196,215 research outputs found

    Peptidyl Prolyl Isomerase A Modulates the Liquid–Liquid Phase Separation of Proline-Rich IDPs

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    [Image: see text] Liquid–liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) and the action of molecular chaperones are tightly connected. An important class of molecular chaperones are peptidyl prolyl isomerases, which enhance the cis/trans-isomerization of proline. However, little is known about the impact of peptidyl prolyl isomerases on the LLPS of IDPs, which often contain many prolines. Here, we demonstrate that the most ubiquitous peptidyl prolyl isomerase, peptidyl prolyl isomerase A (PPIA), concentrates inside liquid-like droplets formed by the Alzheimer’s disease-associated protein tau, as well as inside RNA-induced coacervates of a proline–arginine dipeptide repeat protein. We further show that the recruitment of PPIA into the IDP droplets triggers their dissolution and return to a single mixed phase. NMR-based binding and proline isomerization studies provide insights into the mechanism of LLPS modulation. Together, the results establish a regulatory role of proline isomerases on the liquid–liquid phase separation of proline-rich IDPs

    Dr. Duane M. Jackson, Morehouse College, July 2011

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    This video is a conversation with Dr. Duane M. Jackson. Dr. Jackson talks about his paper, "Recall and the Serial Position Effect: The Role of Primacy and Recency on Accounting Students' Performance." Jackie Daniel, AUC Woodruff Library, is the interviewer

    Design of dual ligands using excessive pharmacophore query alignment : from 7th German Conference on Chemoinformatics: 25 CIC-Workshop Goslar, Germany, 6 - 8 November 2011

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    Dual- or multi-target ligands have gained increased attention in the past years due to several advantages, including more simple pharmacokinetic and phamarcodynamic properties compared to a combined application of several drugs. Furthermore multi-target ligands often possess improved efficacy. We present a new approach for the discovery of dual-target ligands using aligned pharmacophore models combined with a shape-based scoring. Starting with two sets of known active compounds for each target, a number of different pharmacophore models is generated and subjected to pairwise graph-based alignment using the Kabsch-Algorithm. Since a compound may be able to bind to different targets in different conformations, the algorithm aligns pairs of pharmacophore models sharing the same features which are not necessarily at the exactly same spatial distance. Using the aligned models, a pharmacophore search on a multi-conformation-database is performed to find compounds matching both models. The potentially “dual” ligands are scored by a shape-based comparison with the known active molecules using ShaEP. Using this approach, we performed a prospective fragment-based virtual screening for dual 5-LO/sEH inhibitors. Both enzymes play an important role in the arachidonic acid cascade and are involved in inflammatory processes, pain, cardiovascular diseases and allergic reactions. Beside several new selective inhibitors we were able to find a compound inhibiting both enzymes in low micromolar concentrations. The results indicate that the idea of aligned pharmacophore models can be successfully employed for the discovery of dual-target ligands

    "Reflections on the subject of Emigration from Europe with a view to Settlement in the United States" By M. Carey.

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    "Reflections on the subject of Emigration from Europe with a view to Settlement in the United States: containing bried sketches of the moral and political character of those states. By M. Carey, member of the American philosophical, and of the American Antiquarian Society, and author of The Olive Branch, Cindiciae Hibernicae, essays on banking, on political economy, and on internal improvement. To which are now added the English editor's comments on the subject; together with Important Advice to Emigrants, and Cautions Against Impositions Practiced in the Outports

    Proline/arginine dipeptide repeat polymers derail protein folding in amyotrophic lateral sclerosis

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    The most frequent cause of familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are hexanucleotide repeat expansions in the non-coding region of the C9ORF72 gene that are translated into five dipeptide repeat (DPR) proteins. Here, the authors show that proline/arginine (PR) DPRs inhibit the prolyl isomerase PPIA and reveal the molecular mechanism of the impaired protein folding activity of PPIA by performing NMR measurements and determining a PR DPR bound PPIA crystal structure

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Dr. Glendon Swarthout

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    Hosted by Roger M. Busfield, MSU Assistant Professor of Speech and Theater, Meet the Author is designed to introduce a general audience to a contemporary author and their work through in-depth interviews. This episode features a conversation between Dr. Glendon Swarthout, prolific author and English professor at MSU, and assistant professors Sam S. Baskett and Theodore B. Strandness

    AMČR - archeologický záznam C-9132358A

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    Stav: 3Lokalizace/okolnosti: 2 km S od Teplé, 600 m J od Rankovic v louce, ppč. 215, 216.Souhrn/upřesnění: Kruhové tvrziště o průměru 50 m, obklopené příkopem (ppč. 215), širokým 5 m a hlubokým 1,5 m

    Simulation of thermal plant optimization and hydraulic aspects of thermal distribution loops for large campuses

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    Following an introduction, the author describes Texas A&M University and its utilities system. After that, the author presents how to construct simulation models for chilled water and heating hot water distribution systems. The simulation model was used in a $2.3 million Ross Street chilled water pipe replacement project at Texas A&M University. A second project conducted at the University of Texas at San Antonio was used as an example to demonstrate how to identify and design an optimal distribution system by using a simulation model. The author found that the minor losses of these closed loop thermal distribution systems are significantly higher than potable water distribution systems. In the second part of the report, the author presents the latest development of software called the Plant Optimization Program, which can simulate cogeneration plant operation, estimate its operation cost and provide optimized operation suggestions. The author also developed detailed simulation models for a gas turbine and heat recovery steam generator and identified significant potential savings. Finally, the author also used a steam turbine as an example to present a multi-regression method on constructing simulation models by using basic statistics and optimization algorithms. This report presents a survey of the author??s working experience at the Energy Systems Laboratory (ESL) at Texas A&M University during the period of January 2002 through March 2004. The purpose of the above work was to allow the author to become familiar with the practice of engineering. The result is that the author knows how to complete a project from start to finish and understands how both technical and nontechnical aspects of a project need to be considered in order to ensure a quality deliverable and bring a project to successful completion. This report concludes that the objectives of the internship were successfully accomplished and that the requirements for the degree of Degree of Engineering have been satisfied

    Intern experience at CH���M Hill, Inc.: an internship report

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    Includes author's vita"Submitted to the College of Engineering of Texas A&M University in partial fulfillment of the requirement for the degree of Doctor of Engineering."Includes bibliographical referencesA review of the author's internship experience with CH���M HILL, Inc. during the period September 1975 through May 1976 is presented. During this nine month internship the author worked as an Engineer II in the Industrial Processes discipline of this large consulting engineering firm... The author's prime responsibility was as one of three lead design engineers on the design of a large wastewater treatment facility for a pulp mill in Hoquiam, Washington owned by ITT Rayonier Inc. The work generally consisted of the design of individual treatment units and associated piping and pumping. The purpose of the project was to provide wastewater treatment capabilities that would satisfy the effluent limitations (standards) imposed upon the mill by the State of Washington Department of Ecology and the U.S. Environmental Protection Agency. The author's assignment also entailed necessary interaction with the project manager and other CH���M HILL design engineers and support staff members, the client's representatives, and representatives of two other consulting engineering firms working on the project. Thus, the internship position at CH���M HILL provided considerable experience coordinating the author's work with the work of other engineers, guiding the design and administrative efforts of a support staff, and interacting regularly with the client and other consulting firms. This broad exposure to a variety of engineering and organizational problems provided a valuable educational experience
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