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Abstract Understanding the impact of the relativistic motion of a chiral molecule on its optical response is a prime challenge for fundamental science, but it also has a direct practical relevance in our search for extraterrestrial life. To contribute to these significant developments, we describe a multi–scale computational framework that combines quantum chemistry calculations and full–wave optical simulations to predict the chiral optical response from molecules moving at relativistic speeds. Specifically, the effect of a relativistic motion on the transmission circular dichroism (TCD) of three life–essential biomolecules, namely, B–DNA, chlorophyll a, and chlorophyll b, is investigated. Inspired by previous experiments to detect interstellar chiral molecules, we assume that the molecules move between a stationary observer and a light source, and we study the rotationally averaged TCD as a function of the speed of the molecule.We find that the TCD spectrum that contains the signatures of the molecules shifts with increasing speed to shorter wavelengths, with the effects already being visible for moderate velocities.

The average speed and density of road transport are used as indicators of the congestion situation, but do not allow tracking the evolution (stages of formatting, progressing, and vanishing) of traffic congestion. The authors proposed and justified a quantitative indicator of traffic congestion, which allows in an automated mode to identify the congestion situation on the urban road network using hardware and software video recording systems. The purpose of this study is due to the need to study the quantitative characteristics of the proposed indicator at characteristic intersections of urban roads, which will allow us to develop scientifically based recommendations for predicting congestion situations, substantiating, and making optimal decisions on measures to promptly eliminate traffic congestion. The object of study is the traffic flow at three types of intersections of the Perm city road network, equipped with a photo and video recording software and hardware complex. The subject of the study is the regularities of the evolution of the listed deterministic indicators of traffic flows, which can be used for operational forecasting of the formation, development, and elimination of traffic congestion. The theoretical and methodological approach is based on the methods of mathematical statistics used to process the results of observations of traffic flows at different types of intersections using a «sliding window», calculating the average daily value and standard deviation. The initial data were obtained with the help of hardware and software complexes for fixing violations of traffic rules installed on the street and road network of the Perm city. As a result of the study, the rational parameters of the «sliding window» were determined, ensuring the structuring of the traffic congestion indicator; the facts of the congestion situations formation were revealed; the features of the congestion evolution and the presence of problematic traffic directions for which it is advisable to change the traffic light regulation mode were determined. The theoretical and practical significance of the work consists in checking the operability of the proposed indicator and criterion of traffic congestion, which is of practical interest from the point of view of predicting anomalies in the movement of vehicles on the road network, adjusting the operating modes of traffic lights, etc. It is also possible to use the proposed traffic congestion indicator to assess the effectiveness of traffic light regulation on the Perm city road network. The direction of further research is to study the patterns of traffic congestion at intersections of the urban road network, of various types that are not included in this study.

Cardiogenic shock (CS) is a time-sensitive and hemodynamically complex syndrome with a broad spectrum of etiologies and clinical presentations. Despite contemporary therapies, CS continues to maintain high morbidity and mortality ranging from 35 to 50%. More recently, burgeoning observational research in this field aimed at enhancing the early recognition and characterization of the shock state through standardized team-based protocols, comprehensive hemodynamic profiling, and tailored and selective utilization of temporary mechanical circulatory support devices has been associated with improved outcomes. In this narrative review, we discuss the pathophysiology of CS, novel phenotypes, evolving definitions and staging systems, currently available pharmacologic and device-based therapies, standardized, team-based management protocols, and regionalized systems-of-care aimed at improving shock outcomes. We also explore opportunities for fertile investigation through randomized and non-randomized studies to address the prevailing knowledge gaps that will be critical to improving long-term outcomes.

