Dynamics Of Segments Research Articles

Integrating molecular dynamics simulation with small- and wide-angle X-ray scattering to unravel the flexibility, antigen-blocking, and protease-restoring functions in a hindrance-based pro-antibody.

Spatial hindrance-based pro-antibodies (pro-Abs) are engineered antibodies to reduce monoclonal antibodies' (mAbs) on-target toxicity using universal designed blocking segments that mask mAb antigen-binding sites through spatial hindrance. By linking through protease substrates and linkers, these blocking segments can be removed site-specifically. Although many types of blocking segments have been developed, such as coiled-coil and hinge-based Ab locks, the molecular structure of the pro-Ab, particularly the region showing how the blocking fragment blocks the mAb, has not been elucidated by X-ray crystallography or cryo-EM. To achieve maximal effect, a pro-Ab must have high antigen-blocking and protease-restoring efficiencies, but the unclear structure limits its further optimization. Here, we utilized molecular dynamics (MD) simulations to study the dynamic structures of a hinge-based Ab lock pro-Ab, pro-Nivolumab, and validated the simulated structures with small- and wide-angle X-ray scattering (SWAXS). The MD results were closely consistent with SWAXS data (χ2 best-fit = 1.845, χ2 allMD = 3.080). The further analysis shows a pronounced flexibility of the Ab lock (root-mean-square deviation = 10.90 Å), yet it still masks the important antigen-binding residues by 57.3%-88.4%, explaining its 250-folded antigen-blocking efficiency. The introduced protease accessible surface area method affirmed better protease efficiency for light chain (33.03 Å2) over heavy chain (5.06 Å2), which aligns with the experiments. Overall, we developed MD-SWAXS validation method to study the dynamics of flexible blocking segments and introduced methodologies to estimate their antigen-blocking and protease-restoring efficiencies, which would potentially be advancing the clinical applications of any spatial hindrance-based pro-Ab.

The impact of disc degeneration on the dynamic characteristics of the lumbar spine: a finite element analysis.

The dynamics of disc degeneration was analyzed to determine the effect of disc degeneration at the L4-L5 segment on the dynamic characteristics of the total lumbar spine. A three-dimensional nonlinear finite element model of the L1-S1 normal lumbar spine was constructed and validated. This normal model was then modified to construct two degeneration models with different degrees of degeneration (mild, moderate) at the L4-L5 level. Modal analysis, harmonic response analysis, and transient dynamics analysis were performed on the total lumbar spine when experiencing following compressive loading (500N). As the degree of disc degeneration increased, the vibration patterns corresponding to the first three orders of the model's intrinsic frequency were basically unchanged, with the first order being in the left-right lateral bending direction, the second order being in the forward-flexion and backward-extension direction, and the third order being in the axial stretching direction. The nucleus pulposus pressure peaks corresponding to the first order intrinsic frequency for the harmonic response analysis are all on the right side of the model, with sizes of 0.053MPa, 0.061MPa, and 0.036MPa, respectively; the nucleus pulposus pressure peaks corresponding to the second order intrinsic frequency are all at the rear of the model, with sizes of 0.13MPa, 0.087MPa, and 0.11MPa, respectively; and the nucleus pulposus pressure peaks corresponding to the third order intrinsic frequency are all at the front of the model, with sizes of 0.19MPa, 0.22MPa, and 0.22MPa, respectively. The results of the transient analysis indicated that over time, the response curves of the healthy model, the mild model, and the moderate model all exhibited cyclic response characteristics. Intervertebral disc degeneration did not adversely affect the vibration characteristics of the entire lumbar spine system. Intervertebral disc degeneration significantly altered the dynamics of the degenerative segments and their neighboring normal segments. The process of disc degeneration gradually shifted the load from the nucleus pulposus to the annulus fibrosus when the entire lumbar spine was subjected to the same vibratory environment.

