1,720,984 research outputs found
Dataset supporting Development of activators for SERCA2a for heart failure treatments
No full textOur primary aim in the present study is to discover drug-like small-molecule activators that improve SERCA function for the treatment of heart failure. We previously identified a promising hit compound, N-aryl-N-alkyl-thiophene-2-carboxamide (designated compound 1) using an NADH-coupled ATPase activity assay of the skeletal sarco/endoplasmic reticulum (SR) ATPase (SERCA1a) transporter for high-throughput screening (HTS) of a large compound library. At micromolar concentrations, compound 1 activated the Ca2+-ATPase activity and Ca2+-uptake function of the cardiac SERCA isoform (SERCA2a), using cardiac SR. Further, compound 1 increased SR Ca2+ load in cardiomyocytes. Here, we report on the medicinal chemistry development of compound 1, with the goal of improving its potency and efficacy on SERCA2a functional activities. Systemic modification of the three moieties of compound 1 resulted in a gallery of analogs that were functionally evaluated with Ca2+-ATPase activity and Ca2+-uptake measurements on SERCA2a in porcine cardiac SR. Correlation of the effects of the analogs’ chemical structure-activity relationship (SAR) revealed several analogs with improved potency and efficacy. Solubility, stability, and toxicity measurements of a subset of analogs were used to explore the lead-like potential of this chemical group. In this study, we demonstrate a path of using medicinal chemistry for developing drugs to treat heart failure.NIH R01HL139065NIH R01AR082533NIH T32AR007612Brinkmann, Marzena; Wong, Tsung-Yun; Roopnarine, Osha; Yuen, Samantha; Berg, Kaja; Cornea, Razvan; Rebbeck, Robyn; Thomas, David; Aldrich, Courtney. (2025). Dataset supporting Development of activators for SERCA2a for heart failure treatments. Retrieved from the Data Repository for the University of Minnesota (DRUM), https://doi.org/10.13020/pvjn-8w51
Data supporting Large-scale high-throughput screen for cardiac ryanodine receptor targeted therapeutics
Get PDFData to accompany a research article.In high-throughput screening (HTS) assays using fluorescence lifetime (FLT)-detected FRET, we have identified compounds that allosterically modulate the pathologically leaky ryanodine receptor (RyR) calcium release channels. These compounds may prevent or reduce the elevated Ca2+ that fuels arrhythmia, heart failure, and age-related neurodegeneration. RyRs are responsible for intracellular Ca2+ release from endo-plasmic/sarcoplasmic reticulum (ER/SR). The resulting [Ca2+] pulse is a signal for many cellular processes, whereas sustained elevated [Ca2+] is pathologic. Our FRET-based HTS detects the pathology-linked RyR leaky state by monitoring binding of the accessory protein calmodulin and the DPc10 peptide (corresponding to RyR2 residues 2460–2495) known to perturb inter-domain interactions within RyR2. Under conditions mimicking a pathological state, we have screened a 50,000-compound chemical library to identify small-molecule modulators of RyR2 in cardiac SR membranes. This screen yielded 603 compounds that reproducibly altered FRET. Based on FRET response profiles that align with therapeutic potential, 83 of those most promising compounds were purchased and validated by FRET dose response evaluation. Focusing on ten chemical scaffolds that desirably increase A-CaM binding, six representative compounds reduced RyR2 activity as measured by [3H]ryanodine binding. Ca2+ dynamics in HEK293 cells expressing human RyR2 or in cardiomyocytes highlighted the isoxazole group of hits as potentially therapeutic by targeting the pathological RyR2 leak state.Rebbeck, Robyn T; Nikolaienko, Roman; Bovo, Elisa; Solberg, Jonathan C; Brinkmann, Marzena A; Treinen, Levy M; Thompson, Andrew R; Berg, Kaja; Thomas, David; Thomas, Jennifer J; Bers, Donald M; Aldrich, Courtney C; Zima, Aleksey V; Cornea, Razvan L. (2025). Data supporting Large-scale high-throughput screen for cardiac ryanodine receptor targeted therapeutics. Retrieved from the Data Repository for the University of Minnesota (DRUM), https://doi.org/10.13020/q0nb-z977
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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