ТЕКТОНОФИЗИЧЕСКИЕ ИССЛЕДОВАНИЯ АКТИВНОСТИ РАЗЛОМА ВЕРХОВОГО НА СЕВЕРНОМ СКЛОНЕ КИРГИЗСКОГО ХРЕБТА

An active fault was identified on the northern slope of the Kyrgyz ridge in the area near Research Scientific RAS in Bishkek. It belongs to a large system of crustal faults of the ridge. In our study, tectonophysical methods were used to analyse the regularities of the tectonic stress field reconstructed from seismological data on earthquake focal mechanisms. The stress distribution pattern near the investigated fault suggests its activity either in the recent past or at the present time. This conclusion is supported by the fact that at the eastern and western terminations of the fault, crustal stretching zones are located in a crosswise pattern. The Coulomb stresses on the fault surface were analysed, and the analysis results give grounds to state that its long section crossing the Alamedin river valley should be viewed as potentially hazardous. In the field, we observed abundant broken rock fragments and rock falls in the zone where the fault crosses the Alamedin and Aksu river valleys. It is known that rock falls have occurred more often in the last 3–5 years. The study results show slow movements along the fault. These strike-slip displacements have been going on for at least 10–15 years. According to the modern concepts of the preparation stage of an earthquake source, slow displacements along a fault gradually accelerate several years before an earthquake. Therefore, the studied fault (we named it Verkhovoi) should be considered a potentially hazardous zone wherein earthquakes can occur in future. A magnitude from 6.5 to 7.5 may be expected, depending on whether only the eastern part or the entire fault (i.e. 20 or 50 km, respectively) will be involved in a future seismic event. Further studies of the Verkhovoi fault are needed to clarify a trend in the development of slow sliding along the fault, which will allow understanding whether this process precedes dynamic rock failure (i.e. an earthquake) or tends to gradually decrease.Представлены результаты исследования активного разлома вблизи Научной станции РАН в г. Бишкеке. Выделение этого разлома из большой группы разломов для коры Киргизского хребта выполнено на основе тектонофизических методов анализа закономерности поля тектонических напряжений, полученного из сейсмологических данных о механизмах очагов землетрясений. Распределение напряжений вблизи исследованного безымянного разлома на северном склоне Киргизского хребта говорит о его активности либо в недавнем прошлом, либо в настоящее время. Этот вывод опирается на наличие в его восточном и западном окончании крестообразно расположенных секторов растяжения. Анализ кулоновых напряжений на поверхности разлома показал, что его протяженный участок, пересекающий долину р. Аламедин, следует рассматривать как потенциально опасный. Проведенные полевые геологические работы позволили установить, что в районе пересечения этим разломом долин Аламедин и Аксу происходит обильное образование каменных осыпей и вывалов, причем в последние 3–5 лет активность каменных вывалов возросла. На основе полученных данных мы предполагаем, что исследуемый разлом испытывает медленные движения (сдвиги по простиранию), которые продолжаются уже не менее 10–15 лет. Согласно современным представлениям о стадии подготовки очага землетрясения, за несколько лет до его реализации на разломе начинается медленное, постепенно ускоряющееся смещение, поэтому данный разлом следует рассматривать как потенциально опасный для будущего землетрясения. Ожидаемая магнитуда землетрясения от 6.5 до 7.5 и зависит от реализации восточной части или всего разлома протяженностью соответственно 20 и 50 км. Предполагается дальнейшее изучение этого разлома, названного нами «Верховой», с целью выяснения тенденции развития процесса медленного скольжения в динамический срыв – землетрясение или постепенное затухание скольжения

Catalytic cleavage of HEAT and subsequent covalent binding of the tetralone moiety by the SARS-CoV-2 main protease

Here we present the crystal structure of SARS-CoV-2 main protease (Mpro) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization of Mpro with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in the framework of a large X-ray crystallographic screening project of Mpro against a drug repurposing library, consisting of 5632 approved drugs or compounds in clinical phase trials. Further investigations showed that HEAT is cleaved by Mpro in an E1cB-like reaction mechanism into 2-methylene-1-tetralone and tyramine. The catalytic Cys145 subsequently binds covalently in a Michael addition to the methylene carbon atom of 2-methylene-1-tetralone. According to this postulated model HEAT is acting in a pro-drug-like fashion. It is metabolized by Mpro, followed by covalent binding of one metabolite to the active site. The structure of the covalent adduct elucidated in this study opens up a new path for developing non-peptidic inhibitors

X ray screening identifies active site and allosteric inhibitors of SARS CoV 2 main protease

The coronavirus disease COVID 19 caused by SARS CoV 2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID 19, we have performed a high throughput x ray crystallographic screen of two repurposing drug libraries against the SARS CoV 2 main protease Mpro , which is essential for viral replication. In contrast to commonly applied x ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS CoV

A 12 GHZ PULSE COMPRESSOR AND COMPONENTS FOR CLIC TEST STAND

Abstract The X-band power test stand needed for preprocessing and testing of key CLIC RF components is being installed in the test facility CTF3. The test stand includes several 12 GHz XL5 klystrons (50 MW, 1.5 μs) and a pulse compressor (PC) of the SLED-I type to obtain over 120 MW peak power at 230 ns pulse length. A compact compressor of this type based on TE 01 -TE 02 beating wave in high Q-factor compressor's cavities has been designed, produced, and tested at low power level. For testing accelerating structures and so-called "CLIC recirculation principle" of its operation several -3 dB couplers, tuneable phase shifters, and variable power attenuators were also produced and tested. DESIGN OF SLED-I PC In order to provide at 12 GHz an efficient compression of rf pulses with parameters P inp =50 MW, τ inp =1.5μs, aimed to obtain P out =120 MW, τ out =230 ns, it is proposed to use a compact SLED-I pulse compressor 5 ), because Q-factors of spurious modes in an oversized cavity could be comparable with that for operating mode. The compressor of such modified scheme consists of two identical cavities coupled by -3 dB couplers [2], each cavity is based on TE 01 -TE 02 beating wave waveguide which starts from single-mode TE 01 waveguide and finishes by a waveguide of a big enough radius which is necessary in order to provide the mentioned high Q-factors The beating wave (to provide deep modulation of surface field) consists of approximately 80% of the TE 01 mode and only 20% of the TE 02 mode. This mode mixture is produced sequentially by TE 10 -TE 01 "serpent-like" mode converter The cavities in each channel are based on ∅100 mm copper waveguides. Length of each cavity corresponds to 3 beating periods (~600 mm). The mentioned pumping port consists of a ring vacuum vessel which has a set of the 24 circular holes to pump a whole volume of the PC. The mentioned vessel is also partially filled by absorbers. Fine frequency tuning in each of two channels is organized by means of independent, electric, stepping motors which allowed also manual control