Site-specific gains and losses of heterochromatin accelerate the age-related neurodegeneration through the cascading destruction of KDM3B-centered epigenomic network

Epigenetic alterations explained by the “loss of heterochromatin” model have been proposed as a universal mechanism of aging, but the region-specific changes of heterochromatin during aging are unclear. Here, we examine age-dependent transcriptomic profiling of mouse retinal neurons to identify epigenetic regulators involved in heterochromatin loss. RNA sequencing analysis revealed gradual down-regulation of Kdm3b during retinal aging. Disruption of Kdm3b (Kdm3b+/-) in 12-month-old mouse retina decreased the number of cone photoreceptors and changed the morphology of cone ribbon synapses. Integration of transcriptome profiling with epigenomic analysis demonstrated gain of heterochromatin feature in synapse assembly and vesicle transport genes via the accumulation of H3K9 mono- and di-methylation. However, the loss of heterochromatin in apoptotic genes exacerbated retinal neurodegeneration. We propose that this KDM3B-centered epigenomic network is crucial for maintaining cone photoreceptor homeostasis via the modulation of gene-set specific heterochromatin features during aging.

Hydrodynamics of spike proteins dictate a transport-affinity competition for SARS-CoV-2 and other enveloped viruses

Many viruses, such as SARS-CoV-2 or Influenza, possess spike-decorated envelopes. Depending on the virus type, a large variability is present in spikes number, morphology and reactivity, which remains generally unexplained. Since viruses' transmissibility depend on features beyond their genetic sequence, new tools are required to discern the effects of spikes functionality, interaction, and morphology. Here, we postulate the relevance of hydrodynamic interactions in the viral infectivity of enveloped viruses and propose micro-rheological characterization as a platform for viruses differentiation. To understand how the spikes affect virion mobility and infectivity, we investigate the diffusivity of spike-decorate structures using mesoscopic-hydrodynamic simulations. Furthermore, we explored the interplay between affinity and passive viral transport. Our results revealed that the diffusional mechanism of SARS-CoV-2 is strongly influenced by the size and distribution of its spikes. We propose and validate a universal mechanism to explain the link between optimal virion structure and maximal infectivity for many virus families.

Transformation of Digital Management in Enterprises Amidst the COVID-19 Pandemic

This study aims to examine changes in enterprise management during the COVID-19 pandemic and develop a universal mechanism for managing digital transformation. Its methodological basis is represented by a terminological analysis of the concepts of automation, digitalisation and digital transformation. Their close consideration enables us to form a conceptual scheme of business digitalisation. In sum, the study process shows that full-fledged and fruitful digital transformation can be achieved through restructuring a company’s business process management system. By comparing the outcomes of using digital platform-based business models, the most promising one was selected for use. Its practical application was studied in Azerbaijan, Russia, and Switzerland using the Network Readiness Index (NRI). The analysis made it possible to form business development strategies for each country reviewed and to develop a universal mechanism for digital transformation management by means of optimisation and modelling. The findings suggest that in pandemic settings, digital enterprise management concentrates on survival, self-learning and cooperation without intermediaries through innovation and the transformation of business processes. The strategies can be used to adopt digital technologies and attract investment. Further research can be directed at detailing the proposed mechanism.

Indicators of the force interaction of the track and rolling stock when a freight car runs on long irregularities, taking into account the action of longitudinal forces

Authors describe formation mechanism of long irregularities of the railway track and the importance of their elimination for the track facilities. Based on the results of freight train operation modeling on long irregularities in the traction mode, an analysis of the processes occurring during the motion of heavy trains along a track with such deviations was carried out, modeling was carried out on the basis of the “Universal Mechanism” software package. Based on the results of the calculation, interaction between the track and the rolling stock in the vertical plane was assessed in terms of the magnitude of the vertical force and coeffcients: dynamics, stability margin, Nadal, unloading (in percent) of axle springs of freight car springs. Article analizes the nature of the infuence of the irregularity slope on the decrease in the vertical force transmitted from the wheel to the rail and the change in the traction force on the dynamics of freight cars in the train and passing on long irregularities of the longitudinal profle through the indicators of the vertical force.

