VictorJuiz/thesis huggingface dataset:
The development of a novel and efficient HAC vector delivery system to human cells

Human Artificial Chromosomes (HACs) have been confirmed as viable gene expression vectors and a potential tool for gene therapy. However, standard lipid-based delivery methods pose a developmental barrier. The work presented in this thesis includes the development of a novel and efficient HAC vector system for gene delivery into human cells using Herpes Simplex Virus-1 (HSV-1) amplicon technology. The development of HSV-1 amplicons for HAC delivery is a major step forward in the HAC field. In this study, utilising the technology allowed the generation of HACs at a high efficiency in a range of human cell types, which is a significant step in the development for HAC gene expression systems. Further work also showed a significant difference in HAC stability between cell lines. Real-time PCR analysis determined that Aurora B was over expressed in cell lines in which the HACs were unstable. This correlated with high levels of chromosomal instability and was confirmed by western blot analysis. Since Aurora B is a kinase involved in at least two cell cycle checkpoints, cellular phosphorylation levels were perturbed to mimic that observed in the unstable cells, using okadaic acid, which is both a protein phosphatase inhibitor and activates Aurora B. Treatment of cells showed an increase in both HAC and overall chromosomal instability and an increase in histone H3 Serine 10 and Serine 28 phosphorylation. The project also focussed on the development of a gene expression system using HSV-1 amplicons. Two different strategies were explored. Firstly, one approach involved engineering the HPRT genomic locus into an HSV-HAC vector, by Red mediated recombination for complementing the HPRT deficiency in HPRT- HT1080 cells. As an alternative approach, co-infection of two different HSV-1 HAC amplicons for generating a single HAC gene vector was investigated. Initial experiments utilising the latter approach were the most successful and show promise for generating HAC containing genes via this strategy.

Keywords: Artificial Chromosome HSV
Advisor: Larin Monaco, Z
Validation of self-reports for use in contact research

The aim of this thesis was to investigate whether self-report measures of contact are valid for use in research testing the ‘contact hypothesis’. The vast majority of contact research has relied on the assumed validity of self-report methods of data collection (Pettigrew & Tropp, 2006), even though the potential weaknesses of self-report methodology generally have been well documented. This reliance is necessary, as self-reports remain the only practical method so far developed of measuring certain of the facilitating conditions developed by Allport (1954/1979), and particularly of direct and indirect cross-group friendship (Pettigrew, 1998; Wright, Aron, McLaughlin-Volpe, & Ropp, 1997). However, if self-reports are not a valid method for measuring contact, the derived implications of a large portion of the research effort are potentially flawed. This thesis attempted to address this important oversight, using a variety of methods to investigate whether the use of self-reports in future research on intergroup contact is appropriate. Studies 1 and 2 demonstrated that self-reports of contact show considerable resistance to context effects, particularly in comparison with self-reports of the more subjective construct of attitudes. Studies 3-5 demonstrated that self-reports of contact agree with the observer-reports of a single observer who knows the target intimately – the spouse or parent. Studies 6 and 7 replicate this agreement through the consensually supported observer-reports of three close friends of the target, thereby reducing any variance due to individual response biases. Finally, studies 8 and 9 demonstrate the concurrent criterion-related validity of self-reports of contact, in that they are able to predict contact on a very large online network called Facebook, on which real-world rather than purely online friendships are primarily represented. These findings offer considerable support for the validity of self-reports as a suitable method for measuring contact. As self-reports remain the only method which has thus far proven suitable for the measurement of those aspects of contact which are essential for exploration of the contact hypothesis, this thesis presents a very heartening and optimistic conclusion and supports the continued use of self-reports in contact research.

Keywords: observer-reports
predictive validity
context effects
cross-group friendship
self-reports
contact hypothesis
validity
Advisor: Hewstone, M
Post-Keynesian financial spaces, places, and flows: geographies of finance and financial crisis

