Elucidating the interactions between the adhesive and transcriptioanl functions of beta-catenin in normal and cancerous cells

Wnt signalling is involved in a wide range of physiological and pathological processes. The presence of an extracellular Wnt stimulus induces cytoplasmic stabilisation and nuclear translocation of beta-catenin, a protein that also plays an essential role in cadherin-mediated adhesion. Two main hypotheses have been proposed concerning the balance between beta-catenin's adhesive and transcriptional functions: either beta-catenin's fate is determined by competition between its binding partners, or Wnt induces folding of beta-catenin into a conformation allocated preferentially to transcription. The experimental data supporting each hypotheses remain inconclusive. In this paper we present a new mathematical model of the Wnt pathway that incorporates beta-catenin's dual function. We use this model to carry out a series of in silico experiments and compare the behaviour of systems governed by each hypothesis. Our analytical results and model simulations provide further insight into the current understanding of Wnt signalling and, in particular, reveal differences in the response of the two modes of interaction between adhesion and signalling in certain in silico settings. We also exploit our model to investigate the impact of the mutations most commonly observed in human colorectal cancer. Simulations show that the amount of functional APC required to maintain a normal phenotype increases with increasing strength of the Wnt signal, a result which illustrates that the environment can substantially influence both tumour initiation and phenotype.

Establishing continental sovereignty in Africa: risk and opportunity in financial integration - lessons for Africa from a legal perspective

This thesis identifies and defines the new African sovereignty. It establishes a modern sovereignty in Africa hatched from the changing nature of sovereignty in which countries come together at various levels or grades of partial surrender of national sovereignty in order to work closer together for their mutual advantage and benefit. To this end, the narrative zooms in on the central issues within the realms of money matters whereby a new model of monetary sovereignty and monetary solutions is designed in an attempt to ease the recurring tensions and challenges of modern national sovereignty in the continent of Africa. As such, this discussion will offer a historical journey through the constitution of sovereignty, to the birth of the nation state and international public law. It develops the theory of the changing nature of sovereignty within the modern state and opens new lines of inquiry for Africa. In this regard, it draws from juxtaposing and mixing elements of regional and global financial integration as well as retaining national financial sovereignty features to form this new design which I dub continental sovereignty. At its core, the thesis will deal with the legal aspects that stem from the co-mingling of legal systems of nation states and communities at the regional and global levels within the context of financial integration. The argument is that the rule of law remains sacrosanct in monetary management. Effective financial integration is the result of properly structured and managed legal frameworks with robust laws and institutions whether at a national, regional or global level. However, the thesis reveals that in order to avoid undermining the progress of Africa’s financial integration project, any solution for Africa must be immersed within a broader global solution where development issues are addressed and resolved and Africa can form a more central part in all relevant international discussion fora. The work will expound these issues by applying them within a regional and global context, with the state of affairs in Africa forming the nucleus. This application consequently presents the six key themes of the thesis which will be considered therein. They are: a.) regional advantage: which exploits the possibilities of deeper and further financial integration between smaller communal arrangements; b.) regional risk and exposure: the extent to which this deeper form of financial integration can spiral out of control if effected too quickly and too ambitiously; c.) global advantage: which considers the merits of global financial integration and the influence exerted by financial laws on the global financial architecture; d.) global risk and exposure: which considers the challenges of global financial integration especially within the background of the Global Financial Crisis 2007-2008; e.) African challenge: which considers the extent to which this analysis impacts the African economic and financial integration agenda; and f.) development challenge: which examines the extent to which global development issues impact the African solution (continental sovereignty) and the need for any solution for the continent to be roped into a broader global solution within which Africa can form an important part. Even though the thesis requests an optimistic undertone on the progress made so far, it unearths the African problem of multiple national sovereignty and multiple overlapping regional sovereignty constituted as the ‘spaghetti bowl’ dilemma. As such, the unique contribution to knowledge on financial integration in Africa can be echoed in these words: Africa‘s financial integration agenda has had little success in authenticating a systematic and dependable legal framework for monetary management. Efforts made have been incomplete, substandard, and not carefully followed through particularly reflected in the impuissant nature of the judicial enforcement mechanisms. Thus, the thesis argues that, any meaningful answer to the problems dogging the continent is inter alia deeply entrenched within a new form of cooperative monetary sovereignty. In other words, the thesis does not prescribe the creation of new laws; rather it advocates the effective enforcement of existing laws.

