Use of computers to exclude the influence of radiometer instability upon measurement results

A radiometer, practically insensitive to great fluctuations in the equipment amplification coefficient, was developed by dividing the useful signal by a reference signal and modulating the two signals at different frequencies. The signals are simultaneously separated by corresponding synchronous detectors and recorded over two channels. The operation is simplified by replacing the continuous signals by a sampling of discrete values, and using a digital computer. The four steps involved in the process are described and a block diagram is included. This technique not only directly connects the radiometer with the computer, but also records all data provided by the control and signal channels

УДОСКОНАЛЕННЯ ПОЛІТИКИ ФОРМУВАННЯ ТА ЕФЕКТИВНОГО ВИКОРИСТАННЯ ОБОРОТНИХ АКТИВІВ АГРАРНИХ ПІДПРИЄМСТВ

The theoretical preconditions and practical aspects of formation and efficient use of the current assets of the agricultural enterprises are considered in the article. It is established that the current practice of management of formation and use of the current assets in agriculture requires a substantial revision of the forms, methods, principles and tools of its implementation, ensuring a high level of profitability and financial stability. The composition and structure of the current assets of various branches of economy are analyzed. A sample survey of 362 large and medium-sized agricultural enterprises of Kharkiv region was carried out, the activity of which significantly affects the general indicators of the region as a whole.  In order to detect the influence of the share of the own current assets in the sources of their formation on the financial stability of its main indicators, the method of analytical grouping was applied. The tendency has been recorded according to which the tendency towards improvement of financial stability of the surveyed enterprises with increasing the share of the own current assets in the sources of formation is fixed. It is established that the complete abandonment of the borrowed and debt sources significantly reduces the indicators of maneuverability of equity and the own working capital, which requires optimization of the structure of their financing sources. The interrelation between the ratio of the current assets and fixed assets and the tendencies towards changing the efficiency of using the current assets of the agricultural enterprises of Kharkiv region in 2015 – 2016 depending on the depth of their specialization and the reduction of the turnover of the current assets with the growth of the share of the own current assets is investigated.The conceptual model of the policy of current assets management of an agricultural enterprise is proposed, which consists in the organic unity of the purposes, principles, methods, subsystems, and information provision of organizational and economic mechanism implementation to use the current assets effectively. It is substantiated that the proposed components of this mechanism are not exhaustive, and their implementation is not the last stage in the system of financial management of the agricultural enterprises, but only a part of the complex and multicomponent policy of current assets management.Рассмотрены теоретические предпосылки и практические аспекты формирования и эффективного использования оборотных активов аграрных предприятий. Установлено, что современная практика управления формированием и использованием оборотных активов в сельском хозяйстве требует существенного пересмотра форм, методов, принципов и инструментов его осуществления, обеспечивая высокий уровень рентабельности и финансовой устойчивости. Проанализированы состав и структура оборотных активов различных отраслей экономики. Проведено выборочное обследование деятельности 362 крупных и средних сельскохозяйственных предприятий Харьковской области, деятельность которых существенно влияет на общие показатели региона в целом. Для выявления влияния доли собственных оборотных средств в источниках их формирования на финансовую устойчивость по основным ее показателям применен метод аналитической группировки. Зафиксирована тенденция, при которой с увеличением доли собственных оборотных средств в источниках их формирования прослеживается тенденция к улучшению финансовой устойчивости обследованных предприятий. Установлено, что полный отказ от привлеченных и заемных источников значительно уменьшает показатели маневренности собственного капитала и собственных оборотных средств, что требует оптимизации структуры источников их финансирования. Исследована взаимосвязь между соотношением оборотных активов и основных средств и тенденциями эффективности использования оборотных средств аграрных предприятий Харьковской области за 2015—2016 гг. в зависимости от глубины их специализации. Доказано сокращение продолжительности оборота оборотных средств с ростом доли оборотных активов.Предложена концептуальная модель политики управления оборотными активами аграрного предприятия, которая заключается в органическом единстве целей, принципов, методов, подсистем, информационного обеспечения реализации организационно-экономического механизма эффективного использования оборотных активов. Обосновано, что предлагаемые составляющие этого механизма не исчерпывающие, а их реализация не является последним этапом в системе финансового менеджмента аграрных предприятий, а лишь частью сложной и многокомпонентной политики управления оборотными активами.Розглянуто теоретичні передумови і практичні аспекти формування й ефективного використання оборотних активів аграрних підприємств. Установлено, що сучасна практика управління формуванням і використанням оборотних активів у сільському господарстві потребує суттєвого перегляду форм, методів, принципів та інструментів його здійснення, забезпечуючи високий рівень рентабельності та фінансової стійкості. Проаналізовано склад і структуру оборотних активів різних галузей економіки. Проведено вибіркове обстеження  діяльності 362 великих і середніх сільськогосподарських підприємств Харківської області, діяльність яких суттєво впливає на загальні показники регіону в цілому. Для виявлення впливу частки власних оборотних засобів у джерелах їх формування на фінансову стійкість за основними її показниками застосовано метод аналітичного групування. Зафіксовано тенденцію, за якої зі збільшенням частки власних оборотних засобів у джерелах формування простежується тенденція до поліпшення фінансової стійкості обстежених підприємств. Установлено, що повна відмова від залучених і позикових джерел значно зменшує показники маневреності власного капіталу і власних оборотних коштів, що вимагає оптимізації структури джерел їх фінансування. Досліджено взаємозв`язок між співвідношенням оборотних активів та основних засобів і тенденціями до зміни ефективності використання оборотних засобів аграрних підприємств Харківської області за 2015–2016 рр. залежно від глибини  їх спеціалізації та доведено скорочення тривалості обороту оборотних засобів зі зростанням частки оборотних активів.Запропоновано концептуальну модель політики управління оборотними активами аграрного підприємства, яка полягає в органічній єдності цілей, принципів, методів, підсистем, інформаційного забезпечення реалізації організаційно-економічного механізму ефективного використання оборотних активів. Обґрунтовано, що пропоновані складові цього механізму не вичерпні, а їх реалізація не є останнім етапом у системі фінансового менеджменту аграрних підприємств, а лише частиною складної та багатокомпонентної політики управління оборотними активами