This dissertation is a reaction to the public policy failures that culminated in, prolonged, and exacerbated the 2008 financial crisis in the United States. Between the winter of 2007 and the summer of 2009, the US private economy contracted severely. As of the summer of 2014, after a five-year recovery period, employment losses have been restored, but employment growth has not returned the US to its pre-crisis trend. This outcome is not the effect of a transient deviation that regularly happens as the economy moves through the business cycle; nor should the troubles in the US financial sector appear historically anomalous. The world's premier capitalist economy is prone to bouts of financial dysfunction. This feature is not simply a matter of the irrational exuberance of its investors, the euphoria of its speculators, or the folly of its bankers. I argue here that political-economic choices structure the distribution of financial crises at multiple scales. Broadly speaking, I find that the effects of financial crises on growth are uneven, affected by institutional structure, and carry important ramifications for the direction of change in the provision of financial services and its regulatory system. The thesis features four empirical chapters. In the first, I perform an econometric analysis of the effects of a wide variety of financial crises on employment growth by economic sector, for a sample of countries over a thirty-year period. The final three chapters are a case study of the US experience with the 2008 banking crisis and asset market crash, focusing on the role of the banking regulatory system in allocating losses over territory, on the economic performance of metropolitan areas, and on the distribution of losses within the financial sector in two major financial centers, Los Angeles and San Francisco. I reach my conclusions by using standard methodological tools within the sub-field of economic-geography and conceptual insights from the sub-field of financial-geography.

Keywords: Financial crises--case studies
Financial crises--history
Advisor: Wojcik, D
Structure, dynamics, and robustness of ecological networks

Ecosystems are often made up of interactions between large numbers of species. They are considered complex systems because the behaviour of the system as a whole is not always obvious from the properties of the individual parts. A complex system can be represented by a network: a set of interconnected objects. In the case of ecological networks and food webs, the objects are species and the connections are interactions between species. Many complex systems are dynamic and exhibit intricate time series. Time series analysis has been developed to understand a wide range of natural phenomena. This thesis deals with the structure, dynamics, and robustness of ecological networks, the spatial dynamics of fluctuations in a social system, and the analysis of cardiac time series. Biodiversity on Earth is decreasing largely due to human-induced causes. My work looks at the effect of anthropogenic change on ecological networks. In Chapter Two, I investigate predator adaptation on food-web robustness following species extinctions. I identify a new theoretical category of species that may buffer ecosystems against environmental change. In Chapter Three, I study changes in parasitoid-host (consumer-resource) interaction frequencies between complex and simple environments. I show that the feeding preferences of parasitoid species actively change in response to habitat modification. Ecological networks are embedded in spatially-heterogeneous landscapes. In Chapter Four, I assess the role of geography on population fluctuations in an analogous social system. I demonstrate that fluctuations in the number of venture capital firms registered in cities in the United States of America are consistent with spatial and temporal contagion. Understanding how physiological signals vary through time is of interest to medical practitioners. In Chapter Five, I present a technique for quickly quantifying disorder in high frequency event series. Applying the algorithm to patient cardiac time series provides a rapid way to detect the onset of heart arrhythmia. Increasingly, answers to scientific questions lie at the intersection of traditional disciplines. This thesis applies techniques developed in physics and mathematics to problems in ecology and medicine.

Keywords: complex systems
networks
time series
food webs
Advisor: Reed-Tsochas, F
Jones, N
Studies in the measurement, form and interpretation of some electrical properties of normal and pathological human skin in vivo

During the past five years a study has been made of the electrical properties of human skin in vivo both experimentally and theoretically, seeking to make a coherent whole out of the very diverse phenomenology reported in the very scattered literature.
A Fourier transform method was used, employing novel electronic techniques and four non-invasive electrodes on the subject to separately determine the properties of the stratum corneum and the deeper tissues.
Both linear and non-linear, A.C. and D.C. properties were investigated in this way, and the wide perspective obtained has made it possible to re-interpret the findings of previous workers and so assemble a self-consistent model of nearly all the known electrical properties of human skin.
The main conclusions of this work are that:
(a) The small-signal A.C. impedance properties of skin are extremely well fitted by a minor arc of a circle on the complex impedance plane, and the depression of the centre of the circle below the equivalent series resistance axis is very significantly greater in psoriatic skin and in hyper-hydrated normal skin.
(b) This behaviour cannot be adequately interpreted by any extant physical model of skin, but can be adequately interpreted by considering the stratum corneum to be an inhomogeneous or amorphous semiconductor.
(c) The semiconductivity of human skin has been demonstrated both in vitro and in vivo, and was found to have activation enthalpies averaging 0.46 eV (10.63 kcal/mole).
(d) These insights into the mechanisms of electrical charge transport through skin may suggest new ways of characterizing the properties of skin using methods developed for the semiconductor industry.
(e) The results in the literature of "phoreography" should be re-interpreted, with much greater emphasis being placed on the properties of the skin appendages.

