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Polar Rashba-type semiconductor BiTeI doped with magnetic elements constitutes one of the most promising platforms for the future development of spintronics and quantum computing thanks to the combination of strong spin-orbit coupling and internal ferromagnetic ordering. The latter originates from magnetic impurities and is able to open an energy gap at the Kramers point (KP gap) of the Rashba bands. In the current work using angle-resolved photoemission spectroscopy (ARPES) we show that the KP gap depends non-monotonically on the doping level in case of V-doped BiTeI. We observe that the gap increases with V concentration until it reaches 3% and then starts to mitigate. Moreover, we find that the saturation magnetisation of samples under applied magnetic field studied by superconducting quantum interference device (SQUID) magnetometer has a similar behaviour with the doping level. Theoretical analysis shows that the non-monotonic behavior can be explained by the increase of antiferromagnetic coupled atoms of magnetic impurity above a certain doping level. This leads to the reduction of the total magnetic moment in the domains and thus to the mitigation of the KP gap as observed in the experiment. These findings provide further insight in the creation of internal magnetic ordering and consequent KP gap opening in magnetically-doped Rashba-type semiconductors.

This article studies the influence of the EDM process on the technological characteristics of the surface layer of the hard alloy of the processed hob cutter, and on the change in the hardness and roughness parameter of the treated surface.

We show that graphene can be magnetized by coupling to a ferromagnetic Co film through a Au monolayer. The presence of dislocation loops under graphene leads to a ferrimagnetic ordering of moments in the two C sublattices. It is shown that the band gap of ∼80 meV in the K[over ¯] point has a magnetic nature and exists for ferrimagnetic ordering. Interplay between Rashba and exchange couplings is evidenced by spin splitting asymmetry in spin-ARPES measurements and fully supported by DFT calculation of a (9×9) unit cell. Owing to sign-opposite Berry curvatures for K[over ¯] and K[over ¯]^{'} valleys, the synthesized system is promising for the realization of a circular dichroism Hall effect.

Introduction. The diagnosis and appointment of adequate therapy for both alcohol dependence syndrome and somatic pathology of alcoholic origin often depends on the timely establishment of the fact of alcohol abuse, for example, during periodic medical examinations, since most patients either deny the use of alcohol, or significantly underestimate its amount. The aim of the study is to develop a methodology for the objective identification of individuals with risk factors for harmful alcohol consumption that contribute to the development of pathological conditions and diseases that increase the likelihood of developing chronic non-communicable diseases. Materials and methods. Within the framework of the study, 204 people (162 men, 42 women) working in various types of economic activities, aged from 18 to 65 years, were surveyed. All patients were sent to the clinic FSBSI "Izmerov Research Institute of Occupational Health" to pre-or periodic inspections in the order of the health Ministry of Russia from 12.04.2011 No. 302n (ed. by 18.05.2020). All the examined patients underwent a biochemical blood test: carbohydrate deficient transferrin (CDT), gamma-glutamyltranspeptidase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT). Also, all the surveyed were conducted a questionnaire aimed at identifying alcoholism. Statistical processing of the obtained results was carried out using the program STATISTICA 13.2 (Stat Soft Inc., USA). Results. The study of the CDT content in the blood serum of the examined patients revealed an increase above the reference values in 10%, while 7% of the examined patients regularly consumed alcohol during the last 2 weeks (CDT≥2.5%), 3% - consumed moderately (CDT1,2-2,4%). The correlation analysis showed a moderate positive correlation between the results of the questionnaire and the CDT content in the blood serum (r=0.24, p=0.002 with the question about the use of 6 or more doses at a time and r=0.30, p=0.0001 with the total score). Conclusion. The most informative marker of chronic alcohol use is the definition of CDT in combination with a questionnaire aimed at identifying alcoholism. The use of these markers during periodic and preliminary medical examinations can allow a high degree of confidence to identify persons who are prone to chronic alcohol consumption in order to carry out preventive measures and prevent them from working with various sources of increased danger, including work related to the management of vehicles.

How does the thread-cutter configuration with respect to the workpiece axis in roughing affect the shape precision of the external trapezoidal thread and the margin in final grinding? That question is investigated in the present work. An algorithm is outlined for determining the transverse profile of the helical channel in the external trapezoidal thread at the inner, central, and outer diameters. The channel profile calculated from that algorithm determines the cutting-edge profile at the front surface of a cutter positioned perpendicularly to the part’s helical surface for preliminary machining.