Experimentally Testing the Effect of Parent-Adolescent Conflict on HIV Risk, and Investigation of a Neurobiological Moderator of This Effect

Human immunodeficiency virus (HIV) is a condition in which immune cells become destroyed such that the body may become unable to fight off infections. Engaging in risk-taking behaviors (e.g., substance use) puts people at heightened risk for HIV infection, with mid-to-late adolescents at increasing risk (Leigh & Stall, 1993). Environmental and neurological reasons have been suggested for increased risk-taking among adolescents. First, family-level precursors such as parent-adolescent conflict have been significantly associated with and may pose risk for engaging in substance use and risk-taking (Duncan, Duncan, Biglan, & Ary, 1998). Thus, parent-adolescent conflict may be an important proximal influence on HIV risk behaviors (Lester et al., 2010; Rowe, Wang, Greenbaum, & Liddle, 2008). Yet, the temporal relation between parent-adolescent conflict and adolescent HIV risk-taking behaviors is still unknown. Second, at-risk adolescents may carry a neurobiological predisposition for engaging in trait-like expressions of disinhibited behavior and other risk-taking behaviors (Iacono, Malone, & McGue, 2008). When exposed to interpersonally stressful situations, their likelihood of engagement in HIV risk behaviors may increase. To investigate the role of parent-adolescent conflict in adolescent HIV risk-taking behaviors, 49 adolescents ages 14-17 and their parent were randomly assigned to complete a standardized discussion task to discuss a control topic or a conflict topic. Immediately after the discussion, adolescents completed a laboratory risk-taking measure. In a follow-up visit, eligible adolescents underwent electrophysiological (EEG) recording while completing a task designed to assess the presence of a neurobiological marker for behavioral disinhibition which I hypothesized would moderate the links between conflict and risk-taking. First, findings indicated that during the discussion task, adolescents in the conflict condition evidenced a significantly greater psychophysiological stress response relative to adolescents in the control condition. Second, a neurobiological marker of behavioral disinhibition moderated the relation between discussion condition and adolescent risk-taking, such that adolescents evidencing relatively high levels of a neurobiological marker related to sensation-seeking evidenced greater levels of risk-taking following the conflict condition, relative to the control condition. Lastly, I observed no significant relation between parent-adolescent conflict, the neurobiological marker of behavioral disinhibition and adolescent engagement in real-world risk-taking behavior.

Unpolarized transverse momentum dependent parton distribution and fragmentation functions at next-to-next-to-leading order

The transverse momentum dependent parton distribution/fragmentation functions (TMDs) are essential in the factorization of a number of processes like Drell-Yan scattering, vector boson production, semi-inclusive deep inelastic scattering, etc. We provide a comprehensive study of unpolarized TMDs at next-to-next-to-leading order, which includes an explicit calculation of these TMDs and an extraction of their matching coefficients onto their integrated analogues, for all flavor combinations. The obtained matching coefficients are important for any kind of phenomenology involving TMDs. In the present study each individual TMD is calculated without any reference to a specific process. We recover the known results for parton distribution functions and provide new results for the fragmentation functions. The results for the gluon transverse momentum dependent fragmentation functions are presented for the first time at one and two loops. We also discuss the structure of singularities of TMD operators and TMD matrix elements, crossing relations between TMD parton distribution functions and TMD fragmentation functions, and renormalization group equations. In addition, we consider the behavior of the matching coefficients at threshold and make a conjecture on their structure to all orders in perturbation theory.

Capital structure, risk and asymmetric information : theory and evidence

This paper proposes a principal-agent model between banks and firms with risk and asymmetric information. A mixed form of finance to firms is assumed. The capital structure of firms is a relevant cause for the final aggregate level of investment in the economy. In the model analyzed, there may be a separating equilibrium, which is not economically efficient, because aggregate investments fall short of the first-best level. Based on European firm-level data, an empirical model is presented which validates the result of the relevance of the capital structure of firms. The relative magnitude of equity in the capital structure makes a real difference to the profits obtained by firms in the economy.