Thiol‐ene polymerization of double‐decker‐shaped phenyl‐substituted silsesquioxanes and thiol monomers

AbstractPolymers incorporating double‐decker‐shaped phenyl‐substituted silsesquioxane (DDSQ) into the main chain are expected to exhibit excellent thermal stability and significantly reduced dynamics of the polymer segments. In this study, thiol‐ene polymerization at 25 °C for 5 min under 365 nm irradiation was applied for 3,13‐divinyl‐DDSQ (E1) with oxybis(2,1‐ethanediyloxy‐2,1‐ethanediyl) bis(3‐sulfanylpropanoate) (T1) as a bithiol monomer for linear and 2,2‐bis{[(3‐sulfanylpropanoyl)oxy]methyl}butyl 3‐sulfanylpropanoate (T2) as a trithiol monomer for soluble cross‐linked poly(thioether)s. All the resulting poly(thioether)s yielded colorless and transparent films by casting tetrahydrofuran solutions onto glass substrates. These polymers showed a higher decomposition temperature of 5 wt% loss over 350 °C. The films exhibited glass transition temperatures below 25 °C. Scratch scars were made on the surface of the cast films, and the self‐healing behavior was observed after heating at 40 °C. These results suggest that the DDSQ unit suppresses the molecular motion of the polymers and contributes to their self‐healing behavior.

Mapping the profiles and underlying driving mechanisms of the antibiotic resistome and microbiome within a subtropical complex river watershed

Antibiotic resistance is an escalating global concern, leading to millions of annual deaths worldwide. Human activities can impact antibiotic resistance gene (ARG) prevalence in aquatic ecosystems, but the intricate interplay between anthropogenic disturbances and river system resilience, and their respective contributions to the dynamics of different river segments, remains poorly understood. In this study, we investigate the antibiotic resistome and microbiome in water and sediment samples from two distinct sub-watersheds within a specific watershed. Results show a decrease in the number of core ARGs downstream in water, while sediments near densely populated areas exhibit an increase. PCoA ordination reveals clear geographic clustering of resistome and microbiome among samples from strong anthropogenic disturbed areas, reservoir areas, and estuary area. Co-occurrence networks highlight a higher connectivity of mobile genetic elements (MGEs) in disturbed areas compared to reservoir areas, presenting a threat to densely populated areas. Water quality parameters and antibiotics concentration were the key factors shaping the ARG profiles in sediment samples from urban regions. Overall, our study reveals distinct patterns of ARGs in sediment and water samples, emphasizing the importance of considering both anthropogenic and natural factors in comprehending and managing ARG distribution in river systems.

How does the precursor backbone length affect the grafting efficiency and kinetics for bottlebrush polystyrenes prepared by graft-onto Strategy?

The clarification of the potential dependence of grafting efficiency on the backbone length during the graft-onto reaction process is extremely important for subsequent structure–property study. In this work, by using alkyne-functional polypropargyne acrylate (PPANb, Mw/Mn < 1.10 and Nb = 960, 193, 35) and azide-functional polystyrene (PSNs, Mw/Mn < 1.15 and Ns = 54, 38, 22) as the backbone and sidechain precursors, we have investigated the Nb-dependence of the grafting reaction during the graft-onto click process. Specifically, the influence of solution concentration and feed ratio are investigated, and a combination of SEC characterization, Gaussian fitting and theoretical analysis is used to estimate the Nb-dependent grafting reaction for the bottlebrush product (PPANb-g-PSNs). The main findings include: 1) when the reaction time (t) is sufficient long (t = 24 h), the grafting efficiency is found to be nearly irrelevant with Nb, even if we consider 2 ∼ 5 times of difference in the diffusion coefficient (D) based the well-known scaling relation of D ∼ Nb1/2 in the semidilute reaction solution; 2) the time-dependent kinetics investigation further shows abnormal and different pathways for different backbone lengths when 0 min < t < 10 min, but the final grafting efficiency determined at t = 300 min shows no much difference, going back to the preliminary result of equilibrium state at t = 24 h; 3) the origin of abnormal pathways may be attributed to the relatively poor signal-to-noise ratio and potential dependence of dn/dC of PPANb-g-PSNs product on the composition at low grafting density range, which needs clarification in future. For the first time, our result has unambiguously demonstrated that, for a mixed solution of reaction system composed of backbone precursors with their lengths differing by hundreds of times, the polydispersity effect of the backbone length does not affect the final grafting efficiency during the process, no matter for long or short sidechain grafts. The result implies that it is the local dynamics of chain segments, instead of the overall translational diffusion dominates the graft-onto process in the concentration-regime studied.

Translation dynamics in human cells visualized at high resolution reveal cancer drug action.

Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, but their distribution in actively translating human cells remains elusive. We used a cryo-electron tomography-based approach and resolved ribosome structures inside human cells with high resolution. These structures revealed the distribution of functional states of the elongation cycle, a Z transfer RNA binding site, and the dynamics of ribosome expansion segments. Ribosome structures from cells treated with Homoharringtonine, a drug used against chronic myeloid leukemia, revealed how translation dynamics were altered in situ and resolve the small molecules within the active site of the ribosome. Thus, structural dynamics and drug effects can be assessed at high resolution within human cells.

Anomalous Diffusion of Polyelectrolyte Segments on Supported Charged Lipid Bilayers.

This work provides mesoscale models for the anomalous diffusion of a polymer chain on a heterogeneous surface with rearranging randomly distributed adsorption sites. Both the "bead-spring" model and oxDNA model were simulated on supported lipid bilayer membranes with various molar fractions of charged lipids, using Brownian dynamics method. Our simulation results demonstrate that "bead-spring" chains exhibit sub-diffusion on charged lipid bilayers which agrees with previous experimental observations for short-time dynamics of DNA segments on membranes. In addition, the non-Gaussian diffusive behaviors of DNA segments have not been observed in our simulations. However, a simulated 17 base pairs double stranded DNA, using oxDNA model, performs normal diffusion on supported cationic lipid bilayers. Due to the number of positively charged lipids attracted by short DNA is small, the energy landscape that the short DNA experiences during diffusion is not as heterogeneous as that experienced by long DNA chains, which results in normal diffusion rather than sub-diffusion for short DNA.

Correlated motions in DNA: beyond base-pair step models of DNA flexibility.

Traditional mesoscopic models of DNA flexibility use a reductionist-local approach, which assumes that the flexibility of DNA can be expressed as local harmonic movements (at the base-pair step level) in the helical space, ignoring multimodality and correlations in DNA movements, which have in reality a large impact in modulating DNA movements. We present a new multimodal-harmonic correlated model, which takes both contributions into account, providing, with a small computational cost, results of an unprecedented local and global quality. The accuracy of this method and its computational efficiency make it an alternative to explore the dynamics of long segments of DNA, approaching the chromatin range.

The influence of environmental and economic turbulence on civil construction in the region

This article is devoted to the analysis and forecasting of the development of civil engineering in the region in the context of recurring macro-shocks that create political and economic turbulence. The dynamics of the commercial real estate market in St. Petersburg have been studied. The purpose of the article is to study the influence of various factors (including vacancy levels) on market price indicators and to predict the dynamics of its development. Objectives of the study: analyse office, retail, and warehouse real estate in the city, study the degree of influence of the vacancy rate of objects on the market situation; build a forecast of the dynamics of market development, considering the influence of the dynamics of the share of vacant space; identify market trends in an unstable economic situation. The result of the study is a forecast of the dynamics of development of the commercial real estate market in St. Petersburg and, accordingly, civil construction in this region. Based on regression analysis, factors influencing the dynamics of price indicators for commercial premises were identified. The study confirmed the hypothesis about the connection between the dynamics of commercial real estate market segments and key events in the economy. This suggests the need to identify time stages at which the composition and number of key factors changes. The study shows that different segments of the commercial real estate market react differently to the level of vacancy, which is due to their specific functioning.

The development of a management decision-making method based on the analysis of information from space observation systems

The object of this study is the process of making a management decision based on the analysis of information from space surveillance systems. Unlike the well-known ones, the method of making a management decision based on the analysis of information from space surveillance systems involves: – segmentation of an optoelectronic image; – determination and prediction of a priori probabilities of possible environmental states; – an application for making a management decision of a combination of Bayes criteria and a minimum of variance. Experimental studies have been carried out on making a management decision based on the analysis of information from space surveillance systems. To conduct experimental research on making a management decision based on the analysis of information from space surveillance systems, a model problem has been stated. As images from space surveillance systems, images obtained from the WorldView-2 spacecraft (USA) with a difference of four days were considered. The vegetation index was calculated, and the probabilities of degradation dynamics of plant segments were determined. It was established that the maximum value of the estimated functional is achieved when choosing a solution φ1, which is optimal according to the Bayesian criterion and the criterion of minimum variance. The quality of management decision-making was assessed by the well-known and developed methods. To assess the quality of management decision-making, the concepts of objectivity of the decision-making method and the selectivity of the decision-making method by known and developed method were introduced. It has been established that both methods are objective, and the improved method is more selective (the gain is 2.6 times). This becomes possible through the use of information from space surveillance systems.

