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Biologically active compounds of natural or synthetic origin have a complex structure and generally contain various structural groups among which polycyclic cage amines are found. Hexaazaisowurtzitanes are representatives of these amines and studies on their biological activity began less than two decades ago, starting with research on the environmental impact of CL-20. This research helped to evaluate the risks of potential pollution in the habitat environments of living organisms and determine whether the chemical compounds in question could be utilized in pesticides, herbicides, fungicides, or medicinal drugs. The nomenclature of hexaazaisowurtzitane compounds has recently been expanded significantly, and some of them have demonstrated promise in the design of medicinal drugs. This paper review studies the pharmacological activity of the acyl derivatives of hexaazaisowurtzitane. Most of the compounds have been found to possess a high analgesic activity, providing a solution to the pressing issue of pain management in current pharmacology. Analgesic drugs currently used in the clinical practice do not meet all of the efficacy and safety requirements (gastro-, nephro-, hepato-, haematotoxicity, etc.). The material presented in the seven sections of this paper highlights information about hexaazaisowurtzitane derivatives. Furthermore, they have been observed to exhibit anti-inflammatory, anticonvulsant, antihypoxic, and antimetastatic activities, which render them highly promising for evaluation in various fields of medicinal practice. [ABSTRACT FROM AUTHOR]

Hearing loss is one of the most genetically heterogeneous disorders known. Over 120 genes are reportedly associated with non-syndromic hearing loss (NSHL). To date, in Russia, there have been relatively few studies that apply massive parallel sequencing (MPS) methods to elucidate the genetic factors underlying non-GJB2-related hearing loss cases. The current study is intended to provide an understanding of the mutation spectrum in non-GJB2-related hearing loss in a cohort of Russian sensorineural NSHL patients and establish the best diagnostic algorithm. Genetic testing using an MPS panel, which included 33 NSHL and syndromic hearing loss (SHL) genes that might be misdiagnosed as NSHL genes, was completed on 226 sequentially accrued and unrelated patients. As a result, the molecular basis of deafness was found in 21% of the non-GJB2 NSHL cases. The total contribution pathogenic, and likely pathogenic, variants in the genes studied among all hereditary NSHL Russian patients was 12%. STRC pathogenic and likely pathogenic, variants accounted for 30% of diagnoses in GJB2-negative patients, providing the most common diagnosis. The majority of causative mutations in STRC involved large copy number variants (CNVs) (80%). Among the point mutations, the most common were c.11864G>A (p.Trp3955*) in the USH2A gene, c.2171_2174delTTTG (p.Val724Glyfs*6) in the STRC gene, and c.107A>C (p.His36Pro) and c.1001G>T (p.Gly334Val) in the SLC26A4 gene. Pathogenic variants in genes involved in SHL accounted for almost half of the cases with an established molecular genetic diagnosis, which were 10% of the total cohort of patients with non-GJB2-related hearing loss. [ABSTRACT FROM AUTHOR]

Congenital and early onset bilateral sensorineural hearing loss (SNHL) is mainly caused by mutations in numerous genes. The introduction of universal newborn hearing screening (UNHS) has increased the number of infants with mild, moderate, and moderate-to-severe sensorineural hearing loss (SNHL) detected in the first year of life. We aimed to evaluate the audiological features in patients with mild, moderate, and moderate-to-severe SNHL according to genotype. Audiological and genetic data were analyzed for 251 patients and their relatives with congenital bilateral mild, moderate, and moderate-to-severe SNHL. Hearing loss severity, audiogram profile, interaural symmetry, and dynamics of hearing thresholds were analyzed. In this case, 165 patients had GJB2 gene mutations, 30 patients were identified with STRC mutations, and 16 patients had pathogenic or likely pathogenic USH2A mutations. The presence of at least one GJB2 non-truncating variant in genotype led to less severe hearing impairment. The flat and gently sloping audiogram profiles were mostly revealed in all groups. The follow-up revealed the stability of hearing thresholds. GJB2, STRC, and USH2A pathogenic variants were detected in most patients in our cohort and were congenital in most cases. [ABSTRACT FROM AUTHOR]

2D numerical modeling algorithms of multi-component, multi-phase filtration processes of mass transfer in frost-susceptible rocks using nonlinear partial differential equations are a valuable tool for problems of subsurface hydrodynamics considering the presence of free gas, free water, gas hydrates, ice formation and phase transitions. In this work, a previously developed one-dimensional numerical modeling approach is modified and 2D algorithms are formulated through means of the support-operators method (SOM) and presented for the entire area of the process extension. The SOM is used to generalize the method of finite difference for spatially irregular grids case. The approach is useful for objects where a lithological heterogeneity of rocks has a big influence on formation and accumulation of gas hydrates and therefore it allows to achieve a sufficiently good spatial approximation for numerical modeling of objects related to gas hydrates dissociation in porous media. The modeling approach presented here consistently applies the method of physical process splitting which allows to split the system into dissipative equation and hyperbolic unit. The governing variables were determined in flow areas of the hydrate equilibrium zone by applying the Gibbs phase rule. The problem of interaction of a vertical fault and horizontal formation containing gas hydrates was investigated and test calculations were done for understanding of influence of thermal effect of the fault on the formation fluid dynamic. [ABSTRACT FROM AUTHOR]

