
Chapter-VI summarises the work embodied in this thesis and Chapter-VII describes the complete experimental procedures followed in accomplishing the results reported in Chapters II-V.
Single-cell analysis of alternative splicing in normal and malignant stem/progenitor cells
Keywords: next-generation sequencing
splicing
genetics
cancer
single-cell

Alternative splicing is the process of utilising a different combination of exons to generate different isoforms from the same gene. Therefore, alternative splicing represents an additional and underappreciated layer of complexity underlying gene expression. To date, high-throughput single-cell RNA-sequencing (scRNA-seq) analyses have focused on characterising gene expression programme, whereas alternative splicing remains challenging to investigate. One possible reason for the sparsity of single-cell alternative splicing studies is the lack of single-cell alternative splicing analytical frameworks. To this end, we have developed analytical frameworks to comprehensively capture the alternative splicing landscape in health and disease models, and to prioritise actionable spliced genes for downstream experimental studies.
The developed frameworks consist of MARVEL, VALERIE, and IMPACT. MARVEL is an R package that provides comprehensive functionalities for the detection and quantification of alternative splicing events to enable dimension reduction analysis, differential splicing analysis, and functional annotation of differentially spliced genes. Functional annotation features include biological pathway enrichment analysis and nonsense-mediated decay prediction. VALERIE is an R package for visual-based validation of differentially spliced genes identified from MARVEL. IMPACT is an integrated in-house database consisting of a collection of pre-processed publicly available myeloid neoplasm and cancer cell line data for prioritising clinically relevant and druggable spliced genes validated by VALERIE.
We validated and demonstrated the application of our analytical frameworks on scRNA-seq data generated from both plate- (e.g., Smart-seq2) and droplet- (e.g., 10x Genomics) based library preparation methods derived from homogeneous cell lines and heterogeneous haematopoietic stem and progenitor cells in health and disease states. We believe our analytical frameworks will be advantageous to biologists to reveal novel biological insights from scRNA-seq data.