Transformation of the female detective image in the19th and 20th centuries English female detective prose

The article deals with the peculiarities of the image of the female detective in the English female detective prose of the 19 th and 20 th centuries. We have traced the changes in the portrayal of the female detective in English literature and singled out the factors which influenced them. First of all, every writer’s experience and life conditions make an impact on the construction of their images. It is obvious that S. Hopley couldn’t but work secretly as her creator C. Crowe wrote detective using the other name. It was the trend of the nineteenth century. In the first part of the twentieth century, women started to obtain different professions alongside men. A. Christie and D. Sayers had an opportunity to be not only writers but even theoreticians of the genre. That is why Miss Marple and H. Vane were able to show their achievements together with men. And the second part of the twentieth century presented women with total freedom. So, we can read about Sharon McCone who is a successful private detective. The second important fact is the situation in the society which for sure is reflected in the realistic literary works and can be easily noticed in the behaviour of the characters. And the last efficient thing is the plot of the story because it dictates the actions which sometimes do not depend on the personality. The article analyzes the characteristic features of the female detectives belonging to three stages of detective development: detective classics (until the early twentieth century), detective modernism (1910–the 1970s), and detective postmodernism (after the 1970s). The female detective of detective classics is clever and kind but lacks self-confidence and support. Detective modernism shows us an intelligent, smart, very brave, and attentive detective. The woman detective of the postmodern period is smart, courageous, emotional, and hard-working. Thus, we have suggested the canonic image of the female detective. She has a sharp mind, a very high level of knowledge, a sense of responsibility, a strong wish to work, and a little time for her personal life. This woman is pretty, careful, witty, and ready to investigate at any time

Experiments

Despite inherent limitations, the ease and rapidity of their use make transiently expressed reporter gene assays the most frequently used techniques for analyzing promoters and transcriptional regulators. The results of transient reporter gene assays are generally accepted to reflect transcriptional processes correctly, though these assays study regulatory sequences outside of the chromosomal environment and draw conclusions on transcription based on enzyme activity determination. For transient reporter gene assays, often more than one promoter is introduced into one cell. In addition to the one driving the primary reporter gene expression, a further one might serve to ensure the production of an internal control second reporter or/and a trans-acting factor. We demonstrate here by various examples that interference between physically unlinked promoters can profoundly affect reporter expression. Results of reporter gene assays performed by combinations of the cytomegalovirus promoter and various other promoter constructs (human immunodeficiency virus [HIV], Human T-cell Leukemia Virus Type I (HTLV-I), NF-kappa B-responsive, and p53-responsive) and trans-activator factors (HIVT- at and p53) in different host cell lines (U2OS, HeLa, and L929) prove that interference between active transcription units can modify transcription responses dramatically. Since the interference depends on the promoters used, on the amount of transfected DNA, on the host cells, and on other factors, extra caution is required in interpreting results of transient reporter gene assays

Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery