Ozone holds a certain fascination in atmospheric science. It is ubiquitous in the atmosphere, central to tropospheric oxidation chemistry, yet harmful to human and ecosystem health as well as being ...an important greenhouse gas. It is not emitted into the atmosphere but is a byproduct of the very oxidation chemistry it largely initiates. Much effort is focused on the reduction of surface levels of ozone owing to its health and vegetation impacts, but recent efforts to achieve reductions in exposure at a country scale have proved difficult to achieve owing to increases in background ozone at the zonal hemispheric scale. There is also a growing realisation that the role of ozone as a short-lived climate pollutant could be important in integrated air quality climate change mitigation. This review examines current understanding of the processes regulating tropospheric ozone at global to local scales from both measurements and models. It takes the view that knowledge across the scales is important for dealing with air quality and climate change in a synergistic manner. The review shows that there remain a number of clear challenges for ozone such as explaining surface trends, incorporating new chemical understanding, ozone-climate coupling, and a better assessment of impacts. There is a clear and present need to treat ozone across the range of scales, a transboundary issue, but with an emphasis on the hemispheric scales. New observational opportunities are offered both by satellites and small sensors that bridge the scales.
Discrete analogs of pseudo-differential operators and equations in discrete Sobolev–Slobodetsky spaces are considered. Using suitable discrete boundary conditions, we prove the unique solvability of ...the discrete boundary-value problem.
Motivation
Application of chemical named entity recognition (CNER) algorithms allows retrieval of information from texts about chemical compound identifiers and creates associations with ...physical–chemical properties and biological activities. Scientific texts represent low-formalized sources of information. Most methods aimed at CNER are based on machine learning approaches, including conditional random fields and deep neural networks. In general, most machine learning approaches require either vector or sparse word representation of texts. Chemical named entities (CNEs) constitute only a small fraction of the whole text, and the datasets used for training are highly imbalanced.
Methods and results
We propose a new method for extracting CNEs from texts based on the naïve Bayes classifier combined with specially developed filters. In contrast to the earlier developed CNER methods, our approach uses the representation of the data as a set of fragments of text (FoTs) with the subsequent preparati`on of a set of multi-
n
-grams (sequences from one to
n
symbols) for each FoT. Our approach may provide the recognition of novel CNEs. For CHEMDNER corpus, the values of the sensitivity (recall) was 0.95, precision was 0.74, specificity was 0.88, and balanced accuracy was 0.92 based on five-fold cross validation. We applied the developed algorithm to the extracted CNEs of potential Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) inhibitors. A set of CNEs corresponding to the chemical substances evaluated in the biochemical assays used for the discovery of Mpro inhibitors was retrieved. Manual analysis of the appropriate texts showed that CNEs of potential SARS-CoV-2 Mpro inhibitors were successfully identified by our method.
Conclusion
The obtained results show that the proposed method can be used for filtering out words that are not related to CNEs; therefore, it can be successfully applied to the extraction of CNEs for the purposes of cheminformatics and medicinal chemistry.
Calcineurin (CaN) is a serine/threonine phosphatase widely expressed in different cell types and structures including neurons and synapses. The most studied role of CaN is its involvement in the ...functioning of postsynaptic structures of central synapses. The role of CaN in the presynaptic structures of central and peripheral synapses is less understood, although it has generated a considerable interest and is a subject of a growing number of studies. The regulatory role of CaN in synaptic vesicle endocytosis in the synapse terminals is actively studied. In recent years, new targets of CaN have been identified and its role in the regulation of enzymes and neurotransmitter secretion in peripheral neuromuscular junctions has been revealed. CaN is the only phosphatase that requires calcium and calmodulin for activation. In this review, we present details of CaN molecular structure and give a detailed description of possible mechanisms of CaN activation involving calcium, enzymes, and endogenous and exogenous inhibitors. Known and newly discovered CaN targets at pre-and post-synaptic levels are described. CaN activity in synaptic structures is discussed in terms of functional involvement of this phosphatase in synaptic transmission and neurotransmitter release.
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The article presents an analysis of spatial trends in the development of public–private partnership (PPP) in Russia. The analysis is performed on a large base of PPP projects and reveals the main ...spatial imbalances and contradictions, uneven development of PPP across regions of the Russian Federation, and prevalence of small projects. It is emphasized that improving the institutional environment of territories is important for intensification of PPP processes. The current distribution of PPP investments across the Russian Federation indicates that the goals of improving the population’s quality of life prevail over the national-economic goal of strengthening connectivity of the country’s territory.
In connection with the growing spatial unevenness of socioeconomic development in Russia, empirical assessments of the activities of the public sector at the regional level are of scientific ...interest. Russia is a federal state in which all subjects have equal status; therefore, it is assumed that the state should strive to perform its functions equally throughout the country. A review of research into the activities of the public sector showed a lack of studies on its comprehensive assessment using Russian data at a regional level, which determined the aim of this study. The proposed assessment methodology is based on construction of a composite index of 74 indicators of socioeconomic development of regions for 2011–2020, in the formation of which the public sector plays a significant role. The PSP (Public Sector Performance) assessment methodology was modified by the authors by increasing the number of indicators considered and changing the standardization method, taking into account the characteristics of the data set. A procedure was also applied for assigning various weights to indicators through expert assessment of the state’s influence on them. A composite PSP index by region and subindices for eight blocks were calculated: Transport Infrastructure; Healthcare; Education, Science and Innovation; Sports and Culture; Social support; Safety; Ecology; and Economic Development. The Gini coefficient indicates low differentiation of PSP in Russian regions, although the leaders of the final ranking are Moscow and St. Petersburg by a significant margin. The gap behind the leaders is more pronounced in the first three blocks. Authorities can use the results to identify weaknesses of regions, and sectoral spatial gaps; to develop directions for correcting government programs; and to determine the pool of interregional interactions in order to transfer the best administrative cases, projects, and practices from leading regions in the corresponding areas.
