Search results for: Anca Irina Galaction

Authors: Irina S. Kolesnikova, Alexander A. Dolskiy, Natalya A. Lemskaya, Yulia V. Maksimova, Asia R. Shorina, Alena S. Telepova, Alexander S. Graphodatsky, Dmitry V. Yudkin

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A cytogenetic and molecular genetic study of the family with a male child who had mental retardation and autistic features revealed an abnormal chromosome 13 bearing an enlarged p-arm with amplified ribosomal DNA (rDNA) in a boy and his father. Cytogenetic analysis using standard G-banding and FISH with labeled rDNA probes revealed an abnormal chromosome 13 with an enlarged p-arms due to rDNA amplification in a male child, who had clinically confirmed mental retardation and an autistic behavior. This chromosome is evidently inherited from the father, who has morphologically the same chromosome, but is healthy. The karyotype of the mother was normal. Ag-NOR staining showed brightly stained large whole-p-arm nucleolus organizer regions (NORs) in a child and normal-sized NORs in his father with 13p+-NOR-amount mosaicism. qRT-PCR with specific primers showed highly increased levels of 18S, 28S and 5,8 S ribosomal RNA (rRNA) in the patient’s blood samples compared to a normal healthy control donor. Both patient’s father and mother had no elevated levels of rRNAs expression. Thus, in this case, rRNA level seems to correlate with mental retardation in familial individuals with 13p+. Our findings of rRNA overexpression in a patient with mental retardation and his parents may show a possible link between the karyotype (p-arm enlargement due to rDNA amplification), rDNA functionality (rRNA overexpression), functional changes in the brain and mental retardation. The study is supported by Russian Science Foundation Grant 15-15-10001.

Keywords: mental retardation, ribosomal DNA–rDNA, ribosomal RNA–rRNA, nucleolus organizer region–NOR, chromosome 13

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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: Irina Bondarenko, Olga Vandina

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The theory of evolutionary economics is the basis for preparation and application of methods forming the stock market infrastructure development concept. The authors believe that the basis for the process of formation and development of the stock market model infrastructure in Russia is the theory of large systems. This theory considers the financial market infrastructure as a whole on the basis of macroeconomic approach with the further definition of its aims and objectives. Evaluation of the prospects for interaction of securities market institutions will enable identifying the problems associated with the development of this system. The interaction of elements of the stock market infrastructure allows to reduce the costs and time of transactions, thereby freeing up resources of market participants for more efficient operation. Thus, methodology of the transaction analysis allows to determine the financial infrastructure as a set of specialized institutions that form a modern quasi-stable system. The financial infrastructure, based on international standards, should include trading systems, regulatory and supervisory bodies, rating agencies, settlement, clearing and depository organizations. Distribution of financial assets, reducing the magnitude of transaction costs, increased transparency of the market are promising tasks in the solution for questions of services level and quality increase provided by institutions of the securities market financial infrastructure. In order to improve the efficiency of the regulatory system, it is necessary to provide "standards" for all market participants. The development of a clear regulation for the barrier to the stock market entry and exit, provision of conditions for the development and implementation of new laws regulating the activities of participants in the securities market, as well as formulation of proposals aimed at minimizing risks and costs, will enable the achievement of positive results. The latter will be manifested in increasing the level of market participant security and, accordingly, the attractiveness of this market for investors and issuers.

Keywords: institutional infrastructure, financial assets, regulatory system, stock market, transparency of the market

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Authors: Vladimir Zobov, Nail Nazarov, Alexandra Vyshtakalyuk, Vyacheslav Semenov, Irina Galyametdinova, Vladimir Reznik