Molecule which changed the view on skin treatment

Objective — to study the modern classification, mechanisms of action and clinical effects of vitamin A derivatives, to analyze retinoid for local treatment of various dermatoses with a universal mechanism of action at the epidermis and dermis levels. Materials and methods. A review of the literature and an analysis of the results of international clinical trials of drugs based on the natural retinoid of the first generation — tretinoin (retinoic acid) is presented. The works of dozens of authors since 1980s to the present day are analyzed. Most sources provide detailed information on the results of topical retinoids in acne therapy, which are the base of clinical guidelines. Long-term (6 months or more) studies of retinoic acid-based preparations carried out in recent decades have discovered the unique clinical effects of tretinoin in the treatment of skin photoaging, actinic keratosis, etc. They are achieved due to the effect of tretinoid on the nuclear receptors of keratinocytes and fibroblasts. Results and discussion. The molecular mechanisms of action of retinoic acid, realizing the cellular and tissue effects of the most studied retinoid, are systematized and grouped in a single review. It has been proven that a unique feature of tretinin is its ability to activate directly all subtypes of RARs- and, indirectly, RARs-nuclear receptors of skin cells. A new modern drug for external use is presented — AltrenoТМ lotion containing micronized 0.05 % tretinoin in combination with sodium hyaluronate, soluble collagen and glycerin. This combination exhibits the expected clinical efficacy in acne therapy and prevents side effects such as dryness, redness and exfoliation. AltrenoТМ is approved for use in children of 9 years of age and older. Conclusions. Tretinoin (retinoic acid) is a modern powerful retinoid with a universal mechanism of action, recommended for the treatment of acne.

SIMULATION OF A DUAL CLUTCH AUTOMATED TRANSMISSION GEAR SHIFT

A computer dynamic model of an automobile transmission with a double dry clutch, created using the "Universal Mechanism" software package, is presented. Work objective is to analyze the possibility of improving double dry clutch efficiency at various controls of compressive forces of clutch plates. The computer model contains 7 bodies: an engine crankshaft, two clutch plates, two gearbox input shafts for odd and even gears, an output shaft, a fly wheel. The simulation of gear shifting shows that pressing a clutch pedal or letting out the clutch simultaneously, cutoff time increment increases the rotational speed justification of the engine shaft and the input shaft of the actual gear, the total work of the friction forces of both clutches and does not affect the maximum value of clutch plates rotary sliding resistance. Frictional energy of the clutch when shifting gears from lower to higher is greater than when shifting gears from higher to lower. Sequential clutch on-off reduces the total frictional energy of both clutches by 1.17...1.31 times compared to simultaneous one. The model allows looking into different gearshift modes with uniform velocity or accelerated vehicle motion, optimize the gearshift strategy.

Experimental validation of universal plasma blob formation mechanism

Abstract Anomalous plasma transport in the boundary region of a tokamak plasma is commonly associated with the formation and evolution of coherent density structures known as blobs. Recently, a theory for a universal mechanism of plasma blob formation has been put forward. It is based on a breaking process of a radially elongated streamer due to poloidal and radial velocity shears. The theory is well supported by two-dimensional and three-dimensional numerical simulation results but lacks experimental validation. In this work, we report the first ever experimental validation of this universal criterion by testing it against NSTX data on blobs obtained using the gas-puff imaging (GPI) diagnostic. It is found that the criterion is widely satisfied in most L-mode discharges and may explain the significantly larger number of blob events. We also validate the theoretical criterion against ADITYA Langmuir probe data taken in the scrape-off layer region.