QENS study on local segmental dynamics of polyelectrolytes in complex coacervates

The segmental dynamics of complex coacervates were investigated as a function of salt concentration and a charge type using quasi-elastic neutron scattering (QENS). The coacervates were prepared by mixing two oppositely charged polyether-based polyelectrolyte solutions functionalized for cationic ammonium and guanidinium groups or anionic sulfonate groups. For the QENS time scale, the intrinsic ion pairs were considered effective cross-links, and therefore the dynamics of chain segments between the intrinsic junctions were probed. We observed that as salt concentration increases, both the number of mobile chain segments and their segmental dynamics increase for ammonium-based coacervates where the electrostatic interaction primarily governs the phase behavior. However, the guanidinium-based coacervates show slow and nearly identical segmental relaxation independent of the salt concentration, which is potentially attributed to the non-electrostatic interactions. The combination of the chemical structure of ionic moieties, salt concentration, and temperature plays a significant role to determine polymer chain dynamics mainly affected by the strength of ionic bonding.

A coupling model for the cooperative actuation mechanism of thermochemically responsive shape memory polymers

Thermochemically responsive shape memory polymers (SMPs) have attracted great interest in biomedical applications such as drug-releasing capsules and implantable medical stents, because body temperature can drive their shape recovery behaviors. However, it is difficult to determine the configurational dynamics of polymer segments due to the complexities of environmental stimuli (e.g. solute concentration, temperature change, and solvent diffusion). Besides, the cooperative actuation mechanism behind the thermochemical-driven shape memory effect (SME) is still poorly understood. In this study, we describe the effects of temperature and solvent absorption on conformational rearrangements in SMPs using the size change of cooperative rearrangement region (CRR) derived from the Adam–Gibbs model. The quasi-lattice model is further combined with Fick’s second law to characterize the kinetic diffusion behavior of solvent molecules in the CRR. The dependences of dual- and quadruple-SMEs in amorphous SMPs on immersion time, solution concentration, and programming temperature are quantitatively investigated using the proposed model. The theoretical results are also compared with experimental data and a good agreement is achieved. The proposed model is expected to provide theoretical guidance for understanding the working mechanism of thermochemically responsive SMPs and advancing their engineering applications.

Heterogeneous interactions and polymer entropy decide organization and dynamics of chromatin domains

Chromatin is known to be organized into multiple domains of varying sizes and compaction. While these domains are often imagined as static structures, they are highly dynamic and show cell-to-cell variability. Since processes such as gene regulation and DNA replication occur in the context of these domains, it is important to understand their organization, fluctuation, and dynamics. To simulate chromatin domains, one requires knowledge of interaction strengths among chromatin segments. Here, we derive interaction-strength parameters from experimentally known contact maps and use them to predict chromatin organization and dynamics. Taking two domains on the human chromosome as examples, we investigate its three-dimensional organization, size/shape fluctuations, and dynamics of different segments within a domain, accounting for hydrodynamic effects. Considering different cell types, we quantify changes in interaction strengths and chromatin shape fluctuations in different epigenetic states. Perturbing the interaction strengths systematically, we further investigate how epigenetic-like changes can alter the spatio-temporal nature of the domains. Our results show that heterogeneous weak interactions are crucial in determining the organization of the domains. Computing effective stiffness and relaxation times, we investigate how perturbations in interactions affect the solid- and liquid-like nature of chromatin domains. Quantifying dynamics of chromatin segments within a domain, we show how the competition between polymer entropy and interaction energy influence the timescales of loop formation and maintenance of stable loops.

Bond graph modeling of a spatial multi-section soft bionic robot

Bionic manipulators are biologically inspired robots with high-level of dexterity. Modeling and control of a bionic manipulator is a challenging task due to number of redundancies present in the system. The applications of bionic manipulators are found in material transport, pick and place operations. Their application is also explored in areas of skeletal trauma treatment, endoscopy and minimally invasive surgery and inspection. This paper presents a detailed bond graph model of a three-dimensional multi-section bionic manipulator which is modeled as a hybrid manipulator, i.e., a serial manipulator whose links/segments are formed by a parallel manipulator. The base of the mobile manipulator as well as the rotational motion of end-effector have been modeled. The developed bond graph model is validated with MappleSim software. Further a model-based control scheme is developed for the bionic manipulator. The control scheme uses the inverse dynamics of manipulator segments to calculate the command torque components required for trajectory tracking. Proportional-Integral-Derivative (PID) controllers are then used along with the model-based controller for accurate trajectory tracking. The control performance is studied through simulation and animation results of the bionic manipulator. To validate the modeling, an example of bionic manipulator Robotino XT has been considered.

