VictorJuiz/thesis huggingface dataset:
The molecular biology of DNA replication in the archaeon Sulfolobus solfataricus

DNA replication is essential for the propagation of all living organisms. The ability of a cell to accurately duplicate its entire genome is dependent upon the activity of numerous proteins. Identifying the molecular mechanisms by which these proteins act, and determining how they are physically and functionally coordinated at sites of active DNA replication, is central to understanding this essential cellular process. Archaea possess a DNA replication machinery which is ancestral to the one present in eukaryotes, and thus these organisms serve as simplified model systems for understanding the complexities of eukaryotic DNA replication.
This thesis investigates the molecular mechanisms underlying Okazaki fragment maturation in the crenarchaeon Sulfolobus solfataricus, which is essential to the completion of lagging strand DNA replication. Reconstitution of Okazaki fragment maturation in vitro demonstrated that the activities of three enzymes – PolB1, Fen1, and Lig1 – are required for this process in S. solfataricus. Furthermore, it was shown that optimum coordination of their three distinct activities is dependent on the ability of PolB1, Fen1 and Lig1 to simultaneously interact with a single PCNA ring, providing evidence for a mechanism of multi-enzyme coordination which may be universally employed by DNA sliding clamp proteins. The importance of protein flexibility in the accommodation of multiple proteins around a single PCNA was also investigated. Finally, the physical coordination of one of these key maturation enzymes – PolB1 – with other replisome proteins was examined. It was demonstrated that PolB1 exists in a trimeric complex in vivo with two previously unidentified factors, raising the possibility of uncharacterised activities and interactions for this crucial enzyme.
Taken together, these data provide new insights into functionally important protein-protein interactions within the archaeal replisome, and facilitate a greater understanding of the DNA replication machinery in both archaea and eukaryotes.

Keywords: Archaea
DNA replication
DNA sliding clamp
Okazaki fragment
Advisor: Bell, S
Towards a free-electron laser driven by electrons from a laser-wakefield accelerator: simulations and bunch diagnostics

This thesis presents results from two strands of work towards realizing a free-electron laser (FEL) driven by electron bunches generated by a laser-wakefield accelerator (LWFA). The first strand focuses on selecting operating parameters for such a light source, on the basis of currently achievable bunch parameters as well as near-term projections. The viability of LWFA-driven incoherent undulator sources producing nanojoule-level pulses of femtosecond duration at wavelengths of 5 nm and 0.5 nm is demonstrated. A study on the prospective operation of an FEL at 32 nm is carried out, on the basis of scaling laws and full 3-D time-dependent simulations. A working point is selected, based on realistic bunch parameters. At that working point saturation is expected to occur within a length of 1.6 m with peak power at the 0.1 GW-level. This level, as well as the stability of the amplification process, can be improved significantly by seeding the FEL with an external radiation source.
In the context of FEL seeding, we study the ability of conventional simulation codes to correctly handle seeds from high-harmonic generation (HHG) sources, which have a broad bandwidth and temporal structure on the attosecond scale. Namely, they violate the slowly-varying envelope approximation (SVEA) that underpins the governing equations in conventional codes. For this purpose we develop a 1-D simulation code that works outside the SVEA. We carry out a set of benchmarks that lead us to conclude that conventional codes are adequately capable of simulating seeding with broadband radiation, which is in line with an analytical treatment of the interaction.
The second strand of work is experimental, and focuses on on the use of coherent transition radiation (CTR) as an electron bunch diagnostic. The thesis presents results from two experimental campaigns at the MPI für Quantenoptik in Garching, Germany. We present the first set of single-shot measurements of CTR over a continuous wavelength range from 420 nm to 7 μm. Data over such a broad spectral range allows for the first reconstruction of the longitudinal profiles of electron bunches from a laser-wakefield accelerator, indicating full-width at half-maximum bunch lengths around 1.4 μm (4.7 fs), corresponding to peak currents of several kiloampères. The bunch profiles are reconstructed through the application of phase reconstruction algorithms that were initially developed for studying x-ray diffraction data, and are adapted here for the first time to the analysis of CTR data. The measurements allow for an analysis of acceleration dynamics, and suggest that upon depletion of the driving laser the accelerated bunch can itself drive a wake in which electrons are injected. High levels of coherence at optical wavelengths indicate the presence of an interaction between the bunch and the driving laser pulse.

