34 research outputs found

    Hormonal regulation and metabolic roles of CCAAT/enhancer-binding proteins

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    The CCAAT/Enhancer-Binding proteins (C/EBPs) are liver-enriched transcription factors which are known to 'trans'-activate a number of metabolically important genes. The goal of this thesis work has been to advance areas of study on C/EBP isoform regulation and metabolic roles which have not been fully addressed in the current literature. The initial undertaking of this work involved the examination of the effects of hormones and diabetes on C/EBP isoform expression in rat H4IIE hepatoma cells and in rat liver. Treatment of cells with dexamethasone was observed to produce increases in C/EBPá and C/EBPâ mRNA and protein levels. Insulin was observed to produce an interesting bi-phasic response on C/EBPá expression. Treatment of H4IIE cells with 8-chlorophenylthio-cAMP produced greater inductive effects upon C/EBPâ expression than on C/EBPá expression. We observed an inhibition of C/EBPá gene expression in streptozotocin-diabetic rat liver which was reflected by decreases in both its mRNA and protein. However, an interesting alteration in the ratio of alternate C/EBPá translation forms was observed in the streptozotocin-diabetic livers suggesting a potential alteration in the 'trans'-activational activity of C/EBPá. These results suggest that hepatic C/EBP isoforms are under complex control by both hormonal and metabolic signals, which correlates well with their known role as 'trans'-activators of metabolically vital genes. Previous work has demonstrated a role for C/EBPá in mediating the cAMP responsiveness of synthetic phosphoenolpyruvate carboxykinase (PEPCK) promoter constructs within a transiently transfected cell culture system. In order to address the C/EBP isoform requirements for endogenous PEPCK gene expression and regulation, we have produced stable transfected hepatoma cells expressing antisense constructs for the two major C/EBP isoforms in liver. We demonstrate that targeted inhibition of C/EBPá but not C/EBPâ in rat hepatoma H4IIE cells significantly reduces the cAMP responsiveness of the endogenous PEPCK promoter. Cells expressing C/EBPá antisense were characterized by decreases in the levels C/EBPá mRNA and C/EBPá protein levels. The response of PEPCK to cAMP was marginal in C/EBPá antisense expressing cells, compared with a 3-fold induction of PEPCK expression by cAMP observed in wild-type H4IIE cells. The cAMP signaling pathway of C/EBPá antisense expressing cells was intact; in that the cAMP induction of the C/EBPâ gene was similar to that of normal H4IIE cells. Furthermore, the cAMP responsiveness of PEPCK in C/EBPâ antisense expressing cells was nearly identical to that of wild-type H4IIE cells. These data suggest that the á-isoform of C/EBP is specifically required for mediation of the cAMP response of endogenous PEPCK in rat hepatoma cells and cannot be functionally substituted for by C/EBPâ in this context

    Analysis of the structure and function of the S.pombe DNA ligase I protein Cdc17

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    Exploring electroweak symmetry breaking with jet substructure at the ATLAS experiment

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    An important unsolved problem in physics is the nature of electroweak symmetry breaking in the Standard Model. The ATLAS experiment aims to gain insight by studying proton-proton collisions at ps = 14 TeV. In order to di�erentiate between di�erent theoretical models it is important to measure processes where hadrons are produced, such as the hadronic decay of aW, Z or a Higgs boson. However, these decays produce extremely complex signals in the detector which must be analysed carefully. Jet substructure techniques are presented as a novel approach to analysing hadronic signatures relevant to electroweak symmetry breaking. The potential performance of these techniques is evaluated in detail using simulated ATLAS data. Additionally material related to the use of visualisation software to explore ATLAS data is presented

    NREL Photovoltaic Program FY 1995 annual report

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    Enhanced Living Environments

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    This open access book was prepared as a Final Publication of the COST Action IC1303 “Algorithms, Architectures and Platforms for Enhanced Living Environments (AAPELE)”. The concept of Enhanced Living Environments (ELE) refers to the area of Ambient Assisted Living (AAL) that is more related with Information and Communication Technologies (ICT). Effective ELE solutions require appropriate ICT algorithms, architectures, platforms, and systems, having in view the advance of science and technology in this area and the development of new and innovative solutions that can provide improvements in the quality of life for people in their homes and can reduce the financial burden on the budgets of the healthcare providers. The aim of this book is to become a state-of-the-art reference, discussing progress made, as well as prompting future directions on theories, practices, standards, and strategies related to the ELE area. The book contains 12 chapters and can serve as a valuable reference for undergraduate students, post-graduate students, educators, faculty members, researchers, engineers, medical doctors, healthcare organizations, insurance companies, and research strategists working in this area

    Deep Underground Science and Engineering Laboratory - Preliminary Design Report

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    The DUSEL Project has produced the Preliminary Design of the Deep Underground Science and Engineering Laboratory (DUSEL) at the rehabilitated former Homestake mine in South Dakota. The Facility design calls for, on the surface, two new buildings - one a visitor and education center, the other an experiment assembly hall - and multiple repurposed existing buildings. To support underground research activities, the design includes two laboratory modules and additional spaces at a level 4,850 feet underground for physics, biology, engineering, and Earth science experiments. On the same level, the design includes a Department of Energy-shepherded Large Cavity supporting the Long Baseline Neutrino Experiment. At the 7,400-feet level, the design incorporates one laboratory module and additional spaces for physics and Earth science efforts. With input from some 25 science and engineering collaborations, the Project has designed critical experimental space and infrastructure needs, including space for a suite of multidisciplinary experiments in a laboratory whose projected life span is at least 30 years. From these experiments, a critical suite of experiments is outlined, whose construction will be funded along with the facility. The Facility design permits expansion and evolution, as may be driven by future science requirements, and enables participation by other agencies. The design leverages South Dakota's substantial investment in facility infrastructure, risk retirement, and operation of its Sanford Laboratory at Homestake. The Project is planning education and outreach programs, and has initiated efforts to establish regional partnerships with underserved populations - regional American Indian and rural populations
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