Macroscopic Kinetic Effect of Cell-to-Cell Variation in Biochemical Reactions

Genetically identical cells under the same environmental conditions can show strong variations in protein copy numbers due to inherently stochastic events in individual cells. We here develop a theoretical framework to address how variations in enzyme abundance affect the collective kinetics of metabolic reactions observed within a population of cells. Kinetic parameters measured at the cell population level are shown to be systematically deviated from those of single cells, even within populations of homogeneous parameters. Because of these considerations, Michaelis-Menten kinetics can even be inappropriate to apply at the population level. Our findings elucidate a novel origin of discrepancy between in vivo and in vitro kinetics, and offer potential utility for analysis of single-cell metabolomic data

Game of two halves: preparing young elite rugby players for a future beyond the game

The rise to professionalisation in 1995, and the increasing globalisation of rugby has changed the way the sport is viewed and engaged in by talented young athletes. The shift to a more professional work environment, high salaries, and the increased opportunity for young men who, once they leave school, and sometimes before, to seek employment in this workforce, has altered the way young players look, think and behave. With the shift to professionalism, the situation for young elite rugby players has become critical. Many view rugby as a career option, sacrificing education and training in pursuit of lucrative contracts, unaware of the realities of the occupation in which a relatively high number of players ‘don’t make it’. Those young players who are unsuccessful in their pursuit of a rugby career are often left directionless with no education or training in an alternative occupation or profession. In elite sport, retirement can be extremely difficult to cope with if athletes are not adequately prepared, or have not planned for such an event. This lack of preparation can leave athletes vulnerable to the challenges of retirement. The need for knowledge in this study relates to how young elite rugby players make sense of rugby as work, how they understand themselves as athletes, and how they make sense of their opportunities for a life outside rugby. The opportunities, barriers and needs for career development, planning and education to prepare young athletes for a life outside elite rugby and the ways these young men negotiate their lives and their alternatives are largely unknown. This thesis examines the experiences of young men who are part of the first generation of players who will only experience rugby in its professional format, and provides them with a voice as they pursue work as professional rugby players. More specifically, this study explores issues such as rugby as an occupational choice for young men, how players perceive, and are subsequently prepared for, a life outside rugby, their identification with the sport, and their needs and concerns as elite young rugby players. To gain a further understanding of the resources and opportunities available to assist in the development of these young men and their preparation for a life outside rugby, the study also explores coaches’ and managements’ perspectives and the ways in which they approach these relatively new issues facing young athletes. Investigation in this area of young athletes’ experience has been limited, with the majority of research v focusing on recently retired athletes, or those more established in their professional sport career, as opposed to those beginning to embark on, or pursuing a career in professional sport. There has been little research into the career experiences of elite young rugby players as a basis of understanding how best to prepare them for their future experiences both during, and post-elite athletic performance. The study employed a largely qualitative methodology, interviewing twenty-five young elite rugby players (18-22 years of age) in New Zealand and New South Wales, and eight coaching and management staff from rugby union and the wider sports industry. The use of semi-structured in-depth interviews enabled a rich understanding of the experiences of elite young rugby players from the perspectives of the players, coaches and management. A mixed mode approach was used to a limited extent, where additional quantitative data was collected through the use of a questionnaires provided to one group of participants. The main themes that emerged from this inquiry formed key considerations for the preparation of elite young rugby players in their future beyond rugby. These considerations highlighted the career development needs, barriers, opportunities and experiences of elite young rugby players as they pursued a career in professional rugby. Among others, the analysis of interviews identified an identity heavily invested in rugby, unrealistic predictions of their future rugby life cycle, the structure of the work, and support from their clubs and academies as key inhibitors to players career development and post-rugby planning. The study revealed that the involvement in elite rugby largely does not facilitate the accomplishment of developmental tasks that athletes require later in life. In many cases these young men are sacrificing the potential breadth of their future selves in the pursuit of a rugby career. Thus, the study points to the need for a greater focus in the support, assistance and resources for young elite rugby players in their career development and planning for their post-rugby future. These young men are in many cases at risk of having no tangible entry into an occupation or career should they not succeed in professional rugby

The decline in trust in the European Union

After twenty years, the European Union is undoubtedly at a crossroads, as its institutions try to manage the sovereign debt crisis in member states and the uncertainty surrounding the future direction of the project. The challenges the European Union has faced, and the response to them, have drawn considerable attention on the capacity of the European Union to manage the interests of the Europeans. In this dissertation, I discuss the process of Europeanization and why it has resulted in suboptimal outputs. Additionally, I discuss the perception of a democratic deficit in the European Union. The purpose of this is to see how perception of the capacity of the European Union to manage European interests and perception of a democratic deficit impact trust levels on the European Union. Using Eurobarometer 71.3 data, I find support for the hypothesis that those who perceive shortcomings in both of these aspects will be less likely to trust the European Union than those who do not. I argue that this finding makes the handling of sovereign debt crisis very important in determining the levels of trust the EU will enjoy moving beyond the crisis. Finally, I conclude with some thoughts about European identity in the contemporary era, and ask if the construction of a European identity might help the project withstand criticisms over policy and responsiveness

