Search results for: Mikhail Cherdantsev

Authors: Todd Zhou, Mikhail Yurochkin

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Out-of-distribution (OOD) detection is receiving increasing amounts of attention in the machine learning research community, boosted by recent technologies, such as autonomous driving and image processing. This newly-burgeoning field has called for the need for more effective and efficient methods for out-of-distribution generalization methods. Without accessing the label information, deploying machine learning models to out-of-distribution domains becomes extremely challenging since it is impossible to evaluate model performance on unseen domains. To tackle this out-of-distribution detection difficulty, we designed a model selection pipeline algorithm and developed a model selection framework with different impurity and randomness measurements to evaluate and choose the best-performing models for out-of-distribution data. By exploring different randomness scores based on predicted probabilities, we adopted the out-of-distribution entropy and developed a custom-designed score, ”CombinedScore,” as the evaluation criterion. This proposed score was created by adding labeled source information into the judging space of the uncertainty entropy score using harmonic mean. Furthermore, the prediction bias was explored through the equality of opportunity violation measurement. We also improved machine learning model performance through model calibration. The effectiveness of the framework with the proposed evaluation criteria was validated on the Folktables American Community Survey (ACS) datasets.

Keywords: model selection, domain generalization, model fairness, randomness measurements, bias index

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Authors: Piotr J. Balwierz, Mikhail Pachkov, Phil Arnold, Andreas J. Gruber, Mihaela Zavolan, Erik van Nimwegen

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Understanding the key players and interactions in the regulatory networks that control gene expression and chromatin state across different cell types and tissues in metazoans remains one of the central challenges in systems biology. Our laboratory has pioneered a number of methods for automatically inferring core gene regulatory networks directly from high-throughput data by modeling gene expression (RNA-seq) and chromatin state (ChIP-seq) measurements in terms of genome-wide computational predictions of regulatory sites for hundreds of transcription factors and micro-RNAs. These methods have now been completely automated in an integrated webserver called ISMARA that allows researchers to analyze their own data by simply uploading RNA-seq or ChIP-seq data sets and provides results in an integrated web interface as well as in downloadable flat form. For any data set, ISMARA infers the key regulators in the system, their activities across the input samples, the genes and pathways they target, and the core interactions between the regulators. We believe that by empowering experimental researchers to apply cutting-edge computational systems biology tools to their data in a completely automated manner, ISMARA can play an important role in developing our understanding of regulatory networks across metazoans.

Keywords: gene expression analysis, high-throughput sequencing analysis, transcription factor activity, transcription regulation

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Authors: Alexander N. Savostyanov, Tatiana A. Dolgorukova, Elena A. Esipenko, Mikhail S. Zaleshin, Margherita Malanchini, Anna V. Budakova, Alexander E. Saprygin, Tatiana A. Golovko, Yulia V. Kovas

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EEG correlates of mathematical and trait anxiety level were studied in 52 healthy Russian-speakers during execution of error-recognition tasks with lexical, arithmetic and algebraic conditions. Event-related spectral perturbations were used as a measure of brain activity. The ERSP plots revealed alpha/beta desynchronizations within a 500-3000 ms interval after task onset and slow-wave synchronization within an interval of 150-350 ms. Amplitudes of these intervals reflected the accuracy of error recognition, and were differently associated with the three conditions. The correlates of anxiety were found in theta (4-8 Hz) and beta2 (16-20 Hz) frequency bands. In theta band the effects of mathematical anxiety were stronger expressed in lexical, than in arithmetic and algebraic condition. The mathematical anxiety effects in theta band were associated with differences between anterior and posterior cortical areas, whereas the effects of trait anxiety were associated with inter-hemispherical differences. In beta1 and beta2 bands effects of trait and mathematical anxiety were directed oppositely. The trait anxiety was associated with increase of amplitude of desynchronization, whereas the mathematical anxiety was associated with decrease of this amplitude. The effect of mathematical anxiety in beta2 band was insignificant for lexical condition but was the strongest in algebraic condition. EEG correlates of anxiety in theta band could be interpreted as indexes of task emotionality, whereas the reaction in beta2 band is related to tension of intellectual resources.

Keywords: EEG, brain activity, lexical and numerical error-recognition tasks, mathematical and trait anxiety

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Authors: Payam Haghparast, Mikhail V. Sorin, Hakim Nesreddine

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The complex oblique shock phenomenon can be simply assumed as a normal shock at the constant area section to simulate a sharp pressure increase and velocity decrease in 1-D thermodynamic models. The assumed normal shock location is one of the greatest sources of error in ejector thermodynamic models. Most researchers consider an arbitrary location without justifying it. Our study compares the effect of normal shock place on ejector dimensions in 1-D models. To this aim, two different ejector experimental test benches, a constant area-mixing ejector (CAM) and a constant pressure-mixing (CPM) are considered, with different known geometries, operating conditions and working fluids (R245fa, R141b). In the first step, in order to evaluate the real value of the efficiencies in the different ejector parts and critical back pressure, a CFD model was built and validated by experimental data for two types of ejectors. These reference data are then used as input to the 1D model to calculate the lengths and the diameters of the ejectors. Afterwards, the design output geometry calculated by the 1D model is compared directly with the corresponding experimental geometry. It was found that there is a good agreement between the ejector dimensions obtained by the 1D model, for both CAM and CPM, with experimental ejector data. Furthermore, it is shown that normal shock place affects only the constant area length as it is proven that the inlet normal shock assumption results in more accurate length. Taking into account previous 1D models, the results suggest the use of the assumed normal shock location at the inlet of the constant area duct to design the supersonic ejectors.

Keywords: 1D model, constant area-mixing, constant pressure-mixing, normal shock location, ejector dimensions

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Authors: Bezuglov Eduard, Ryland Morgans, Talibov Oleg, Kalinin Evgeny, Butovsky Mikhail, Savin Evgeny, Tzgoev Eduard, Artemii Lazarev, Bekzhan Pirmakhanov, Anthony C. Hackney

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Currently, there is conflicting evidence regarding the efficacy of citrulline for physical performance and post-exercise recovery. Moreover, the vast majority of studies conducted used physically active volunteers from the general population and heterogeneous exercise protocols that are not specific to most sports. A single use of citrulline, regardless of the dose, will not have a significant effect on physical performance and post-exercise recovery in highly trained soccer players performing sport-specific exercises at maximum intensity. To evaluate the effectiveness of a single administration of citrulline at various doses in adult male professional soccer players performing sport-specific exercise at maximum intensity. A randomized, double-blind, placebo-controlled study analyzing eighteen soccer players from the top divisions of several European countries. The participants were randomized into three groups of six and performed a field-based soccer-specific test at 115% VO2max for 18-minutes. Comparative analysis of the cardiovascular system, physical activity, subjective perceived fatigue and post-exercise recovery was conducted. There were no statistically significant differences in more than one analyzed parameter. A single application of 3 to 6 grams of citrulline does not affect physical performance, subjective feeling of fatigue and post-exercise recovery in adult professional soccer players who have performed a sport-specific test. Currently, citrulline cannot be recommended for use as a supplement in adult professional soccer players