The current study aims to examine how students' intentions to use 4.5G mobile phones are affected by the social-economic factors of performance expectancy, cost, effort expectancy, and social influence. This study is based on the perspectives of the unified theory of acceptance and use of technology (UTAUT). The central assumption of this study is that when students use 4.5G mobile services to source information at university, their academic performance is likely to improve. From eight private and public universities in Malaysia, 2117 students were enrolled in this study. We investigated the effects of gender and awareness as moderators on the relationships among the variables of interest. The findings showed that social influence and performance expectancy positively affected university students' intentions to use 4.5G mobile phones. The researchers conducted a multigroup analysis to confirm the moderating effect of gender among the underlying relationships in the model. Structural equation modeling analysis indicated that, unlike awareness, gender did not moderate social influence, effort expectancy, performance expectancy, or the cost of students' intentions to use 4.5G mobile phones. The implications of the proposed approach, considering the digital transformation concept, could be a topic for future research. [ABSTRACT FROM AUTHOR]

This paper investigates the impact of the moderate growth of government borrowing on debt sustainability in 11 Russian regions over about 10 years, starting in 2010. The current study aims to assess the debt sustainability of the Russian region's budget by determining Euclidean distance budget constraints and cluster analysis. This study is based on the methodology of hierarchical cluster analysis, which makes it possible to isolate regions of accumulation of objects from the aggregate data and combine them into homogeneous segments. The central hypothesis of this study is that by using this method, it is possible to increase the accuracy of the values that limit budget constraints in a region's financial system. This study, using open data from the Federal State Statistics Service, is based on a database of statistical, financial, and economic indicators of the Russian economy. The calculations include about 45 macroeconomic indicators, which reflect the ratios of socio-economic development of the region's financial system. The methodology described in the paper for assessing the debt sustainability of budget policy proves the need to calculate six indicators and determine the debt limits for the regions of each cluster. It finds a need to reduce the high debt burden of 46% of the regions belonging to the Northwestern Federal District. Confidence intervals for the debt limit suggest that the negative growth effect of high debt may start from levels of around 5% of the debt-to-GDP ratio and about 43% of the debt-to-revenue ratio. The results indicate that regions with a high level of debt sustainability include St. Petersburg city, the Leningrad region, and the Kaliningrad region. From a state debt policy perspective, the results provide additional arguments for debt reduction for the Republic of Komi, the Republic of Karelia, the Arkhangelsk region, and the Pskov region. The general conclusion of the study boils down to the need to reduce the debt burden of the budgets of some regions of the SFZO, as well as to the need to change the upper limits of debt, which are equally set for all regions by the Budget Code of the Russian Federation, to differentiated values of public domestic debt, taking into account the results obtained in the study. [ABSTRACT FROM AUTHOR]

Among the most important characteristics of autonomous vehicles are the safety and robustness in various traffic situations and road conditions. In this paper, we focus on the development and analysis of the extended version of the canonical proportional-derivative PD controllers that are known to provide a good quality of steering on non-slippery (dry) roads. However, on slippery roads, due to the poor yaw controllability of the vehicle (suffering from understeering and oversteering), the quality of control of such controllers deteriorates. The proposed predicted PD controller (PPD controller) overcomes the main drawback of PD controllers, namely, the reactiveness of their steering behavior. The latter implies that steering output is a direct result of the currently perceived lateral- and angular deviation of the vehicle from its intended, ideal trajectory, which is the center of the lane. This reactiveness, combined with the tardiness of the yaw control of the vehicle on slippery roads, results in a significant lag in the control loop that could not be compensated completely by the predictive (derivative) component of these controllers. In our approach, keeping the controller efforts at the same level as in PD controllers by avoiding (i) complex computations and (ii) adding additional variables, the PPD controller shows better quality of steering than that of the evolved (via genetic programming) models. [ABSTRACT FROM AUTHOR]

The most important characteristics of autonomous vehicles are their safety and their ability to adapt to various traffic situations and road conditions. In our research, we focused on the development of controllers for automated steering of a realistically simulated car in slippery road conditions. We comparatively investigated three implementations of such controllers: a proportional-derivative (PD) controller built in accordance with the canonical servo-control model of steering, a PID controller as an extension of the servo-control, and a controller designed heuristically via the most versatile evolutionary computing paradigm: genetic programming (GP). The experimental results suggest that the controller evolved via GP offers the best quality of control of the car in all of the tested slippery (rainy, snowy, and icy) road conditions. [ABSTRACT FROM AUTHOR]