VictorJuiz/thesis huggingface dataset:
Single-molecule studies of transcription initiation

Single-molecule Förster resonance energy transfer (smFRET) has emerged as an important tool for studying biological reactions. This thesis describes smFRET investigations into the mechanism of bacterial transcription initiation.
We developed protocols to immobilize RNAP-DNA initiation complexes using vesicles and antibodies. We used these techniques to show that the transcription bubble conformation in immobilized complexes exhibits inter-molecular heterogeneity. We observed large FRET changes that we attribute to transcription bubble opening and closing dynamics. We found that σ70 region 3.2 (σR3.2) influences the kinetics of the bubble dynamics, which supports proposals that σR3.2 interacts with the transcription bubble template strand.
We extended our investigations to RNA synthesis and were able to observe abortive initiation cycles directly. We observed RNAP pausing and backtracking for the first time in transcription initiation. We obtained data suggesting that σR3.2 stabilises short RNAs at the active centre and forms a barrier to the extension of RNAs longer than 5-nt in length.
We extended our abortive initiation assay to observe signal changes that we attribute to promoter escape. Our data revealed the number of abortive cycles that occur prior to escape, the kinetics of promoter escape, and pausing events that may have some regulatory function.
We investigated the conformational dynamics of the RNAP β' clamp and observed dynamic conformational changes between clamp-open and clamp-closed states. Our work confirms proposals that the clamp remains stably closed once the open complex (RPO) is formed. We investigated what affect the antibiotics Myxopyronin and Lipiarmycin have on the clamp conformation. Our results revealed that Myxopyronin traps the clamp in a closed conformation, while Lipiarmycin traps it in an open conformation.
Overall, we made a number of novel observations that we believe advance our understanding of the mechanism of transcription. We hope that the discoveries reported here will direct future research efforts into RNAP function.

Keywords: Abortive Initiation
RNAP
Transcription
Advisor: Kapanidis, A
The CLASS act and long-term care policy: the politics of long-term care financing reform in the United States

This thesis seeks to contribute to the knowledge base about social policy in the United States, using long-term care (LTC) financing policy reform as an illustrative example. Specifically, this thesis explores LTC financing reform efforts during three U.S. Presidential administrations: Bill Clinton (1993-2001), George W. Bush (2001-2009), and Barack Obama (2009-2010). Within this historical framework, the LTC provisions of the Health Security Act of 1993, the development of the Community Living Assistant Services and Supports or 'CLASS' Act during the Bush Administration, and the legislative success of the CLASS Act as a part of the Patient Protection and Affordable Care Act of 2010 provide comparable cases to compare the drivers of social policy.
Drawing on the explanatory frameworks of the welfare state such as ideology, historical institutionalism, and an actor-centered approach to policy analysis, this thesis argues that successful path-departing legislation is difficult to achieve due, in part, to the presumed high costs of social programs and the complex institutional framework of the American political system. Policy outcomes result from the interaction between the complex processes and dynamics of the political system through which policy change (or the failure to change) actually occurs. The fact that the CLASS Act was politically successful, yet administratively inoperable as designed, reinforces the argument that social policy outcomes in the United States are reflective of a complex, enduring struggle of competing ideologies. This continual struggle, coupled with a heightened concern over cost control and fiscal austerity, helps to ensure that policies which are legislatively successful within the institutional architecture of the American political system are unlikely to produce major expansions of the welfare state. Social change is therefore highly difficult to achieve, even in the face of significant unmet social needs. Comprehensive reform of U.S. LTC financing arrangements will remain an elusive goal for the foreseeable future. Instead, incremental, highly pro-market solutions are likely to be the types of policies promoted in the years of ahead.

Keywords: American Public Policy
Health Policy
Long-Term Care Financing
Advisor: Surender, R
Saunders, A
Inelastic J/[psi] photoproduction in electron-proton collisions at HERA

The development of a neural network based electron finder designed for the ZEUS calorimeter is described. A study of elastic and inelastic J/ψ meson production in electron-proton collisions at HERA using the ZEUS detector is presented. During the 1993 and 1994 running periods, the ZEUS detector collected ~ 500 nb-1 and ~ 3 pb-1 of data respectively. The direct inelastic J/ψ photoproduction cross-section is measured for both running periods and an attempt is made to extract the gluon density inside the proton using the 1994 inelastic J/ψ sample.
Nuclear structure studies involving polarised iodine, samarium and europium