Advisor: Ryan, T
Towards the definition of an 'eating disorder'

This dissertation is concerned with the diagnosis and classification of clinical eating disorders such as anorexia nervosa and bulimia nervosa. There were four overarching aims. The first was to describe the clinical characteristics of patients with the neglected DSM-FV eating disorder diagnosis "eating disorder NOS" and compare them with those of patients with bulimia nervosa. It was found that the two groups were remarkably similar. The second was to examine how the classificatory problems associated with this diagnosis might be solved. Three solutions were proposed and the clinical utility of two of them examined. It was concluded that the best interim solution was to broaden the diagnostic criteria for anorexia nervosa and bulimia nervosa and re-label the remaining cases of eating disorder NOS as either binge eating disorder or as a new eating disorder diagnosis. The third aim was to derive an operational definition of what constitutes an "eating disorder" This involved developing an interview-based measure of functional impairment secondary to eating disorder features and administering it to a large sample of people exhibiting the full range of eating disorder psychopathology. Multivariate statistics identified specific severity levels on five eating disorder features that were strongly associated with the presence of a clinically significant level of impairment. These eating disorder features were: the pursuit of strict dietary rules, objective bulimic episodes, purging episodes, dissatisfaction with shape and weight, and over-concern with maintaining strict control over eating. The presence of two or more of these features above the identified thresholds was most predictive of a clinically significant level of impairment. Thus, an impairment-based, transdiagnostic, provisional operational definition of an eating disorder was derived. The fourth aim was to develop a clinically useful, easily administered measure of psychosocial impairment secondary to eating disorder features. Such an instrument was created. Studies of its psychometric properties, reliability, validity and sensitivity to change all supported its use. Certain of the research strategies used in this dissertation could be usefully applied to other psychiatric disorders.

Advisor: Fairburn, C
Electron-phonon interactions in low dimensional structures

Transport properties of the two-dimensional electron gas (2DEG) in high magnetic fields are used to investigate scattering processes affecting the resistivity of GaAs-GaAlAs and GaInAs-InP heterojunctions and quantum wells: especially coupling of electrons to acoustic and optic phonons; and transitions between electric subbands.
The experiments fall into two groups:
A systematic study of magnetophonon resonance (MPR) between 30K and 300K. Resonance positions indicate a coupling substantially below the LO phonon energy, expected from 3D measurements. GaAs-GaAlAs hetero junctions show amplitudes varying smoothly with electron density (ns) and closely related to the 4K mobility. On rotation in magnetic field they decrease rapidly as the resonance position returns to the LO value. In modulation doped structures the damping factor is determined by remote impurity scattering. As ns is increased in GaInAs-InP the coupling frequency decreases dramatically from the GaAs-like LO at 272cm-1 to the InAs-like TO at 226cm-1. At higher electric fields the 'normal' MPR maxima invert, starting at low magnetic fields, to form 'hot electron' MPR minima, with maximum amplitude at ~60K. This is the first direct observation of HEMPR in 2D and is explained in a diffusion picture. At lower electric fields, additional resonances are identified with resonant cooling by inter-subband scattering. Comparisons are made with calculations and explanations sought including consideration of interface phonons; coupled plasmon-phonon modes; and shifts of the resonance positions due to the shape of the density of states.
Low temperature magnetoresistance measurements in GaAs-GaAlAs heterojunctions with more than one occupied electric subband. Shubnikov-de Haas oscillations in perpendicular magnetic fields contain non-additive terms at electron temperatures > 2K where acoustic phonon mediated inter-subband scattering is comparable to intra-subband scattering. Subband separations and greatly enhanced g-factors [largest for electrons in the upper subband ] are deduced from the oscillations. Damping of the oscillations in field, gives values for quantum lifetimes (τs), much smaller than τtʼ, deduced from mobility. With two subbands occupied τs is always largest for the upper subband, while relative sizes of τt depend on sample quality. Study of electron energy loss rates, from thermal damping of the oscillations, shows enhancement in the region kTe ~ ħωcʼ, which is evidence for cyclotron phonon emission. Depopulating subbands in parallel fields causes the resistance to drop, by up to 60%, due to suppression of inter-subband scattering. Systematic studies show this scattering rate is independent of ns.

