Transcriptional regulation of human topoisomerase II beta : a thesis presented to Massey University in partial fulfilment of the requirements for the degree of Master of Science in Biochemistry

Pages 24 and 25 are missing from the original copy.Topoisomerase II has an essential role in maintaining the DNA in the correct topological state required for various cellular processes. Its mechanism of action involves the introduction of a double-Dstranded break into the DNA, passage of a different piece of DNA through the break, followed by the religation of the DNA. Topoisomerase II, in humans, exists as two different isoforms: topoisomerase II alpha, which is cell cycle-Dregulated and highly expressed in rapidly proliferating cells, and topoisomerase II beta, which is ubiquitously expressed and it is not under the influence of the cell cycle. Several chemotherapeutic drugs have been designed to interfere with the catalytic mechanism of the topoisomerase II enzyme. By either stabilising the DNA cleavage complex or interfering with another step of the mechanism, these topoisomerase II targeted drugs promote the entry of the cell into cell death pathways. An increasing problem in the treatment of cancer with these drugs is the rising number of patients with inherited or developed drug-resistance. It has been shown that drug-resistance, at least in part, results from the down-regulation of topoisomerase II expression. The expression of a gene is a highly regulated process and the initiation of transcription represents a major point of regulation. Prior to this study little was known regarding the regulation of transcription of topoisomerase II beta. Understanding the processes surrounding the regulation of this enzyme would provide some insight as to how it is down regulated in drug-resistance. The focus of this study was to examine the role of three elements in the topoisomerase II beta promoter, GCI, ICB1, and ICB2 and the transcription factors that bind to them. Electrophoretic mobility shifts assays revealed that Sp1, Sp3, NF-Y and two uncharacterised proteins are capable of binding to the promoter in vitro. Transient transfection assays showed in vivo that Sp1 was able to activate transcription and that Sp3 inhibited transcription driven by the topoisomerase II beta promoter. In addition the key activating elements appear to be ICB2 and GC1, while ICB1 is inhibitory

Safety and Knowledge in God

In recent ”secular’ Epistemology, much attention has been paid to formulating an ”anti-luck’ or ”safety’ condition; it is now widely held that such a condition is an essential part of any satisfactory post-Gettier reflection on the nature of knowledge. In this paper, I explain the safety condition as it has emerged and then explore some implications of and for it arising from considering the God issue. It looks at the outset as if safety might be ”good news’ for a view characteristic of Reformed Epistemology, viz. the view that if Theism is true, many philosophically unsophisticated believers probably know that it’s true. A sub-conclusion of my paper though suggests that as safety does not by itself turn true belief into knowledge, the recent focus on it is not quite such good news for Reformed Epistemologists as they may have hoped: it’s not that safety provides a new route by which they can reach this sort of conclusion. But safety is still good news for their view at least in the sense that there is no reason arising from considering it to count these philosophically unsophisticated believers as not knowing that there’s a God. I conclude by reflecting that good news for Reformed Epistemology is perhaps bad news for the discipline of Philosophy of Religion more generally, as there’s a possible ”reflection destroys knowledge’-implication to be drawn. Those who have been led to their religious beliefs in at least some philosophically unsophisticated ways seem to enjoy much safer religious beliefs than those who have been led to their religious beliefs by philosophical reflection, so the discipline as a whole will be adversely affected if safety is eventually accorded the role of a necessary condition for knowledge

Measuring Economic Growth in New Zealand

This paper examines New Zealand’s ranking in the OECD based on real GDP per capita. The fall in ranking experienced by New Zealand implies that real GDP per capita growth in New Zealand has been relatively poor in comparison to other OECD countries. The paper examines the history of New Zealand’s growth rate and explores the differences between various techniques for measuring average growth rates. The approaches are all shown to be variants of the average annual growth rate but differ in terms of the weighting structure used. Ultimately, the most appropriate technique depends on the underlying data generating process. The implications of data construction techniques for measured growth rates are discussed and differences between the growth rates obtained from different data sources are illustrated. The paper also illustrates the sensitivity of New Zealand growth rates to the sample period chosen.Economic Growth; Measuring Growth; International Comparisons

iPod tours: a new approach to induction

This article is based on a presentation given at a conference organized by cpd 25 in April 2007; “The Library in the Interactive Environment: Practical use of technology to improve the student experience”. It describes the development and creation of an iPod induction tour for the Main Library at Sheffield University, with input from students. It also discusses the use and evaluation of the tour, and concludes by describing how the Library is using the experience to consider other technologies to introduce our students to library services

Memory transfer optimization for a lattice Boltzmann solver on Kepler architecture nVidia GPUs