Keywords: citrulline, performance, recovery, soccer players

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Authors: Andrey V. Khromov, Antonida V. Makhotenko, Ekaterina A. Snigir, Svetlana S. Makarova, Natalia O. Kalinina, Valentin V. Makarov, Mikhail E. Taliansky

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Due to its simplicity, CRISPR/Cas9 has become widely used and capable of inducing mutations in the genes of organisms of various kingdoms. The aim of this work was to develop applications for the efficient modification of DNA coding sequences of phytoene desaturase (PDS), coilin and vacuolar invertase (Solanum tuberosum) genes, and to develop a new nanoparticles carrier efficient technology to deliver the CRISPR/Cas9 system for editing the plant genome. For each of the genes - coilin, PDS and vacuolar invertase, five single RNA guide (sgRNAs) were synthesized. To determine the most suitable nanoplatform, two types of NP platforms were used: magnetic NPs (MNPS) and gold NPs (AuNPs). To test the penetration efficiency, they were functionalized with fluorescent agents - BSA * FITS and GFP, as well as labeled Cy3 small-sized RNA. To measure the efficiency, a fluorescence and confocal microscopy were used. It was shown that the best of these options were AuNP - both in the case of proteins and in the case of RNA. The next step was to check the possibility of delivering components of the CRISPR/Cas9 system to plant cells for editing target genes. AuNPs were functionalized with a ribonucleoprotein complex consisting of Cas9 and corresponding to target genes sgRNAs, and they were biolistically bombarded to axillary buds and apical meristems of potato plants. After the treatment by the best NP carrier, potato meristems were grown to adult plants. DNA isolated from this plants was sent to a preliminary fragment of the analysis to screen out the non-transformed samples, and then to the NGS. The present work was carried out with the financial support from the Russian Science Foundation (grant No. 16-16-04019).

Keywords: biobombardment, coilin, CRISPR/Cas9, nanoparticles, NPs, PDS, sgRNA, vacuolar invertase

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Authors: Ekaterina Zubkova, Irina Beloglazova, Iurii Stafeev, Konsyantin Dergilev, Yelena Parfyonova, Mikhail Menshikov

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Mesenchymal stromal cells from adipose tissue (MSC) currently are widely used in regenerative medicine to restore the function of damaged tissues, but that is significantly hampered by their heterogeneity. One of the modern approaches to overcoming this obstacle is the polarization of cell subpopulations into a specific phenotype under the influence of cytokines and other factors that activate receptors and signal transmission to cells. We polarized MSC with factors affecting the inflammatory signaling and functional properties of cells, followed by verification of their expression profile and ability to affect the polarization of macrophages. RT-PCR evaluation showed that cells treated with LPS, interleukin-17, tumor necrosis factor α (TNF α), primarily express pro-inflammatory factors and cytokines, and after treatment with polyninosin polycytidic acid and interleukin-4 (IL4) anti-inflammatory factors and some proinflammatory factors. MSC polarized with pro-inflammatory cytokines showed a more robust pro-angiogenic effect in fibrin gel bead 3D angiogenesis assay. Further, we evaluated the possibility of paracrine effects of MSCs on the polarization of intact macrophages. Polarization efficiency was assesed by expression of M1/M2 phenotype markers CD80 and CD206. We showed that conditioned media from MSC preincubated in the presence of IL-4 cause an increase in CD206 expression similar to that observed in M2 macrophages. Conditioned media from MSC polarized in the presence of LPS or TNF-α increased the expression of CD80 antigen in macrophages, similar to that observed in M1 macrophages. In other cases, a pronounced paracrine effect of MSC on the polarization of macrophages was not detected. Thus, our study showed that the polarization of MSC along the pro-inflammatory or anti-inflammatory pathway allows us to obtain cell subpopulations that have a multidirectional modulating effect on the polarization of macrophages. (RFBR grants 20-015-00405 and 18-015-00398.)

Keywords: angiogenesis, cytokines, mesenchymal, polarization, inflammation

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Authors: Jorge A. Cruz-Morales, Joel Vargas, Arlette A. Santiago, Mikhail A. Tlenkopatchev

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In industrial processes such as oil extraction and refining, products are handled or generated in the gas phase, which represents a challenge in terms of treatment and purification. During the past three decades, new scientific findings and technological advances in separation based on the use of membranes have led to simpler and more efficient gas separation processes, optimizing the use of energy and generating less pollution. This work reports the synthesis and ring-opening metathesis polymerization (ROMP) of new structural isomers based on norbornene dicarboximides bearing trifluoromethyl moieties, specifically N-2-trifluoromethylphenyl-exo,endo-norbornene-5,6-dicarboximide (2a) and N-3-trifluoromethylphenyl-exo,endo-norbornene-5,6-dicarboximide (2b), using tricyclohexylphosphine [1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene][benzylidene] ruthenium dichloride (I), bis(tricyclohexylphosphine) benzylidene ruthenium (IV) dichloride (II), and bis(tricyclohexylphosphine) p-fluorophenylvinylidene ruthenium (II) dichloride (III). It was observed that the -CF3 moiety attached at the ortho position of the aromatic ring increases thermal and mechanical properties of the polymer, whereas meta substitution has the opposite effect. A comparative study of gas transportation in membranes, based on these fluorinated polynorbornenes, showed that -CF3 ortho substitution increases permeability of the polymer membrane as a consequence of the increase in both gas solubility and gas diffusion. In contrast, gas permeability coefficients of the meta-substituted polymer membrane are rather similar to those of that which is non-fluorinated; this can be attributed to a lower fractional free volume. The meta-substituted polymer membrane, besides showing the largest permselectivity coefficients of all the isomers studied here, was also found to have one of the largest permselectivity coefficients for separating H2/C3H6 into glassy polynorbornene dicarboximides.

