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The goals of this exercise are essentially threefold: (1) to rescrutinize, archaeologically, epigraphically and linguistically, the pre-Roman inscriptions of the justly famous Negau A and B helmets, (2) to identify "eastward graphemic drift" in preRoman northern Italy and (3) to reconsider and perhaps identify the origin of the Germanic runes in light of (1) and (2). While moving toward these goals, we cite but a sampling of the burgeoning literature, some of which may not be generally known or easily accessible, in these rapidly expanding venues; see Ellis (1998) for a recent overview in English.
The Sclerocoelus galapagensis group is defined and revised, including the description of S. galapagensis new species from the Galapagos Islands; S. caribensis new species from the Caribbean and adjacent areas; S. brasilensis new species from Brazil, Ecuador, Colombia, and Panama; S. hemorrhoidal is new species from Ecuador and Venezuela; and S. andensis new species from Argentina, Bolivia, and Venezuela. The south Atlantic species Sclerocoelus subbrevipennis (Frey), new combination, is redescribed as a member of the S. galapagensis group, and is considered the sister species to the rest of the species group. A key to species, character matrix, and cladogram are provided.
The bromodomain and PHD-finger containing transcription factor (BPTF) is part of the nucleosome remodeling factor (NURF) complex and has been implicated in multiple cancer types. Here, we report the discovery of a potent and selective chemical probe targeting the bromodomain of BPTF with an attractive pharmacokinetic profile enabling cellular and in vivo experiments in mice. Microarray-based transcriptomics in presence of the probe in two lung cancer cell lines revealed only minor effects on the transcriptome. Profiling against a panel of cancer cell lines revealed that the antiproliferative effect does not correlate with BPTF dependency score in depletion screens. Both observations and the multi-domain architecture of BPTF suggest that depleting the protein by proteolysis targeting chimeras (PROTACs) could be a promising strategy to target cancer cell proliferation. We envision that the presented chemical probe and the related negative control will enable the research community to further explore scientific hypotheses with respect to BPTF bromodomain inhibition.
This paper proposes a new sound rule for Proto-Slavic, according to which *g (from PIE *g, *gw, *gh, and *gwh) was lost before *m. This development was posterior to Winter’s law and the merger of voiced and aspirated stop in Slavic. The operation of the rule is illustrated by new etymologies of four Slavic words: *ama, *jama ‘hole, pit’, *těmę ‘sinciput’, *mąžь ‘husband, man’, and *remy ‘leather belt’.
Giulio Camillo (1480 - 1544) was as well-known in his era as Bill Gates is now. Just like Gates he cherished a vision of a universal Storage and Retrieval System, and just like Microsoft Windows, his ‘Theatre of the Memory’ was, despite constant revision, never completed. Camillo’s legendary Theatre of Memory remained only a fragment, its benefits only an option for the future. When it was finished, the user - so he predicted - would have access to the knowledge of the whole universe. On account of his promising invention, Camillo’s contemporaries called him ‘the divine’. For others, like Erasmus or the Parisian scholars, he was just a ‘quack’, but also this only shows that his reception was as strong as is the case with the computer gurus of our days. Still, Camillo was forgotten immediately after his death. No trace is left of his spectacular databank - except a short treatise which he dictated on his deathbed and which was formulated in the future tense: ‘L’Idea del Theatro’ (1550). ...
In the ignorance which still prevails regarding many details of the breeding-habits of the Cuckoo, we have a goof object lesson of how well Nature is able to guard her secrets, since, after years of careful and methodical investigation by distinguished naturalists, comparatively few authentic facts have been established. ...
Covalent inhibition has become more accepted in the past two decades, as illustrated by the clinical approval of several irreversible inhibitors designed to covalently modify their target. Elucidation of the structure-activity relationship and potency of such inhibitors requires a detailed kinetic evaluation. Here, we elucidate the relationship between the experimental read-out and the underlying inhibitor binding kinetics. Interactive kinetic simulation scripts are employed to highlight the effects of in vitro enzyme activity assay conditions and inhibitor binding mode, thereby showcasing which assumptions and corrections are crucial. Four stepwise protocols to assess the biochemical potency of (ir)reversible covalent enzyme inhibitors targeting a nucleophilic active site residue are included, with accompanying data analysis tailored to the covalent binding mode. Together, this will serve as a guide to make an educated decision regarding the most suitable method to assess covalent inhibition potency. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.