Low Temperature Nuclear Orientation (LTNO) is an important technique in the study of nuclei far from stability. The theory of LTNO and its application to the measurement of static nuclear moments and other quantities of spectroscopic interest are reviewed.
The off-line facility at Oxford was used to study the decay of 133I→133Xe and 135I→135Xe. 133I having Z=53 and N=80 has three protons above the closed shell Z=50 and two neutrons holes in N=82 shell, while 135I has fully closed neutron shell since it has N=82, and they are of considerable theoretical interest since a wide variety of the theoretical nuclear models may be used to describe the observed levels close to the stable double closed shell structure. Another aim is to search for the nuclear magnetic dipole moment of the ground state of 135I. Nuclear orientation of 133IFe and 135IFe enabled the mixing ratios of several transitions in the decay scheme of 133I and 135I to be determined. From temperature dependence for 135I, the nuclear magnetic moment of 135I has been deduced. Also temperature dependence for 133I, analysed using a simple model, gave value for the magnetic hyperfine field that differed from previous published values. The method of combining nuclear orientation with NMR has become a very popular technique in recent years for determining nuclear magnetic dipole moments very precisely. The purpose of the NMR/ON experiment was to measure the hyperfine field with greater precision and to get some idea of the proportion of nuclei subject to it.
Light Eu and Sm nuclei have attracted attention as systems with the number of protons right below the Z=64 subshell gap and the number of neutrons approaching N=82 major shell closure. Odd-proton, odd-neutron and odd-odd nuclei near the A=140 region have been investigated in the framework of the particle-triaxial rotor model. Main attention has been paid to explanation of experimental magnetic dipole and electric quadrupole moments of ground and isomeric states. Model predictions for deformation parameters of 136-142Sm even-even cores have been extracted.

Advisor: Stone, N
Entanglement detection and fractional quantum Hall effect in optical lattices

We consider the purity-based entanglement detection scheme introduced in [C. Moura Alves and D. Jaksch, Phys. Rev. Lett. 93, 110501 (2004)]. We describe how it could be implemented in an optical lattice using two-atom loss, and prove that in this form it detects all pure entangled states even without any spatial resolution. We then prove that correcting for certain reasonable types of experimental error is possible, and practical for error rates up to the order of one over the number of lattice sites considered. Limited spatial resolution similarly becomes a significant improvement over no spatial resolution only at nearly single site level. We also show how to use this process for state parameter estimation and collapse-revival evidence of entanglement, for which it remains useful even when the error rate is too high to permit unambiguous entanglement detection. We also consider an optical lattice bosonic analogue of the fractional quantum Hall (FQH) effect. This system can reach high “magnetic fields” very difficult to attain in the solid state FQH system, where the discrete nature of the lattice becomes important. Near simple rational numbers l/n of flux quanta per lattice cell, we find that the single particle states become nearly periodic with period n lattice sites, and have an n fold degeneracy which leads to FQH states resembling those of n-internal-state particles. Standard time of flight expansion would reveal this periodicity and be able to distinguish FQH states from vortex lattice or Mott insulator states. Shot noise correlation would provide further information on the nature of the FQH states.

Keywords: quantum Hall
entanglement
optical lattice
Advisor: Jaksch, D
Laser-induced grating spectroscopy in non-uniform temperature fields and flames

The application of Laser-Induced Grating Spectroscopy (LIGS) to thermometry of temperature-controlled ethylene flows and an ethylene-air flame from a Gülder burner is studied. A model for simulating the effect of contributions from regions of different temperature within the LIGS probe volume is developed for comparison with experimental data. The model includes a weighted sum of contributions from regions at a single temperature to the total signal intensity. An appropriate experimental set-up is constructed for this study, with careful consideration given to the dimensions of the probe volume. Temperature measurements are made in a dual flow of ethylene, where the probe volume contains two distinct temperature regions: one from an unheated flow and the second from a temperature-controlled hot flow. The model is shown to correspond well with experimental data; the presence of two discrete contributions, 293 ± 2 K and 310 ± 2K (0.6 – 0.7% precision), is identified in the LIGS signal from the cooler region.
LIGS signals are recorded at several spatial positions in the lower region of a flame with fixed stoichiometry. Signals measured in the 0.0 – 5.0 mm height above burner (HAB) range and the 0.0 – 3.5 mm radial position range are analysed using MATLAB; temperature information is extracted with precisions of 0.9 – 4.4%. The OH* distribution in the flame is recorded during a chemiluminescence experiment to identify the location of the reaction zone. The model is used to demonstrate that derived temperatures are the spatial average of a continuous temperature gradient within the probe volume. The suitability of LIGS for thermometry in environments with unknown temperature gradients is thus verified. Comparisons are made between the flame measurements and ethylene flow data; simple changes to improve the model are proposed. Strong non-oscillatory decay features in the LIGS signal, indicative of the laser heating of soot, are reported at HAB 20.0 – 50.0 mm; relevant implications are discussed.