A combined study of local structural, electric and ferroelectric properties of SrTiO $$_{3}$$ 3 /La $$_{0.7}$$ 0.7 Sr $$_{0.3}$$ 0.3 MnO $$_{3}$$ 3 /BaTiO $$_{3}$$ 3 heterostructures was performed by Piezoresponse Force Microscopy, tunneling Atomic Force Microscopy and Scanning Tunneling Microscopy in the temperature range 30–295 K. The direct correlation of film structure (epitaxial, nanocrystalline or polycrystalline) with local electric and ferroelectric properties was observed. For polycrystalline ferroelectric films the predominant polarization state is defined by the peculiarity of screening the built-in field by positively charged point defects. Based on Scanning Tunneling Spectroscopy results, it was found that a sequent voltage application provokes the modification of local resistive properties related to the redistribution of point defects in thin ferroelectric films. A qualitative analysis of acquired Piezoresponse Force Microscopy, tunneling Atomic Force Microscopy and Scanning Tunneling Microscopy images together with Scanning Tunneling Spectroscopy measurements enabled us to conclude that in the presence of structural defects the competing processes of electron injection, trap filling and the drift of positively charged point defects drives the change of resistive properties of thin films under applied electric field. In this paper, we propose a new approach based on Scanning Tunneling Microscopy/Spectroscopy under ultrahigh vacuum conditions to clarify the influence of point defects on local resistive properties of nanometer-thick ferroelectric films.

The proposed mathematical model permits shaping of worm mills for the machining of parts with helical surfaces. The model includes a module generating matrices for the spatial transformation of coordinate systems. An algorithm is presented for formulating a model of the worm-mill surface. Shaping is completed in one stage, without determining the profile of the conjugate helical rack.

In-plane heterostructures of hexagonal boron nitride (h-BN) and graphene (Gr) have recently appeared in the focus of material science research owing to their intriguing and tunable electronic properties. However, disclosure of the atomic structure and properties of one-dimensional heterojunctions between Gr and h-BN domains remains a largely unexplored and challenging task. Here, we report an approach to obtain a perfectly oriented and atomically thin hybrid h-BN–Gr heterolayer on the Co(0001) surface. A perfect matching of the lattice parameters ensures an epitaxial growth of both Gr and h-BN on the close-packed Co surface. High crystalline quality of the resulting interface allowed us to uncover the structural and electronic properties of the lateral h-BN/Gr heterojunctions by means of complementary microscopic and spectroscopic techniques. In particular, we established the coexistence of two types of zigzag boundaries made of B–C bonds, while the boundaries with N–C bonds were found to be unfavorable. ...

INTRODUCTION: Phenazepam is commonly administered to patients diagnosed with major depressive disorder. Some proportion of such patients do not show adequate response to treatment regimen containing phenazepam, whereas many of them experience type A adverse drug reactions. Previous studies showed that CYP2D6 IS involved in the biotransformation of phenazepam, the activity of which is highly dependent on the polymorphism of the gene encoding it. Objective. The objective of the study was to evaluate the impact of 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of phenazepam, using findings on enzymatic activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels in patients suffering from major depressive disorder. MATERIAL AND METHODS: The study enrolled 191 patients with recurrent depressive disorder (age −40.0 ± 16.3 years). Treatment regimen included phenazepam in an average daily dose of 6.0 ± 2.3 mg per day. Treatment efficacy was assessed using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels we performed the real-time polymerase chain reaction (PCR Real-time). The activity of CYP2D6 was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6M-THBC/pinoline). Therapeutic drug monitoring has been performed using HPLC-MS/MS. RESULTS: Our findings didn’t reveal the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 6.0 [4.0; 8.0] and (GA) 6.0 [5.0; 7.8], p > 0.999; the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 4.0] and (GA) 3.0 [3.0; 3.0], p > 0.999. We didn’t reveal a statistical significance for concentration/dose indicator of phenazepam in patients with different genotypes: (GG) 0.812 [0.558; 1.348] and (GA) 0.931 [0.630; 1.271], p = 0.645). Analysis of the results of the pharmacotranscriptomic part of the study didn’t show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 22.5 [16.9; 29.8], (GA) 22.7 [15.7; 31.5], p = 0.695. At the same time, correlation analysis didn’t reveal a statistically significant relationship between the phenazepam efficacy profile evaluated by changes in HAMA scale scores and the hsa-miR-370-3p plasma concentration: rs = −0.01, p = 0.866. Also, we didn’t reveal the correlation between the miRNA concentration and safety profile: rs = 0.07, p = 0.348. Also we did not reveal the relationship between the CYP2D6 enzymatic activity (as evaluated by 6M-THBC/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = −0.14, p = 0.056. At the same time, correlation analysis did not reveal a statistically significant relationship between the phenazepam concentration and the hsa-miR-370-3p plasma concentration: rs = −0.05, p = 0.468. CONCLUSION: The effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of phenazepam was not demonstrated in a group of 191 patients with recurrent depressive disorder. At the same time, hsa-miR-370-3p does not remain a promising biomarker for assessing the level of CYP2D6 expression, because it does not correlate with encoded isoenzyme activity.

