2,896 research outputs found

    microRNA-205-5p is a modulator of insulin sensitivity that inhibits FOXO function

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    Objectives: Hepatic insulin resistance is a hallmark of type 2 diabetes and obesity. Insulin receptor signaling through AKT and FOXO has important metabolic effects that have traditionally been ascribed to regulation of gene expression. However, whether all the metabolic effects of FOXO arise from its regulation of protein-encoding mRNAs is unknown. Methods: To address this question, we obtained expression profiles of FOXO-regulated murine hepatic microRNAs (miRNAs) during fasting and refeeding using mice lacking Foxo1, 3a, and 4 in liver (L-Foxo1,3a, 4). Results: Out of 439 miRNA analyzed, 175 were differentially expressed in Foxo knockouts. Their functions were associated with insulin, Wnt, Mapk signaling, and aging. Among them, we report a striking increase of miR-205-5p expression in L-Foxo1,3a,4 knockouts, as well as in obese mice. We show that miR-205-5p gain-of-function increases AKT phosphorylation and decreases SHIP2 in primary hepatocytes, resulting in FOXO inhibition. This results in decreased hepatocyte glucose production. Consistent with these observations, miR-205-5p gain-of-function in mice lowered glucose levels and improved pyruvate tolerance. Conclusions: These findings reveal a homeostatic miRNA loop regulating insulin signaling, with potential implications for in vivo glucose metabolism

    CAPRI versus AGLINK-COSIMO: Two partial equilibrium models - Two baseline approaches

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    The agricultural modelling world has generated several models aiming at the analysis of the response of the sector to certain changes in exogenous mainly policy variables. Among those, the CAPRI modelling system developed by a consortium centred on the University of Bonn and the AGLINK-COSIMO model, a joint product of the OECD and the FAO, are well known and accepted as comprehensive tools. This analysis focuses on a qualitative comparison of both models and particularly on the process of setting up the baseline. The baseline is a medium-term projection of agricultural markets reflecting current policies and those already decided upon. This projection in turn serves as the base for comparisons when analyzing scenarios. It is shown that CAPRI uses generic and automatic procedures whenever possible for conducting the database and the baseline, while AGLINK-COSIMO puts more emphasis on expert knowledge in this process. Both approaches are shown to have certain advantages while the conclusion that a combination of them would potentially improve both models will be drawn from this analysis.CAPRI, AGLINK-COSIMO, Baseline process, Agricultural and Food Policy,

    After the Addendum: Author Rights Management and/as Library Service

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    This report presents the findings from a qualitative study of Rice University faculty attitudes and practices around author rights conducted by Marcel LaFlamme, a graduate student in the Department of Anthropology, during his tenure as a Fondren Fellow. This project was supervised by Shannon Kipphut-Smith, Fondren Library’s scholarly communications liaison

    Ruskin traduzido: Sesame and Lilies por Proust e Catalán

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    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Literatura, Florianópolis, 2009.Este trabalho parte da análise das traduções da obra Sesame and Lilies, de John Ruskin, para o francês e para o castelhano para fazer um exame de questões ligadas ao gênero ensaístico, à tradução de ensaios e à autoria. Para isso, analisarei a tradução de Marcel Proust para o francês e seu paratexto e a tradução para o castelhano feita por Miguel Catalán e o respectivo paratexto.This study analises the translations of Sesame and Lilies, by John Ruskin, into French and Spanish in order to examine issues related to the essay as a literary genre, to the translation of essays and to authorship. This exam will be carried out by analising the translation into French by Marcel Proust and its paratext and the translation into Spanish by Miguel Catalán, accompanied by its paratext

    Into the Single-Verse : Subtle gene expression differences between virtually identical single cells are informative of gene regulation

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    The ability to profile transcriptomes and proteomes in a high-throughput fashion in single cells has truly revolutionized functional genomics, and countless functional and regulatory insights have been based on these technologies. While major applications include the discovery of new cell types and the a posteriori sorting of cell populations, studies of gene expression noise and gene co-expression have made use of this inter-cellular heterogeneity in a genuine quantitative fashion. Yet, there are still major limitations to overcome. First, strong dynamic processes, such as cell cycle or differentiation axes, tend to overshadow more subtle underlying regulatory processes. While this has sparked the development of tools that can identify and correct these biases at large, few insights into the subtleties of gene regulation have been published thus far. The majority of studies still focus on drastic changes such as differentiation or disease. We address this issue in paper I and to a limited extend in paper II and paper III through the elimination of major confounders during experimental design. In these papers, we show that variation and covariation of miRNAs, mRNAs and proteins between individual cells of a homogeneous non-dynamic population are informative of gene regulation. Second, while single-cell technologies are booming, with new technologies being published every day, the co-profiling of RNA and protein in the same single cells still remains a major challenge. All current technologies are limited either by protein location or throughput, or require invasive cell fixation that can compromise mRNA stability. We overcome these limitations in paper II through the combination of quantitative single-cell RNA sequencing with proximity extension assays for protein detection. Using this technology, SPARC, we show that transcription factor protein, but not transcription factor RNA, covaries with the RNA expression of its targets. We also show that translation is a major mediator of the shift in variation from the RNA to the protein level. Third, some technologies still suffer from limited sensitivity. While, for instance, the first single-cell miRNA detection already succeeded in 2006 and the first single-cell small RNA sequencing technique was published in 2016, few insights into miRNA dynamics or function have been gained from single-cell data since. Using an optimized single-cell small RNA sequencing protocol, we quantify the miRNA transcriptome of close to 200 single cells in paper III. We show that variation and covariation can be linked to miRNA transcription and turnover. Integrating miRNA and miRNA target data from all three papers, we present evidence that the induction of variation on the RNA level and the buffering of protein expression noise are naturally occurring for many miRNAs. In summary, we present new strategies and new protocols that overcome existing limitations in the field, and we present regulatory insights that were enabled by quantitative measurements of single-cell gene expression variation and covariation