Keywords: gas transport membranes, polynorbornene dicarboximide, ROMP, structural isomers

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Authors: Mikhail Panes, Sergei Pozniak, Nikolai Pozniak

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Purpose: To evaluate the effectiveness of intrastromal donor limbal segments implantation for treatment of progressive keratoconus considering on main characteristics of corneal endothelial cells. Setting: Outpatient ophthalmic clinic. Methods: Twenty patients (20 eyes) with progressive keratoconus II-III of Amsler classification were recruited. The worst eye was treated with the transplantation of donor limbal segments in the recipient corneal stroma, while the fellow eye was left untreated as a control of functional and morphological changes. Furthermore, twenty patients (20 eyes) without progressive keratoconus was used as a control of corneal endothelial cells changes. All patients underwent a complete ocular examination including uncorrected and corrected distance visual acuity (UDVA, CDVA), slit lamp examination fundus examination, corneal topography and pachymetry, auto-keratometry, Anterior Segment Optical Coherence Tomography and Corneal Endothelial Specular Microscopy. Results: After two years, statistically significant improvement in the UDVA and CDVA (on the average on two lines for UDVA and three-four lines for CDVA) were noted. Besides corneal astigmatism decreased from 5.82 ± 2.64 to 1.92 ± 1.4 D. Moreover there were no statistically significant differences in the changes of mean spherical equivalent, keratometry and pachymetry indicators. It should be noted that after two years there were no significant differences in the changes of the number and form of corneal endothelial cells. It can be regarded as a process stabilization. In untreated control eyes, there was a general trend towards worsening of UDVA, CDVA and corneal thickness, while corneal astigmatism was increased. Conclusion: Intrastromal donor segments implantation is a safe technique for keratoconus treatment. Intrastromal donor segments implantation is an efficient procedure to stabilize and improve progressive keratoconus.

Keywords: corneal endothelial cells, intrastromal donor limbal segments, progressive keratoconus, surgical treatment of keratoconus

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Authors: Debabrata Adhikari, Mikhail Matveev, Louise Brown, Jan Kočí, Andy Long

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Resin transfer molding (RTM) is increasingly used for manufacturing high-quality composite structures due to its additional advantages over prepregs of low-cost out-of-autoclave processing. However, to retain the advantages, it is critical to reduce the void content during the injection. Reinforcements commonly used in RTM, such as woven fabrics, have dual-scale porosity with mesoscale pores between the yarns and the micro-scale pores within the yarns. Due to the fabric geometry and the nature of the dual-scale flow, the flow front during injection creates a complicated fingering formation which leads to void formation. Analytical modeling of void formation for woven fabrics has been widely studied elsewhere. However, there is scope for improvement to the reduction in void formation in 3D fabrics wherein the in-plane yarn layers are confined by additional through-thickness binder yarns. In the present study, the structural morphology of the tortuous pore spaces in the 3D fabric has been studied and implemented using open-source software TexGen. An analytical model for the void and the fingering formation has been implemented based on an idealized unit cell model of the 3D fabric. Since the pore spaces between the yarns are free domains, the region is treated as flow-through connected channels, whereas intra-yarn flow has been modeled using Darcy’s law with an additional term to account for capillary pressure. Later the void fraction has been characterised using the criterion of void formation by comparing the fill time for inter and intra yarn flow. Moreover, the dual-scale two-phase flow of resin with air has been simulated in the commercial CFD solver OpenFOAM/ANSYS to predict the probable location of voids and validate the analytical model. The use of an idealised unit cell model will give the insight to optimise the mesoscale geometry of the reinforcement and injection parameters to minimise the void content during the LCM process.

Keywords: 3D fiber, void formation, RTM, process modelling

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Authors: Vadim V. Zefirov, Victor E. Sizov, Marina A. Pigaleva, Igor V. Elmanovich, Mikhail S. Kondratenko, Marat O. Gallyamov

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This work presents a novel method for treating porous hydrophobic polyolefin membranes using supercritical carbon dioxide that allows usage of the modified membrane in redox flow batteries with an aqueous electrolyte. Polyolefin membranes are well known and widely used, however, they cannot be used as separators in redox flow batteries with an aqueous electrolyte since they have insufficient wettability, and therefore do not provide sufficient proton conductivity. The main aim of the presented work was the development of hydrophilic composites based on cheap membranes and precursors. Supercritical fluid was used as a medium for the deposition of the hydrophilic phase on the hydrophobic surface of the membrane. Due to the absence of negative capillary effects in a supercritical medium, a homogeneous composite is obtained as a result of synthesis. The in-situ synthesized silicon oxide nanoparticles and the chitosan polymer layer act as the hydrophilic phase and not only increase the affinity of the membrane towards the electrolyte, but also reduce the pore size of the polymer matrix, which positively affects the ion selectivity of the membrane. The composite material obtained as a result of synthesis has enhanced hydrophilic properties and is capable of providing proton conductivity in redox flow batteries. The morphology of the obtained composites was characterized by electron microscopy. To analyze the phase composition, infrared spectroscopy was used. The hydrophilic properties were studied by water contact angle measurements. In addition, the proton conductivity and ion selectivity of the obtained samples were studied, and tests in real redox flow batteries were performed. As a result, modified membrane was characterised in detail and moreover it was shown that modified cheap polyolefin membranes have pronounced proton conductivity and high ion selectivity, so their performance in a real redox flow battery approaches expensive commercial analogues, reaching 70% of energy efficiency.

Keywords: carbon dioxide, chitosan, polymer membrane, redox flow batteries, silica nanoparticles, supercritical fluid

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Authors: Jae Ni Jang, Young Uk Kim

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Background: Chat Generative Pre-training Transformer-3 (ChatGPT; San Francisco, California, Open Artificial Intelligence) is an artificial intelligence chatbot based on a large language model designed to generate human-like text. As the usage of ChatGPT is increasing among less knowledgeable patients, medical students, and anesthesia and pain medicine residents or trainees, we aimed to evaluate the accuracy of ChatGPT-3 responses to questions about the American Society of Anesthesiologists (ASA) classification based on patients’ underlying diseases and assess the quality of the generated responses. Methods: A total of 47 questions were submitted to ChatGPT using textual prompts. The questions were designed for ChatGPT-3 to provide answers regarding ASA classification in response to common underlying diseases frequently observed in adult patients. In addition, we created 18 questions regarding the ASA classification for pediatric patients and pregnant women. The accuracy of ChatGPT’s responses was evaluated by cross-referencing with Miller’s Anesthesia, Morgan & Mikhail’s Clinical Anesthesiology, and the American Society of Anesthesiologists’ ASA Physical Status Classification System (2020). Results: Out of the 47 questions pertaining to adults, ChatGPT -3 provided correct answers for only 23, resulting in an accuracy rate of 48.9%. Furthermore, the responses provided by ChatGPT-3 regarding children and pregnant women were mostly inaccurate, as indicated by a 28% accuracy rate (5 out of 18). Conclusions: ChatGPT provided correct responses to questions relevant to the daily clinical routine of anesthesiologists in approximately half of the cases, while the remaining responses contained errors. Therefore, caution is advised when using ChatGPT to retrieve anesthesia-related information. Although ChatGPT may not yet be suitable for clinical settings, we anticipate significant improvements in ChatGPT and other large language models in the near future. Regular assessments of ChatGPT's ASA classification accuracy are essential due to the evolving nature of ChatGPT as an artificial intelligence entity. This is especially important because ChatGPT has a clinically unacceptable rate of error and hallucination, particularly in pediatric patients and pregnant women. The methodology established in this study may be used to continue evaluating ChatGPT.