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The aim of this study was to investigate hepatoprotective properties of the Xymedon derivative L-ascorbate 1- (2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one (XD), which exhibits high efficiency as actoprotector. The study was carried out on 68 male albino rats weighing 250-400 g using preventive exposure to the test preparation. Effectiveness of XD win comparison with effectiveness of Xymedon (original substance) after administration of the compounds in identical doses. Maximum dose was 20 mg/kg. The animals orally received Xymedon or its derivative in doses of 10 and 20 mg/kg over 4 days. In 1-1.5 h after drug administration, CCl4 in vegetable oil (1:1) in a dose of 2 ml/kg. Controls received CCl4 but without hepatoprotectors. Intact control group consisted of rats, not receiving CCl4 or other compounds. The next day after the last administration of CCl4 and compounds under study animals were dehematized under ether anesthesia, blood and liver samples were taken for biochemical and histological analysis. Xymedon and XD administered according to the preventice scheme, exerted hepatoprotective effects: Xymedon — in the dose of 20 mg/kg, XD — in doses of 10 and 20 mg/kg. The drugs under study had different effects on liver condition, affected by induction with CCl4. Xymedon had a more pronounced effect both on the ALT level, which can be elevated not only due to destructive changes in hepatocytes, but also as a cholestasis manifestation, and on the serum total protein level, which reflects protein synthesis in liver. XD had a more pronounced effect on AST level, which is one of the markers of hepatocyte damage. Lower effective dose of XD — 10 mg/kg, compared to Xymedon effective according to, and its pronounced effect on AST, the hepatocyte cytolysis marker, is indicative of its higher preventive effectiveness, compared to Xymedon. This work was performed with the financial support of Russian Science Foundation (grant No: 14-50-00014).

Keywords: hepatoprotectors, pyrimidine derivatives, toxic liver damage, xymedon

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Authors: Ola Jon Mork, Irina Emily Hansen

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The European Growth Strategy Program calls for more efficient methods for knowledge creation and innovation. This study contributes with new insights into the Singapore Innovation System; more precisely how knowledge processes are facilitated. The research material is collected by visiting the different innovation locations in Singapore and depth interview with key persons. The different innovation actors web sites and brochures have been studied. Governmental reports and figures have also been studied. The findings show that facilitation of Knowledge Processes in the Singapore Innovation System has a basic structure with three processes, which is 1) Idea capturing – 2)Technology and Business Execution – 3)Idea Realization. Dedicated innovation parks work with the most promising entrepreneurs; more precisely: finding the persons with the motivation to 'change the world'. The innovation park will facilitate these entrepreneurs for 100 days, where they also will be connected to a global network of venture capital. And, the entrepreneurs will have access to mentors from these venture companies. Research institutes parks work with the development of world leading technology. To facilitate knowledge development they connect with industrial companies which are the most promising applicators of their technology. Knowledge facilitation is the main purpose, but this cooperation/testing is also serving as a platform for funding. Probably this is cooperation is also attractive for world leading companies. Dedicated innovation parks work with facilitation of innovators of new applications and perfection of products for the end- user. These parks can be specialized in special areas, like health products and life science products. Another example of this is automotive companies giving research call for these parks to develop and innovate new products and services upon their technology. Common characteristics for the knowledge facilitation in the Singapore Innovation System are a short trial period for promising actors, normally 100 days. It is also a strong focus on training of the entrepreneurs. Presentations and diffusion of knowledge is an important part of the facilitation. Funding will be available for the most successful entrepreneurs and innovators.

Keywords: knowledge processes, facilitation, innovation, Singapore innovation web

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Authors: Thomas Louis, Irina Primac, Florent Morfoisse, Tania Durre, Silvia Blacher, Agnes Noel

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In vitro and in vivo lymphangiogenesis assays are essential for the identification of potential lymphangiogenic agents and the screening of pharmacological inhibitors. In the present study, we analyse three biological models: in vitro lymphatic endothelial cell spheroids, in vivo ear sponge assay, and in vivo lymph node colonisation by tumour cells. These assays provide suitable 3D models to test pro- and anti-lymphangiogenic factors or drugs. 3D images were acquired by confocal laser scanning and light sheet fluorescence microscopy. Virtual scan microscopy followed by 3D reconstruction by image aligning methods was also used to obtain 3D images of whole large sponge and ganglion samples. 3D reconstruction, image segmentation, skeletonisation, and other image processing algorithms are described. Fixed and time-lapse imaging techniques are used to analyse lymphatic endothelial cell spheroids behaviour. The study of cell spatial distribution in spheroid models enables to detect interactions between cells and to identify invasion hierarchy and guidance patterns. Global measurements such as volume, length, and density of lymphatic vessels are measured in both in vivo models. Branching density and tortuosity evaluation are also proposed to determine structure complexity. Those properties combined with vessel spatial distribution are evaluated in order to determine lymphangiogenesis extent. Lymphatic endothelial cell invasion and lymphangiogenesis were evaluated under various experimental conditions. The comparison of these conditions enables to identify lymphangiogenic agents and to better comprehend their roles in the lymphangiogenesis process. The proposed methodology is validated by its application on the three presented models.

Keywords: 3D image segmentation, 3D image skeletonisation, cell invasion, confocal microscopy, ear sponges, light sheet microscopy, lymph nodes, lymphangiogenesis, spheroids

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Authors: Manav Sabharwal, Ruda Rai Md, Candace Parker, James Ridley

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Wheat is one of the most commonly consumed grains worldwide, which contains gluten. Nowadays, gluten intake is considered to be a trigger for GRDs, including Celiac disease (CD), a common genetic disease affecting 1% of the US population, non-celiac gluten sensitivity (NCGS) and wheat allergy. NCGS is being recognized as an acquired gluten-sensitive enteropathy that is prevalent across age, ethnic and geographic groups. The cause of this entity is not fully understood, and recent studies suggest that it is more common in participants with irritable bowel syndrome (IBS), with iron deficiency anemia, symptoms of fatigue, and has considerable overlap in symptoms with IBS and Crohn’s disease. However, these studies were lacking in availability of complete serologies, imaging tests and/or pan-endoscopy. We performed a prospective study of 745 adult patients who presented to an outpatient clinic for evaluation of chronic upper gastro-intestinal symptoms and subsequently underwent an upper endoscopic (EGD) examination as standard of care. Evaluation comprised of comprehensive celiac antibody panel, inflammatory bowel disease (IBD) serologic markers, duodenal biopsies and Small Bowel Video Capsule Endoscopy (VCE), when available. At least 6 biopsy specimens were obtained from the duodenum and proximal jejunum during EGD, and CD3+ Intraepithelial lymphocytes (IELs) and villous architecture were evaluated by a single experienced pathologist, and VCE was performed by a single experienced gastroenterologist. Of the 745 patients undergoing EGD, 12% (93/745) patients showed elevated CD3+ IELs in the duodenal biopsies. 52% (387/745) completed a comprehensive CD panel and 7.2% (28/387) were positive for at least 1 CD antibody (Tissue transglutaminase (tTG), being the most common antibody in 65% (18/28)). Of these patients, 18% (5/28) showed increased duodenal CD3+ IELs, but 0% showed villous blunting or distortion to meet criteria for CD. Surprisingly, 43% (12/28) were positive for at 1 IBD serology (ASCA, ANCA or expanded IBD panel (LabCorp)). Of these 28 patients, 29% (8/28) underwent a SB VCE, of which 100 % (8/8) showed significant jejuno-ileal mucosal lesions diagnostic for IBD. Findings of abnormal CD antibodies (7.2%, 28/387) and increased CD3+ IELs on duodenal biopsy (12%, 93/745) were observed frequently in patients with UGI symptoms undergoing EGD in an outpatient clinic. None met criteria for CD, and a high proportion (43%, 12/28) showed evidence of overlap with IBD. This suggests a potential causal link of acquired GRDs to underlying inflammation and gut mucosal barrier disruption. Further studies to investigate a role for abnormal antigen presentation of dietary gluten to gut associated lymphoid tissue as a cause are justified. This may explain a high prevalence of GRDs in the population and correlation with IBS, IBD and other gut inflammatory disorders.

Keywords: celiac, gluten sensitive enteropathy, lymphocitic enteritis, IBS, IBD

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Authors: James Skon, Irina Beshentseva, Michelle Polak

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Wifi solutions come in two major classes. Small Office/Home Office (SOHO) WiFi, characterized by inexpensive WiFi routers, with one or two service set identifiers (SSIDs), and a single shared passphrase. These access points provide no significant user management or monitoring, and no aggregation of monitoring and control for multiple routers. The other solution class is managed enterprise WiFi solutions, which involve expensive Access Points (APs), along with (also costly) local or cloud based management components. These solutions typically provide portal based login, per user virtual local area networks (VLANs), and sophisticated monitoring and control across a large group of APs. The cost for deploying and managing such managed enterprise solutions is typically about 10 fold that of inexpensive consumer APs. Low revenue organizations, such as schools, non-profits, non-government organizations (NGO's), small businesses, and even homes cannot easily afford quality enterprise WiFi solutions, though they may need to provide quality WiFi access to their population. Using available lower cost Wifi solutions can significantly reduce their ability to provide reliable, secure network access. This project explored and created a new approach for providing secured managed enterprise WiFi based on low cost hardware combined with both new and existing (but modified) open source software. The solution provides a cloud based management interface which allows organizations to aggregate the configuration and management of small, medium and large WiFi solutions. It utilizes a novel approach for user management, giving each user a unique passphrase. It provides unlimited SSID's across an unlimited number of WiFI zones, and the ability to place each user (and all their devices) on their own VLAN. With proper configuration it can even provide user local services. It also allows for users' usage and quality of service to be monitored, and for users to be added, enabled, and disabled at will. As inferred above, the ultimate goal is to free organizations with limited resources from the expense of a commercial enterprise WiFi, while providing them with most of the qualities of such a more expensive managed solution at a fraction of the cost.