Long Range Communication between the Drug-Binding Sites and Nucleotide Binding Domains of the Efflux Transporter ABCB1.

The ABC efflux pump P-glycoprotein (P-gp) transports a wide variety of drugs and is inhibited by others. Some drugs stimulate ATP hydrolysis at the nucleotide binding domains (NBDs) and are transported, others uncouple ATP hydrolysis and transport, and others inhibit ATP hydrolysis. The molecular basis for the different behavior of these drugs is not well understood despite the availability of several structural models of P-gp complexes with ligands bound. Hypothetically, ligands differentially alter the conformational dynamics of peptide segments that mediate the coupling between the drug binding sites and the NBDs. Here, we explore by hydrogen-deuterium exchange mass spectrometry the dynamic consequences of a classic substrate and inhibitor, vinblastine and zosuquidar, binding to mouse P-gp (mdr1a) in lipid nanodiscs. The dynamics of P-gp in nucleotide-free, pre-hydrolysis, and post-hydrolysis states in the presence of each drug reveal distinct mechanisms of ATPase stimulation and implications for transport. For both drugs, there are common regions affected in a similar manner, suggesting that particular networks are the key to stimulating ATP hydrolysis. However, drug binding effects diverge in the post-hydrolysis state, particularly in the intracellular helices (ICHs 3 and 4) and neighboring transmembrane helices. The local dynamics and conformational equilibria in this region are critical for the coupling of drug binding and ATP hydrolysis and are differentially modulated in the catalytic cycle.

Influence of Sulfur-Curing Conditions on the Dynamics and Crosslinking of Rubber Networks: A Time-Domain NMR Study.

The characterization of the structural and dynamic properties of rubber networks is of fundamental importance in rubber science and technology to design materials with optimized mechanical properties. In this work, natural and isoprene rubber networks obtained by curing at three different temperatures (140, 150, and 170 °C) and three different sulfur contents (1, 2, and 3 phr) in the presence of a 3 phr accelerator were studied using a combination of low-field time-domain NMR (TD-NMR) techniques, including 1H multiple-quantum experiments for the measurement of residual dipolar couplings (Dres), the application of the Carr–Purcell–Meiboom–Gill pulse sequence for the measurement of the transverse magnetization decay and the extraction of 1H T2 relaxation times, and the use of field cycling NMR relaxometry for the determination of T1 relaxation times. The microscopic properties determined by TD-NMR experiments were discussed in comparison with the macroscopic properties obtained using equilibrium swelling, moving die rheometer, and calorimetric techniques. The obtained correlations between NMR observables, crosslink density values, maximum torque values, and glass transition temperatures provided insights into the effects of the vulcanization temperature and accelerator/sulfur ratio on the structure of the polymer networks, as well as on the effects of crosslinking on the segmental dynamics of elastomers. Dres and T2 were found to show linear correlations with the crosslink density determined by equilibrium swelling, while T1 depends on the local dynamics of polymer segments related to the glass transition, which is also affected by chemical modifications of the polymer chains occurring during vulcanization.

Big data architecture and data mining analysis for market segment applications of differential global navigation satellite system (GNSS) services: case study of the analysis of the demand for navigation and agriculture

AbstractLocation and navigation services based on global navigation satellite systems (GNSS) are needed for real-time high-precision positioning applications in relevant economic sectors, such as precision agriculture, transport, civil engineering or mapping. Real-time navigation users of GNSS networks have significantly increased all around the world, since the 1990s, and usage has exceeded initial expectations. Therefore, if the evolution of GNSS network users is monitored, the dynamics of market segments can be studied. The implementation of this hypothesis requires the treatment of big volumes of navigation data over several years and the continuous monitoring of customers. This paper is focused on the management of massive connection of GNSS users in an efficient way, in order to obtain analysis and statistics. Big data architecture and data analyses based on data mining algorithms have been implemented as the best way to approach the hypothesis. Results demonstrate the dynamic of users of different market segments, the increasing demand over the years and, specifically, conclusions are obtained about the trends, year-on-year correlation and business volume recovering after economic crisis periods.