Aim
During early post‐natal development, arterial contraction depends less on Ca2+‐signalling pathways but more on changes in Ca2+‐sensitivity compared to adult animals. Whether this difference is ...related to Rho‐kinase, one of the major players affecting Ca2+‐sensitivity, is unknown for intact vessels. Thus, we tested the hypothesis that Rho‐kinase critically contributes to the higher Ca2+‐sensitivity of contraction in intact arteries of 1‐week‐old rats.
Methods
We studied 1‐week‐old, 4‐ to 5‐week‐old and 10‐ to 12‐week‐old rats performing isometric myography, Ca2+‐fluorimetry and Western blotting using intact saphenous arteries and arterial pressure measurements under urethane anaesthesia.
Results
In 10‐ to 12‐week‐old rats, methoxamine (MX) produced vasoconstriction associated with an increase in Ca2+i and Ca2+‐sensitivity. In contrast, in 1‐week‐old rats these contractions were accompanied only by an increase in Ca2+‐sensitivity. All MX‐induced effects were reduced by the Rho‐kinase inhibitor Y‐27632; this reduction was complete only in 1‐week‐old rats. The Rho‐kinase specific site Thr855 on MYPT1 was increasingly phosphorylated by MX in vessels of 1‐week‐old, but not 10‐ to 12‐week‐old rats; this effect was also inhibited completely by Y‐27632. The Rho‐kinase inhibitor fasudil in a dose not affecting the pressor response to MX in 4‐ to 5‐week‐old rats reduced it considerably in 1‐week‐old rats.
Conclusion
Our results suggest that the higher Ca2+‐sensitivity of arterial contraction in 1‐week‐old compared to 10‐ to 12‐week‐old rats is due to a greater Rho‐kinase activity. Constitutively active Rho‐kinase contributes to MX‐induced contraction in 10‐ to 12‐week‐old rats. In 1‐week‐old rats, additional Rho‐kinase activation is involved. This remodelling of the Rho‐kinase pathway is associated with its increased contribution to adrenergic arterial pressure responses.
Reactive oxygen species (ROS) have been considered for many years as negative regulators in the cardiovascular system. Indeed, excessive production of ROS characterizes many cardiovascular diseases. ...The damaging effect of ROS can be especially pronounced in a newborn organism, since during this period their vasoconstrictor effect in pulmonary arteries remains as high as in pre-term fetus and the antioxidant systems have not yet formed. Therefore, in the first hours and days of independent life, pulmonary arteries tend to contract, primarily due to the low bioavailability of endothelial NO, which increases the risk of developing pulmonary hypertension in newborns. At the same time, during the perinatal period, ROS play an important role in the adaptive reactions of the circulatory system. ROS provide occlusion of the ductus arteriosus and separation of the pulmonary and systemic circulations soon after birth, and also contribute to the contraction of peripheral vessels during hypoxia, which often accompanies the delivery, and therefore provide priority blood supply to the brain in these conditions. The vasomotor effect of ROS is also pronounced in early postnatal ontogenesis, but it has a different character. In the first weeks of life, the action of ROS serves as one of the mechanisms for increasing endothelium-dependent relaxation of pulmonary vessels. In addition, during early postnatal ontogeny, ROS may play an important role in the regulation of systemic vascular tone. This review outlines the current understanding of the vasomotor role of ROS in the vessels of the pulmonary and systemic circulations and considers the mechanisms of ROS effects on the functioning of vascular endothelial and smooth muscle cells in the perinatal and early postnatal periods.
The activity of many physiological mechanisms depends on pH; therefore, maintaining a normal pH in the body is one of the important tasks of homeostatic regulation. Shifts in the acid–base balance ...can be associated with both pathological and physiological processes. Physiological acidosis in skeletal muscles appears due to physical exercise as muscle contractions may significantly reduce pH in muscle fibers and interstitium. However, after the cessation of contractions, the pH level rapidly normalizes, which is largely ensured by the work of the circulatory system, which removes metabolic products from the muscle. Acidosis causes vasodilatation by affecting the activities of numerous mechanisms in smooth muscle and endothelial cells and by inhibiting vasoconstrictor nerve influence. Vasodilation and increased muscle blood flow are favorable to recovery of the skeletal muscle performance following intense contractions.
We study some discrete boundary value problems for discrete elliptic pseudo-differential equations in a half-space. These statements are related with a special periodic factorization of an elliptic ...symbol and a number of boundary conditions depends on an index of periodic factorization. This approach was earlier used by authors for studying special types of discrete convolution equations. Here we consider more general equations and functional spaces.
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