Keywords: wifi, enterprise, cloud, managed

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Authors: Ádám Vass, István Bakos, Irina Borbáth, Zoltán Pászti, István Sajó, András Tompos

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Important requirements for the anode side electrocatalysts of polymer electrolyte membrane (PEM) fuel cells are CO-tolerance, stability and corrosion resistance. Carbon is still the most common material for electrocatalyst supports due to its low cost, high electrical conductivity and high surface area, which can ensure good dispersion of the Pt. However, carbon becomes degraded at higher potentials and it causes problem during application. Therefore it is important to explore alternative materials with improved stability. Molybdenum-oxide can improve the CO-tolerance of the Pt/C catalysts, but it is prone to leach in acidic electrolyte. The Mo was stabilized by isovalent substitution of molybdenum into the rutile phase titanium-dioxide lattice, achieved by a modified multistep sol-gel synthesis method optimized for preparation of Ti0.7Mo.3O2-C composite. High degree of Mo incorporation into the rutile lattice was developed. The conductivity and corrosion resistance across the anticipated potential/pH window was ensured by mixed oxide – activated carbon composite. Platinum loading was carried out using NaBH4 and ethylene glycol; platinum content was 40 wt%. The electrocatalyst was characterized by both material investigating methods (i.e. XRD, TEM, EDS, XPS techniques) and electrochemical methods (cyclic-voltammetry, COads stripping voltammetry, hydrogen oxidation reaction on rotating disc electrode). The electrochemical activity of the sample was compared to commercial 40 wt% Pt/C (Quintech) and PtRu/C (Quintech, Pt= 20 wt%, Ru= 10 wt%) references. Enhanced CO tolerance of the electrocatalyst prepared using the Ti0.7Mo.3O2-C composite material was evidenced by the appearance of a CO-oxidation related 'pre-peak' and by the pronounced shift of the maximum of the main CO oxidation peak towards less positive potential compared to Pt/C. Fuel cell polarization measurements were also carried out using Bio-Logic and Paxitech FCT-150S test device. All details on the design, preparation, characterization and testing by both electrochemical measurements and fuel cell test device of electrocatalyst supported on Ti0.7Mo.3O2-C composite material will be presented and discussed.

Keywords: anode electrocatalyst, composite material, CO-tolerance, TiMoOx

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Authors: Elena I. Oprita, Oana Craciunescu, Rodica Tatia, Teodora Ciucan, Reka Barabas, Orsolya Raduly, Anca Oancea