Attention focuses on the production of the spherical front surface of a ball-end mill, close to the transition from the cylindrical section. Analysis of the possible interference of the grinding wheel and the mill permits recommendations for decreasing the errors. The shaping errors due to plane approximation of the curvilinear front surface are discussed.

The production of the rake surface in different sections of a grinding wheel is considered, with identification of the appropriate fitting parameter. The parameters of the cylindrical section in ball-end mills are plotted against the selected fitting parameter.

The shaping of the toroidal cutting section of end mills is considered. Methods are devised for selecting the positional parameters in shaping the helical rake surface on the toroidal section. Relations are established between the geometric parameters of the end mill in the toroidal section.

A numerical method is proposed for the shaping of tools used in machining complex surfaces with a periodical profile, including screw surfaces. A heuristic approach to Mathcad programming is adopted. The mathematical formulation includes a module generating spatial transformations of the coordinate systems in matrix form. On that basis, a numerical model of a hob profile is constructed. This approach permits single-stage shaping, without determining the profile of the associated helical gear.

The possibility of formation of ordered silicon structures, including silicene, on the graphite substrate surface has been studied. The effect of various conditions of depositing silicon atoms on a finite structure has also been studied. The data on the surface morphology has been obtained by atomic force microscopy, and the electronic structure has been studied by Auger electron spectroscopy.

Aims Valid measures to identify harmful alcohol use are important. Alcohol Use Disorders Identification Test (AUDIT) is a validated questionnaire used to self-report harmful drinking in several cultures and settings. Phosphatidylethanol 16:0/18:1 (PEth) is a direct alcohol biomarker measuring alcohol consumption levels. The aim of this study was to investigate how PEth levels correlate with AUDIT-QF and weekly grams of alcohol consumed among patients in two urban hospitals. In addition, we wanted to investigate the predictive value of PEth in identifying harmful alcohol use as defined by AUDIT-QF and weekly grams of alcohol cutoffs. Methods A cross-sectional study comprising acute medically ill patients with measurable PEth levels (≥0.030 μM) admitted to two urban hospitals in Oslo, Norway (N = 931) and Moscow, Russia (N = 953) was conducted using PEth concentrations in whole blood, sociodemographic data and AUDIT-QF questionnaires. Results PEth levels from patients with measurable PEth were found to be positively correlated with AUDIT-QF scores, with PEth cutpoints of 0.128 μM (Oslo) and 0.270 μM (Moscow) providing optimal discrimination for harmful alcohol use defined by AUDIT-QF (the difference between cities probably reflecting different national drinking patterns in QF). When converting AUDIT-QF into weekly grams of alcohol consumed, the predictive value of PEth improved, with optimal PEth cutpoints of 0.327 (Oslo) and 0.396 (Moscow) μM discriminating between harmful and non-harmful alcohol use as defined in grams (≥350 grams/week). Conclusions By using PEth levels and converting AUDIT-QF into weekly grams of alcohol it was possible to get an improved rapid and sensitive determination of harmful alcohol use among hospitalized patients., Short Summary: AUDIT-QF among acute medically ill patients was found to be positively correlated with the alcohol biomarker PEth, with improved predictive value of PEth when converting AUDIT-QF to weekly grams of alcohol. PEth may be used to discriminate harmful alcohol use in clinical settings.

A combined study of local structural, electric and ferroelectric properties of SrTiO$$_{3}$$ 3 /La$$_{0.7}$$ 0.7 Sr$$_{0.3}$$ 0.3 MnO$$_{3}$$ 3 /BaTiO$$_{3}$$ 3 heterostructures was performed by Piezoresponse Force Microscopy, tunneling Atomic Force Microscopy and Scanning Tunneling Microscopy in the temperature range 30–295 K. The direct correlation of film structure (epitaxial, nanocrystalline or polycrystalline) with local electric and ferroelectric properties was observed. For polycrystalline ferroelectric films the predominant polarization state is defined by the peculiarity of screening the built-in field by positively charged point defects. Based on Scanning Tunneling Spectroscopy results, it was found that a sequent voltage application provokes the modification of local resistive properties related to the redistribution of point defects in thin ferroelectric films. A qualitative analysis of acquired Piezoresponse Force Microscopy, tunneling Atomic Force Microscopy and Scanning Tunneling Microscopy images together with Scanning Tunneling Spectroscopy measurements enabled us to conclude that in the presence of structural defects the competing processes of electron injection, trap filling and the drift of positively charged point defects drives the change of resistive properties of thin films under applied electric field. In this paper, we propose a new approach based on Scanning Tunneling Microscopy/Spectroscopy under ultrahigh vacuum conditions to clarify the influence of point defects on local resistive properties of nanometer-thick ferroelectric films.