Keywords: American Society of Anesthesiologists, artificial intelligence, Chat Generative Pre-training Transformer-3, ChatGPT

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Authors: Mikhail O. Eremin

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Present work is devoted to experimental study and numerical modelling of failure of rocks typical for Kuzbass coal basin (Russia). The main goal was to define strength and deformation characteristics of rocks on the base of uniaxial compression and three-point bending loadings and then to build a mathematical model of failure process for both types of loading. Depending on particular physical-mechanical characteristics typical rocks of Kuzbass coal basin (sandstones, siltstones, mudstones, etc. of different series – Kolchuginsk, Tarbagansk, Balohonsk) manifest brittle and quasi-brittle character of failure. The strength characteristics for both tension and compression are found. Other characteristics are also found from the experiment or taken from literature reviews. On the base of obtained characteristics and structure (obtained from microscopy) the mathematical and structural models are built and numerical modelling of failure under different types of loading is carried out. Effective characteristics obtained from modelling and character of failure correspond to experiment and thus, the mathematical model was verified. An Instron 1185 machine was used to carry out the experiments. Mathematical model includes fundamental conservation laws of solid mechanics – mass, impulse, energy. Each rock has a sufficiently anisotropic structure, however, each crystallite might be considered as isotropic and then a whole rock model has a quasi-isotropic structure. This idea gives an opportunity to use the Hooke’s law inside of each crystallite and thus explicitly accounting for the anisotropy of rocks and the stress-strain state at loading. Inelastic behavior is described in frameworks of two different models: von Mises yield criterion and modified Drucker-Prager yield criterion. The damage accumulation theory is also implemented in order to describe a failure process. Obtained effective characteristics of rocks are used then for modelling of rock mass evolution when mining is carried out both by an open-pit or underground opening.

Keywords: damage accumulation, Drucker-Prager yield criterion, failure, mathematical modelling, three-point bending, uniaxial compression

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Authors: Alexander N. Savostyanov, Tatyana A. Dolgorukova, Elena A. Esipenko, Mikhail S. Zaleshin, Margherita Malanchini, Anna V. Budakova, Alexander E. Saprygin, Yulia V. Kovas

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The present study compared spectral-power indexes and cortical topography of brain activity in a sample characterized by different levels of trait and mathematical anxiety. 52 healthy Russian-speakers (age 17-32; 30 males) participated in the study. Participants solved an error recognition task under 3 conditions: A lexical condition (simple sentences in Russian), and two numerical conditions (simple arithmetic and complicated algebraic problems). Trait and mathematical anxiety were measured using self-repot questionnaires. EEG activity was recorded simultaneously during task execution. Event-related spectral perturbations (ERSP) were used to analyze spectral-power changes in brain activity. Additionally, sLORETA was applied in order to localize the sources of brain activity. When exploring EEG activity recorded after tasks onset during lexical conditions, sLORETA revealed increased activation in frontal and left temporal cortical areas, mainly in the alpha/beta frequency ranges. When examining the EEG activity recorded after task onset during arithmetic and algebraic conditions, additional activation in delta/theta band in the right parietal cortex was observed. The ERSP plots reveled alpha/beta desynchronizations within a 500-3000 ms interval after task onset and slow-wave synchronization within an interval of 150-350 ms. Amplitudes of these intervals reflected the accuracy of error recognition, and were differently associated with the three (lexical, arithmetic and algebraic) conditions. The level of trait anxiety was positively correlated with the amplitude of alpha/beta desynchronization. The level of mathematical anxiety was negatively correlated with the amplitude of theta synchronization and of alpha/beta desynchronization. Overall, trait anxiety was related with an increase in brain activation during task execution, whereas mathematical anxiety was associated with increased inhibitory-related activity. We gratefully acknowledge the support from the №11.G34.31.0043 grant from the Government of the Russian Federation.

Keywords: anxiety, EEG, lexical and numerical error-recognition tasks, alpha/beta desynchronization

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Authors: Mikhail V. Khachaturyan, Inga A. Koryagina, Eugenia V. Klicheva

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In modern conditions, scientific judgment of problems in developing mechanisms of value creation and risk management acquires special relevance. Formation of economic knowledge has resulted in the constant analysis of consumer behavior for all players from national and world markets. Effective mechanisms development of the demand analysis, crucial for consumer's characteristics of future production, and the risks connected with the development of this production are the main objectives of control systems in modern conditions. The modern period of economic development is characterized by a high level of globalization of business and rigidity of competition. At the same time, the considerable share of new products and services costs has a non-material intellectual nature. The most successful in Russia is the contemporary development of small innovative firms. Such firms, through their unique technologies and new approaches to process management, which form the basis of their intellectual capital, can show flexibility and succeed in the market. As a rule, such enterprises should have very variable structure excluding the tough scheme of submission and demanding essentially new incentives for inclusion of personnel in innovative activity. Realization of similar structures, as well as a new approach to management, can be constructed based on value-oriented management which is directed to gradual change of consciousness of personnel and formation from groups of adherents included in the solution of the general innovative tasks. At the same time, valuable changes can gradually capture not only innovative firm staff, but also the structure of its corporate partners. Introduction of new technologies is the significant factor contributing to the development of new valuable imperatives and acceleration of the changing values systems of the organization. It relates to the fact that new technologies change the internal environment of the organization in a way that the old system of values becomes inefficient in new conditions. Introduction of new technologies often demands change in the structure of employee’s interaction and training in their new principles of work. During the introduction of new technologies and the accompanying change in the value system, the structure of the management of the values of the organization is changing. This is due to the need to attract more staff to justify and consolidate the new value system and bring their view into the motivational potential of the new value system of the organization.