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Healing of osteochondral defects requires repair of the damaged articular cartilage, the underlying subchondral bone and the interface between these tissues (the functional calcified layer). For this purpose, developing a single monophasic scaffold that can regenerate two specific lineages (cartilage and bone) becomes a challenge. The aim of this work was to develop variants of biodegradable cross-linked composite hydrogel based on natural polypeptides (gelatin), polysaccharides components (chondroitin-4-sulphate and hyaluronic acid), in a ratio of 2:0.08:0.02 (w/w/w) and mixed with Si-hydroxyapatite (Si-Hap), in two ratios of 1:1 and 2:1 (w/w). Si-Hap was synthesized and characterized as a better alternative to conventional Hap. Subsequently, both composite hydrogel variants were cross-linked with (N, N-(3-dimethylaminopropyl)-N-ethyl carbodiimide (EDC) and enriched with a small bioactive molecule (icariin). The small molecule icariin (Ica) (C33H40O15) is the main active constituent (flavonoid) of Herba epimedium used in traditional Chinese medicine to cure bone- and cartilage-related disorders. Ica enhances osteogenic and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), facilitates matrix calcification and increases the specific extracellular matrix (ECM) components synthesis by chondrocytes. Afterward, the composite hydrogels were characterized for their physicochemical properties in terms of the enzymatic biodegradation in the presence of type I collagenase and trypsin, the swelling capacity and the degree of crosslinking (TNBS assay). The cumulative release of Ica and real-time concentration were quantified at predetermined periods of time, according to the standard curve of standard Ica, after hydrogels incubation in saline buffer at physiological parameters. The obtained cross-linked composite hydrogels enriched with small-molecule Ica were also characterized for morphology by scanning electron microscopy (SEM). Their cytocompatibility was evaluated according to EN ISO 10993-5:2009 standard for medical device testing. Thus, analyses regarding cell viability (Live/Dead assay), cell proliferation (Neutral Red assay) and cell adhesion to composite hydrogels (SEM) were performed using NCTC clone L929 cell line. The final results showed that both cross-linked composite hydrogel variants enriched with Ica presented optimal physicochemical, structural and biological properties to be used as a natural scaffold able to repair osteochondral defects. The data did not reveal any toxicity of composite hydrogels in NCTC stabilized cell lines within the tested range of concentrations. Moreover, cells were capable of spreading and proliferating on both composite hydrogel surfaces. In conclusion, the designed biodegradable cross-linked composites enriched with Si and Ica are recommended for further testing as natural temporary scaffolds, which can allow cell migration and synthesis of new extracellular matrix within osteochondral defects.

Keywords: composites, gelatin, osteochondral defect, small molecule

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Authors: Daria Lozovskaia

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This paper is focused on the news coverage of public opinion polls about Russian full-scale invasion of Ukraine in Russian state-controlled media. After the announcement of the start of the so-called “Special Military Operation” on February 24, 2022, the number of publications of the results of public opinion polls increased many times over, and the poll numbers began to be discussed on social media and in the Kremlin’s official informational agenda. Headlines like "72 Percent of Russian Citizens Support the Operation " or "Russians Believe in Victory in the Special Military Operation" have become prominent parts of Russian state propaganda news stories and newspapers. At the same time, public opinion in Russia, as a concept and model, differs from the generally accepted democratic concept and has its own specifics. As a result, public opinion polls and their results, especially after February 24, have a number of features in the form of the dominance of the discourse of political elites in the media, which leads to a decrease in public awareness, the prevalence of the effect of joining the majority and a high number of non-responses due to fear of reprisals. The aim of this study was to determine the role of public opinion polls in the system of Russian war propaganda in Ukraine. For this purpose, were selected publications of the Russian media, the agenda of which corresponds to the official information policy of the Russian authorities. First, using frame analysis for the categories "Explicit trust", "Implicit trust", "Implicit distrust" and "Explicit distrust", provided by Irina Dusakova, the broadcast level of trust in the data of public opinion polls was determined. The results of this phase of the study showed that the Russian media broadcast an absolute level of confidence in public opinion polls regarding support for the war in Ukraine. The second stage of the study was the content analysis of publications. The categories of this analysis were derived from Anna Morelli's 10 Principles of Military Propaganda and Haavard Koppang's Definition of Propaganda to determine the purposes of the use of public opinion polls by Russian propaganda. The results of the study not only confirmed the widespread hypothesis that public opinion polls in Russia are used as a tool of state propaganda, but also showed that their purpose is to demonstrate the consolidation of society in support of the war and President Vladimir Putin.