The helical groove, which has a complex shape in the radial section, strongly affects the performance of solid ceramic mills. The accuracy of shaping is strongly affected by the size of the grinding wheel and the kinematic parameters of its movement and rotation relative to the workpiece. Although it is possible to obtain the aforementioned properties using the existing methods, there does not exist a general approach the determination the acceptable ranges of the diameter of the grinding wheel and radius of curvature of its profiling section. In this paper we have analyzed the main features of the design of the profiling sections of grinding wheels, have formed a set of initial parameters that most efficiently implement the trajectory of the shaping movement, which in turn constitutes a new general method of shaping for the helical surfaces of ceramic cutters, have analyzed the character of rolling of a set of profiling sections on a helical surface, have derived new analytical relationships determining impacts of the grinding wheel design and parameters controlling the trajectory of the grinding wheel movement on the shape of the cutter profile in the axial section, and have demonstrated advantages of the developed general approach in designing a new ceramic mill. The new method of shaping allows to unambiguously realize movements of the grinding wheel on various machine layouts and to exclude the displacement of the shaping point by replacing rotation with displacement. Further development of this method will make it possible to replace five- coordinate machines with four-coordinate ones when manufacturing milling cutters with a helical surface that can significantly reduce the production costs.

Citalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681GA polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age-38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.

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ObjectivesThe use of psychoactive prescription medication is increasing in the general population. This is a cause for concern, particularly among the elderly, where physiological changes related to senescence increase the risk for adverse effects. While previous studies regarding psychoactive substance use have generally been population based, we sought to determine the frequency of such use among acutely hospitalised patients.SettingTwo emergency departments (EDs), one in Oslo and one in Moscow, admitting patients to Departments of Internal Medicine.Participants5583 patients aged ≥18 years participated, distributed evenly between genders and study locations. Patients unable to give informed consent were excluded. The study sites did not admit patients with surgical conditions and/or injuries.Primary and secondary outcomesThe presence of psychoactive substances was determined through blood analysis using liquid chromatography-mass spectrometry. Secondary outcomes comprised demographic data (including age, gender, employment and marital status), degree of psychological distress, concurrent alcohol use, and self-reported alcohol, psychoactive drug and illicit substance use.Results32.3% in Oslo and 12% in Moscow were positive for one or more psychoactive medicinal drugs (benzodiazepines, z-hypnotics, opioids or barbiturates). In Oslo, medicinal drug use was associated with being aged 61 to 70 years (OR 2.40, 95% CI 1.61 to 3.58) compared with 18 to 40 years, and psychological distress (OR 2.61, 95% CI 2.06 to 3.30). In Moscow, psychoactive medicinal drug use was also associated with psychological distress (OR 1.68, 95% CI 1.18 to 2.39), and was less common among patients aged 41 to 60 years (OR 0.62, 95% CI 0.43 to 0.88) than among patients aged 18 to 40 years.ConclusionA significant proportion of admitted patients used one or more psychoactive medicinal drugs, in particular benzodiazepines (Oslo and Moscow) and opiates (Oslo). We suggest formalised screening for inappropriate prescription drug use and increased adherence to clinical prescription guidelines.

A shaping method is proposed for cutting a trapezoidal thread on a spindle shaft. This method offers the possibility of using cutters with the same profile in cutting threads of different inclination, depending on the corresponding tolerances.

Results from experiments conducted for the parameter Residual Organic Solvents during the course of developing a draft regulation for the drug substance of the innovative pharmacological agent thrombaptanib are reported. The structure of the compound is given. Its pharmacological action is described. A list of potential residual organic solvents was compiled by analyzing the synthetic scheme and manufacturing technology. A separate part of the work describes in detail a developed GC-MS procedure for determining residual organic solvents. Validation results of the procedure for Specificity, Linearity, Accuracy, Precision, and Reproducibility are presented. The validation protocol for the procedure at the time of the studies followed domestic guides for validation that were written based on existing international documents because there was no existing GPM for validation in the current edition of the SP RF. A test sample of thrombaptanib was analyzed using the developed procedure for Residual Organic Solvents. The developed procedure was included in the Residual Organic Solvents section of the draft regulation.

