1,147 research outputs found

    The Escape Artists

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    My thesis, “The Escape Artists”, is a collection of short fiction that represents most of the work I did as a creative writing master’s student. The title is taken from my longest story, a narrative about a young man’s struggle to avoid violence in a federal prison. As a title, “The Escape Artists” also captures major themes in my other stories; characters often pursue emotional escapism or literally seek to evade predators in my fiction. As a writer, I often explore breakdowns in social order, so my stories tend to be set in turbulent, oppressive political climates or else inside domestic struggles – a loss in a family or isolation between couples. The major concern of my writing is the way in which characters young and old, privileged and unprivileged, respond to challenges put upon them by contemporary circumstances outside their control. By setting my work in distinct locales, such as rural Egypt, urban New York, suburban Denver, or inside a South Dakota prison, I hope to offer a worldly reading. Through main characters that are children, young adults, and middle-aged men, I also wish to demonstrate the way priorities and insecurities evolve with age

    Brain Enriched microRNAs Open the Neurogenic Potential of Adult Human Fibroblasts

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    The seemingly limitless capacities of mammals to sense, respond, and manipulate their environments stems from their structurally and functionally diverse nervous systems. Establishing these complex behaviors requires the integration of many biological phenomena including, morphogenetic gradients, cell-cell signaling, transcriptional networks, cell migration and epigenetic gene regulation. As mammalian development progresses, these pathways coordinate the production of highly specialized neuronal and glial cells, that connect and communicate with another in an even more complex manner. While evolution has shaped a multitude of pathways to produce numerous favorable traits, it has also created an intricate system vulnerable to disease. The loss of different types of neurons, each responsible for specialized biochemical communications within the brain and spinal cord, results in a wide variety of neurological and neurodegenerative diseases. Unfortunately, many of these diseases are uniquely human and cannot be wholly studied in model organisms such as Mus musculus or Drosophila melanogaster. Further, their location and absolute necessity precludes isolation directly from patients. Fortunately, advances in our understanding of genetic pathways that specify neuronal cell fates during development have enabled the directed differentiation of embryonic and induced pluripotent stem cells (iPSCs) into specific neuronal subtypes. This knowledge has been further leveraged to directly convert (reprogram) non-neuronal somatic cells into neurons, bypassing the induction of pluripotency. Specifically, ectopically expressing small non-coding microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124), with transcription factors in human adult fibroblasts is sufficient to generate functionally mature neuronal subtypes. These direct conversion modalities may prove invaluable in the study of late-onset neurodegenerative diseases, as the original age of human fibroblasts is maintained in converted neurons in contrast to the cellular rejuvenation observed in iPSCs. However, little is known about the epigenetic and molecular events that accompany direct cell-fate conversion limiting the utility of these features. Further, the capacity of miRNAs alone to overcome cell fate barriers has largely been unexplored. Within this thesis I provide mechanistic insights into the cell-fate pioneering activity of miR-9/9*-124. These results demonstrate that miRNAs induce remodeling of chromatin accessibilities, DNA methylation and the transcriptome leading to the generation of functionally excitable neurons. Surprisingly, during neuronal reprogramming, miR-9/9*-124 opens neuronal gene loci embedded in heterochromatic regions while simultaneously repressing fibroblast loci, revealing how miRNAs may overcome the cell-fate barrier that exists in human fibroblasts. These findings led to the discovery of a miRNA-induced permissive neurogenic ground state capable of generating multiple, clinically relevant neuronal subtypes. As such, I show that the addition of motor neuron factors, ISL1 and LHX3, can function as terminal selectors to specify neuronal conversion to a highly enriched population of human spinal cord motor neurons. Altogether, the work contained within this thesis identifies miRNA-mediated epigenetic remodeling events underlying direct neuronal conversion of human fibroblasts and a modular platform capable of generating multiple, clinically relevant neuronal subtypes directly from patients

    Reverse Zoonosis of Pandemic A(H1N1)pdm09 Influenza Viruses at the Swine/Human Interface