Keywords: propaganda, public opinion, public opinion polls, Russian studies

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Authors: Irina Belozerova

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In the recent years, the number of crimes against peace and humanity has constantly been increasing. The development of the international community is inseparably connected to the compliance with the law which protects the rights and interests of citizens in all of their manifestations. The provisions of the law of criminal procedure are no exception. The rights of the victims of genocide, of the war crimes and the crimes against humanity, require particular attention. These crimes fall within the jurisdiction of the International Criminal Court governed by the Rome Statute of the International Criminal Court. These crimes have the following features. First, any such crime has a mass character and therefore requires specific regulation in the international criminal law and procedure and the national criminal law and procedure of different countries. Second, the victims of such crimes are usually children, women and old people; the entire national, ethnic, racial or religious groups are destroyed. These features influence the classification of victims by the age criterion. Article 68 of the Rome Statute provides for protection of the safety, physical and psychological well-being, dignity and privacy of victims and witnesses and thus determines the procedural status of these persons. However, not all the persons whose rights have been violated by the commission of these crimes acquire the status of victims. This is due to the fact that such crimes affect a huge number of persons and it is impossible to mention them all by name. It is also difficult to assess the entire damage suffered by the victims. While assessing the amount of damages it is essential to take into account physical and moral harm, as well as property damage. The procedural status of victims thus gains an exclusive character. In order to determine the full extent of the damage suffered by the victims it is necessary to collect sufficient evidence. However, it is extremely difficult to collect the evidence that would ensure the full and objective protection of the victims’ rights. While making requests for the collection of evidence, the International Criminal Court faces the problem of protection of national security information. Religious beliefs and the family life of victims are of great importance. In some Islamic countries, it is impossible to question a woman without her husband’s consent which affects the objectivity of her testimony. Finally, the number of victims is quantified by hundreds and thousands. The assessment of these elements demands time and highly qualified work. These factors justify the creation of a mechanism that would help to collect the evidence and establish the truth in the international criminal proceedings. This mechanism will help to impose a just and appropriate punishment for the persons accused of having committed a crime, since, committing the crime, criminals could not misunderstand the outcome of their criminal intent.

Keywords: crimes against humanity, evidence in international criminal proceedings, international criminal proceedings, protection of victims

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Authors: Beate Englich, Linda Schlittenbauer, Christiane Pfeifer, Isabel Kratochvil, Michael Borte, Gabriele I. Stangl, Martin von Bergen, Thorsten Reemtsma, Irina Lehmann, Kristin M. Junge

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The worldwide production of endocrine disrupting compounds (EDC) has risen dramatically over the last decades, as so has the prevalence for obesity. Many EDCs are believed to contribute to this obesity epidemic, by enhancing adipogenesis or disrupting relevant metabolism. This effect is most tremendous in the early prenatal period when priming effects find a highly vulnerable time window. Therefore, we investigate the impact of parabens on childhood overweight development and adipogenesis in general. Parabens are ester of 4-hydroxy-benzoic acid and part of many cosmetic products or food packing. Therefore, ubiquitous exposure can be found in the westernized world, with exposure already starting during the sensitive prenatal period. We assessed maternal cosmetic product consumption, prenatal paraben exposure and infant BMI z-scores in the prospective German LINA cohort. In detail, maternal urinary concentrations (34 weeks of gestation) of methyl paraben (MeP), ethyl paraben (EtP), n-propyl paraben (PrP) and n-butyl paraben (BuP) were quantified using UPLC-MS/MS. Body weight and height of their children was assessed during annual clinical visits. Further, we investigated the direct influence of those parabens on adipogenesis in-vitro using a human mesenchymal stem cell (MSC) differentiation assay to mimic a prenatal exposure scenario. MSC were exposed to 0.1 – 50 µM paraben during the entire differentiation period. Differentiation outcome was monitored by impedance spectrometry, real-time PCR and triglyceride staining. We found that maternal cosmetic product consumption was highly correlated with urinary paraben concentrations at pregnancy. Further, prenatal paraben exposure was linked to higher BMI Z-scores in children. Our in-vitro analysis revealed that especially the long chained paraben BuP stimulates adipogenesis by increasing the expression of adipocyte specific genes (PPARγ, ADIPOQ, LPL, etc.) and triglyceride storage. Moreover, we found that adiponectin secretion is increased whereas leptin secretion is reduced under BuP exposure in-vitro. Further mechanistic analysis for receptor binding and activation of PPARγ and other key players in adipogenesis are currently in process. We conclude that maternal cosmetic product consumption is linked to prenatal paraben exposure of children and contributes to the development of infant overweight development by triggering key pathways of adipogenesis.

Keywords: adipogenesis, endocrine disruptors, paraben, prenatal exposure

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Authors: Elene Zhuravliova, Tamar Barbakadze, Irina Kalandadze, Elnari Zaalishvili, Lali Shanshiashvili, David Mikeladze