The relevance of the present paper is justified by the need to search for a scientifically based criterion for the formation, development and elimination of traffic congestion using modern highly efficient mathematical methods of information processing. It seems necessary to study the results of using the rescaled range, statistical, fractal, harmonic, and wavelet analysis of time series formed by the time (duration) of the movement of cars in a stream along a road section in the absence and presence of traffic congestion. The object of study is a section of the road network equipped with a software and hardware complex that allows measuring the characteristics of any car in the flow of transport. The subject of the study is the patterns of changes in the duration of movement of individual cars in the absence and presence of a congestion situation. The purpose of this study is a quantitative indicator of the formation, evolution, and elimination of traffic congestion. The basis of the theoretical and methodological approach is the use of modern highly efficient mathematical methods for processing information about traffic flows received from stationary complexes of photo and video recording of traffic violations. As a result of the study of time series, decompositions of the analyzed time series by harmonics and wavelets are constructed, statistical and fractal characteristics of the time series under consideration are determined. The analysis of the obtained results is carried out, the features of the obtained dependencies are revealed. The theoretical and practical significance of the work lies in the scientific substantiation of the quantitative characteristics of traffic congestion, which is of practical interest from the point of view of predicting anomalies in the movement of vehicles on the road network, making decisions on managing the operation of traffic lights, etc. The direction of further research is an in-depth analysis of the identified indicator and determination on its basis of a criterion for determining the stages of formation, evolution, and elimination of traffic congestion at intersections of the street and road network of a large industrial city.

CYP2C and CYP3A cytochromes are induced by a variety of compounds and affect the pharmacokinetics and pharmacodynamics of a large number of drugs. Currently, the possibility of using copper coordination compounds in antitumor therapy is being actively studied. Evaluation of potential interactions between new molecules and P450 cytochromes is necessary at an early stage of drug design.The aim. To study the modulating effect of Cu(II) complexes with enamine and tetrazole derivatives on CYP2C9, CYP2C19 and CYP3A4 and their cytotoxic and antiproliferative properties on normal human lung fibroblasts MRC-5 and a 3D model of hepatocellular carcinoma HepG2.Materials and methods. Cytotoxic and antiproliferative activities of copper(II) complexes – [CuL2] (1), [Cu2(bipy)2(PT)4] (2), [Cu2(phen)2(PT)4] (3), {[Cu(phen)(MT)2]∙H2O}n (4) (L – anion of 2-anilinomethylidene-5,5-dimethylcyclohexane-1,3-dione; PT – 5-phenyltetrazolate anion; MT – 5-methyltetrazolate anion; bipy – 2,2’-bipyridine; phen – 1,10-phenanthroline) – were examined in 2D and 3D models using fluorescence-based phenotypic screening. The modulating effect on CYP2C9, CYP2C19 and CYP3A4 was studied using fluorescence-based targeted screening. The results of CYP3A4 expression were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR).Results. Complex (1) increases the CYP3A4 expression and does not affect CYP2C9 and CYP2C19 expression. Complex (2) has no modulating effect on CYP2C and CYP3A. Complexes with 1,10-phenatrolin (3) and (4) induce CYP3A4, inhibit CYP2C9 and do not affect CYP2C19 expression. All compounds have a dose-dependent cytotoxic effect on HepG2 and MRC-5: the compound with 5-methyltetrazolate anion (4) has the same effect on cell lines, compounds with 5-phenyltetrazolate anion (2) and (3) have selective effect. Complexes with 1,10-phenatrolin are effective on both 2D and 3D models.Conclusion. The [Cu2(phen)2(FT)4] complex (3) can be used as a basis for creating an antitumor compound, but further modification of the structure is required to increase the selectivity to tumor cells.

