1,808 research outputs found

    Synthesis and evaluation of cerebroprotective activity of novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives containing residues of amino acids and dipeptides

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    Neurodegenerative processes of the central nervous system are an important socially significant problem of modern society. They cause many diseases, such as Alzheimer's disease and cerebral ischemia, which significantly reduce the quality of human life and can lead to disability or death. The aim of this study was to synthesize novel 6,7-dimethoxyquinazolin-4(3H)-one derivatives with the remains of neuroactive amino acids and dipeptides in order to investigate their cerebroprotective properties. As a result of the study, 13 novel 6,7-dimetho-xyquinazolin-4(3H)-one derivatives were synthesized. Cerebral ischemia in rats was reproduced by irreversible right-sided occlusion of the middle cerebral artery using the Tamura method, and the area of brain necrosis was evaluated. Cognitive functions were evaluated in the Y-maze test. Among the studied quinazolinone derivatives, compounds 3i, 3j and 3k have the most pronounced cerebrotropic activity, which is not inferior to ethylmethylhydroxypyridine succinate in terms of pharmacological activity, making them promising objects for further research

    Synthesis, in vitro and docking studies of 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one derivatives as agents for the treatment of Alzheimer's disease

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    Alzheimer's disease is a chronic neurodegenerative disease, which is characterized mainly by a progressive decrease in intellectual abilities, memory impairment and a change in a person's personality. Unfortunately, there are practically no medicines that act on pathogenesis of Alzheimer's disease. The development of new highly effective medicines for the treatment of this pathology is an actual area of pharmaceutical research. The aim of this work is to search among 2-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine-4(3H)-one effective compounds with an anticholinesterase and an antiamyloid activities. As a result, it was found that compounds 4d, 4e and 4f have the high anticholinesterase ability, which in their structure contain residues of hydroxy-methoxyphenyl fragments. Structures 4c, 4g, 4h, 4j, 4k, 4m, 4n and 4p showed slightly less activity, the effect of which did not differ statistically from that of Donepezil. Compounds 4c, 4e, 4k and 4m have the greatest ability to inhibit the formation of the amyloid, comparable to GV-971. It should be noted that the molecular docking data are consistent with the results of the determination of the anticholinesterase activity of the studied compounds obtained in vitro. Thus, the prospects for future studies of these compounds in the possibility of creating a pharmaceutical active substance for the treatment of neurodegenerative diseases have been revealed

    Mathematical Model of Forest Fire Soil-thrower Movement

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    The design of a forest fire soil-thrower made to prevent and eliminate ground forest fires is presented. A mathematical model of machine movement has been developed, which enables to study the laws of the interaction process of the design with the soil. It is accepted that the machine has two degrees of freedom. The mathematical model has been obtained using the Lagrange equations of the second kind. The design and technological parameters of the forest fire soil-throwing machine, affecting the efficiency of its work, including mass and width of the grip of the ripper casing, mass, radius and frequency of rotation of the milling tool, the number and geometric parameters of the blades are taken into account. Mathematical model enables to determine the effect of these parameters on the characteristics of the movement of ripper casing and milling working body. A mathematical model is needed to synchronize the translational motion of the unit and the rotational motion of the rotor. Formulas have been obtained for the steady motion of the forest fire soil-thrower, that determine the hauling power of tractor and torque that ensures the operation of milling tools

    Fast general two- and three-body interatomic potential

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    We introduce a new class of machine learning interatomic potentials - fast General Two- and Three-body Potential (GTTP) which are as fast as conventional empirical potentials and require computational time that remains constant with increasing fitting flexibility. GTTP does not contain any assumptions about functional form of two- and three-body interactions. These interactions can be modeled arbitrarily accurately potentially by thousands of parameters not affecting resulting computational cost. Time complexity is O(1) per every considered pair or triple of atoms. The fitting procedure is reduced to simple linear regression on ab initio calculated energies and forces and leads to effective two- and three-body potential which reproduces quantum many-body interactions as accurately as possible. Our potential can be made continuously differentiable any number of times at the expense of increased computational time. We made a number of performance tests on one-, two- and three-component systems. Flexibility of the introduced approach makes the potential transferable in terms of size and type of atomic systems. We show, that trained on randomly generated structures with just 8 atoms in the unit cell, it significantly outperforms common empirical interatomic potentials in the study of large systems, such as grain boundaries in polycrystalline materials.Comment: Removing Timofey Frolov from the co-authors due to the policy of the Lawrence Livermore National Laboratory (his place of work