The Lattice Boltzmann method (LBM) for solving fluid flow is naturally well suited to an efficient implementation for massively parallel computing, due to the prevalence of local operations in the algorithm. This paper presents and analyses the performance of a 3D lattice Boltzmann solver, optimized for third generation nVidia GPU hardware, also known as `Kepler'. We provide a review of previous optimisation strategies and analyse data read/write times for different memory types. In LBM, the time propagation step (known as streaming), involves shifting data to adjacent locations and is central to parallel performance; here we examine three approaches which make use of different hardware options. Two of which make use of `performance enhancing' features of the GPU; shared memory and the new shuffle instruction found in Kepler based GPUs. These are compared to a standard transfer of data which relies instead on optimised storage to increase coalesced access. It is shown that the more simple approach is most efficient; since the need for large numbers of registers per thread in LBM limits the block size and thus the efficiency of these special features is reduced. Detailed results are obtained for a D3Q19 LBM solver, which is benchmarked on nVidia K5000M and K20C GPUs. In the latter case the use of a read-only data cache is explored, and peak performance of over 1036 Million Lattice Updates Per Second (MLUPS) is achieved. The appearance of a periodic bottleneck in the solver performance is also reported, believed to be hardware related; spikes in iteration-time occur with a frequency of around 11Hz for both GPUs, independent of the size of the problem.Comment: 12 page

Aggregate Growth and the Efficiency of Labour Reallocation

We consider the potential importance of labour market efficiency for aggregate growth. The idea is that efficient labour markets move workers more quickly from low to high productivity sites, thereby raising aggregate productivity growth. We define a measure of labour market efficiency as a structural parameter from a matching function. Using labour market data on 15 OECD countries, we estimate this and show that it has a significant effect on growth. The results are robust to a number of different estimation techniques. The quantitative impact of market efficiency is not trivial.growth, labour market efficiency, labour market institutions

Creating an iPod library tour

[FIRST PARAGRAPH] Over the years, traditional tours of the Main Library for new students had become unviable, primarily because of the huge numbers of students on many programmes and the short induction period. The value of such tours had also been questioned and most Liaison Librarians had replaced them with presentations to large groups in lecture theatres. A printed self-guided tour had been available for some time, but was looking dated. The concept of the iPod tour provided the opportunity to supplement other induction activities with something that students could download and use when they chose to, using innovative technologies. Planning for the project started towards the end of June 2005 and the deadline was Intro Week towards the end of September

The Australian fashion report 2015: the truth behind the barcode

Examines the increased risk of child and forced labour in the fashion industry, as many local companies are unable to trace or fail to monitor their supply chains. Introduction It’s been two years since the fatal Rana Plaza factory collapse in Bangladesh, an event which saw the lives of 1,100 factory workers tragically cut short and is now recorded as the second worst industrial accident of all time. The event sparked the collective conscience of consumers, retailers, investors and governments to know more about the people producing our clothes and how they are treated. The 2013 Australian Fashion Report, released in the wake of the accident, helped to shed some light on these questions by assessing the efforts of companies to protect workers in their supply chain from exploitation and the egregious practice of modern slavery, awarding each company grades from A to F.   This report updates and expands that research, adding an additional 18 companies representing over 91 brands. Of the companies researched in our last publication, a remarkable two thirds have improved their labour rights management systems, 100% now have codes of conduct (up from 85%) and the number of companies that actively engaged with the research process has increased from 54% to 94%.   Some companies that have made significant improvements include Kmart, which has released a complete list of its direct suppliers, a huge step towards transparency; The Cotton On Group, which has taken big steps forward to identify suppliers deeper in their supply chain; and H&M, Zara, Country Road and the Sussan Group which have demonstrated that they have made efforts towards paying better wages for workers overseas.   The Fairtrade companies once again are a stand out, with all their brands receiving A grades. Etiko still retains top honours, having traced its entire supply chain and taken action to ensure workers at the inputs and final stage of manufacturing levels of the supply chain are being paid a living wage. Etiko’s performance is only matched by the newcomer, Audrey Blue, who shares Etiko’s supply chain. The Cotton On Group takes honours for being the highest rated, non-Fairtrade Australian retailer, while H&M and Inditex, the two biggest fashion retailers in the world, are amongst the best rated international brands, receiving A-grades while also taking action to ensure workers at the final stage of production are being paid above the minimum wage. Only Hanesbrands received a higher grade, an A, but has yet to demonstrate any action on improving worker wages.       &nbsp

Braiding and fusion of non-Abelian vortex anyons

We demonstrate that certain vortices in spinor Bose-Einstein condensates are non-Abelian anyons and may be useful for topological quantum computation. We perform numerical experiments of controllable braiding and fusion of such vortices, implementing the actions required for manipulating topological qubits. Our results suggest that a new platform for topological quantum information processing could potentially be developed by harnessing non-Abelian vortex anyons in spinor Bose-Einstein condensates.Comment: 16 pages, 3 figures, 6 supplementary figures; added details of the H-charge, J. K. Slingerland added to author lis

Harnessing technology to provide the support that trainees require to write high quality reflective statements

Trainees work within schools spending 80% of their time away from University. The one day a week during which they are based at Warwick is full of content delivery, subject knowledge improvement and pedagogy training. The course uses ICT to support trainees, through Moodle as the VLE for online course delivery and Mahara as the e-portfolio for assessment, where trainees display their evidence against the eight teaching standards. Trainees produce an e-portfolio where they write reflective statements to demonstrate their development over the course of the year; this evidence enables them to achieve 30 CAT points, which trainees can count towards an MA qualification