Keywords: free electron lasers
laser-plasma interactions
laser plasma accelerators
synchrotron radiation
laser wakefield acceleration
Advisor: Hooker, S
Bartolini, R
Parental human investment: economic stress and time allocation in Russia

A decade of growth and wealth generation in Russia ended in 2009 with the collapse in GDP and rising unemployment. This Great Recession added new economic challenges to the ‘old’ problems facing children and families, including widening income inequalities and the phenomenon of social orphanage. One question is how the new and existing material pressures affect parent–child relationships. This research contributes to the answer by examining, in aggregate terms, the role poverty plays in the allocation of parental time in this emerging economy. Utilising a nationally representative sample of children, it explores how child interactions with parents are affected by aggregate and idiosyncratic shocks.
Drawing on the rational choice paradigm and its critique, we put forward the Parental Time Equilibrium as an analytical guide to the study. This theoretical approach presents individual decisions concerning time spent with children over the long term as the product of a defined equilibrium between resources and demands for involvement. We test this approach through pooled cross-sectional and panel analyses based on the Russian Longitudinal Monitoring Survey dataset from 2007 to 2009.
Children in low-income households face the double disadvantage of a lack of money and time investments at home, with both persistent and transient poverty being associated with lower than average parental time inputs in the sample. Moreover, while on average, we find that children do maintain the amount of time they spend with their parents under conditions of severe financial strain, low–income children lose out on play time with the mother. Material resources cannot be considered in isolation from structural disadvantages, of which rural location in particular is detrimental for parent–child time together. The study demonstrates that the cumulative stress of adverse macro-economic conditions and depleted material resources makes it difficult for parents to sustain their human investment in children.
The evidence this study provides on the associations between economic stress and pa-rental time allocations advances our knowledge of the disparities of in the childhood experience in modern Russian society. The findings strongly support the equal importance of available resources and basic demand for involvement, thus drawing policy attention to the need to address both in the best interests of children.

Keywords: recession
economic stress
poverty experience
rural
family stress model
disparities
idiosyncratic shocks
aggregate shocks
RLMS
Russian children
parenting
disadvantage
time allocation
Russia
parental investments
Advisor: Walker, R
Protecting civilians in internal armed conflict: the International Committee of the Red Cross and the Office of the United Nations High Commissioner for Refugees

This thesis examines the approaches taken by the International Committee of the Red Cross (ICRC) and the Office of the High Commissioner for Refugees (UNHCR) to the protection of civilians during internal armed conflict, both at the level of global policy and at the level of implementation in the Colombian context. The thesis explains how the ICRC and UNHCR approach protection, why each has adopted its particular approach, and how and why the effectiveness of each approach is limited. In doing so, it offers a theoretical framework for explaining the approaches taken by international organizations (IOs) to new tasks within their mandates as well as policy implications for the ICRC, UNHCR and other humanitarian agencies. From a theoretical perspective, this research shows that factors internal to the IO carry greater explanatory power than external factors. Most significantly, when an IO expands into a new issue-area, it frames the new task in terms of the existing tasks within its mandate, replicating the specific goals and the means of pursuing those goals. The extent to which the approach is then adapted to the specificities of the new issue-area depends on the ‘bureaucratic personality’ of the IO, and specifically the extent to which decisions are informed by field-level experience. Internal conflicts by definition include armed non-state actors, and the analysis in this thesis emphasises both their significance in determining civilian security and their neglect in existing approaches to protection. While the ICRC seeks to reduce the threat posed by all armed actors (state and non-state) in its work at the field level, it relies heavily on an international legal framework which prioritises states and this partially undermines its attention to non-state actors at the field level. UNHCR retains a state-centric focus at both the field level and the level of global policy. From a policy perspective, therefore, the thesis advocates greater attention to armed non-state actors both at the level of practice and in the development of protection norms.

Keywords: UNHCR
civilian protection
internal conflict
internal displacement
Colombia
humanitarian policy
ICRC
Advisor: Welsh, J
A secular mind: towards a cognitive anthropology of atheism

This thesis presents descriptive and explanatory accounts of both non-theism, the lack of belief in the existence of supernatural agents, and strong atheism, the moral opposition to such beliefs on the grounds that they are both harmful and signs of weak character. Based on my fieldwork with non-theist groups and individuals in the United States, United Kingdom, and Denmark, an online survey of over 3,000 non-theists from over 50 countries, and theories from both the social and cognitive sciences, I offer a new account of why nations with low economic and normative threats produce high levels of non-theism. This account is offered in place of the common explanation that religious beliefs provide comfort in threatening circumstances, which I show to be both anthropologically and psychologically problematic. My account centres on the role of threats, both existential and normative, in increasing commitment to ingroup ideologies, many of which are religious, and the important role of witnessing displays of commitment to religious beliefs in producing such beliefs in each new generation. In environments with low levels of personal and normative threat, commitment to religious ideologies decreases, extrinsic reasons for religious participation decrease, and superstitious actions decrease. Given the human tendency to believe the communications of others to the extent that they are backed up by action, such a decrease in displays of commitment to religious beliefs leads to increased non-theism in the span of a generation. In relation to strong atheism, I document a correlation, both geographical and chronological, between strong atheism and the presence of religious beliefs and demands in the public sphere. I then offer an explanation of this correlation based on the effects of threats against a modern normative order characterized by philosopher Charles Taylor as a system of mutual benefit and individual liberty.