    Towards an advanced observation system for the marine Arctic in the framework of the Pan-Eurasian Experiment (PEEX)

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    The Arctic marine climate system is changing rapidly, which is seen in the warming of the ocean and atmosphere, decline of sea ice cover, increase in river discharge, acidification of the ocean, and changes in marine ecosystems. Socio-economic activities in the coastal and marine Arctic are simultaneously changing. This calls for the establishment of a marine Arctic component of the Pan-Eurasian Experiment (MA-PEEX). There is a need for more in situ observations on the marine atmosphere, sea ice, and ocean, but increasing the amount of such observations is a pronounced technological and logistical challenge. The SMEAR (Station for Measuring Ecosystem-Atmosphere Relations) concept can be applied in coastal and archipelago stations, but in the Arctic Ocean it will probably be more cost-effective to further develop a strongly distributed marine observation network based on autonomous buoys, moorings, autonomous underwater vehicles (AUVs), and unmanned aerial vehicles (UAVs). These have to be supported by research vessel and aircraft campaigns, as well as various coastal observations, including community-based ones. Major manned drift-ing stations may occasionally be comparable to terrestrial SMEAR flagship stations. To best utilize the observations, atmosphere-ocean reanalyses need to be further developed. To well integrate MA-PEEX with the existing terrestrialatmospheric PEEX, focus is needed on the river discharge and associated fluxes, coastal processes, and atmospheric transports in and out of the marine Arctic. More observations and research are also needed on the specific socioeconomic challenges and opportunities in the marine and coastal Arctic, and on their interaction with changes in the climate and environmental system. MA-PEEX will promote international collaboration; sustainable marine meteorological, sea ice, and oceanographic observations; advanced data management; and multidisciplinary research on the marine Arctic and its interaction with the Eurasian continent.Peer reviewe

    Overview: Recent advances in the understanding of the northern Eurasian environments and of the urban air quality in China – a Pan-Eurasian Experiment (PEEX) programme perspective

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    The Pan-Eurasian Experiment (PEEX) Science Plan, released in 2015, addressed a need for a holistic system understanding and outlined the most urgent research needs for the rapidly changing Arctic-boreal region. Air quality in China, together with the long-range transport of atmospheric pollutants, was also indicated as one of the most crucial topics of the research agenda. These two geographical regions, the northern Eurasian Arctic-boreal region and China, especially the megacities in China, were identified as a "PEEX region". It is also important to recognize that the PEEX geographical region is an area where science-based policy actions would have significant impacts on the global climate. This paper summarizes results obtained during the last 5 years in the northern Eurasian region, together with recent observations of the air quality in the urban environments in China, in the context of the PEEX programme. The main regions of interest are the Russian Arctic, northern Eurasian boreal forests (Siberia) and peatlands, and the megacities in China. We frame our analysis against research themes introduced in the PEEX Science Plan in 2015. We summarize recent progress towards an enhanced holistic understanding of the land-atmosphere-ocean systems feedbacks. We conclude that although the scientific knowledge in these regions has increased, the new results are in many cases insufficient, and there are still gaps in our understanding of large-scale climate-Earth surface interactions and feedbacks. This arises from limitations in research infrastructures, especially the lack of coordinated, continuous and comprehensive in situ observations of the study region as well as integrative data analyses, hindering a comprehensive system analysis. The fast-changing environment and ecosystem changes driven by climate change, socio-economic activities like the China Silk Road Initiative, and the global trends like urbanization further complicate such analyses. We recognize new topics with an increasing importance in the near future, especially "the enhancing biological sequestration capacity of greenhouse gases into forests and soils to mitigate climate change" and the "socio-economic development to tackle air quality issues".Peer reviewe

    Design, Performance, and Calibration of the CMS Hadron-Outer Calorimeter

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    The CMS hadron calorimeter is a sampling calorimeter with brass absorber and plastic scintillator tiles with wavelength shifting fibres for carrying the light to the readout device. The barrel hadron calorimeter is complemented with an outer calorimeter to ensure high energy shower containment in the calorimeter. Fabrication, testing and calibration of the outer hadron calorimeter are carried out keeping in mind its importance in the energy measurement of jets in view of linearity and resolution. It will provide a net improvement in missing \et measurements at LHC energies. The outer hadron calorimeter will also be used for the muon trigger in coincidence with other muon chambers in CMS

    Identification of heavy-flavour jets with the CMS detector in pp collisions at 13 TeV

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    Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated tt\mathrm{t}\overline{\mathrm{t}} events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The heavy-flavour jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV)