101,896 research outputs found

    Mass spectrometry-based characterization of histones in clinical samples: applications, progresses, and challenges

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    In the last 15 years, increasing evidence linking epigenetics to various aspects of cancer biology has prompted the investigation of histone post-translational modifications (PTMs) and histone variants in the context of clinical samples. The studies performed so far demonstrated the potential of this type of investigations for the discovery of both potential epigenetic biomarkers for patient stratification and novel epigenetic mechanisms potentially targetable for cancer therapy. Although traditionally the analysis of histones in clinical samples was performed through antibody-based methods, mass spectrometry (MS) has emerged as a more powerful tool for the unbiased, comprehensive, and quantitative investigation of histone PTMs and variants. MS has been extensively used for the analysis of epigenetic marks in cell lines and animal tissue and, thanks to recent technological advances, is now ready to be applied also to clinical samples. In this review, we will provide an overview on the quantitative MS-based analysis of histones, their PTMs and their variants in cancer clinical samples, highlighting current achievements and future perspectives for this novel field of research. Among the different MS-based approaches currently available for histone PTM profiling, we will focus on the ‘bottom-up’ strategy, namely the analysis of short proteolytic peptides, as it has been already successfully employed for the analysis of clinical samples

    Use of IDeS Method to Design an Innovative HYICE Sportscar

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    In the contemporary automobile scene, environmental effect abatement is being increasingly sought; this demands a full rethinking of the entire system and entails more than just the reduction in exhaust pollutant emissions. Currently, the most popular approach is the electrification of automobiles, which significantly reduces pollution in major urban areas while simultaneously posing a new set of problems. The two types of zero-emission vehicles that are now being developed the most are hydrogen fuel cells and battery electric cars, but another option is the Hydrogen Internal Combustion Engine (HYICE) engine, which is highly advantageous in terms of pollutants, aside from Nitrogen Oxides (NOx), which can be considerably decreased. The purpose of this study is to develop a novel vehicle design that transports this type of technology into a sporting context while striving for considerable environmental benefits and integrating them into a society where the love of automobiles still has a strong following. The cutting-edge Industrial Design Structure (IDeS) methodology is used in this work, and a sample structure was created to demonstrate how the problems and technical limitations represented can be solved. The steps of the methodology are followed to shape the final product, with careful consideration given to the design of the styling component through the use of the Stylistic Design Engineering (SDE) method. With the ultimate goal of achieving sustainable driving pleasure, the study looks into whether recyclable materials can be used for the body and whether extremely light materials can be used for the chassis

    Bibliographie Hilarion G. Petzold 1958 – 2009 mit Anhang als Einführung

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    Dieses Archiv enthält die Gesamtbibliographie der Werke des Autors nebst einiger Texte „Über H. G. Petzold“ im Schlussteil der Bibliographie sowie einen Anhang mit einer Einführung in die Architektur des Werkes in seinem wissenslogischen Aufbau als Ausarbeitung seines „Tree of Science Modells“ (2007).This archive contains the complete bibliography of the author and some texts about H. G. Petzold, moreover an epilogue with an introduction to the architecture of the works in its epistemological structure and composition and as an elaborations of Petzold’s „Tree of Science Modell (2007).https://www.fpi-publikation.de/polyloge/01-2009-petzold-h-g-gesamtbibliographie-h-g-petzold-1958-2009-updating-november2009/peerReviewedpublishedVersio

    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

    Author-springer.pdf

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    A truncated and catalytically inactive isoform of KDM5B histone demethylase accumulates in breast cancer cells and regulates H3K4 tri-methylation and gene expression

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    KDM5B histone demethylase is overexpressed in many cancers and plays an ambivalent role in oncogenesis, depending on the specific context. This ambivalence could be explained by the expression of KDM5B protein isoforms with diverse functional roles, which could be present at different levels in various cancer cell lines. We show here that one of these isoforms, namely KDM5B-NTT, accumulates in breast cancer cell lines due to remarkable protein stability relative to the canonical PLU-1 isoform, which shows a much faster turnover. This isoform is the truncated and catalytically inactive product of an mRNA with a transcription start site downstream of the PLU-1 isoform, and the consequent usage of an alternative ATG for translation initiation. It also differs from the PLU-1 transcript in the inclusion of an additional exon (exon-6), previously attributed to other putative isoforms. Overexpression of this isoform in MCF7 cells leads to an increase in bulk H3K4 methylation and induces derepression of a gene cluster, including the tumor suppressor Cav1 and several genes involved in the interferon-alpha and -gamma response. We discuss the relevance of this finding considering the hypothesis that KDM5B may possess regulatory roles independent of its catalytic activity.</p

    The Right to Strike under the United States Constitution: Theory, Practice, and Possible Implications for Canada

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    Answering critics of the Canadian Supreme Court's judgment in B.C. Health, the author argues that the Court laid the foundation for a principled and durable doctrine protecting constitutional labour rights, one that goes directly to the heart of the matter — the inequality of workers’ power in the employment relation. In the author’s view, two paths could lead from B.C. Health to the recognition of Charter protec- tion for a right to strike: one that treats the right as an accessory to col- lective bargaining, and one that upholds the right directly on the basis of the Charter values of equality and participation. The author supports the latter approach, contending that constitutional rights should be defined in relation to fundamental values, in a way that is not contingent on time-bound or fact-sensitive assessments about the role of strikes within a particular collective bargaining regime. Although a Charter right to strike may involve the courts in difficult choices about when to defer to legislative policy decisions, and courts may lack the institutional capac- ity to deal effectively with labour law issues, the author points out that judges can look to ILO standards for expert guidance. Noting that the U.S. experience in this area might be of considerable use to Canadians, the author concludes by providing an overview of American case law concerning a constitutional right to strike.Peer reviewe

    Jacopo Robusti called Tintoretto,

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    "Cheaper reissue, 1907."Bibliography: p. xi-xii.Mode of access: Internet

    Robust Estimation of Dimension Reduction Space

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    Most dimension reduction methods based on nonparametric smoothing are highly sensitive to outliers and to data coming from heavy-tailed distributions.We show that the recently proposed methods by Xia et al.(2002) can be made robust in such a way that preserves all advantages of the original approach.Their extension based on the local one-step M-estimators is sufficiently robust to outliers and data from heavy tailed distributions, it is relatively easy to implement, and surprisingly, it performs as well as the original methods when applied to normally distributed data.Dimension reduction;Nonparametric regression;M-estimation
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