Transcription-Coupled DNA Supercoiling in Escherichia Coli: Mechanisms and Biological Functions

Transcription by RNA polymerase can induce the formation of hypernegatively supercoiled DNA both in vivo and in vitro. This phenomenon has been explained by a “twin-supercoiled-domain” model of transcription where a positively supercoiled domain is generated ahead of the RNA polymerase and a negatively supercoiled domain behind it. In E. coli cells, transcription-induced topological change of chromosomal DNA is expected to actively remodel chromosomal structure and greatly influence DNA transactions such as transcription, DNA replication, and recombination. In this study, an IPTG-inducible, two-plasmid system was established to study transcription-coupled DNA supercoiling (TCDS) in E. coli topA strains. By performing topology assays, biological studies, and RT-PCR experiments, TCDS in E. coli topA strains was found to be dependent on promoter strength. Expression of a membrane-insertion protein was not needed for strong promoters, although co-transcriptional synthesis of a polypeptide may be required. More importantly, it was demonstrated that the expression of a membrane-insertion tet gene was not sufficient for the production of hypernegatively supercoiled DNA. These phenomenon can be explained by the “twin-supercoiled-domain” model of transcription where the friction force applied to E. coli RNA polymerase plays a critical role in the generation of hypernegatively supercoiled DNA. Additionally, in order to explore whether TCDS is able to greatly influence a coupled DNA transaction, such as activating a divergently-coupled promoter, an in vivo system was set up to study TCDS and its effects on the supercoiling-sensitive leu-500 promoter. The leu-500 mutation is a single A-to-G point mutation in the -10 region of the promoter controlling the leu operon, and the AT to GC mutation is expected to increase the energy barrier for the formation of a functional transcription open complex. Using luciferase assays and RT-PCR experiments, it was demonstrated that transient TCDS, “confined” within promoter regions, is responsible for activation of the coupled transcription initiation of the leu-500 promoter. Taken together, these results demonstrate that transcription is a major chromosomal remodeling force in E. coli cells.

Acceptance of smartphone-based mobile shopping:mobile benefits, customer characteristics, perceived risk and the impact of application context

Despite their generally increasing use, the adoption of mobile shopping applications often differs across purchase contexts. In order to advance our understanding of smartphone-based mobile shopping acceptance, this study integrates and extends existing approaches from technology acceptance literature by examining two previously underexplored aspects. Firstly, the study examines the impact of different mobile and personal benefits (instant connectivity, contextual value and hedonic motivation), customer characteristics (habit) and risk facets (financial, performance, and security risk) as antecedents of mobile shopping acceptance. Secondly, it is assumed that several acceptance drivers differ in relevance subject to the perception of three mobile shopping characteristics (location sensitivity, time criticality, and extent of control), while other drivers are assumed to matter independent of the context. Based on a dataset of 410 smartphone shoppers, empirical results demonstrate that several acceptance predictors are associated with ease of use and usefulness, which in turn affect intentional and behavioral outcomes. Furthermore, the extent to which risks and benefits impact ease of use and usefulness is influenced by the three contextual characteristics. From a managerial perspective, results show which factors to consider in the development of mobile shopping applications and in which different application contexts they matter.

Bullying Involvement and Adolescent Substance Use: A Study of Multilevel Risk and Protective Factors

Thesis (Master, Psychology) -- Queen's University, 2016-08-02 13:18:40.65

The legitimation of risk and Bt cotton: a case study of Bantala village in Warangal, Andhra Pradesh, India

This article explores Ulrich Beck’s theorisation of risk society through focusing on the way in which the risk of Bt cotton is legitimated by six cultivators in Bantala, a village in Warangal, Andhra Pradesh, in India. The fieldwork for this study was conducted between June 2010 and March 2011, a duration chosen to coincide with a cotton season. The study explores the experience of the cultivators using the ‘categories of legitimation’ defined by Van Leeuwen. These are authorisation, moral evaluation, rationalisation and mythopoesis. As well as permitting an exploration of the legitimation of Bt cotton by cultivators themselves within the high-risk context of the Indian agrarian crisis, the categories also serve as an analytical framework with which to structure a discourse analysis of participant perspectives. The study examines the complex trade-off, which Renn argues the legitimation of ambiguous risk, such as that associated with Bt technology, entails. The research explores the way in which legitimation of the technology is informed by wider normative conceptualisations of development. This highlights that, in a context where indebtedness is strongly linked to farmer suicides, the potential of Bt cotton for poverty alleviation is traded against the uncertainty associated with the technology’s risks, which include its purported links to animal deaths. The study highlights the way in which the wider legitimation of a neoliberal approach to development in Andhra Pradesh serves to reinforce the choice of Bt cotton, and results in a depoliticisation of risk in Bantala. The research indicates, however, that this trade-off is subject to change over time, as economic benefits wane and risks accumulate. It also highlights the need for caution in relation to the proposed extension of Bt technology to food crops, such as Bt brinjal (aubergine).

