In this study a combination of computer tools for coupling and virtual screening is detailed, in 108 active molecules and 3620 decoys to find stabilizers for G quadruplex. To have more precise results, combinations of coupling programs with fifteen energy scoring functions were applied. The validation and evaluation of the metrics was done with the CompScore genetic algorithm. The results showed an increase in BEDROC and EF of 50% compared to other strategies, as well as reflecting early recognition of active (...) molecules. From these results it is possible to work with the molecules that showed a good early recognition and evaluate their effect as G4 stabilizers. This ensures more efficient and accurate results in the preclinical stage for the development of anticancer drugs. Keywords: Enrichment metrics; telomere; G quadruplex ; CompScore. References [1]M. Porru, P. Zizza, M. Franceschin, C. Leonetti and A. Biroccio. «EMICORON: A multi-targeting G4 ligand with a promising preclinical profile» 2017. Biochimica et Biophysica Acta - General Subjects, 1861, 1362–1370. [Online]. Available: https://doi.org/10.1007/s00294-018-0836-6. [2]K. Tomita. «How long does telomerase extend telomeres? Regulation of telomerase release and telomere length homeostasis». Current Genetics, 64, 1177–1181. 2018. [Online]. Available: https://doi.org/10.1016/j.bbagen. 2016.11.010. [3]M. Jafri, S. Ansari, M. Alqahtani and J. Shay. «Roles of telomeres and telomerase in cancer, and advances in telomerase-targeted therapies. Genome Medicine., 2016. [Online]. Available: https://doi.org/10.3390/ijms19020482. [4]J. Huppert and S. Balasubramanian. «G-quadruplexes in promoters throughout the human genome». 35, 406–413. 2007. [Online]. Available: https://doi.org/10.1016/j.bbapap.2017.06.012. [5]S. Joy, Vijayakumar, S. Choi and H. Sunhye. «Role of computer-aided drug design in modern drug discovery». Archives of Pharmacal Research. 2015. [Online]. Available: https://doi.org/10.1007/s12272-015-0640-5. [6]S. Asamitsu, S. Obata, Z. Yu, T. Bando and H. Sugiyama. «Recent Progress of Targeted G-Quadruplex-Preferred Ligands Toward Cancer Therapy». Molecules, 24, 429. 2019. [En línea]. Available: https://doi.org/10.3390/molecules24030429. [7]R. Monsen and J. Trent. «Biochimie G-quadruplex virtual drug screening : A review». Biochimie, 152, 134–148. 2018. [Online]. Available: https://doi.org/10.1039/c9cc06748e. [8]J. Beauvarlet, P. Bensadoun, E. Darbo, G. Labrunie, E. Richard, I. Draskovic and M. Djavaheri-mergny. «Modulation of the ATM / autophagy pathway by a G-quadruplex ligand tips the balance between senescence and apoptosis in cancer cells». 1–18. 2019. [Online]. Available: https://doi.org/10.1093/nar/gkz095. [9].Z. Crees, J. Girard, Z. Rios, G. Botting, K. Harrington and C. Shearrow. « Oligonucleotides and G-quadruplex stabilizers: targeting telomeres and telomerase in cancer therapy».2014. [Online]. Available: https://doi.org/10.2174/1381612820666140630100702. [10].M. Meier, A. Moya-torres, N. Krahn, M. Mcdougall, L. Orriss, E. Mcrae and T. Patel. «Structure and hydrodynamics of a DNA Gquadruplex with a cytosine bulge»., 1–13. 2018. [Online]. Available: https://doi.org/10.1093/nar/gky307. (shrink)

Thomas Kuhn’s The Structure of Scientific Revolutions offers an insightful and engaging theory of science that speaks to scholars across many disciplines. Though initially widely misunderstood, it had a profound impact on the way intellectuals and educated laypeople thought about science. K. Brad Wray traces the influences on Kuhn as he wrote Structure, including his ‘Aristotle epiphany’, his interactions, and his studies of the history of chemistry. Wray then considers the impact of Structure on the social sciences, on the history (...) of science, and on the philosophy of science, where the problem of theory change has set the terms of contemporary realism/anti-realism debates. He examines Kuhn’s frustrations with the Strong Programme sociologists’ appropriations of his views, and debunks several popular claims about what influenced Kuhn as he wrote Structure. His book is a rich and comprehensive assessment of one of the most influential works in the modern sciences. (shrink)

Purpose: To show the convergences between Josef Mitterer's non-dualizing way of speaking and actor-network theory. Method: Comparative analysis of Mitterer's non-dualizing philosophy and actor-network philosophy. Findings: Profound convergences between the two accounts may lead to a unified account that could redefine traditional philosophical problems. Benefits: The paper extends the range of Mitterer's non-dualizing philosophy and actor-network theory enabling both to face new problems. Among them, extended non-dualizing philosophy may undergo empirical investigations.

Incongruity and anachronism characterize Ovid's treatment of the gods and mythological figures in the Metamorphoses; frequently the resulting discrepancy between the superhuman world of mythology and characteristic aspects of Roman society serves to pillory that society as well as to undermine the dignity of the traditional mythology. Linguistic parody is one of the tools Ovid uses to highlight these discrepancies. An example recently noted is that of the serenade delivered by Polyphemus the landlubber to his marine beloved, Galatea : by (...) casting this in the form of Gebetsparodie, Ovid mocks the literary topoi of the paraclausithyron as well as reducing the heroic status of the mythological protagonists. I suggest that in Tiresias’ brief appearance in Metamorphoses 3 Ovid imitates the pedantic locutions of jurists’ language in order to demonstrate how trivial and undignified are the preoccupations of the bickering Olympians. (shrink)

Moutoussis, K., A. Maier, S. Zeki and N. K. Logothetis: Seeing invisible motion: responses of area V5 neurons in the awake-behaving macaque. Soc. for Neurosci. Abstr. 390.11, 1.