Keywords: atheism
morality
strong atheism
commitment displays
cognition
existential security
non-theism
secularization
threat
Advisor: Whitehouse, H
Shear wave heterogeneity in the lower mantle from seismic tomography

To date, most shear velocity heterogeneity models in the lower mantle have been derived using long period data. Comparatively little use has been made of the vast ISC database of shear wave arrival times, which covers the years 1964 to 1991. The aim of this study is to use this database to construct global models of shear wave heterogeneity in the lower mantle and compare it with existing P models using similar period data in order to evaluate the hypothesis that P and S heterogeneity are proportional.
In order to reproduce the resolution operator inherent in these existing models, the same parameterization has been employed; lateral dependence is in terms of spherical harmonics up to degree and order 6, and radial dependence in terms of a quartic polynomial. The inversion uses data from over 4500 events selected according to criteria which minimize the bias introduced by uneven source receiver coverage. Despite having approximately one sixth of the amount of data the model correlates well with a P wave model computed using data from the same events, and this in turn is almost identical to models computed by other authors using similar inversion methods.
Assuming proportionality of P and S heterogeneity, a joint inversion of the P and S data has been performed. The resultant model correlates extremely well with the P model of this study, and similar variance reductions are obtained for both the P and S datasets as were found in the original inversions. Several model parameterizations have been used to try to investigate the dependence of the model expansion on the results. Consequently, taking into account results from synthetic experiments and from experiments into trade-offs with other inversion parameters, the average ratio of relative S to P heterogeneity d ln vsandfrasl;d ln vp throughout the lower mantle is constrained to be in the interval (1.8,2.1) with emphasis on higher values within these bounds. This value is in agreement with other studies using similar period data, and the upper bound is close to the optimum value of 2.27 obtained by Li et al., 1991 from normal mode data, suggesting that the ratio is at least only weakly dependent on frequency. In addition evidence is presented that the ratio is increasing with depth although attempts to extract specific gradients have failed because of the very poor distribution of S rays in the deepest mantle.

Advisor: Woodhouse, J
The internal dynamics of rebel groups: politics of material viability and organisational capacity in the RUF of Sierra Leone

This thesis examines the internal dynamics of the Revolutionary United Front of Sierra Leone over the course of the civil war waged from 1991-2002. It does so in two parts, looking first at the RUF’s organizational capacity—its ability to emerge and survive as a group; and second, at its material viability—the logistics and procurement of food, weapons, and other resources required to sustain war.
The RUF has become a paradigmatic case for the study of war and rebel groups in Africa. Although much has been written on the group and its violence, comparatively little is known about the inner-workings of the organization and how a largely forcibly recruited group of ill-equipped thousands managed to pose a viable threat to the state for over a decade. Through a fine-grained, case-based analysis, this study applies research on the microdynamics of violence in civil war to the structural and logistical mechanics that underpin it. Doing so contextualizes debates about resource wars, collective violence, and mobilization and onset within the RUF’s own strategies for controlling these aspects of war- making.
New primary material, including rebel archive documents, describes the extensive military and civilian governance structures through which order and cohesion were established and enforced. Tracking the success and failure of these mechanisms helps explain the disconnect between rebel rhetoric and behaviour. A detailed examination of the RUF’s material capacity applies this organizational analysis to the group’s strategic priorities for survival. It reorients the resource war debate toward what actually fuels fighting on the ground. Food has long been overlooked as the primary requirement for group survival, and ammunition the basic element of military viability. These ‘low politics’ of survival explain the nature of the war and underscore the importance of shifting factors, such as territorial control, in shaping rebel behaviour. Finally, the ‘high politics’ of international arms trades and global diamond markets illumine changes in the RUF’s firepower and personalization of power, returning to the organizational failings that ultimately led to the group’s dissolution.