Advisor: Ewart, P
Modelling of calcium handling in genetically modified mice

This thesis develops biophysically-based data-driven mathematical models of intracellular calciumdynamics in ventricularmyocytes for both normal and genetically modified mouse hearts, based on species- and temperature-consistent experimental data. The models were subsequently applied to quantitatively examine the changes in calcium dynamics in mice with cardiomyocyte-specific knockout (KO) of the cardiac sarco/endoplasmic reticulum ATPase (SERCA2) gene, to determine the contributing mechanisms which underlie the ultimate development of heart failure in these animals. In Chapter 1, with emphasis on calcium dynamics and calcium regulation in heart failure, an overview of cardiac electrophysiology, excitation-contraction coupling and mathematical models of cardiac electrophysiology is provided. In Chapter 2, models of calcium dynamics in the ventricular myocytes from the C57BL/6 mouse heart at a physiological temperature is developed and validated based on species- and temperature-consistent measurements. In Chapter 3, the C57BL/6 model framework is re-parameterised to experimental data from the control and SERCA2 KO mice at 4 weeks after gene deletion. The models are then used to quantitatively characterise changes in calcium dynamics in the KO animals and the role of the compensatory mechanisms. In Chapter 4, the model framework is extended to include differential distributions of ion channels in the sarcolemma and the calcium dynamics in the sub-sarcolemmal space, with parameters in these sub-components fitted to experimentally measured calcium dynamics from the control and KO cardiomyocytes at 7-week after gene deletion. Finally in Chapter 5, conclusions are drawn, the limitations of this study are discussed, and the future extensions to this study are described.

Keywords: genetically modified mice
mathematical modelling
cardiac electriphysiology
Calcium handling
Advisor: Smith, N
Casadei, B
Photoemission spectra of nanostructured solar cell interfaces from first principles

Photovoltaic (PV) technologies could provide abundant, clean and secure energy through the conversion of sunlight into electricity, but currently are too expensive to compete with conventional sources of power. Novel PV devices incorporating nanostructured materials, such as the dye-sensitized solar cell (DSC), have been identified as viable, low-cost alternatives to traditional solar cell designs. In spite of technological progress in the field over the last twenty years, the underlying physics governing DSC operation is still not well understood. In this thesis, first-principles (i.e. parameter-free) calculations are performed with the aim of connecting experimentally-measured photoemission data to the underlying atomistic and electronic structure of interfaces found in DSCs. The principal system under study is the interface between anatase titanium dioxide (TiO2) and the "N3" dye molecule, one of the most widely-investigated device designs in DSC research. Atomistic models of the interface are determined within density-functional theory. Core-level spectra of these interface models are then calculated using a ∆SCF approach. Comparison of the calculations to published experimental data finds that intermolecular interactions have a significant effect on the spectra. Next, the electronic structure of bulk TiO2 and of isolated N3 molecules is calculated using the GW approximation and ∆SCF method respectively. For the former, it is shown that including Hubbard U corrections in the initial Hamiltonian reduces the GW gap by 0.4 eV. These calculations are then used to determine the valence photoemission spectrum of the full interface. By including image-charge effects, thermal broadening and configurational disorder, quantitative agreement with experimentally-measured spectra is demonstrated. In addition to the N3/TiO2 system, calculations of the core-level spectra of the interfaces between TiO2 and H2O and bi-isonicotinic acid are also presented. The thesis concludes with a study of the X2Y3/TiO2 interfaces (X=Sb, Bi; Y=S, Se) found in recently-developed semiconductor-sensitized solar cells.

Keywords: photoemission spectroscopy
excited states
molecular photovoltaics
Advisor: Giustino, F
Judicial statecraft in Kenya and Uganda

Transitional justice has undergone tremendous shifts since it was first used in Latin American and Eastern European countries to address post-authoritarian and post-communist legacies of atrocity and repression. In particular, the establishment of the International Criminal Court (ICC) has increased the demand for prosecutions within a field that was previously marked by compromise and non-prosecution. While there are increasing expectations that countries with unresolved claims of human rights abuses should enact transitional justice policies, most of the literature on the subject largely omits to explain how elites from those countries choose among the possible options of transitional justice, and specifically, how they choose among international prosecutions, domestic prosecutions, and truth-seeking. Using case studies of Kenya and Uganda, this dissertation examines this decision-making process to understand how elites choose and reject different transitional justice policies. Theoretically, the research examines how preferences for transitional justice policies are constituted through “judicial statecraft”: the strategic efforts by heterogeneous, interest-pursuing elites to use justice-related policies as carrots and sticks in the overall contestation of power. The research finds that the choices of elites about judicial statecraft depend on three factors: the extent to which the elites are secure that their policy choices cannot be subverted from within; the cost and credibility of transitional justice threats; and the effects, both intended and unintended, of history.