Scheduling based optimization in software defined radio and wireless networks

The objective of this work is to enable dynamic sharing of software-defined radio (SDR) transceivers through the concepts of hardware virtualization and real-time resource management. SDR is a way to build a digital radio that consists of a software back-end for digital signal processing (DSP) and an analog front-end transceiver for waveform generation and reception. This work proposes the use of a virtualization layer to decouple back-end SDR software from front-end transceivers. With this arrangement, front-ends are said to be virtualized, and it becomes possible to share a limited number of front-ends among many SDR back-ends through different multiplexing techniques. In the first work, the hardware/software infrastructure needed for such a system is explored. An intelligent resource management algorithm is presented that demonstrates a potential increase in the number of supported SDR back-ends. The second work presents an exploration of this system\u27s application to aircraft telemetry systems and the potential improvements to reliability. The work includes a reliability model for virtualized SDR aircraft telemetry systems as well as simulations demonstrating changes in performance as hardware fails. In the final work, an improved resource management algorithm based on Markov decision process (MDP) is proposed. This approach addresses concerns wireless regulatory agencies and standards bodies may raise regarding performance degradation caused by sharing transceivers. The process of sharing transceivers causes service disruptions to occur whenever the instantaneous demand for front-ends exceeds capacity. This MDP approach provides a feasibility test and a guarantee that all SDRs can stay within their respective wireless specifications. The proposed technique guarantees Pareto efficient distribution of resources. To make this approach possible, a connection is established between dynamic transceiver sharing and equivalent interference --Abstract, page iv

Chemical and strutural properties of DNA-abasic site cross-links

Here, we report on the formation of DNA interstrand cross-links. These cross-links form from abasic sites, an endogenous type of DNA damage. We have utilized gel electrophoresis, NMR, mass spectrometry and liquid chromatography to identify the location, DNA sequence specificity, stability and some structural information for these interstrand cross-links. Additionally, we have synthesized a small molecule standard which is identical to the enzymatically digested cross-link from duplex DNA. This synthetic standard can be used to increase sensitivity for future detection of DNA-abasic site cross-links

The resurgence of the far-right in European politics: analysis of the French, Italian, Austrian, and Belgian cases

The resurgence of the far-right in European politics has been cause for alarm on a continent which so recently suffered the consequences of the rise of fascism in the early twentieth century. Political observers have looked on anxiously while far-right parties in Austria and Italy have participated in the governing coalitions of those countries. In 2002, Jean Marie Le Pen stunned the world with his advancement into the second round of the French Presidential election. Why is the radical-right so strong right now? Why do voters cast their ballots in support of far-right parties? In this thesis, I have examined these questions and offered some insight into how far-right parties rose to prominence in France, Italy, Austria, and Belgium. I hypothesize that voters who supported far-right parties in the last parliamentary elections have less trust in both domestic and supranational political institutions, follow politics less closely, are more likely to feel alienated, and are more likely to feel that immigrants take away jobs than their counterparts who supported mainstream parties. My findings reveal that these hypotheses were particularly accurate in France and Belgium, but did not correctly depict the sentiments of Italian far-right voters. This finding suggests that far-right parties are perhaps not as similar as some people believe, but are characterized by different goals and platforms that appeal to different bases cross-nationally

Relative Stability of Network States in Boolean Network Models of Gene Regulation in Development

Progress in cell type reprogramming has revived the interest in Waddington's concept of the epigenetic landscape. Recently researchers developed the quasi-potential theory to represent the Waddington's landscape. The Quasi-potential U(x), derived from interactions in the gene regulatory network (GRN) of a cell, quantifies the relative stability of network states, which determine the effort required for state transitions in a multi-stable dynamical system. However, quasi-potential landscapes, originally developed for continuous systems, are not suitable for discrete-valued networks which are important tools to study complex systems. In this paper, we provide a framework to quantify the landscape for discrete Boolean networks (BNs). We apply our framework to study pancreas cell differentiation where an ensemble of BN models is considered based on the structure of a minimal GRN for pancreas development. We impose biologically motivated structural constraints (corresponding to specific type of Boolean functions) and dynamical constraints (corresponding to stable attractor states) to limit the space of BN models for pancreas development. In addition, we enforce a novel functional constraint corresponding to the relative ordering of attractor states in BN models to restrict the space of BN models to the biological relevant class. We find that BNs with canalyzing/sign-compatible Boolean functions best capture the dynamics of pancreas cell differentiation. This framework can also determine the genes' influence on cell state transitions, and thus can facilitate the rational design of cell reprogramming protocols.Comment: 24 pages, 6 figures, 1 tabl

The Quest for an Independent Scotland: The Impact of Culture, Economics, and International Relations Theory on Votes of Self-Determination

In the contemporary world, the true locus of sovereignty is up for debate. The drive for Scottish independence from the United Kingdom, within the larger context of the European Union illustrates trends within this relocation of sovereignty. Traditional research focused primarily on the cultural and identity issues at play, as well as economic issues. This work broadens the scope by placing the independence struggle within a complex international context. The shift from a purely realist state system interpretation to that of a refereed Pacific Union illustrates when nationalist and separatist movements can find conditions that allow for a viable secessionist movement. This sheds light on why Scotland has chosen to formally pursue independence in the last decade. Additionally, this work takes into account the theoretical implications of a hard Brexit, soft Brexit, and no Brexit on the future timing of secessionist referenda in Scotland