Keywords: power
women
armed groups
small wars
conflict
insurgency
security
politics
gender
Sierra Leone
internal conflict
Africa
revolution
civil war
violence
war
international relations
rebellion
Advisor: Anderson, D
Analytic Results in 2D Causal Dynamical Triangulations: A Review

We describe the motivation behind the recent formulation of a nonperturbative path integral for Lorentzian quantum gravity defined through Causal Dynamical Triangulations (CDT). In the case of two dimensions the model is analytically solvable, leading to a genuine continuum theory of quantum gravity whose ground state describes a two-dimensional "universe" completely governed by quantum fluctuations. One observes that two-dimensional Lorentzian and Euclidean quantum gravity are distinct. In the second part of the review we address the question of how to incorporate a sum over space-time topologies in the gravitational path integral. It is shown that, provided suitable causality restrictions are imposed on the path integral histories, there exists a well-defined nonperturbative gravitational path integral including an explicit sum over topologies in the setting of CDT. A complete analytical solution of the quantum continuum dynamics is obtained uniquely by means of a double scaling limit. We show that in the continuum limit there is a finite density of infinitesimal wormholes. Remarkably, the presence of wormholes leads to a decrease in the effective cosmological constant, reminiscent of the suppression mechanism considered by Coleman and others in the context of a Euclidean path integral formulation of four-dimensional quantum gravity in the continuum. In the last part of the review universality and certain generalizations of the original model are discussed, providing additional evidence that CDT define a genuine continuum theory of two-dimensional Lorentzian quantum gravity.

Keywords: hep-th
Investigations into the regulation of sister chromatid cohesion

Cohesin, a ring-shaped complex composed of four subunits, is an essential player involved in timely and accurate segregation of genetic material at mitosis and meiosis. Cohesin performs a highly conserved role by topologically embracing sister chromatids until their concerted disjunction at anaphase, when the α-kleisin subunit of the ring is irreversibly cleaved by separase. A central part of the cohesin cycle is its cleavage-independent removal from chromatin through the action of the releasing complex.
In more complex eukaryotes, stabilisation of cohesin on DNA depends on the presence of sororin, a small functionally conserved protein whose association with cohesin is thought to counteract the releasing reaction. The first part of this thesis aimed to address the discrepancy of a sororin orthologue never having been identified in S. cerevisiae. This was undertaken using an imaging-based approach to screen a subset of the yeast genome for proteins with cohesin-like localisation. The screen was streamlined such that candidate genes had periodically cycling mRNA transcripts, similarly to cohesin subunits. No novel cohesin-associated proteins could be identified, although this could be in part due to technical limitations of the screen.
The precise molecular details of cohesin’s function and regulation remain poorly understood. A conclusive way to address many questions about cohesion as a whole would be to set up an in vitro assay capable of reconstructing cohesin loading, cohesion establishment, and the releasing reaction. The second part of this thesis aimed to establish a reliable purification protocol for the S. cerevisiae cohesin complex using a bacterial expression system for use in such biochemical assays. While purification of all components of the cohesin trimer (Smc1, Smc3, Scc1) was achieved successfully, the complex could not be confirmed to assemble functionally, as determined by chemical crosslinking of the Smc3/Scc1 interface.

Keywords: sister chromatid cohesion
protein purification
cohesin
sororin
yeast
Advisor: Nasmyth, K
Integrating and querying semantic annotations

Semantic annotations are crucial components in turning unstructured text into more meaningful and machine-understandable information. The acquisition of the mass of semantically-enriched information would allow applications that consume the information to gain wide benefits.
At present there are a plethora of commercial and open-source services or tools for enriching documents with semantic annotations. Since there has been limited effort to compare such annotators, this study first surveys and compares them in multiple dimensions, including the techniques, the coverage and the quality of annotations.
The overlap and the diversity in capabilities of annotators motivate the need of semantic annotation integration: middleware that produces a unified annotation with improved quality on top of diverse semantic annotators. The integration of semantic annotations leads to new challenges, both compared to usual data integration scenarios and to standard aggregation of machine learning tools. A set of approaches to these challenges are proposed that perform ontology-aware aggregation, adapting Maximum Entropy Markov models to the setting of ontology-based annotations. These approaches are further compared with the existing ontology-unaware supervised approaches, ontology-aware unsupervised methods and individual annotators, demonstrating their effectiveness by an overall improvement in all the testing scenarios. A middleware system – ROSeAnn and its corresponding APIs have been developed.
In addition, this study also concerns the availability and usability of semantic-rich data. Thus the second focus of this thesis aims to allow users to query text annotated with different annotators by using both explicit and implicit knowledge. We describe our first step towards this, a query language and a prototype system – QUASAR that provides a uniform way to query multiple facets of annotated documents. We will show how integrating semantic annotations and utilizing external knowledge help in increasing the quality of query answers over annotated documents.

Keywords: machine learning
information extraction
Advisor: Benedikt, M