Keywords: governance in Africa
International Criminal Court
post-conflict justice
truth and reconciliation commission
accountability
Uganda
socio-legal studies
Kenya
transitional justice
international criminal justice
Advisor: Anderson, D
The six-voiced secular madrigals of Luca Marenzio

Luca Marenzio has long been acknowledged as one of the greatest masters of the Italian madrigal, yet no collected edition of his works exists: in particular relatively few of the six-voiced madrigals are available in published form, and criticism has tended to concentrate on the five-voiced works.
This thesis presents an Edition with Commentary of the six-voiced madrigals published in six books between 1581 and 1595. Two polychoral madrigals and a madrigal by Antonio Bicci also found in those books are included in an Appendix, together with two furtner madrigals included by Phalèse in his 1594 edition of Books I-V, which proved a valuable collative source.
The Commentary presents a stylistic study of the madrigals in the Edition and a critical survey of their place in Marenzio's output, together with an editorial commentary and extensive bibliographical material. Following an outline of the madrigal's chief characteristics, Chapter One presents a biographical and critical account of Marenzio's work. Each book of madrigals is considered individually and in relation to his stylistic development. Finally the chapter treats briefly of his influence, with contemporary and historical comment. A stylistic analysis of the music in this Edition follows, considering particularly the relationship between music and text, texture, form, tonality and chromaticism. The poets, forms and principal sources of the texts are then considered. Chapter Four discusses the Edition - sources, notation, tempo, pitch and musica ficta - and concludes with a note on performance.
Two Critical Commentaries deal respectively with music and text, the latter providing a comparison between musical and literary versions and listing poets (some newly discovered) and literary sources. The Bibliography lists all published appearances of the six-voiced madrigals and provides a complete reference for the literary sources consulted. The complete texts of the madrigals are given in an Appendix.
The Muscovite ruling oligarchy of 1547-1564

In recent decades considerable progress has been made in elucidating the assumptions and the dynamics of Muscovite court politics, and further scrutiny is attempted in this enquiry into the ruling oligarchy of 1547-1564. Chapters 1 to 3 are devoted to groundwork. In Chapter 1 an introduction to the ruling oligarchy is provided against the background of Muscovy's contemporary government and population. The goal of territorial aggrandisement pursued by Muscovite rulers from Ivan HI favoured "rationalisation" of the central government and reforms of the army's discipline and technology; moreover, the wars of conquest left untouched no element of the population. Tsar Ivan and his exercise of authority were especially strongly affected: the precedents established by earlier rulers encouraged him to consider Muscovy his private votchina. but such an attitude became increasingly anachronistic as the realms expanded and the tasks of governing it grew too complex for any one man. During the Oprichnina he attempted to resolve this contradiction by ruling autocratically; autocratic rule and those circumstances favouring it by 1564 are the dissertation's main theme. Even before 1564 Ivan IV was the central actor in Muscovite politics, and criteria are advanced whereby advisers close enough to qualify for the ruling oligarchy are identified. The mid-sixteenth century, as a prelude to autocracy, was a critical moment in Muscovite politics; the rich and varied historiography is surveyed in Chapter 2. The sources - their authors, dates, and value as historical evidence - are critically assessed in Chapter 3. Chapter 4 to 7 comprise the heart of the dissertation. In Chapters 4 to 6 an attempt is made to identify members of the ruling oligarchy of 1546-1564; their political behaviour and where feasible, their political attitudes are explored. In Chapter 7 the attitudes individual members maintained towards particular reforms envisaged at mid-century are explored. The dissertation's main conclusions are systematically expounded in Chapter 8, and as appropriate, their broader implications for Russian and European history are brought out.
China's engagement with global nuclear order since 1949

This thesis explores China’s engagement with global nuclear order since 1949. In particular, China’s engagement refers to the process of creating, consolidating and maintaining nuclear order by assessing the methods it adopts, as well as the motivations behind its policy and the implications of its actions for global nuclear order. Overall, it is argued that in the 1950s and 1960s, even before nuclear order existed, China had an inadvertent hand in its creation, contributing to American and Soviet thinking about how best to build an order, as well as offering its own ideas based on socialist proliferation. Then, in the 1980s and 1990s, China engaged in the process of consolidating nuclear order by developing alternative thinking on nuclear deterrence that challenged mainstream strategies such as mutual assured destruction; and by joining important institutions, for instance the Non Proliferation Treaty in 1992 and the Comprehensive Test Ban Treaty in 1996. In addition, during this period, China began to promote a new vision for nuclear order: that of a more representative order. China’s current engagement, at a time when global nuclear order is perceived by many to be under significant strain, is less clear: while China remains committed to key global nuclear institutions and a minimal nuclear strategy; Beijing is also wary of deeper commitments, in particular multilateral arms control processes that might unfairly constrain its nuclear force capabilities relative to other nuclear weapons states.

Keywords: nuclear weapons
China
Advisor: Foot, R