Keywords: value, risk, creation, problems, organization

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Authors: Mikhail V. Khachaturyan, Inga A. Koryagina, Maria Nikishova

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The study investigates the impact of the ongoing financial crisis, started in the 2^nd half of 2014, on marketing budgets spent by Fast-moving consumer goods companies. In these conditions, special importance is given to efficient possessory risk management systems. The main objective for establishing and developing possessory risk management systems for FMCG companies in a crisis is to analyze the data relating to the external environment and consumer behavior in a crisis. Another important objective for possessory risk management systems of FMCG companies is to develop measures and mechanisms to maintain and stimulate sales. In this regard, analysis of risks and threats which consumers define as the main reasons affecting their level of consumption become important. It is obvious that in crisis conditions the effective risk management systems responsible for development and implementation of strategies for consumer demand stimulation, as well as the identification, analysis, assessment and management of other types of risks of economic security will be the key to sustainability of a company. In terms of financial and economic crisis, the problem of forming and developing possessory risk management systems becomes critical not only in the context of management models of FMCG companies, but for all the companies operating in other sectors of the Russian economy. This study attempts to analyze the specifics of formation and development of company possessory risk management systems. In the modern economy, special importance among all the types of owner’s risks has the risk of reduction in consumer activity. This type of risk is common not only for the consumer goods trade. Study of consumer activity decline is especially important for Russia due to domestic market of consumer goods being still in the development stage, despite its significant growth. In this regard, it is especially important to form and develop possessory risk management systems for FMCG companies. The authors offer their own interpretation of the process of forming and developing possessory risk management systems within owner’s management models of FMCG companies as well as in Russian economy in general. Proposed methods and mechanisms of problem analysis of formation and development of possessory risk management systems in FMCG companies and the results received can be helpful for researchers interested in problems of consumer goods market development in Russia and overseas.

Keywords: FMCG companies, marketing budget, risk management, owner, Russian economy, organization, formation, development, system

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Authors: Konstantin S. Vainutis, Mark E. Andreev, Anastasia N. Voronova, Mikhail Yu. Shchelkanov

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Introduction: The trematodes from the family Cyclocoelidae (cyclocoelids) belong to the superfamily Echinostomatoidea infecting air sacs and trachea of wild birds. At present, the family Cyclocoelidae comprises nine valid genera in three subfamilies: Cyclocoelinae (type taxon), Haematotrephinae, and Typhlocoelinae. To our best knowledge, in this study, molecular genetic methods were used for the first time for studying cyclocoelids from the Russian Far East. Here we provide the data on the morphology and phylogeny of cyclocoelids from gadwall from the Russian Far East. The morphological and genetic data obtained for cyclocoelids indicated the necessity to revise the previously proposed classification within the family Cyclocoelidae. Objectives: The first objective was performing the morphological study of cyclocoelids found in M. strepera from the Russian Far East. The second objective is to reconstruct the phylogenetic relationships of the studied trematodes with other cyclocoelids using the 28S gene. Material and methods: During the field studies in the Khasansky district of the Primorsky region, 21 cyclocoelids were recovered from the air sacs of a single gadwall Mareca strepera. Seven samples of cyclocoelids were overstained in alum carmine, dehydrated in a graded ethanol series, cleared in clove oil, and mounted in Canada balsam. Genomic DNA was extracted from four cyclocoelids using the alkaline lysis method HotShot. The 28S rDNA fragment was amplified using the forward primer Digl2 and the reverse primer 1500R. Results: According to morphological features (ovary intratesticular, forming a triangle with the testes), the studied worms belong to the subfamily Cyclocoelinae Stossich, 1902. In particular, the highest morphological similarity was observed in relation to the trematodes of the genus Cyclocoelum Brandes, 1892 – genital pores are pharyngeal. However, the genetic analysis has shown significant discrepancies between the trematodes studied regarding the genus Cyclocoelum. On the phylogenetic tree, these trematodes took the sister position in relation to the genus Morishitium (previously considered in the subfamily Szidatitrematinae). Conclusion: Based on the results of the morphological and genetic studies, cyclocoelids isolated from Mareca strepera are suggested to be described in the previously unknown genus and differentiated from the type genus Cyclocoelum of the type subfamily Cyclocoelinae. Considering the available molecular data, including described cyclocoelids, the family Cyclocoelidae comprises ten valid genera in the three subfamilies mentioned above.

Keywords: new species, trematoda, phylogeny, cyclocoelidae

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Authors: Mikhail O. Eremin

Abstract:

Seismic activity around the world is clearly a threat to people's lives, as well as infrastructure and capital construction. It is the instability of the latter to powerful earthquakes that most often causes human casualties. Therefore, during construction it is necessary to take into account the risks of large-scale natural disasters. The task of assessing the risks of natural disasters is one of the most urgent at the present time. The final goal of any study of earthquakes is forecasting. This is especially important for seismically active regions of the planet where earthquakes occur frequently. Gorni Altai is one of such regions. In work, we developed the physical-mathematical model of stress-strain state evolution of loaded geomedium with the purpose of numerical simulation of seismic process accompanying the formation of Chuya-Kuray fault zone Gorni Altay, Russia. We build a structural model on the base of seismotectonic and paleoseismogeological investigations, as well as SRTM-data. Base of mathematical model is the system of equations of solid mechanics which includes the fundamental conservation laws and constitutive equations for elastic (Hooke's law) and inelastic deformation (modified model of Drucker-Prager-Nikolaevskii). An initial stress state of the model correspond to gravitational. Then we simulate an activation of a buried dextral strike-slip paleo-fault located in the basement of the model. We obtain the stages of formation and the structure of Chuya-Kuray fault zone. It is shown that results of numerical simulation are in good agreement with field observations in statistical sense. Simulated seismic process is strongly bound to the faults - lineaments with high degree of inelastic strain localization. Fault zone represents en-echelon system of dextral strike-slips according to the Riedel model. The system of surface lineaments is represented with R-, R'-shear bands, X- and Y-shears, T-fractures. Simulated seismic process obeys the laws of Gutenberg-Richter and Omori. Thus, the model describes a self-similar character of deformation and fracture of rocks and geomedia. We also modified the algorithm of determination of separate slip events in the model due to the features of strain rates dependence vs time.

Keywords: Drucker-Prager model, fault zone, numerical simulation, Riedel bands, seismic process, strike-slip fault

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Authors: Mikhail Zimin, Svetlana Zimina, Maxim Zimin

Abstract:

Without question, the basic method of prevention of human and material losses is the provision for adequate strength of constructions. At the same time, seismic load has a stochastic character. So, at all times, there is little danger of earthquake forces exceeding the selected design load. This risk is very low, but the consequences of such events may be extremely serious. Very dangerous are also occasional mistakes in seismic zoning, soil conditions changing before temblors, and failure to take into account hazardous natural phenomena caused by earthquakes. Besides, it is known that temblors detrimentally affect the environmental situation in regions where they occur, resulting in panic and worsening various disease courses. It may lead to mistakes of personnel of hazardous production facilities like the production and distribution of gas and oil, which may provoke severe accidents. In addition, gas and oil pipelines often have long mileage and cross many perilous zones by contrast with buildings. This situation increases the risk of heavy accidents. In such cases, complex monitoring of potential earthquake localities would be relevant. Even though the number of successful real-time forecasts of earthquakes is not great, it is well in excess, such as may be under random guessing. Experimental performed time-lapse study and analysis consist of searching seismic, biological, meteorological, and light earthquake precursors, processing such data with the help of fuzzy sets, collecting weather information, utilizing a database of terrain, and computing risk of slope processes under the temblor in a given setting. Works were done in a real-time environment and broadly acceptable results took place. Observations from already in-place seismic recording systems are used. Furthermore, a look back study of precursors of known earthquakes is done. Situations before Ashkhabad, Tashkent, and Haicheng seismic events are analyzed. Fairish findings are obtained. Results of earthquake forecasts can be used for predicting dangerous natural phenomena caused by temblors such as avalanches and mudslides. They may also be utilized for prophylaxis of some diseases and their complications. Relevant software is worked out too. It should be emphasized that such control does not require serious financial expenses and can be performed by a small group of professionals. Thus, complex monitoring of potential earthquake localities, including short-term earthquake forecasts and analysis of possible hazardous consequences of temblors, may further the safety of pipeline facilities.