The relevance of the work is the specific properties of the wavelet analysis, which make it possible to identify not only the amplitude-scale (frequency) characteristics of the time series under consideration, but also the evolution of these characteristics during the observation time. As a result of the study, it is advisable to identify those indicators of the intensity of traffic flow that may turn out to be indicators of possible problematic situations (congestion, traffic accidents, etc.). It is advisable to use them in the future when regulating and controlling traffic on the basis of processing information about traffic flows that comes from stationary video recording complexes of traffic violations. The object of study is a road with intensive one-way traffic, equipped with a software and hardware complex that allows measuring the characteristics of the flow of motor transport. The subject of the study is the daily intensity of the flow of cars. The purpose of this study is to identify patterns in the indicators evolution obtained using wavelet analysis as a result of processing of the time series of the car traffic intensity on the road network. As a theoretical and methodological approach, the wavelet transforms using the MHat wavelet, and the Morlet wavelet is used. The approach used by the authors allowed us to establish the correspondence of some characteristics obtained during the wavelet analysis with the evolution of the traffic flow intensity function during the daily observation time, which is the scientific novelty of the study. The wavelet analysis of the data of the video surveillance software and hardware complexes obtained during the day allowed us to construct time dependences of amplitude-scale (frequency) indicators of the car traffic intensity on the road connecting the central and rear areas of the city of Perm. As a result of the study of time series, experimental three-dimensional distributions of wavelet images, scalograms, skeletons and scalegrams of the function of the daily intensity of the traffic flow were obtained. An explanation of the characteristic features of the obtained dependencies and their relationship with the initial function of the traffic flow intensity is proposed. The practical significance lies in obtaining amplitude-scale (frequency) characteristics as a result of wavelet analysis of the traffic intensity using MHat and Morlet wavelets, which is of practical interest from the point of view of predicting the movement of vehicles, controlling the operation of traffic lights, monitoring the operation of equipment, etc. The direction of further research is to obtain, process, analyze and generalize the results of performing amplitude-scale wavelet analysis for time series of traffic flow intensity on parts of the road network with different vehicle traffic intensity.

The relevance of the work is due to the predictive properties of the Hurst indicator (index), which make it possible to identify the presence/absence of a trend in the observed stochastic process, which it is advisable to use when regulating and controlling traffic to reduce congestion, traffic accidents based on processing information about traffic flows coming from stationary video recording complexes of traffic violations. The object of investigation is a section of road with intensive one-way traffic, equipped with a software and hardware complex that allows measuring the characteristics of the flow of motor transport. The subject of the study is the daily intensity of the cars flow during the week, from Monday to Sunday. The purpose of this study is to identify the patterns of evolution of the indicators included in the Hurst index, based on the processing of time series of the intensity of motor transport traffic on the road network. As a theoretical and methodological approach, the rescaled range analysis, or the definition of Hurst exponent, is used. The approach developed by the authors allowed us to establish the regularities of the evolution of mean values, standard deviations, accumulated and rescaled range, Hearst exponents, which is the scientific novelty of the performed analysis. Data processing of video surveillance software and hardware complexes made it possible to construct time-dependent indicators of the intensity of car traffic on a road with a consistently high flow of vehicles connecting the central and remote areas of the city of Perm, at various intervals of averaging by days of the week. As a result of the study of time series, dependences on the time of average values, standard deviations, accumulated and rescaled ranges, Hearst exponents were obtained. It is shown that the found characteristics of the traffic flow intensity on a road with a high traffic intensity differ significantly from similar characteristics obtained earlier for roads with a relatively low intensity. The practical significance lies in the use of predictive properties of the Hurst indicator in analyzing the intensity of the flow of vehicles for predicting the movement of vehicles, controlling the operation of traffic lights, monitoring the operation of equipment, etc. The direction of further research is to obtain, process and determine rescaled ranges and Hurst exponents for time series of traffic flow intensity on other sections of the road network.

We introduce a systematic way to obtain expressions for computing the amount of fundamental quantities such as helicity and angular momentum contained in static matter, given its charge and magnetization densities. The method is based on a scalar product that we put forward which is invariant under the ten-parameter conformal group in three-dimensional Euclidean space. This group is obtained as the static restriction (frequency ω=0) of the symmetry group of Maxwell equations: The fifteen-parameter conformal group in 3+1 Minkowski spacetime. In an exemplary application, we compute the helicity and angular momentum squared stored in a magnetic Hopfion.