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    The 2009 pandemic influenza A(H1N1)pdm09 virus emerged from the swine population. Despite frequent zoonotic events, swine influenza viruses had not become established in humans previously and little is known about host-barriers which prevent swine influenza viruses from efficiently infecting humans. Thus, the emergence of the H1N1pdm09 viruses in humans and the subsequent reverse zoonoses back to swine offered an extremely valuable opportunity to expand current knowledge. We used our active swine farm surveillance platform in combination with viruses from the USDA surveillance program to look for evidence of interspecies transmission of H1N1pdm09 viruses in the US. We found phylogenetic evidence for multiple human to swine transmission events, all of which were transient suggesting that the human adapted viruses of swine origin had lost some fitness for swine. Based on our phylogenetic analysis we selected representative H1N1pdm09 viruses from the tips of swine and human sub-lineages for further study. Intriguingly, we found that after being re-introduced into the swine population, the human H1N1pdm09 viruses rapidly lost replicative fitness in human cells. Together these data provide support for a model where transmission of viruses from human to swine leads to rapid adaptation for the swine host which comes at the expense of optimal fitness for human

    Investigation of Degradation in Polythiophene-Fullerene Based Solar Cells

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    This dissertation investigates the degradation of conjugated polymer poly(3-hexylthiophene) (P3HT). Specifically, exposure of polymer solutions to air and light, and aging of thin films in air and dark has been probed. Solutions of either P3HT or blend of P3HT and phenyl-C61-butyric acid methyl ester (PCBM) were mixed in air and light, and also in dark and inert atmosphere. Thin films of these solutions where then spin coated for UV-vis and Raman characterization. Hole only diodes and photovoltaic devices were also realized and characterized for mobility measurements and photovoltaic performance. Characterizations were repeated after aging the thin films in dark and air for two weeks, and then again after a short annealing at elevated temperature. PCBM was found to reduce the magnitude of P3HT degradation. Solutions mixed in dark and argon were found to respond with a reduction of absorption characteristics when annealed. Solutions mixed in light and air were found to respond with an increase in absorption characteristics when annealed

    Millimeter-Wave Measurements of High Level and Low Activity Glass Melts: Annual Report FY2000

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    Automated and Scalable: Account-Based B2B Marketing for Startup Companies

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    Advances in digital marketing strategy have opened the floodgates for forward-thinking marketers to rewrite how modern business-to-business marketing is done from a strategic and tactical aspect. This paper discusses a fundamental shift that has been pervading the business-to-business marketing space, i.e., the adoption of Account-Based Marketing (ABM). ABM bridges the gap between marketing to an individual and marketing to the broader organization in an automated and scalable fashion. Specifically, we aim to provide a practical guide regarding some best ABM practices for startup companies. Startup companies typically look to drive rapid growth in both revenue and number of customers; however, go-to-market resources are often limited. For these companies, automating and scaling an ABM becomes an essential part of their growth. We discuss three data sources valuable for ABM program for startups, and the development of a robust account intelligence program and customized go-to-market campaign. The practice introduced in this paper can serve as a starting point for startup companies that plan to drive rapid revenue growth through a focused account-based strategy

    P1_1 "Prepare for Titanfall"

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    In the popular digital entertainment title Titanfall, “titans”, or large metal exoskeletons are dropped onto the battlefield on Earth, from a region in low earth orbit (LEO) at approximately 160 km. From start to finish, this process takes approximately 10 seconds in-game, subsequently requiring an average velocity of around 1.6x104 ms-1. This paper aims to incorporate the often neglected aspect of quadratic drag into the dynamical calculations in order to show that the time required for this movement is closer to 223.2 seconds once the correct atmospheric impacts have been accounted for

    P1_2 The Temperature of Jupiter

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    It is well known that there is a discrepancy between Jupiter’s observed surface temperature, quantified through infrared emissions, and the theorised temperature based on the approximation that Jupiter acts as a black body. This paper will attempt to assess the additional contribution of three popular factors to the excess heat output of Jupiter; gravitational collapse, heat emission from radio-isotopes and the differentiation of He and
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