Advisor: Nicholas, R
Probabilistic models of RNA secondary structure

This thesis develops probabilistic models of RNA secondary structure. The first chapter introduces RNA secondary structure prediction, in particular stochastic context-free grammars (SCFGs), and considers a novel method for automated design of SCFGs. Many SCFGs are found with a similar predictive quality as those commonly used for RNA secondary structure prediction. The second chapter discusses the effect alignment quality, evolutionary distance between sequences, and number of sequences in an alignment have on RNA secondary structure prediction. By combining statistical alignment and SCFG models we can, in a statistically sound setting, average structure predictions over the space of alignments to decrease loss created by poor alignments. The third chapter incorporates additional biological information about RNA secondary structure formation into the decoding of the SCFG posterior distribution. Combining iterative helix formation, phylogenetic modelling, and a distance function between alignment columns leads to the an improvement in the accuracy of comparative RNA secondary structure prediction. Finally, appendices briefly discuss further work concerning probabilistic models of RNA secondary structure which may be of interest to the reader.

Keywords: RNA secondary structure
bioinformatics
Advisor: Hein, J
Expanding health care services for poor populations in developing countries: Exploring India’s RSBY national health insurance programme for low-income groups

Health is deemed central to a nation’s development. Accordingly, health care reform and expansion are key policy priorities in developing countries. Many such nations are now testing various methods of funding and delivering health care to local disadvantaged populations. Similarly, India launched the Rashtriya Swasthya Bima Yojana (RSBY) national health insurance programme for low-income groups in 2008. The RSBY intends preventing catastrophic health-related expenditure by improving recipients’ access to hospital-based care.
This thesis is an in-depth qualitative evaluation of the RSBY in Delhi state. It examines the RSBY’s effectiveness in fulfilling its goals and meeting local health care needs. Walt and Gilson’s (1994) actors-content-process-context model informs the research design and an actor-centred “responsive” (Stake 1975) or “constructivist” approach guides data analysis.
Three research questions are examined: (i). Why was a health insurance programme launched and why now? Why was this model favoured over alternate methods of service expansion? (ii). Is the RSBY delivered as intended? If not, why? (iii) How does the RSBY affect patients’ access to services?
The findings are based on documentary sources, observation of implementation sites and activities and 164 semi-structured interviews with RSBY policymakers, insurers, NGOs, doctors, and patients.
The results show improved access to curative and surgical care for RSBY patients. However, RSBY’s focus on hospitalisation and omission of primary and outpatient services had undesired negative effects. The lack of ambulatory facilities led RSBY patients to self-medicate or use dubious quality informal providers. By only allowing inpatient care, the RSBY also seemingly encouraged the substitution of outpatient care with costlier hospitalisations. In effect, the RSBY’s design contributed to cost increases and poor patient outcomes.
While more funds and human resources were needed to improve RSBY implementation, the performance of frontline agencies could potentially improve through more stable, longer-term contracts. Similarly, modifying RSBY’s monetary incentives for doctors may lead to better service delivery by them.
By evaluating the RSBY’s strong points and shortcomings, this thesis provides key lessons on strengthening policy design and health service delivery in developing countries. Thereby, it makes a broader contribution to understanding the determinants of successful policymaking.

Keywords: low and middle income countries
social health insurance
health policy
social policy
Advisor: Surender, R
Insect metapopulation dynamics

Metapopulation ecology has developed to explain the population dynamics that occur in spatially structured landscapes. In this study, I combined an empirical laboratory approach, using metapopulation microcosms of Callosobruchus maculatus and its endospecific parasitoid Anisopteromalus calandrae, with mathematical population models in order to investigate several fundamental metapopulation processes.
Population dynamics in these systems can be studied at two scales; the local patch-wise scale and the regional metapopulation scale. Here I demonstrate that in both homogeneous and heterogeneous landscapes knowledge of local scale demographic processes is necessary in order to understand regional metapopulation dynamics. The differences in the rate and net direction of dispersal between patches as a result of the permeability of the matrix in homogeneous systems and density-dependent dispersal in heterogeneous systems were also explored.
Metapopulation dynamics rely on a balance between local extinctions and recolonisations. Therefore, increasing local mortality rates is likely to be detrimental to the persistence of the system. Here, the impact of several common harvesting strategies on the persistence of a host-parasitoid metapopulation was examined. Contrary to expectation I discovered that harvesting in these systems increased both local and regional population sizes. The increased population size as a result of increased mortality was explained in terms of a hydra effect, where harvesting relaxed density-dependence acting on local host populations.
The results presented in this thesis are relevant for the monitoring, management and conservation of natural metapopulations and the development of sustainable harvesting strategies in structured landscapes.

Keywords: population dynamics
dispersal
population modelling
metapopulation
spatial ecology
Bruchid
landscape
Advisor: Bonsall, MB