The relevance of this work is determined by the need to find modern ways to process the information about traffic flows for regulating and controlling the movement of transport and pedestrians, to reduce congestion, road accidents, etc. The object of study is a part of road with heavy two-way traffic, equipped with a software and hardware complex that allows to measure the characteristics of the transport flow. The subject of the study is the daily intensity of the cars flow during the week, from Monday to Sunday. The purpose of this study is to analyze the amplitudes, frequencies, and periods of harmonic functions obtained by decomposing the time series of road traffic intensities to identify the main patterns of traffic flow formation. As a theoretical and methodological approach, the decomposition of the function of the traffic flow intensity in the Fourier series with respect to harmonic functions is used. The approach developed by the authors using the fast Fourier transform procedure made it possible to determine the amplitude-frequency characteristics of the time series under consideration, which is a scientific novelty of the analysis. It is proposed to use the «period-amplitude» characteristics as physically more meaningful instead of the «frequency-amplitude» dependencies traditionally used for the analysis. The processing of data obtained from software and hardware complexes allowed us to determine dependences of the car flow intensity on the road of the Perm city at different averaging intervals, to describe the features of the motor transport movement on the road under consideration. As a result of the study, the amplitude-frequency characteristics of time series are obtained. It is shown that the individual harmonics of the Fourier series expansion of the traffic flow intensity, which exhibits the properties of a random function, duplicate the periodicity of the global, local, and intermediate extremes of the original function and have similar periods. The practical significance consists in the use of the decomposition of the function of the traffic flow intensity in the Fourier series of harmonic functions for predicting traffic flows, controlling the operation of traffic lights, monitoring the operation of equipment, as well as in the reconstruction, design and construction of roads and road objects. The study will continue in the direction of obtaining, processing and determining the «period-amplitude» characteristics for time series of traffic flow intensity for other road networks.

The relevance of the manuscript is due to the need to process and analyze the information accumulated by the complexes of photo-video recording of traffic violations, which will further develop mathematical, computational and simulation models of road transport, solve problems of optimization and management of traffic flows, make management decisions to reduce the number of congestion and reduce the anthropogenic load on the environment. The object of the study is a part of a three-lane road with heavy one-way traffic, equipped with a software and technical complex that allows measuring the main characteristics of the traffic flow (vehicle speeds, including the average values on the controlled road part, driving time, etc.). The subject of the study is the traffic flow intensity during a 7-day time (from Monday to Sunday). The analysis of the obtained dependences allowed us to formulate a hypothesis about the presence of determin- istic and stochastic components in the traffic flow intensity, which is a random function of time, and the verification of which is the purpose of this study. Statistical processing of the obtained data is used as a theoretical and methodological approach, as well as the assumption that the traffic flow intensity can be represented by the sum of deterministic and stochastic components. The developed approach using the smoothing procedure allowed us to select both components, and this is a scientific novelty of the analysis performed. As a result of the study, it is shown that the deterministic component of the traffic flow intensity for working days is qualitatively different from the deterministic component for weekends. Statistical indicators of probabilistic distributions of traffic flow intensities and random components selected from them are determined. Estimates of the correspondence of the selected curves to the normal law of probability distribution are obtained using the Kolmogorov and Pearson criteria, which contradict each other. Practical significance consists in the use of a deterministic component for predicting traffic flows, controlling the operation of traffic lights, monitoring the operation of equipment, as well as in the reconstruction, design and construction of roads and road objects. The direction of further research is to obtain, statistically process and generalize data on the traffic flows intensity in other parts of the road network.