Revealing three-dimensional structure of individual colloidal crystal grain by coherent x-ray diffractive imaging

We present results of a coherent x-ray diffractive imaging experiment performed on a single colloidal crystal grain. The full three-dimensional (3D) reciprocal space map measured by an azimuthal rotational scan contained several orders of Bragg reflections together with the coherent interference signal between them. Applying the iterative phase retrieval approach, the 3D structure of the crystal grain was reconstructed and positions of individual colloidal particles were resolved. As a result, an exact stacking sequence of hexagonal close-packed layers including planar and linear defects were identified.Comment: 8 pages, 5 figure

Femtosecond x-ray diffraction from an aerosolized beam of protein nanocrystals

We demonstrate near-atomic-resolution Bragg diffraction from aerosolized single granulovirus crystals using an x-ray free-electron laser. The form of the aerosol injector is nearly identical to conventional liquid-microjet nozzles, but the x-ray-scattering background is reduced by several orders of magnitude by the use of helium carrier gas rather than liquid. This approach provides a route to study the weak diffuse or lattice-transform signal arising from small crystals. The high speed of the particles is particularly well suited to upcoming MHz-repetition-rate x-ray free-electron lasers

On the use of multilayer Laue lenses with X-ray Free Electron Lasers

Multilayer Laue lenses were used for the first time to focus x-rays from an X-ray Free Electron Laser (XFEL). In an experiment, which was performed at the European XFEL, we demonstrated focusing to a spot size of a few tens of nanometers. A series of runs in which the number of pulses per train was increased from 1 to 2, 3, 4, 5, 6, 7, 10, 20 and 30 pulses per train, all with a pulse separation of 3.55 us, was done using the same set of lenses. The increase in the number of pulses per train was accompanied with an increase of x-ray intensity (transmission) from 9% to 92% at 5 pulses per train, and then the transmission was reduced to 23.5 % when the pulses were increased further. The final working condition was 30 pulses per train and 23.5% transmission. Only at this condition we saw that the diffraction efficiency of the MLLs changed over the course of a pulse train, and this variation was reproducible from train to train. We present the procedure to align and characterize these lenses and discuss challenges working with the pulse trains from this unique x-ray source

Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser.

G-protein-coupled receptors (GPCRs) signal primarily through G proteins or arrestins. Arrestin binding to GPCRs blocks G protein interaction and redirects signalling to numerous G-protein-independent pathways. Here we report the crystal structure of a constitutively active form of human rhodopsin bound to a pre-activated form of the mouse visual arrestin, determined by serial femtosecond X-ray laser crystallography. Together with extensive biochemical and mutagenesis data, the structure reveals an overall architecture of the rhodopsin-arrestin assembly in which rhodopsin uses distinct structural elements, including transmembrane helix 7 and helix 8, to recruit arrestin. Correspondingly, arrestin adopts the pre-activated conformation, with a ∼20° rotation between the amino and carboxy domains, which opens up a cleft in arrestin to accommodate a short helix formed by the second intracellular loop of rhodopsin. This structure provides a basis for understanding GPCR-mediated arrestin-biased signalling and demonstrates the power of X-ray lasers for advancing the frontiers of structural biology

Femtosecond X-ray diffraction from an aerosolized beam of protein nanocrystals

High-resolution Bragg diffraction from aerosolized single granulovirus nanocrystals using an X-ray free-electron laser is demonstrated. The outer dimensions of the in-vacuum aerosol injector components are identical to conventional liquid-microjet nozzles used in serial diffraction experiments, which allows the injector to be utilized with standard mountings. As compared with liquid-jet injection, the X-ray scattering background is reduced by several orders of magnitude by the use of helium carrier gas rather than liquid. Such reduction is required for diffraction measurements of small macromolecular nanocrystals and single particles. High particle speeds are achieved, making the approach suitable for use at upcoming high-repetition-rate facilities.Use of the Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, is supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under contract No. DE-AC02-76SF00515. Parts of the sample delivery system used at LCLS for this research were funded by the NIH grant P41GM103393, formerly P41RR001209. In addition to DESY, this work has been supported by the excellence cluster ‘The Hamburg Center for Ultrafast Imaging – Structure, Dynamics and Control of Matter at the Atomic Scale’ of the Deutsche Forschungsgemeinschaft (CUI, DFG-EXC1074), the Gottfried Wilhelm Leibniz Program of the DFG, the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) through the Synergy Grant AXSIS (ERC-2013-SyG 609920) and the Consolidator Grant COMOTION (ERC-Ku¨pper-614507), the Helmholtz Association ‘Initiative and Networking Fund’, and the Australian Research Council’s Discovery Projects funding scheme (DP170100131). RAK acknowledges support from an NSF STC award (1231306)

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