Keywords: risk, earthquake, monitoring, forecast, precursor

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Authors: Debabrata Adhikari, Mikhail Matveev, Louise Brown, Andy Long, Jan Kočí

Abstract:

A good understanding of mesoscale permeability of complex architectures in fibrous porous preforms is of particular interest in order to achieve efficient and cost-effective resin impregnation of liquid composite molding (LCM). Fabrics used in structural reinforcements are typically woven or stitched. However, 3D fabric reinforcement is of particular interest because of the versatility in the weaving pattern with the binder yarn and in-plain yarn arrangements to manufacture thick composite parts, overcome the limitation in delamination, improve toughness etc. To predict the permeability based on the available pore spaces between the inter yarn spaces, unit cell-based computational fluid dynamics models have been using the Stokes Darcy model. Typically, the preform consists of an arrangement of yarns with spacing in the order of mm, wherein each yarn consists of thousands of filaments with spacing in the order of μm. The fluid flow during infusion exchanges the mass between the intra and inter yarn channels, meaning there is no dead-end of flow between the mesopore in the inter yarn space and the micropore in the yarn. Several studies have employed the Brinkman equation to take into account the flow through dual-scale porosity reinforcement to estimate their permeability. Furthermore, to reduce the computational effort of dual scale flow, scale separation criteria based on the ratio between yarn permeability to the yarn spacing was also proposed to quantify the dual scale and negligible micro-scale flow regime for the prediction of mesoscale permeability. In the present work, the key parameter to identify the influence of intra yarn permeability on the mesoscale permeability has been investigated with the systematic study of weft and warp yarn spacing on the plane weave as well as the position of binder yarn and number of in-plane yarn layers on 3D weave fabric. The permeability tensor has been estimated using an OpenFOAM-based model for the various weave pattern with idealized geometry of yarn implemented using open-source software TexGen. Additionally, scale separation criterion has been established based on the various configuration of yarn permeability for the 3D fabric with both the isotropic and anisotropic yarn from Gebart’s model. It was observed that the variation of mesoscale permeability Kxx within 30% when the isotropic porous yarn is considered for a 3D fabric with binder yarn. Furthermore, the permeability model developed in this study will be used for multi-objective optimizations of the preform mesoscale geometry in terms of yarn spacing, binder pattern, and a number of layers with an aim to obtain improved permeability and reduced void content during the LCM process.

Keywords: permeability, 3D fabric, dual-scale flow, liquid composite molding

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Authors: Mikhail V. Khachaturyan

Abstract:

The article analyzes problems of improving the management systems of the ownership risks in the conditions of the transformation of the Russian economy. Among the main sources of threats business owners should highlight is the inefficiency of the implementation of business models and interaction with hired managers. In this context, it is particularly important to analyze the relationship of business models and ownership risks. The analysis of this problem appears to be relevant for a number of reasons: Firstly, the increased risk appetite of the owner directly affects the business model and the composition of his holdings; secondly, owners with significant stakes in the company are factors in the formation of particular types of risks for owners, for which relations have a significant influence on a firm's competitiveness and ultimately determines its survival; and thirdly, inefficient system of management ownership of risk is one of the main causes of mass bankruptcies, which significantly affects the stable operation of the economy as a whole. The separation of the processes of possession, disposal and use in modern organizations is the cause of not only problems in the process of interaction between the owner and managers in managing the organization as a whole, but also the asymmetric information about the kinds and forms of the main risks. Managers tend to avoid risky projects, inhibit the diversification of the organization's assets, while owners can insist on the development of such projects, with the aim not only of creating new values for themselves and consumers, but also increasing the value of the company as a result of increasing capital. In terms of separating ownership and management, evaluation of projects by the ratio of risk-yield requires preservation of the influence of the owner on the process of development and making management decisions. It is obvious that without a clearly structured system of participation of the owner in managing the risks of their business, further development is hopeless. In modern conditions of forming a risk management system, owners are compelled to compromise between the desire to increase the organization's ability to produce new value, and, consequently, increase its cost due to the implementation of risky projects and the need to tolerate the cost of lost opportunities of risk diversification. Improving the effectiveness of the management of ownership risks may also contribute to the revitalization of creditors on implementation claims to inefficient owners, which ultimately will contribute to the efficiency models of ownership control to exclude variants of insolvency. It is obvious that in modern conditions, the success of the model of the ownership of risk management and audit is largely determined by the ability and willingness of the owner to find a compromise between potential opportunities for expanding the firm's ability to create new value through risk and maintaining the current level of new value creation and an acceptable level of risk through the use of models of diversification.

Keywords: improving, ownership risks, problem, Russia

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Authors: Tatiana N. Astakhova, Alexander E. Saprygin, Tatyana A. Golovko, Alexander N. Savostyanov, Mikhail S. Vlasov, Natalia V. Borisova, Alexandera G. Karpova, Urana N. Kavai-ool, Elena D. Mokur-ool, Nikolay A. Kolchanov, Lubomir I. Aftanas

Abstract:

