1,725,170 research outputs found
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
Toward Understanding the Molecular Recognition of Albumin by p53-Activating Stapled Peptide ATSP-7041
No full textReactivation of tumor-suppressing
activity of p53 protein by targeting
its negative regulator MDM2/MDMX has been pursued as a potential anticancer
strategy. A promising dual inhibitor of MDM2/MDMX that has been developed
and is currently in clinical trials is the stapled peptide ATSP-7041.
The activity of this molecule is reported to be modulated in the presence
of serum. Albumin is the most abundant protein in serum and is known
to bind reversibly to several molecules. To study this interaction,
we develop a protocol combining molecular modeling, docking, and simulations.
Exhaustive docking of the peptide with representative simulated structures
of human serum albumin led to the identification of probable binding
sites on the surface of the protein, including both known canonical
and novel binding sites. Sequence differences at putative peptide-binding
sites in human and mouse albumin result in differing interaction energies
with the peptide and enable us to rationalize the observed differences
in vivo. In general, the
findings should help in guiding the design of features in such peptides
that may affect their distribution and cell permeability, opening
a new window in structure-guided design strategies
Antitumor activity of SK-7041, a novel histone deacetylase inhibitor, in human lung and breast cancer cells
No full textBackground: A class of synthetic histone deacetylase (HDAC) inhibitors, which are hybrids of trichostatin A and MS-275 were previously developed. In this study, the antitumor effects of SK-7041, one of those novel HDAC inhibitors, was evaluated on lung and breast cancer cell lines. Materials and Methods: Human lung and breast cancer cells, as well as normal human bronchial epithelial (NHBE) cells were treated with SK-7041, and results were compared with those of cells treated with suberoylanilide hydroxamic acid (SAHA). Results: SK-7041 induced time-dependent histone hyperacetylation and showed more potent cytotoxicity than SAHA in cancer cells. These antiproliferative effects of SK-7041 were due to apoptotic cell death caused by G21M-phase arrest and to a lesser extent to G1 arrest. Moreover, SK-7041 inhibited cancer cell proliferation more selectively than NHBE cell proliferation. Conclusion: These results suggest that SK-7041 may have potential anticancer activity.N
Identification of the Stapled α-Helical Peptide ATSP-7041 as a Substrate and Strong Inhibitor of OATP1B1 In Vitro
No full textATSP-7041, a stapled α-helical peptide that inhibits murine double minute-2 (MDM2) and MDMX activities, is a promising modality targeting protein–protein interactions. As peptides of molecular weights over 1000 Da are not usually evaluated, data on the drug–drug interaction (DDI) potential of stapled α-helical peptides remain scarce. Here, we evaluate the interaction of ATSP-7041 with hepatic cytochrome P450s (CYPs; CYP1A2, CYP2C9, CYP2C19, CYP3A4, and CYP2D6) and transporters (organic anion transporting polypeptides (OATPs; OATP1B1 and OATP1B3), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP)). ATSP-7041 demonstrated negligible metabolism in human liver S9 fraction and a limited inhibition of CYP activities in yeast microsomes or S9 fractions. On the contrary, a substantial uptake by OATPs in HEK 293 cells, a strong inhibition of OATP activities in the cells, and an inhibition of P-gp and BCRP activities in reversed membrane vesicles were observed for ATSP-7041. A recent report describes that ALRN-6924, an ATSP-7041 analog, inhibited OATP activities in vivo; therefore, we focused on the interaction between ATSP-7041 and OATP1B1 to demonstrate that ATSP-7041, as a higher molecular weight stapled peptide, is a substrate and strong inhibitor of OATP1B1 activity. Our findings demonstrated the possibility of transporter-mediated DDI potential by high molecular weight stapled peptides and the necessity of their evaluation for drug development
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
Episodic encoding is more than the sum of its parts: An fMRI investigation of multifeatural contextual encoding
No full textEpisodic memories are characterized by their contextual richness, yet little is known about how the various features comprising an episode are brought together in memory. Here we employed fMRI and a multidimensional source memory procedure to investigate processes supporting the mnemonic binding of item and contextual information. Volunteers were scanned while encoding items for which the contextual features (color and location) varied independently, allowing activity elicited at the time of study to be segregated according to whether both, one, or neither feature was successfully retrieved on a later memory test. Activity uniquely associated with successful encoding of both features was identified in the intra-parietal sulcus, a region strongly implicated in the support of attentionally mediated perceptual binding. The findings suggest that the encoding of disparate features of an episode into a common memory representation requires that the features be conjoined in a common perceptual representation when the episode is initially experienced
Fendage et/ou rainurage après le maximum glaciaire tardif en Europe occidentale, entre continuité et innovation ?
No full textCommunicants : Margot Damery (doctorante UMR 7041 ArScAn, « Archéologies environnementales ») ; Laure Fontana (CNRS, UMR 7041 ArScAn, « Archéologies environnementales ») Au cours du Paléolithique supérieur en Europe occidentale, plusieurs techniques ont été utilisées pour traiter les matériaux osseux. La fracturation des bois de cervidés par fendage a été la première technique reconnue et attestée depuis la période de l'Aurignacien (±40 000 BP). Le fendage est une technique qui permet de ..
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
20th Annual Meeting of the European Association of Archaeologists, Istanbul (10-14 septembre 2014)
No full textPlusieurs membres de l'équipe Archéologies Environnementales (UMR 7041) présentent des communications au 20e congrès annuel de l'European Association of Archaeologists. Philippe FAJON (MCC – UMR 7041, France) et Bogdan SANDRIC (INP – Ministerul Culturii, Romania) participeront au session « Iron age landscape in a comparative perspective », en présentant la communication : "Gaulish and Dacian settlements organised the landscape in the same way at both extremities of Europe – An archeogeograph..
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