In addition to vaccines, antiviral drugs are essential for suppressing COVID-19. Although several inhibitor candidates were reported for SARS-CoV-2 main protease, most are highly polar ...peptidomimetics with poor oral bioavailability and cell membrane permeability. Here, we conducted structure-based virtual screening and in vitro assays to obtain hit compounds belonging to a new chemical space, excluding peptidyl secondary amides. In total, 180 compounds were subjected to the primary assay at 20 μM, and nine compounds with inhibition rates of >5% were obtained. The IC50 of six compounds was determined in dose–response experiments, with the values on the order of 10–4 M. Although nitro groups were enriched in the substructure of the hit compounds, they did not significantly contribute to the binding interaction in the predicted docking poses. Physicochemical properties prediction showed good oral absorption. These new scaffolds are promising candidates for future optimization.
Social media activity on a research article is considered to be an altmetric, a new measure to estimate research impact. Demonstrating software on Twitter is a powerful way to attract attention ...from a larger audience. Twitter integration of software can also lower the barriers to trying the tools and make it easier to save and share the output. We present three case studies of Twitter bots for cheminformatics: retrosynthetic analysis, 3D molecule viewer, and 2D chemical structure editor. These bots make software research more accessible to a broader range of people and facilitate the sharing of chemical knowledge, concepts, and ideas.
The electron density distribution in the vicinity of the lunar surface was explored with the radio occultation technique using a subsatellite on the SELENE mission. Although the measurements suffer ...from contamination by the terrestrial ionosphere and interplanetary plasma, an analysis of more than 300 measurements provides adequate statistics and reveals a general trend. The result suggests that a dense ionosphere covering the whole sunlit side, as suggested by the radio occultation measurements on the Soviet Luna 19 and 22 missions, does not exist. However, weak signatures of electron density enhancement with densities on the order of 100 cm−3 are observed below 30 km altitude at solar zenith angles less than 60°. The statistically averaged density reaches a peak at around 15 km altitude and decreases gradually at higher altitudes and toward the surface. Although the suggested electron layer is thinner and less extended horizontally than that reported by Luna 19 and 22, the existence of such an ionized layer is still difficult to explain by conventional ionosphere generation mechanisms. An alternative source of electrons may be required.
Key Points
Electron density near the lunar surface was measured by radio occultation
Repeated observations revealed the dependence on the solar zenith angle
Weak signature of density enhancement was observed near sub‐solar region
We propose a new iterative screening contest method to identify target protein inhibitors. After conducting a compound screening contest in 2014, we report results acquired from a contest held in ...2015 in this study. Our aims were to identify target enzyme inhibitors and to benchmark a variety of computer-aided drug discovery methods under identical experimental conditions. In both contests, we employed the tyrosine-protein kinase Yes as an example target protein. Participating groups virtually screened possible inhibitors from a library containing 2.4 million compounds. Compounds were ranked based on functional scores obtained using their respective methods, and the top 181 compounds from each group were selected. Our results from the 2015 contest show an improved hit rate when compared to results from the 2014 contest. In addition, we have successfully identified a statistically-warranted method for identifying target inhibitors. Quantitative analysis of the most successful method gave additional insights into important characteristics of the method used.
Institutionalized government support for artwork incorporated into transportation environments has a history spanning more than 80 years in the United States. Although the Federal Transit ...Administration has a history of policy guidelines, and the American Public Transportation Association, and Americans for the Arts have developed best practices for the successful integration of artworks during the planning and construction phases of transportation projects, little research exists concerning the public life of those artworks during the operational phase, beyond maintenance concerns. This paper examines an artist-led tour program initiated by the Los Angeles County Metropolitan Transportation Authority (Metro), as a case study, to demonstrate one way contemporary artistic practices are strategically implemented to further community engagement, by extending the reach of existing, integrated artworks during a capital project’s operational phase. The study begins with a context for public art in transportation environments, including a brief overview of the tradition of government support for public art in the United States. Artworks integrated within the Metro system are examined with a focus on features that engage customers as landmarks, inspire responses from participants rooted in the memory of historical events or popular culture, and respond to pre-programmed cues. Lastly, this research discusses the transformational value offered by contemporary artistic practices rooted in relational aesthetics, approaches that prioritize transitory experience over material product, by providing continued engagement with communities beyond the planning and construction phases, as examined through an artist-led tour program developed by Metro.
During the SELENE (Kaguya) mission the dual‐spacecraft radio occultation technique was used to investigate the electron population in the vicinity of the lunar surface. One pair of coherent S‐band ...radio signals from one spacecraft was used to probe the possible electron density enhancement near the Moon, and another signal pair from the other spacecraft measured the solar wind and the terrestrial ionosphere plasma fluctuations, which also exist in the measurement by the former signal pair. The results suggest that any stable ionosphere with densities comparable to the ones observed by the Soviet Luna 19 and 22 missions does not exist near the terminator at high latitudes, although the occurrence of temporal or localized density enhancements cannot be ruled out.
Key Points
We measured the electron density around the moon by the dual‐spacecraft method
Dual‐spacecraft technique can remove the effects of the earth ionosphere
Lunar ionosphere can appear temporally, which is associated with the lunar dust
Radio occultation observations of the solar corona at solar offset distances of 12.8–36.9 RS were performed from December of 2000 to January of 2001, using the Nozomi spacecraft (Planet-B) of Japan. ...Phase scintillation spectra up to the frequency of ~10 Hz were obtained in two-way mode with S-band uplink and X-band downlink. The spectra cannot be represented by a single power law especially for small offset distances. That is, at low frequencies (large scales) the spectra show slopes indicative of Kolmogorov, a local flattening occurs from ~0.5 Hz (scale ~600 km) to ~3 Hz (~100 km), and a steepening occurs again at higher frequencies. This three-component nature of the spectrum was observed with a single method for the first time, although the spectral shape is variable and the three-component feature is not always evident.
The space orbiting radio telescope, HALCA, was placed into highly elliptical earth orbit on February 12, 1997. A master oscillator on board is phase locked to a reference signal generated by a ...hydrogen maser frequency standard in a ground tracking station. The frequency and the phase of the satellite oscillator are monitored in the ground tracking station. This paper provides a brief summary of the phase transfer link and gives the stability of the phase transfer link before and after the launch. Also this paper gives the discussions on the atmospheric phase fluctuations and the statistical property.
The SELENE Project of Japan includes three spacecraft: a main orbiting satellite and two subsatellites. Among many scientific objectives of the Project is the exploration of plasma formations above ...the lunar surface. The thin plasma layer above the area of the Moon, presented to the Sun, was first detected in radio occultation experiments conducted during 1972 with the Soviet lunar satellite “Luna-19”. The SELENE Project radio science experiment will be realized by means of a dual S- and X- band transmitter installed onboard the orbiter and Earth based antennas. The effect of the thin plasma layer near the Luna can be hidden by the fluctuations of the total electron content of the Earth's ionosphere. Dual spacecraft occultation configurations can remove partially the influence of the Earth's ionosphere. Several dual spacecraft configurations are discussed and upper error limits of total electron content measurements are estimated.