Simulation of Crane Trolley Motion Control to Reduce Load Sway

the work aims to develop a method for controlling a crane trolley, providing a decrease in the swinging of the load on the rope at a given positioning accuracy and minimum time for moving the load. Computer simulation of the trolley controlled movement with a load on a rope was carried out within the "Universal Mechanism" software. The 2D computer model includes a trolley with a pulley, a rope with a hook, and a load. T-force represents the wind force effect. The control system (CS) contains three blocks that ensure the movement of the trolley with limited speed and acceleration, the positioning accuracy of the trolley, limiting the deviation and acceleration of a load. List of requirements for the crane CS comprises six issues. The simulation results illustrate the satisfactory performance of the proposed method. The swing angle and trolley positioning accuracy can be controlled within the acceptable range and the external wind disturbance on the load can be successfully suppressed. The optimal parameters of the proportional-differential corrective control, which ensure the minimum travel time of the trolley with limited oscillation of the load, have been determined. The optimal values of the control parameters depend on the inertial characteristics of the load. The maximum permissible values of speed, acceleration, and positioning errors of the trolley limit from above the optimal values of the control parameters.

ПАРАДИГМА ФОРМУВАННЯ МЕХАНІЗМУ ЗМІЦНЕННЯ ЕКОНОМІЧНОЇ БЕЗПЕКИ ПІДПРИЄМНИЦЬКОЇ ДІЯЛЬНОСТІ

Economic security embraces all spheres of activity, and brings neglect over by it’s to the negative (catastrophic) consequences, decline of different aspects of development the industries of economy, separate types of enterprise. Therefore there is a requirement in forming a paradigm of mechanism the strengthening economic security of entrepreneurial activity in obedience to the doctrines of economy development of Ukraine. A research aim is directed on forming of effective mechanism of strengthening economic security according to terms of business development, dynamics of moving the national economy, level of innovative diffusions and existent internal and external calls. Methodological basis of research became modern normative, legal, legislative aspects of strengthening economic security and eliminated of existent threats in the process of business developments. In the researches was using methods of dialectics, principles of scientific cognition, instruments of economic analysis for the sake of forming the effective mechanism of strengthening economic security of enterprise. The basic hypothesis of research became supposition about possibility of creation of universal mechanism of strengthening economic security that can provide stable development of entrepreneurial activity in the different spheres of national economy. Exposition of basic material. in the article are investigated the threats that influence on economic security of enterprise. Underline, that each of threats can have the mechanisms strengthening of economic security, that consist with facilities, instruments, methods and forms composition, that it can be enough unique, depending on the type of enterprise. Originality and practical meaningfulness of research are confirmed by the offered composition of facilities, methods, forms and instruments of mechanism the strengthening of economic security that it is universal from one hand, and from other is allowing to tune the specific of activity the separate type of enterprise. Conclusions and prospects of further researches. It is well-proven that the mechanism of strengthening the economic security of enterprise must provide possibilities of the effective functioning of business and be the element of mechanism the economic security of the system of higher level. For every businessman there are the absolutely individual approaches to forming of mechanism the strengthening of economic security that depends from material and technical and financial resources, quality and structure of management entrepreneurial activity; state and regional support, legislative and legal base of functioning. Further researches will be directed on adaptation of the offered mechanism of strengthening the economic security, its monitoring and correcting, going out the requirements of internal and external environment of business and dynamics of global economic changes

Symbolic revolutions. Mobilizing a neglected Bourdieusian concept for historical sociology

The article builds on a recent literature that has sought to underscore the relevance of Bourdieu’s field theory for historical-sociological analysis. It draws attention to symbolic revolutions, a concept that has been given short shrift in this literature and even in Bourdieu’s own expositions of his field-theoretical apparatus. The article argues that symbolic revolutions denote a universal mechanism of field-internal change which extends and complements a conceptual battery of mostly structural universals of fields. In a synoptic reading of Bourdieu’s field-theoretical work, the article fleshes out an ideal type of symbolic revolutions, with special regard to its dialectical features. It adds further analytical purchase to the concept by highlighting continuities and parallels with the work of Thomas Kuhn and Karl Mannheim. Finally, it argues that more recent studies by other authors on transformations in the psychiatric field, the field of social and human sciences, and the political field are in fact discussing instances of symbolic revolutions. It thus shows how the concept can help identify common properties among highly heterogeneous phenomena, opening up new avenues for historical-sociological investigations that can more systematically relate the general and the particular.