Patient-Specific Variations in Local Strain Patterns on the Surface of a Trussed Titanium Interbody Cage.

Introduction: 3D printed trussed titanium interbody cages may deliver bone stimulating mechanobiological strains to cells attached at their surface. The exact size and distribution of these strains may depend on patient-specific factors, but the influence of these factors remains unknown. Therefore, this study aimed to determine patient-specific variations in local strain patterns on the surface of a trussed titanium interbody fusion cage. Materials and Methods: Four patients eligible for spinal fusion surgery with the same cage size were selected from a larger database. For these cases, patient-specific finite element models of the lumbar spine including the same trussed titanium cage were made. Functional dynamics of the non-operated lumbar spinal segments, as well as local cage strains and caudal endplate stresses at the operated segment, were evaluated under physiological extension/flexion movement of the lumbar spine. Results: All patient-specific models revealed physiologically realistic functional dynamics of the operated spine. In all patients, approximately 30% of the total cage surface experienced strain values relevant for preserving bone homeostasis and stimulating bone formation. Mean caudal endplate contact pressures varied up to 10 MPa. Both surface strains and endplate contact pressures varied more between loading conditions than between patients. Conclusions: This study demonstrates the applicability of patient-specific finite element models to quantify the impact of patient-specific factors such as bone density, degenerative state of the spine, and spinal curvature on interbody cage loading. In the future, the same framework might be further developed in order to establish a pipeline for interbody cage design optimizations.

Reassortment and evolutionary dynamics of tilapia lake virus genomic segments

The tilapia lake virus (TiLV), a highly infectious negative-sense single-stranded segmented RNA virus, has caused several outbreaks worldwide since its first report from Israel in 2014, and continues to pose a major threat to the global tilapia industry. Despite its economic importance, little is known about the underlying mechanisms in the genomic evolution of this highly infectious viral pathogen. Using phylogenomic approaches to the genome sequences of TiLV isolates from various geographic regions, we report on the pervasive role of reassortment, selection, and mutation in TiLV evolution. Our findings provided the evidence of genome-wide reassortment in this newly discovered RNA virus. The rate of non-synonymous (dN) to synonymous (dS) substitutions was less than one (dN/dS = 0.076 to 0.692), indicating that each genomic segment has been subjected to purifying selection. Concurrently, the rate of nucleotide substitution for each genomic segment was in the order of 1–3 × 10−3 nucleotide substitutions per site per year, which is comparable to the rate of other RNA viruses. Collectively, in line with the results of the previous studies, our results demonstrated that reassortment is the dominant force in the evolution and emergence of this highly infectious segmented RNA virus.

FINTECH TOOLS IN THE FOREIGN ECONOMIC ACTIVITY OF THE EAEU COUNTRIES

A study of the use of Fintech tools in the field of foreign economic activity of the EAEU countries was conducted. The article highlights the role of digitalization in the development of the market of goods, services and capital in integration associations. Based on the actual data, the analysis of the situation in the sectors of the financial market of the EAEU countries was carried out and the features consisting in a high degree of differentiation of the development and dynamics of various segments of the financial market were highlighted. The analysis of Fintech tools has shown that in the field of foreign economic activity and support of foreign trade contracts concluded within the framework of the EAEU, there is no single electronic system which allows to effectively support export-import operations and promote interaction and development of corporate entities and enterprises of all forms of ownership. The analysis of existing approaches to the use of electronic systems in the field of foreign trade has shown that most of them are based on mobile operator platforms, which limits the development of digital tools. The unavailability of digital technologies or their absence in a number of EAEU countries indicates the underdevelopment of the digital culture of citizens of the EAEU countries. The article suggests ways to solve the current situation by creating a unified electronic trading system and a unified marketplace with the possibility of opening remote access to a variety of financial instruments for individuals and to attract the capital of companies; increasing the quantitative and qualitative parameters of the development of the financial center; unifying the reporting and auditing system of issuing companies, as well as ensuring the availability and transparency of innovative regulatory and control systems.