Alprazolam is used in the treatment of patients with anxiety disorders comorbid with alcohol use disorder. Some proportion of these patients does not respond adequately to treatment with alprazolam, while many of them experience dose-dependent adverse drug reactions. Results of the previous studies have shown that CYP3A is involved in the biotransformation of alprazolam, the activity of which is dependent, inter alia, on the polymorphism of the encoding gene. Objective The objective of our study was to investigate the effect of 99366316G>A polymorphism of the CYP3A4 gene on the concentration/dose indicator of alprazolam in patients with anxiety disorders comorbid with alcohol use disorder, using findings on enzymatic activity of CYP3A (as evaluated by the 6-beta-hydroxy-cortisol/cortisol ratio measurement) and on CYP3A4 expression level obtained by measuring the miR-27b plasma concentration levels in patients with anxiety disorders comorbid with alcoholism. Material and methods Our study enrolled 105 patients with anxiety disorders comorbid with alcohol use disorder (age - 37.8±14.6 years). Therapy included alprazolam in an average daily dose of 5.6±2.4 mg per day. Treatment efficacy was evaluated using the psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels, we performed the real-time polymerase chain reaction. The activity of CYP3A was evaluated using the HPLC-MS/MS method by the content of the endogenous substrate of the given isoenzyme and its metabolite in urine (6- beta-hydroxy-cortisol/cortisol). Therapeutic drug monitoring (TDM) has been performed using HPLC-MS/MS. Results Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMA scores at the end of the treatment course): (GG) 3.0 [2.0; 5.0] and (GA) 4.0 [4.0; 5.0], p = 0.007; at the same time, the statistical significance in the safety profile was not obtained (the UKU scores): (GG) 3.0 [2.0; 3.8] and (GA) 3.0 [1.5; 4.0], p = 0.650. We revealed a statistical significance for concentration/dose indicator of alprazolam in patients with different genotypes: (GG) 1.583 [0.941; 2.301] and (GA) 2.888 [2.305; 4.394], p = 0.001). Analysis of the results of the pharmacotranscriptomic part of the study didn't show the statistically significant difference in the miR-27b plasma levels in patients with different genotypes: (GG) 25.6 [20.4; 28.8], (GA) 25.7 [19.7; 33.1], p = 0.423. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam efficacy profile evaluated by changes in HAMA scale scores and the miR-27b plasma concentration: rs = 0.20, p = 0.042. Also, we didn’t reveal the correlation between the miRNA concentration and safety profile: rs = 0.15, p = 0.127. In addition, we revealed the relationship between the CYP3A enzymatic activity (as evaluated by 6-beta-hydroxycortisol/ cortisol ratio measurement) and the miR-27b plasma concentration: rs = −0.27, p = 0.006. At the same time, correlation analysis revealed a statistically significant relationship between the alprazolam concentration and the miR-27b plasma concentration: rs = 0.28, p = 0.003. Conclusion The effect of genetic polymorphism of the CYP3A4 gene on the efficacy and safety profiles of alprazolam was demonstrated in a group of 105 patients with anxiety disorders comorbid with alcohol use disorder. At the same time, miR-27b remains a promising biomarker for assessing the level of CYP3A4 expression, because it correlates with the encoded isoenzyme's activity.

Introduction Tobacco smoking is a major preventable risk factor for noncommunicable diseases. The aim of this study was to investigate predictors of tobacco smoking among acute medically ill patients admitted to a Moscow hospital, and the association between smoking and alcohol use. Methods Patients admitted to the V. P. Demikhov hospital in Moscow from November 2016 through December 2017 were asked to participate in this study (inclusion criteria were acute medically ill patients aged ≥18 years). Sociodemographic data were collected, in addition to questionnaires on mental distress (Hopkins Symptom Checklist 5), alcohol use (Alcohol Use Disorder Identification Test 4, AUDIT-4) and smoking (Fagerström Test for Nicotine Dependence). Results A total of 3009 patients were recruited to the study. Using a binary logistic regression model adjusted for all variables, it was found that living without a partner resulted in a higher risk of smoking tobacco compared to being married or living with a partner (odds ratio, OR=1.60 for divorced, p=0.001; and OR=1.62 for single, p=0.002), and being economically non-active resulted in a higher risk compared to being economically active (OR=1.47; p=0.003). Harmful alcohol use (AUDIT-4 score ≥5 [for females] / 7 [for males]) resulted in a higher risk of smoking compared to those without harmful alcohol use (OR=4.04; p

This review is about the significance of the use of lipidomic analysis for identifying susceptibility to skin diseases., This review is about the significance of the use of lipidomic analysis for identifying susceptibility to skin diseases. Exactly this article describes the use of lipidomic analysis in different studies to detect abnormalities in the lipid composition of the skin to diagnose and prevent various dermatological diseases.

The paper presents the method of extension of the class of applicable radiofrequency signals by means of introduction of additional polarization modulation. The expressions describing the signals with complex modulation are presented. The method of formation and emission of this type of signals is given. The models of signals with complex modulation are given.