    Jean-Marcel Jeanneney à l'OFCE - Fondations et contributions (1981-1989).

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    Jean-Marcel Jeanneney était un économiste rare, à la fois théoricien, empiriste et praticien. C’est son aventure à la tête de l’OFCE que ce livre raconte, ou plutôt qu’il laisse l’auteur lui-même conter au travers d’articles écrits depuis le premier jour de son premier mandat de Président de notre institution. Ce recueil s’ouvre sur une introduction qui rappelle l'attachement du fondateur de l’OFCE au « libéralisme intellectuel», cette indépendance vis-à-vis des idées reçues qu’il jugeait indispensable à la conduite de politiques publiques raisonnables. Il est ensuite structuré en trois parties dont les titres font écho à une oe uvre marquante de Jean-Marcel Jeanneney : Vouloir le débat public en économie, Une mémoire au service de la prospective et Écoute le monde qui vient : intégration globale et unification européenne. Ce volume est un hommage à la mémoire de Jean-Marcel Jeanneney mais plus encore à sa présence. Les textes rassemblés ici par Jean-Paul Fitoussi et Éloi Laurent nous rappellent l’actualité des enseignements les plus précieux de Jean-Marcel Jeanneney : honnêteté, courage et espérance.

    Some Marks in Marcel Iancu’s Creation

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    The paper emphasises some aspects of Marcel Iancu’s creation during his dadaist period in Zürich and after his return in Romania where he was one of avant-garde movement leaders and author of some important theoretical articles

    Data for: Author Ranking Evaluation at Scale

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    This data consists of two test data sets of researchers that have (1) received one or more prestigious prizes for the long-lasting and high impact contribution to their fields (596 data entries) and (2) author names of ACM fellows (1000 data entries).Each author in the data sets is matched to the corresponding ACM author profileID and multiple Microsoft Academic Graph author entity IDs (name disambiguated). It also includes citation counts, publication counts, download counts from various sources (ACM Digital Library, Google Scholar, Microsoft Academic)

    Marcel Schwob Digital Collection

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    This project outlines the discovery and digitization of previously unpublished correspondence composed by late 19th century author and literary critic, Marcel Schwob. Inspired by the inquiry of Bibliothèque Nationale Librarian Bernard Gauthier, Professor Daryl Lee alerted me to the presence of Marcel Schwob materials at BYU. I found that former BYU Professor John Green established a Marcel Schwob Memorial Collection and successfully published two books using the materials he gathered: Chroniques and Correspondance Inédite. After thoroughly researching the catalogued Schwob materials at BYU and comparing the contents to other Schwob publications, I found 72 previously unpublished letters. The majority of the letters (62) were written by Schwob to family members, and the remaining 9 letters were written to Schwob by colleagues. International interest in Marcel Schwob materials is one of many indicators representing renewed interest in the author, his work, and his influence. Recent publications also reflect growing Schwob interest. In Marcel Schwob, d\u27hier et d\u27aujourd\u27hui (2002), Christian Berg and Yves Vadé shed new light on Schwob through the observations of his contemporaries and modern-day essays on the importance of his contes. In addition, Jean Lorrain: Lettres à Marcel Schwob (2006) furthers the effort to better understand Schwob through a collection of correspondence. In light of this renewed interest, I determined that the previously unpublished correspondence would serve as a useful research tool for Schwob scholars. With the guidance and assistance of employees at the Harold B. Lee Library, I subsequently converted the correspondence into a digital publication. Creating a digital publication is a multifaceted undertaking requiring the involvement and expertise of different individuals and library departments. I successfully learned how to use both the hardware and software involved in the digitization process, thereby facilitating my completion of project deliverables, including: scanning and transcribing the letters; writing letter summaries (in both French and English), extracting names, and completing other metadata; uploading metadata using the Lee Library\u27s external database; establishing authority control records; writing website content (in both French and English), and publicizing the project. This document contains the major deliverables found in the digital publication, specifically the website content, the letter transcriptions, and the metadata

    Die tonlosen Stimmen

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    Marcel Beyer is one of the most prominent German-language writers. His contribution discusses the challenges of non-fictional narratives while focusing on Russia's war of aggression against Ukraine. The author wrote his essay as part of his 'Poetikdozentur' at the Bergische Universität Wuppertal
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