The aim of the study is to compare behaviorally and EEG reactions in Turkic-speaking inhabitants of Siberia (Tuvinians and Yakuts) and Russians during the recognition of syntax errors in native and foreign languages. 63 healthy aboriginals of the Tyva Republic, 29 inhabitants of the Sakha (Yakutia) Republic, and 55 Russians from Novosibirsk participated in the study. All participants completed a linguistic task, in which they had to find a syntax error in the written sentences. Russian participants completed the task in Russian and in English. Tuvinian and Yakut participants completed the task in Russian, English, and Tuvinian or Yakut, respectively. EEG’s were recorded during the solving of tasks. For Russian participants, EEG's were recorded using 128-channels. The electrodes were placed according to the extended International 10-10 system, and the signals were amplified using ‘Neuroscan (USA)’ amplifiers. For Tuvinians and Yakuts EEG's were recorded using 64-channels and amplifiers Brain Products, Germany. In all groups 0.3-100 Hz analog filtering, sampling rate 1000 Hz were used. Response speed and the accuracy of recognition error were used as parameters of behavioral reactions. Event-related potentials (ERP) responses P300 and P600 were used as indicators of brain activity. The accuracy of solving tasks and response speed in Russians were higher for Russian than for English. The P300 amplitudes in Russians were higher for English; the P600 amplitudes in the left temporal cortex were higher for the Russian language. Both Tuvinians and Yakuts have no difference in accuracy of solving tasks in Russian and in their respective national languages (Tuvinian and Yakut). However, the response speed was faster for tasks in Russian than for tasks in their national language. Tuvinians and Yakuts showed bad accuracy in English, but the response speed was higher for English than for Russian and the national languages. With Tuvinians, there were no differences in the P300 and P600 amplitudes and in cortical topology for Russian and Tuvinian, but there was a difference for English. In Yakuts, the P300 and P600 amplitudes and topology of ERP for Russian were the same as Russians had for Russian. In Yakuts, brain reactions during Yakut and English comprehension had no difference and were reflected foreign language comprehension -while the Russian language comprehension was reflected native language comprehension. We found out that the Tuvinians recognized both Russian and Tuvinian as native languages, and English as a foreign language. The Yakuts recognized both English and Yakut as a foreign language, only Russian as a native language. According to the inquirer, both Tuvinians and Yakuts use the national language as a spoken language, whereas they don’t use it for writing. It can well be a reason that Yakuts perceive the Yakut writing language as a foreign language while writing Russian as their native.

Keywords: EEG, language comprehension, native and foreign languages, Siberian inhabitants

Procedia PDF Downloads 531

Authors: Tatiana N. Astakhova, Alexander E. Saprygin, Tatyana A. Golovko, Alexander N. Savostyanov, Mikhail S. Vlasov, Natalia V. Borisova, Alexandera G. Karpova, Urana N. Kavai-ool, Elena D. Mokur-ool, Nikolay A. Kolchanov, Lubomir I. Aftanas

Abstract:

The study is dedicated to the research of brain activity in bilingual inhabitants of Siberia. We compared behavioral reactions and event-related potentials in Turkic-speaking inhabitants of Siberia (Tuvinians and Yakuts) and Russians. 63 healthy aboriginals of the Tyva Republic, 29 inhabitants of the Sakha (Yakutia) Republic, and 55 Russians from Novosibirsk participated in the study. All the healthy and right-handed participants, matched on age and sex, were students of different universities. EEG’s were recorded during the solving of linguistic tasks. In these tasks, participants had to find a syntax error in the written sentences. There were four groups of sentences: Russian, English, Tuvinian, and Yakut. All participants completed the tasks in Russian and English. Additionally, Tuvinians and Yakuts completed the tasks in Tuvinian or Yakut respectively. For Russians, EEG's were recorded using 128-channels according to the extended International 10-10 system, and the signals were amplified using “Neuroscan (USA)” amplifiers. For Tuvinians and Yakuts, EEG's were recorded using 64-channels and amplifiers Brain Products, Germany. In all groups, 0.3-100 Hz analog filtering and sampling rate 1000 Hz were used. As parameters of behavioral reactions, response speed and the accuracy of recognition were used. Event-related potentials (ERP) responses P300 and P600 were used as indicators of brain activity. The behavioral reactions showed that in Russians, the response speed for Russian was faster than for English. Also, the accuracy of solving tasks was higher for Russian than for English. The peak P300 in Russians were higher for English, the peak P600 in the left temporal cortex were higher for the Russian language. Both Tuvinians and Yakuts have no difference in accuracy of solving tasks in Russian and in their respective national languages. However, the response speed was faster for tasks in Russian than for tasks in their national language. Tuvinians and Yakuts showed bad accuracy in English, but the response speed was higher for English than for Russian and the national languages. This can be explained by the fact that they did not think carefully and gave a random answer for English. In Tuvinians, The P300 and P600 amplitudes and cortical topology were the same for Russian and Tuvinian and different for English. In Yakuts, the P300 and P600 amplitudes and topology of ERP for Russian were the same as what Russians had for Russian. In Yakuts, brain reactions during Yakut and English comprehension had no difference, and were reflected to foreign language comprehension - while the Russian language comprehension was reflected to native language comprehension. We found out that the Tuvinians recognized both Russian and Tuvinian as native languages, and English as a foreign language. The Yakuts recognized both English and Yakut as a foreign language, and only Russian as a native language. According to the inquirer, both Tuvinians and Yakuts use the national language as a spoken language, whereas they don’t use it for writing. It can well be a reason that Yakuts perceive the Yakut writing language as a foreign language while writing Russian as their native.

Keywords: EEG, ERP, native and foreign languages comprehension, Siberian inhabitants

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Authors: Augustas Vaitkevicius, Mikhail Korjik, Eugene Tretyak, Ekaterina Trusova, Gintautas Tamulaitis

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Silicate materials are widely used as luminescent materials in amorphous and crystalline phase. Lithium silicate glass is popular for making neutron sensitive scintillation glasses. Cerium-doped single crystalline silicates of rare earth elements and yttrium have been demonstrated to be good scintillation materials. Due to their high thermal and photo-stability, silicate glass ceramics are supposed to be suitable materials for producing light converters for high power white light emitting diodes. In this report, the influence of glass composition and crystallization on photoluminescence (PL) of different silicate glasses was studied. Barium (BaO-2SiO₂) and lithium (Li₂O-2SiO₂) glasses were under study. Cerium, dysprosium, erbium and europium ions as well as their combinations were used for doping. The influence of crystallization was studied after transforming the doped glasses into glass ceramics by heat treatment in the temperature range of 550-850 degrees Celsius for 1 hour. The study was carried out by comparing the photoluminescence (PL) spectra, spatial distributions of PL parameters and quantum efficiency in the samples under study. The PL spectra and spatial distributions of their parameters were obtained by using confocal PL microscopy. A WITec Alpha300 S confocal microscope coupled with an air cooled CCD camera was used. A CW laser diode emitting at 405 nm was exploited for excitation. The spatial resolution was in sub-micrometer domain in plane and ~1 micrometer perpendicularly to the sample surface. An integrating sphere with a xenon lamp coupled with a monochromator was used to measure the external quantum efficiency. All measurements were performed at room temperature. Chromatic properties of the light emission from the glasses and glass ceramics have been evaluated. We observed that the quantum efficiency of the glass ceramics is higher than that of the corresponding glass. The investigation of spatial distributions of PL parameters revealed that heat treatment of the glasses leads to a decrease in sample homogeneity. In the case of BaO-2SiO₂: Eu, 10 micrometer long needle-like objects are formed, when transforming the glass into glass ceramics. The comparison of PL spectra from within and outside the needle-like structure reveals that the ratio between intensities of PL bands associated with Eu²⁺ and Eu³⁺ ions is larger in the bright needle-like structures. This indicates a higher degree of crystallinity in the needle-like objects. We observed that the spectral positions of the PL bands are the same in the background and the needle-like areas, indicating that heat treatment imposes no significant change to the valence state of the europium ions. The evaluation of chromatic properties confirms applicability of the glasses under study for fabrication of white light sources with high thermal stability. The ability to combine barium and lithium glass matrixes and doping by Eu, Ce, Dy, and Tb enables optimization of chromatic properties.