Introduction: Sertralineis commonly administered topatients with depressive disorders comorbid with alcohol use disroder. Some part of such patients do not respond adequately to treatment regimen containing sertraline, whereas many of them experience type A adverse drug reactions (type A ADRs). Previous studies have shown that CYP2D6 is involved in the metabolism of sertraline, the activity of which is considerablydependent on the polymorphism of the gene encoding it. Objective: The objective of the study was to investigate the impact of 1846G>A polymorphism of the CYP2D6 gene on the concentration/dose indicator of sertralinepatients diagnosed with depressive disorders comorbid with alcoholism, using findings on activity of CYP2D6 (as evaluated by the 6M-THBC/pinoline ratio measurement) and on CYP2D6 expression level obtained by measuring the hsa-miR-370-3p plasma concentration levels patients suffering from depressive disorders comorbid with alcoholism. Material and Methods: The study included 120 patients with depressive disorders comorbid with alcoholism (age - 40.5±14.7 years). Therapy included sertraline in an average daily dose of 88.8±35.6 mg per day. Treatment efficacy was assessed using the validated psychometric scales. Therapy safety was assessed using the UKU Side-Effect Rating Scale. For genotyping and estimation of the microRNA (miRNA) plasma levels we performed the real-time polymerase chain reaction (PCR Real-time). The activity of CYP2D6 was assessed with HPLC-MS/MS method by the content of the endogenous substrate of given isoenzyme and its metabolite in urine (6M-THBC/pinoline). Theraputic drug monitoring (TDM) has been performed using HPLC-MS/MS. Results: Our study revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 1.0 [1.0; 2.0] and (GA) 4.0 [3.0; 5.0], p < 0.001; at the same time, the statistical significance in the safety profile was obtained (the UKU scores): (GG) 3.0 [2.0; 3.0] and (GA) 3.0 [3.0; 3.0], p = 0.018. We didn't reveal a statistical significance for concentration/dose indicator of sertraline in patients with different genotypes: (GG) 0.749 [0.593; 1.277] and (GA) 1.030 [0.829; 1.257], p = 0.052). Analysis of the results of the pharmacotranscriptomic part of the study didn’t show the statistically significant difference in the hsa-miR-370-3p plasma levels in patients with different genotypes: (GG) 23.4 [16.3; 29.3], (GA) 26.1 [16.5; 28.9], p = 0.945. At the same time, correlation analysis didn't reveal a statistically significant relationship between the sertraline efficacy profile evaluated by changes in HAMD scale scores and the hsa-miR-370-3p plasma concentration: rs = -0.05, p = 0.592. Also, we didn't reveal the correlation between the miRNA concentration and safety profile: rs = 0.07, p = 0.421. Also we revealed the relationship between the CYP2D6 enzymatic activity (as evaluated by 6M-THBC/pinoline ratio measurement) and the hsa-miR-370-3p plasma concentration: rs = -0.25, p = 0.005. At the same time, correlation analysis revealed a statistically significant relationship between the sertraline concentration and the hsa-miR-370-3p plasma concentration: rs = 0.30, p < 0.001. Conclusion: Thus, the effect of genetic polymorphism of the CYP2D6 gene on the efficacy and safety profiles of sertraline was demonstrated in a group of 120 patients with depressive disorders comorbid with alcoholism. At the same time, hsa-miR-370-3p remains a promising biomarker for assessing the level of CYP2D6 expression, because it correlates with encoded isoenzyme activity. Funding Statement: This work was supported by the grant of the Russian Science Foundation (project No. 18- 75-10073). This work was financially supported by the project 16-15-00227 entitled “Fundamental research and exploratory research in priority areas of research” of the Russian Science Foundation. Declaration of Interests: The authors declare that there is no conflict of interest regarding the publication of this article. Ethics Approval Statement: The local ethical committee of the Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation approved the research (The protocol No. 6 from 5/16/2017).

Synthesis of a graphene monolayer atop Ni(111) film deposited on HOPG using method of “internal solid-state carbon source” due to low-temperature segregation of carbon atoms through Ni film from the Ni/HOPG interface was studied by core level and valence band photoelectron spectroscopy. The atomic structure and morphology were studied by STM. It was established that the synthesis of graphene occurs via a stage of transformation from the surface carbide phase (with stoichiometry Ni2C) as a result of the surface carbide decomposition. We consider that such transformation is a necessary stage of the graphene synthesis. We have shown that the method of “solid-state carbon source” indeed results in a graphene monolayer formation on top of Ni film. A graphene monolayer begins to form even under annealing at 180 °C. Formation of practically full graphene covering with well-ordered structure takes place even at temperature of 260–270 °C. The formed graphene is strongly coupled to the Ni substrate. STM images show formation of well-ordered atomic hexagonal surface structure characteristic for graphene monolayer. Intercalation of Au atoms leads to formation of the p(9 × 9) superstructure and blocks strong coupling. It testifies that the main part of the surface is covered by epitaxial graphene on Ni. Keywords: Graphene, Segregation, Synthesis, Carbide phase, Intercalation

The implementation of future graphene-based electronics is essentially restricted by the absence of a band gap in the electronic structure of graphene. Options of how to create a band gap in a reproducible and processing compatible manner are very limited at the moment. A promising approach for the graphene band gap engineering is to introduce a large-scale sublattice asymmetry. Using photoelectron diffraction and spectroscopy we have demonstrated a selective incorporation of boron impurities into only one of the two graphene sublattices. We have shown that in the well-oriented graphene on the Co(0001) surface the carbon atoms occupy two nonequivalent positions with respect to the Co lattice, namely top and hollow sites. Boron impurities embedded into the graphene lattice preferably occupy the hollow sites due to a site-specific interaction with the Co pattern. Our theoretical calculations predict that such boron-doped graphene possesses a band gap that can be precisely controlled by the dopant concentration. B-graphene with doping asymmetry is, thus, a novel material, which is worth considering as a good candidate for electronic applications.

