422 research outputs found

    The MDS Mortality Risk Index: The Evolution Of A Method For Predicting 6-month Mortality In Nursing Home Residents

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    Accurate prognosis is vital to the initiation of advance care planning particularly in a vulnerable, at risk population such as care home residents. The aim of this paper is to report on the revision and simplification of the MDS Mortality Rating Index (MMRI) for use in clinical practice to predict the probability of death in six months for care home residents

    Meritor brake assembly bench part setup process improvement

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    In partnership with Meritor\u27s Manning, South Carolina facility, this capstone project focuses on the changeover process of a drum brake assembly for industrial trucks. The changeover process is the downtime an operator spends preparing the workstation for the next set of brake orders. This team\u27s objective is to use process improvement techniques to reduce downtime in between brake orders. Once the customer needs were determined, the team developed concepts to increase the efficiency of the changeover process time. The concepts consisted of real world applications and the utilization of a discrete event simulation software called Arena. In addition to the Arena model, the team has begun testing individual concepts. With the results from these tested concepts, the team will be able to effectively develop solutions to reduce downtime of operators during the changeover process

    Investigating the Justice System Response to Domestic Violence in Missouri

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    One in four women will experience domestic violence in their lifetimes. Each year, 5.3 million domestic violence assaults occur in the United States alone and domestic violence is the leading cause of injury to women. Yet, despite the prevalence of domestic violence, little empirical research on the justice system\u27s response to it exists. This paper seeks to describe a state funded project that was created to assess and compare responses to domestic violence throughout the state of Missouri. The project lasted for three years and was conducted by an interdisciplinary team of University of Missouri-Columbia (MU) professors and students

    Super-Bridges Suspended Over Carbon Nanotube Cables

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    In this paper the new concept of super-bridges, i.e. kilometre-long bridges suspended over carbon nanotube cables, is introduced. The analysis shows that the use of realistic (thus defective) carbon nanotube bundles as suspension cables can enlarge the current limit main span by a factor of 3.Comment: 17 pages, 6 figures, 2 table

    Functional Diversity and Structural Disorder in the Human Ubiquitination Pathway

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    The ubiquitin-proteasome system plays a central role in cellular regulation and protein quality control (PQC). The system is built as a pyramid of increasing complexity, with two E1 (ubiquitin activating), few dozen E2 (ubiquitin conjugating) and several hundred E3 (ubiquitin ligase) enzymes. By collecting and analyzing E3 sequences from the KEGG BRITE database and literature, we assembled a coherent dataset of 563 human E3s and analyzed their various physical features. We found an increase in structural disorder of the system with multiple disorder predictors (IUPred - E1: 5.97%, E2: 17.74%, E3: 20.03%). E3s that can bind E2 and substrate simultaneously (single subunit E3, ssE3) have significantly higher disorder (22.98%) than E3s in which E2 binding (multi RING-finger, mRF, 0.62%), scaffolding (6.01%) and substrate binding (adaptor/substrate recognition subunits, 17.33%) functions are separated. In ssE3s, the disorder was localized in the substrate/adaptor binding domains, whereas the E2-binding RING/HECT-domains were structured. To demonstrate the involvement of disorder in E3 function, we applied normal modes and molecular dynamics analyses to show how a disordered and highly flexible linker in human CBL (an E3 that acts as a regulator of several tyrosine kinase-mediated signalling pathways) facilitates long-range conformational changes bringing substrate and E2-binding domains towards each other and thus assisting in ubiquitin transfer. E3s with multiple interaction partners (as evidenced by data in STRING) also possess elevated levels of disorder (hubs, 22.90% vs. non-hubs, 18.36%). Furthermore, a search in PDB uncovered 21 distinct human E3 interactions, in 7 of which the disordered region of E3s undergoes induced folding (or mutual induced folding) in the presence of the partner. In conclusion, our data highlights the primary role of structural disorder in the functions of E3 ligases that manifests itself in the substrate/adaptor binding functions as well as the mechanism of ubiquitin transfer by long-range conformational transitions. © 2013 Bhowmick et al

    A Generic Platform for Cellular Screening Against Ubiquitin Ligases

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    Ubiquitin signalling regulates most aspects of cellular life, thus deregulation of ubiquitylation has been linked with a number of diseases. E3 ubiquitin ligases provide substrate selectivity in ubiquitylation cascades and are therefore considered to be attractive targets for developing therapeutic molecules. In contrast to established drug target classes, such as protein kinases, GPCRs, hormone receptors and ion channels, ubiquitin drug discovery is in its early stages. This is, in part, due to the complexity of the ubiquitylation pathways and the lack of robust quantitative technologies that allow high-throughput screening of inhibitors. Here we report the development of a Ubiquitin Ligase Profiling system, which is a novel and generic cellular technology designed to facilitate identification of selective inhibitors against RING type E3 ubiquitin ligases. Utilization of this system requires a single co-transfection of cells with assay vectors, thereby enabling readout of E3 ubiquitin ligase catalytic activity within the cellular environment. Therefore, our robust high-throughput screening platform offers novel opportunities for the development of inhibitors against this difficult-to-target E3 ligase enzyme class
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