148 research outputs found

    Quantitative Determination of Spatial Protein-protein Proximity in Fluorescence Confocal Microscopy

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    To quantify spatial protein-protein proximity (colocalization) in fluorescence microscopic images, cross-correlation and autocorrelation functions were decomposed into fast and slowly decaying components. The fast component results from clusters of proteins specifically labeled and the slow one from background/image heterogeneity. We show that the calculation of the protein-protein proximity index and the correlation coefficient are more reliably determined by extracting the fast-decaying component.Comment: 19 pages, 5 figure

    Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

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    Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

    Virology under the microscope—a call for rational discourse

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    Viruses have brought humanity many challenges: respiratory infection, cancer, neurological impairment and immunosuppression to name a few. Virology research over the last 60+ years has responded to reduce this disease burden with vaccines and antivirals. Despite this long history, the COVID-19 pandemic has brought unprecedented attention to the field of virology. Some of this attention is focused on concern about the safe conduct of research with human pathogens. A small but vocal group of individuals has seized upon these concerns – conflating legitimate questions about safely conducting virus-related research with uncertainties over the origins of SARS-CoV-2. The result has fueled public confusion and, in many instances, ill-informed condemnation of virology. With this article, we seek to promote a return to rational discourse. We explain the use of gain-of-function approaches in science, discuss the possible origins of SARS-CoV-2 and outline current regulatory structures that provide oversight for virological research in the United States. By offering our expertise, we – a broad group of working virologists – seek to aid policy makers in navigating these controversial issues. Balanced, evidence-based discourse is essential to addressing public concern while maintaining and expanding much-needed research in virology

    Multi-User GeoGebra for Virtual Math Teams

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    The Math Forum is an online resource center for pre-algebra, algebra, geometry and pre-calculus. Its Virtual Math Teams (VMT) service provides an integrated web-based environment for small teams to discuss mathematics. The VMT collaboration environment now includes the dynamic mathematics application, GeoGebra. It offers a multi-user version of GeoGebra, which can be used in concert with VMT’s chat, web browsers, curricula and wiki repository

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    BnF-Partenariats, Collection sonore - BelieveContient une table des matière

    Enhancing mathematical communication for virtual math teams

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    The Math Forum is an online resource center for pre-algebra, algebra, geometry and pre-calculus. Its Virtual Math Teams (VMT) service provides an integrated web-based environment for small teams of people to discuss math and to work collaboratively on math problems or explore interesting mathematical micro-worlds together. The VMT Project studies the online math discourse that takes place during sessions of virtual math teams working on open-ended problem-solving tasks. In particular, it investigates methods of group cognition that are employed by teams in this setting. The VMT environment currently integrates social networking, synchronous text chat, a shared whiteboard for drawing, web browsers and an asynchronous wiki for exchanging findings within the larger community. A simple version of MathML is supported in the whiteboard, chat and wiki for displaying mathematical expressions. The VMT Project is currently integrating the dynamic mathematics application, GeoGebra, into its collaboration environment. This will create a multi-user version of GeoGebra, which can be used in concert with the chat, web browsers, curricular topics and wiki repository
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