Parameter specification in the trochoidal machining of a slot of constant width is considered. A formula is proposed for the displacement increment of the shaping circle as a function of the cutting depth.

In the present study we synthesized nano-thin epitaxial Pt x Gd alloys on Pt(111) single crystal surface covered with well-oriented graphene and investigated their electronic and atomic structure at different stages of synthesis. Low-energy electron diffraction, photoelectron spectroscopy and scanning tunneling microscopy data suggest that deposition of Gd on the graphene/Pt(111) system and its further intercalation at 1080 ° C lead to formation of nano-thin Pt 5 Gd alloy covered with a quasi-freestanding graphene. We demonstrate that atomically flat alloy surface is terminated by Pt atomic layer with “kagome” structure. Control of graphene doping through variation of the alloy stoichiometry may open up new opportunities in developing advanced electronics. Owing to a well-known catalytic activity of Pt 5 Gd alloy, our thin-film system is promising for low-cost production of catalysts in the near future.

Background Phosphatidylethanols (PEths) are specific, direct alcohol biomarkers that can be determined in human blood to distinguish between heavy and social drinking. PEth 16:0/18:1 is among the most predominant PEth homologues in human blood. The aim of the study was to develop a high throughput and sensitive UHPLC-MS/MS method for the determination of PEth 16:0/18:1 in whole blood. Methods Whole blood samples were prepared by 96-well supported liquid extraction (SLE). Extracted samples were analyzed for PEth 16:0/18:1 by reversed phase UHPLC-MS/MS. Results The developed UHPLC-MS/MS method was fully validated in whole blood with PEth 16:0/18:1-D5 as internal standard. Intermediate precision and intermediate accuracy were within ≤± 12% and ≤± 17%, respectively, at PEth 16:0/18:1 concentrations of 1.4-2112 ng/mL (2.0-3004 nmol/L). Limit of quantification (LOQ) was 1.7 ng/mL (2.4 nmol/L). Conclusion For the first time, 96-well SLE was used for preparation of a PEth homologue in biological samples. A mixture of tert-butyl methyl ether and 2-propanol (5:1, v:v) was chosen as organic eluent based on an evaluation of extraction recovery, purity of extracts, and evaporation time. The developed UHPLC-MS/MS method can be used for high throughput analyses and sensitive determinations of PEth 16:0/18:1 in whole blood.

The application of the screening techniques for the purpose of chemical toxicological and forensic chemical analysis has the objective to detect and identify the life-threatening substances within the shortest possible time period for distinguishing them from a large number of other chemical compounds amenable to the toxicological evaluation. Such methods acquire special importance for forensic chemical expertise in the cases of a negative result of the primary examination. The present article provides information about the history of development of the screening techniques.Использование скрининговых методов в химико-токсикологическом и судебно-химическом анализе преследует цель за минимальное время обнаружить или исключить из большого круга соединений, подлежащих токсикологическому исследованию, одно или несколько веществ. Таким методам придают 'судебно-химическое значение при отрицательном результате'. В статье представлена история развития скрининговых методов.

2-ethyl-6-methyl-3-hydroxypyridine (EMHP) succinate is the original antioxidant and antihypoxic drug commonly prescribed in Russia. The objective of this study was to develop a rapid, simple and sensitive high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method for EMHP quantitation in rat brain tissue with the use of a bead beating homogenizer. The comparison between two approaches to brain tissue preparation was performed, when spiking the blank brain tissue with EMHP reference standard and internal standard (IS) before and after homogenization step. Chromatographic separation was achieved using Zorbax Eclipse Plus C18 column (1.8 μm, 2.1 × 50 mm) and elution was performed with the mobile phase, consisting of 10 mM of ammonium formate aqueous solution with 0.1% formic acid as solvent A and 0.1% formic acid in methanol as solvent B [44%(А):56%(В), v/v]. Flow rate was 0.4 mL/min and the total run time for each sample analysis was 2.0 min. EMHP and amantadine, IS of this study, were analyzed in positive ionization mode. Ion transitions of m/z 138.0 → 123.0 for EMHP and m/z 152.0 → 135.0 for amantadine were selected in multiple reaction monitoring mode. The developed method for EMHP determination in rat brain samples was validated for selectivity, linearity, accuracy, precision, matrix effects, and stability. The lower and upper limits of quantification were determined to be 1 and 1500 ng/g, respectively. The developed and validated HPLC-MS/MS method was successfully applied to determine EMHP concentrations in rat brain tissue following the intraperitoneal administration at a dose of 3.4 mg/kg.

Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.Fosfolipaza D (PLD, klassifikatsionnyĭ nomer - EC 3.1.4.4) iavliaetsia odnim iz kliuchevykh fermentov, osushchestvliaiushchikh gidroliz fosfolipidov kletochnykh membran. V stat'e rassmotreny i obobshcheny dannye, nakoplennye ob izvestnykh na segodniashniĭ den' 6-ti izoformakh PLD, obnaruzhennykh v organizme cheloveka, otnosiashchiesia k ikh stroeniiu, roli v fiziologicheskikh i patologicheskikh protsessakh. Privoditsia sravnitel'nyĭ analiz stroeniia izoform PLD. Opisan mekhanizm reaktsiĭ gidroliza i transfosfatidilirovaniia, kataliziruemykh PLD. Analiziruetsia rol' PLD1 i PLD2 v patogeneze nekotorykh onkologicheskikh i infektsionnykh zabolevaniĭ, tromboticheskikh sostoianiĭ i neĭrodegenerativnykh rasstroĭstv. Pokazana perspektivnost' poiska selektivnykh ingibitorov dlia izoform PLD s tsel'iu vozmozhnogo ikh vkliucheniia v skhemu lecheniia razlichnykh zabolevaniĭ, a takzhe okharakterizovany uzhe sozdannye ingibitory PLD. Privedena kharakteristika biomarkera zloupotrebleniia alkogolem fosfatidilétanola (PEth), obrazuiushchegosia v rezul'tate reaktsii transfosfatidilirovaniia fosfolipidov v organizme cheloveka.

A rich class of spintronics-relevant phenomena require implementation of robust magnetism and/or strong spin-orbit coupling (SOC) to graphene, but both properties are completely alien to it. Here, we for the first time experimentally demonstrate that a quasi-freestanding character, strong exchange splitting and giant SOC are perfectly achievable in graphene at once. Using angle- and spin-resolved photoemission spectroscopy, we show that the Dirac state in the Au-intercalated graphene on Co(0001) experiences giant splitting (up to 0.2 eV) while being by no means distorted due to interaction with the substrate. Our calculations, based on the density functional theory, reveal the splitting to stem from the combined action of the Co thin film in-plane exchange field and Au-induced Rashba SOC. Scanning tunneling microscopy data suggest that the peculiar reconstruction of the Au/Co(0001) interface is responsible for the exchange field transfer to graphene. The realization of this "magneto-spin-orbit" version of graphene opens new frontiers for both applied and fundamental studies using its unusual electronic bandstructure., The authors acknowledge support by the Saint Petersburg State University (Grant 15.61.202.2015), German-Russian Interdisciplinary Science Center (G-RISC) funded by the German Federal Foreign Office via the German Academic Exchange Service (DAAD) and Russian-German laboratory at BESSY II (Helmholtz-Zentrum Berlin). The funding by the University of the Basque Country (Grants GIC07IT36607 and IT-756-13), the Spanish Ministry of Science and Innovation (Grants FIS2013-48286-C02-02-P, FIS2013-48286-C02-01-P, and FIS2016-75862-P) and Tomsk State University competitiveness improvement programme (Project No. 8.1.01.2017) is also gratefully acknowledged. I.P.R. acknowledges support by the Ministry of Education and Science of the Russian Federation within the framework of the governmental program “Megagrants” (state task no. 3.8895.2017/P220).

Using photoelectron diffraction and spectroscopy, we explore the structural and electronic properties of the hexagonal boron nitride (h-BN) monolayer epitaxially grown on the Co(0001) surface. Perfect matching of the lattice parameters allows formation of a well-defined interface where the B atoms occupy the hollow sites while the N atoms are located above the Co atoms. The corrugation of the h-BN monolayer and its distance from the substrate were determined by means of R-factor analysis. The obtained results are in perfect agreement with the density functional theory (DFT) predictions. The electronic structure of the interface is characterized by a significant mixing of the h-BN and Co states. Such hybridized states appear in the h-BN band gap. This allows to obtain atomically resolved scanning tunneling microscopy (STM) images from the formally insulating 2D material being in contact with ferromagnetic metal. The STM images reveal mainly the nitrogen sublattice due to a dominating contribution of nitrogen orbitals to the electronic states at the Fermi level. We believe that the high quality, well-defined structure and interesting electronic properties make the h-BN/Co(0001) interface suitable for spintronic applications., L.V.Ya. acknowledges the RSF (Grant No. 16-42-01093). A.V.T., V.O.S., K.A.B., O.Yu.V., and D.Yu.U. acknowledge St. Petersburg State University for research Grant No. 11.65.42.2017. M.V.K. and I.I.O. acknowledge the RFBR (Grant No. 16-29-06410). C.L. acknowledges the DFG (Grant Nos. LA655-17/1 and LA655-19/1).