Atopic diseases remain one of the most common childhood diseases. At the beginning of life, atopic dermatitis (AD) occurs, and only then bronchial asthma (BA). This staged development of sensitization and transformation of clinical manifestations is called the atopic march. Are the genetic factors of predisposition to AD the same for BA? There is still no definite answer to this question. Mutations in the filaggrin gene (FLG) are known to impair skin barrier function. Filaggrin is expressed not only in the skin, but also in the respiratory organs of the nasal mucosa, lungs, and bronchi. Filaggrin defects lead not only to disruption of the skin barrier, but also to an increase in the Th2 response and increased production of IgE, typical of bronchial asthma. Therefore, mutations in the FLG gene can be a risk factor for the development of not only AD, but also BA.The aim of this study was to compare the values of the association of mutations in the FLG gene with AD and BA in the Russian sample.Material and methods. Case-control study design. We used 265 blood samples from children. 4 mutations in the filaggrin gene were identified by real-time PCR. The association of mutations with disease was assessed by odds ratio.Results. We showed a strongly pronounced association of the deletion of 4 nucleotides (2282del4) with AD, but not with BA, although for patients with atopic BA the indicator of the association of this mutation with the disease was higher than for the group with symptoms of bronchial asthma identified by the ISAAC questionnaire. These results lead to the conclusion that the role of the filaggrin gene for BA is much less significant than for AD.

Abstract This study was aimed at analyzing the relations of metastasis to regional lymph nodes (RLNs) with histopathological indicators of invasive breast carcinoma of no special type (IC-NST) and its cytokine profile. Enzyme-linked immunosorbent assays were performed to determine concentrations of IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1Ra, TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF-A, and MCP-1 in the culture supernatant of IC-NST samples from 48 female patients. Histopathological indicators (degree of tumor cell differentiation, mitoses, and others) and ER, PR, Her2/neu, Ki-67, and CD34 expression levels were determined. By means of three types of neural network models, it was shown that for different parameters of the output layer, different groups of parameters are involved that have predictive value regarding metastasis to RLNs. As a result of multi-dimensional cluster analysis, three clusters were formed with different cytokines profiles of IC-NST. Different correlations between indicators of cytokine production by IC-NST and its histopathological parameters were revealed in groups with different cytokine profiles. It was shown that at simultaneous evaluation of the production of even two cytokines, the importance of which relationship with metastasis was revealed by neural network modeling, can increase the probability of determining the presence of metastasis in the RLNs.

Background: Spontaneous heparin-induced thrombocytopenia is a pro-thrombotic syndrome in which anti-heparin antibodies develop without heparin exposure. Case presentation: A 78-year-old man who underwent a successful lumbar laminectomy presented to the hospital 5 days after discharge for stroke-like symptoms and was found to have acute infarcts of the bilateral frontal lobes. The patient was found to be severely thrombocytopenic and was incidentally found to have an inferior wall myocardial infarction. Further investigation led to the diagnosis of bilateral lower extremity deep vein thromboses. His overall clinical presentation prompted a detailed hematologic workup that indicated positivity for heparin-induced thrombocytopenia despite no previous exposure to heparin products. Conclusions: This case illustrates a patient with no prior lifetime heparin exposure who underwent laminectomy with subsequent development of acute infarcts of the bilateral frontal lobes, an inferior wall myocardial infarction, and bilateral lower extremity deep vein thromboses, with concern for sequelae of spontaneous heparin-induced thrombocytopenia.

Xanthine derivatives have been a great area of interest for the development of potent bioactive agents. Thirty-eight methylxanthine derivatives as acetylcholinesterase inhibitors (AChE) were designed and synthesized. Suzuki–Miyaura cross-coupling reactions of 8-chlorocaffeine with aryl(hetaryl)boronic acids, the CuAAC reaction of 8-ethynylcaffeine with several azides, and the copper(I) catalyzed one-pot three-component reaction (A3-coupling) of 8-ethynylcaffeine, 1-(prop-2-ynyl)-, or 7-(prop-2-ynyl)-dimethylxanthines with formaldehyde and secondary amines were the main approaches for the synthesis of substituted methylxanthine derivatives (yield 53–96%). The bioactivity of all new compounds was evaluated by Ellman’s method, and the results showed that most of the synthesized compounds displayed good and moderate acetylcholinesterase (AChE) inhibitory activities in vitro. The structure-activity relationships were also discussed. The data revealed that compounds 53, 59, 65, 66, and 69 exhibited the most potent inhibitory activity against AChE with IC50 of 0.25, 0.552, 0.089, 0.746, and 0.121 μM, respectively. The binding conformation and simultaneous interaction modes were further clarified by molecular docking studies.