Keywords: glass ceramics, luminescence, phosphor, silicate

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Authors: Alla Ovsyannikova, Oksana Rymar, Elena Shakhtshneider, Mikhail Voevoda

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In Siberia endocrinologists increasingly noted young patients with the course of diabetes mellitus differing from 1 and 2 types. Therefore we did a molecular genetic study for this group of patients to verify the monogenic forms of diabetes mellitus in them and researched the characteristics of this pathology. When confirming the monogenic form of diabetes, we performed a correction therapy for many patients (transfer from insulin to tablets), prevented specific complications, examined relatives and diagnosed their diabetes at the preclinical stage, revealed phenotypic characteristics of the pathology which led to the high significance of this work. Materials and Methods: We observed 5 patients (4 families). We diagnosed MODY (Maturity Onset Diabetes of the Young) during the molecular genetic testing (direct automatic sequencing). All patients had a full clinical examination, blood samples for biochemical research, determination of C-peptide and TSH, antibodies to b-cells, microalbuminuria, abdominal ultrasound, heart and thyroid ultrasound, examination of ophthalmologist. Results: We diagnosed 3 rare types of MODY: two women had MODY8, one man – MODY6 and man and his mother - MODY12. Patients with types 8 and 12 had clinical features. Age of onset hyperglycemia ranged from 26 to 34 years. In a patient with MODY6 fasting hyperglycemia was detected during a routine examination. Clinical symptoms, complications were not diagnosed. The patient observes a diet. In the first patient MODY8 was detected during first pregnancy, she had itchy skin and mostly postprandial hyperglycemia. Upon examination we determined glycated hemoglobin 7.5%, retinopathy, non-proliferative stage, peripheral neuropathy. She uses a basic bolus insulin therapy. The second patient with MODY8 also had clinical manifestations of hyperglycemia (pruritus, thirst), postprandial hyperglycemia and diabetic nephropathy, a stage of microalbuminuria. The patient was diagnosed autoimmune thyroiditis. She used inhibitors of DPP-4. The patient with MODY12 had an aggressive course. In the detection of hyperglycemia he had complaints of visual impairment, intense headaches, leg cramps. The patient had a history of childhood convulsive seizures of non-epileptic genesis, without organic pathology, which themselves were stopped at the age of 12 years. When we diagnosed diabetes a patient was 28 years, he had hypertriglyceridemia, atherosclerotic plaque in the carotid artery, proliferative retinopathy (lacerocoagulation). Diabetes and early myocardial infarction were observed in three cases in family. We prescribe therapy with sulfonylureas and SGLT-2 inhibitors with a positive effect. At the patient's mother diabetes began at a later age (30 years) and a less aggressive course was observed. She also has hypertriglyceridemia and uses oral hypoglycemic drugs. Conclusions: 1) When young patients with hyperglycemia have extrapancreatic pathologies and diabetic complications with a short duration of diabetes we can assume they have one of type of MODY diabetes. 2) In patients with monogenic forms of diabetes mellitus, the clinical manifestations of hyperglycemia in each succeeding generation are revealed at an earlier age. Research had increased our knowledge of the monogenic forms of diabetes. The reported study was supported by RSCF, research project No. 14-15-00496-P.

Keywords: diabetes mellitus, MODY diabetes, monogenic forms, young patients

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Authors: Inas Raafat, Azza El Bassiouny, Waldemar L. Olszewsky, Nagui E. Mikhail, Mona Nossier, Nora E. I. El-Bassiouni, Mona Zoheiry, Houda Abou Taleb, Noha Abd El-Aal, Ali Baioumy, Shimaa Attia

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Background: Orthotopic liver transplantation is an established treatment for patients with severe acute and end-stage chronic liver disease. The shortage of donor organs continues to be the rate-limiting factor for liver transplantation throughout the world. Hepatocyte transplantation is a promising treatment for several liver diseases and can, also, be used as a "bridge" to liver transplantation in cases of liver failure. Aim of the work: This study was designed to develop a highly efficient protocol for isolation and transplantation of hepatocytes in experimental Lewis rat model to provide satisfactory guidelines for future application on humans.Materials and Methods: Hepatocytes were isolated from the liver by double perfusion technique and bone marrow cells were isolated by centrifugation of shafts of tibia and femur of donor Lewis rats. Recipient rats were subjected to sub-lethal dose of irradiation 2 days before transplantation. In a laparotomy operation the spleen was injected by freshly isolated hepatocytes and bone marrow cells were injected intravenously. The animals were sacrificed 45 day latter and splenic sections were prepared and stained with H & E, PAS AFP and Prox1. Results: The data obtained from this study showed that the double perfusion technique is successful in separation of hepatocytes regarding cell number and viability. Also the method used for bone marrow cells separation gave excellent results regarding cell number and viability. Intrasplenic engraftment of hepatocytes and live tissue formation within the splenic tissue were found in 70% of cases. Hematoxylin and eosin stained splenic sections from 7 rats showed sheets and clusters of cells among the splenic tissues. Periodic Acid Schiff stained splenic sections from 7 rats showed clusters of hepatocytes with intensely stained pink cytoplasmic granules denoting the presence of glycogen. Splenic sections from 7 rats stained with anti-α-fetoprotein antibody showed brownish cytoplasmic staining of the hepatocytes denoting positive expression of AFP. Splenic sections from 7 rats stained with anti-Prox1 showed brownish nuclear staining of the hepatocytes denoting positive expression of Prox1 gene on these cells. Also, positive expression of Prox1 gene was detected on lymphocytes aggregations in the spleens. Conclusions: Isolation of liver cells by double perfusion technique using collagenase buffer is a reliable method that has a very satisfactory yield regarding cell number and viability. The intrasplenic route of transplantation of the freshly isolated liver cells in an immunocompromised model was found to give good results regarding cell engraftment and tissue formation. Further studies are needed to assess function of engrafted hepatocytes by measuring prothrombin time, serum albumin and bilirubin levels.

Keywords: Lewis rats, hepatocytes, BMCs, transplantation, AFP, Prox1

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

Abstract:

The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

Procedia PDF Downloads 150