Pairs trading in the UK equity market: risk and return

In this paper, we provide the first comprehensive UK evidence on the profitability of the pairs trading strategy. Evidence suggests that the strategy performs well in crisis periods, so we control for both risk and liquidity to assess performance. To evaluate the effect of market frictions on the strategy, we use several estimates of transaction costs. We also present evidence on the performance of the strategy in different economic and market states. Our results show that pairs trading portfolios typically have little exposure to known equity risk factors such as market, size, value, momentum and reversal. However, a model controlling for risk and liquidity explains a far larger proportion of returns. Incorporating different assumptions about bid-ask spreads leads to reductions in performance estimates. When we allow for time-varying risk exposures, conditioned on the contemporaneous equity market return, risk-adjusted returns are generally not significantly different from zero.

Yoga and loss: an autoethnographical exploration of grief, mind, and body

The author explores her experience of yoga as a therapeutic tool in recovering from the impact of losing a close friend to suicide. The benefits of yoga include improved emotional self-regulation, a more positive relationship with self, and the emergence of a new personal physical reality. An autoethnographical approach permits a necessarily ambiguous and messy in-depth exploration of yoga as a resource for well-being. Nevertheless, it is hoped that it will serve as a means of promoting further study into the role of cultural resources, particularly body-based practices, as means of coming to terms with traumatic loss.

Youth psychosocial adjustment in the context of parental illness: risk and protective factors

Young carers might experience both psychological distress and positive changes from living with their chronically ill parent. However, little is known about why some young carers do well with their situation and experience positive outcomes, whereas others do not. In this regard, this dissertation aims to investigate how parental chronic illness affects young carers’ psychosocial adjustment through risk (i.e., unmet needs) and protective factors (i.e., benefit finding, emotion regulation). This main goal has been addressed by conducting three studies presented in Chapters 2–4. Chapter 2 has examined the mediating role of unmet needs on the relationship between illness unpredictability and youth psychosocial adjustment (i.e., quality of life and internalizing problems). In this regard, it has been found that levels of unmet needs significantly mediated the relationship between illness unpredictability and offspring health-related quality of life. In the systematic review with meta-analysis presented within Chapter 3, it has been sought to investigate the mediating role of the protective factors (i.e., benefit finding and emotion regulation) in the relationship between caregiving components and youth psychosocial adjustment in young carers. This study has shown the significant associations between caregiving components and psychosocial adjustment in young carers not only directly, but also indirectly through protective factors. Finally, to expand on previous findings, a qualitative study in Chapter 4 has examined the unique experiences of young carers, as well as the effects of the COVID-19 global pandemic. This study has yielded a deeper understanding of how protective factors may be operated during young carers’ lived experiences before and during the COVID-19 global pandemic. Overall, this dissertation has shed light on the pivotal role played by risk and protective factors in caregiving components that serve as key determinants that can enhance positive psychosocial outcomes as well as concurrently mitigate adverse psychosocial consequences among young carers.

Do jumps matter for volatility forecasting? Evidence from energy markets

This paper characterizes the dynamics of jumps and analyzes their importance for volatility forecasting. Using high-frequency data on four prominent energy markets, we perform a model-free decomposition of realized variance into its continuous and discontinuous components. We find strong evidence of jumps in energy markets between 2007 and 2012. We then investigate the importance of jumps for volatility forecasting. To this end, we estimate and analyze the predictive ability of several Heterogenous Autoregressive (HAR) models that explicitly capture the dynamics of jumps. Conducting extensive in-sample and out-of-sample analyses, we establish that explicitly modeling jumps does not significantly improve forecast accuracy. Our results are broadly consistent across our four energy markets, forecasting horizons, and loss functions