Mga2 transcription factor regulates an oxygen-responsive lipid homeostasis pathway in fission yeast

Eukaryotic lipid synthesis is oxygen-dependent with cholesterol synthesis requiring 11 oxygen molecules and fatty acid desaturation requiring 1 oxygen molecule per double bond. Accordingly, organisms evaluate oxygen availability to control lipid homeostasis. The sterol regulatory element-binding protein (SREBP) transcription factors regulate lipid homeostasis. In mammals, SREBP-2 controls cholesterol biosynthesis, whereas SREBP-1 controls triacylglycerol and glycerophospholipid biosynthesis. In the fission yeast Schizosaccharomyces pombe, the SREBP-2 homolog Sre1 regulates sterol homeostasis in response to changing sterol and oxygen levels. However, notably missing is an SREBP-1 analog that regulates triacylglycerol and glycerophospholipid homeostasis in response to low oxygen. Consistent with this, studies have shown that the Sre1 transcription factor regulates only a fraction of all genes up-regulated under low oxygen. To identify new regulators of low oxygen adaptation, we screened the S. pombe nonessential haploid deletion collection and identified 27 gene deletions sensitive to both low oxygen and cobalt chloride, a hypoxia mimetic. One of these genes, mga2, is a putative transcriptional activator. In the absence of mga2, fission yeast exhibited growth defects under both normoxia and low oxygen conditions. Mga2 transcriptional targets were enriched for lipid metabolism genes, and mga2Δ cells showed disrupted triacylglycerol and glycerophospholipid homeostasis, most notably with an increase in fatty acid saturation. Indeed, addition of exogenous oleic acid to mga2Δ cells rescued the observed growth defects. Together, these results establish Mga2 as a transcriptional regulator of triacylglycerol and glycerophospholipid homeostasis in S. pombe, analogous to mammalian SREBP-1

Democratization Prospects in the Arab World

The Arab Spring protests were massive pro-democracy protests which occurred throughout the Arab world in the early 2010s. These protests were primarily met with failure, with Tunisia being the only state involved in these protests that democratized following them. In response to this movement, authoritarian and semi-democratic countries in the Arab World have been cracking down on freedom of speech, limiting the civil society in their states, and increasing the oversight of international non-government organizations in their countries, in the hopes to hinder the development of future democratization attempts. This study, titled “Democratization Potential in the Arab World Post Arab-Spring” will hope to answer three research questions: 1.) What factors led to the Arab Spring? 2.) What factors led to Tunisia being the only democracy to result from the Arab Spring? 3.) How should western states support democratization efforts in the Arab World? To answers these questions, an in-depth literature review will be conducted on the geopolitical context of Tunisia, the history of the Arab World, public opinions towards democratization in Arab States, and democratization literature. The study will also include a model comparing Middle Eastern states in attempt to determine which factors led to success within Tunisia. This research is significant, as the vast majority of democratization assistance programs perpetrated by the United States have resulted in a failure. If the creation of a democratic world remains a foreign policy goal of the United States, then a different policy approach is required

Precision Statistics for Biased Tracers of Large-Scale Structure

In this dissertation, we analyze pre-existing statistical tools and improve them to better describe the clustering and evolution of galaxies on large-scales. We use ``galaxies" as a place-holder here since most of our work is applicable to objects that co-evolve with matter and are largely dominated by gravity throughout their evolution. These objects are termed biased tracers of matter. Statistics of biased tracers are of interest since the resulting tools can be used to uncover the precise composition of our local universe and to connect observable structure to the initial conditions in the early universe. In the first two sections of this work, we introduce the field of modern cosmology and cover the basics of perturbation theory needed for later sections. The following three sections consist of three separate studies. In the first study, we analyze scenarios when the sample size of an observation is small, and we quantify the sample variance, resulting in a more accurate model than had previously existed. This sample variance can be crucial in connecting local astrophysical observations to large-scale cosmology. We apply our variance model to recent observations of the warm-hot intergalactic medium in the context of the missing baryon problem and find that the pre-existing estimates of the error need to be revised. The following two sections focus on a different topic but are related. They explore the assumption of the continuity equation for biased tracers in the context of perturbation theory. The continuity equation states that the number density of a biased tracer is conserved over time such that, e.g., the tracers do not undergo significant mergers. The first of these studies shows that the linear order clustering of tracers is over-predicted if the biased tracers are not conserved. The second of these two studies extends this analysis to higher perturbative order and finds a simple relation between scenarios when continuity is violated and when it is not. We conclude this dissertation with some remarks on the prospects for these works

Scalable framework for heterogeneous clustering of commodity FPGAs

A combination of parallelism exploitation and application specific hardware is increasingly being used to address the computational requirements of a diverse and extensive set of application areas. These targeted applications have specific computational requirements that often are not able to be implemented optimally on general purpose processors and have the potential to experience substantial speedup on dedicated hardware. While general parallelism has been exploited at various levels for decades, the advent of heterogeneous cluster computing has allowed applications to be accelerated through the use of intelligently mapped computational tasks to well-suited hardware. This trend has continued with the use of dedicated ASIC and FPGA coprocessors to off-load particularly intensive computations. With the inclusion of embedded microprocessors into otherwise reconfigurable FPGA fabric, it has become feasible to construct a heterogeneous cluster composed of application specific hardware resources that can be programatically treated as fully functional and independent cluster nodes via a standard message passing interface. The contribution of this thesis is the development of such a framework for organizing heterogeneous clusters of reconfigurable FPGA computing elements into clusters that enable development of complex systems delivering on the promise of parallel reconfigurable hardware. The framework includes a fully featured message passing interface implementation for seamless communication and synchronization among nodes running in an embedded Linux operating system environment while managing hardware accelerators through device driver abstractions and standard APIs. A set of application case studies deployed on a test platform of Xilinx Virtex-4 and Virtex-5 FPGAs demonstrates functionality, elucidates performance characteristics, and promotes future research and development efforts