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Background: Multiple sclerosis (MS) is an inflammatory, neurodegenerative disease, which is accompanied by demyelination and autoimmune response to myelin proteins. Among post-translational modifications, which mediate the modulation of inflammatory pathways during MS, methylation is the main one. The methylation of DNA, also amino acids lysine and arginine, occurs in the cell. It was found that decreased trans-methylation is associated with neuroinflammatory diseases. Therefore, abnormal regulation of the methyl cycle could induce demyelination through the action on PAD (peptidyl-arginine-deiminase) gene promoter. PAD takes part in protein citrullination and targets myelin basic protein (MBP), which is affected during demyelination. To determine whether MBP charge isomers are changing the methyl cycle, we have estimated the concentrations of methyl cycle metabolites in MBP-activated primary astrocytes and oligodendrocytes. For this purpose, the action of the citrullinated MBP- C8 and the most cationic MBP-C1 isomers on the primary cells were investigated. Methods: Primary oligodendrocyte and astrocyte cell cultures were prepared from whole brains of 2-day-old Wistar rats. The methyl cycle metabolites, including homocysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), were estimated by HPLC analysis using fluorescence detection and prior derivatization. Results: We found that the action of MBP-C8 and MBP-C1 induces a decrease in the concentration of both methyl cycle metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), in astrocytes compared to the control cells. As for oligodendrocytes, the concentration of SAM was increased by the addition of MBP-C1, while MBP-C8 has no significant effect. As for SAH, its concentration was increased compared to the control cells by the action of both MBP-C1 and MBP-C8. A significant increase in homocysteine concentration was observed by the action of the MBP-C8 isomer in both oligodendrocytes and astrocytes. Conclusion: These data suggest that MBP charge isomers change the concentration of methyl cycle metabolites. MBP-C8 citrullinated isomer causes elevation of homocysteine in astrocytes and oligodendrocytes, which may be the reason for decreased astrocyte proliferation and increased oligodendrocyte cell death which takes place in neurodegenerative processes. Elevated homocysteine levels and subsequent abnormal regulation of methyl cycles in oligodendrocytes possibly change the methylation of DNA that activates PAD gene promoter and induces the synthesis of PAD, which in turn provokes the process of citrullination, which is the accompanying process of demyelination. Acknowledgment: This research was supported by the SRNSF Georgia RF17_534 grant.

Keywords: myelin basic protein, astrocytes, methyl cycle metabolites, homocysteine, oligodendrocytes

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Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Alexander V. Laikov, Alexander V. Shestopalov

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Background. Neuropathy is a common complication of obesity. In this regard, the content of neurotrophins in such patients is of particular interest. Neurotrophins are the proteins that regulate neuron survival and neuroplasticity and include brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). However, the risk of complications depends on the metabolic type of obesity. Metabolically unhealthy obesity (MUHO) is associated with a high risk of complications, while this is not the case with metabolically healthy obesity (MHO). Therefore, the aim of our work was to study the effect of the obesity metabolic type on serum neurotrophins levels. Patients, materials, methods. The study included 134 healthy donors and 104 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=40) and MUHO (n=55). In the blood serum, the concentration of BDNF and NGF was determined. In addition, the content of adipokines (leptin, asprosin, resistin, adiponectin), myokines (irisin, myostatin, osteocrin), indicators of carbohydrate, and lipid metabolism were measured. Correlation analysis revealed the relationship between the studied parameters. Results. We found that serum BDNF concentration was not different between obese patients and healthy donors, regardless of obesity metabolic type. At the same time, in obese patients, there was a decrease in serum NGF level versus control. A similar trend was characteristic of both MHO and MUHO. However, MUHO patients had a higher NGF level than MHO patients. The literature indicates that obesity is associated with an increase in the plasma concentration of NGF. It can be assumed that in obesity, there is a violation of NGF storage in platelets, which accelerates neurotrophin degradation. We found that BDNF concentration correlated with irisin levels in MUHO patients. Healthy donors had a weak association between NGF and VEGF levels. No such association was found in obese patients, but there was an association between NGF and leptin concentrations. In MHO, the concentration of NHF correlated with the content of leptin, irisin, osteocrin, insulin, and the HOMA-IR index. But in MUHO patients, we found only the relationship between NGF and adipokines (leptin, asprosin). It can be assumed that in patients with MHO, the replenishment of serum NGF occurs under the influence of muscle and adipose tissue. In the MUHO patients only the effect of adipose tissue on NGF was observed. Conclusion. Obesity, regardless of metabolic type, is associated with a decrease in serum NGF concentration. We showed that muscle and adipose tissues make a significant contribution to the serum NGF pool in the MHO patients. In MUHO there is no effect of muscle on the NGF level, but the effect of adipose tissue remains.

Keywords: neurotrophins, nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: Irina M. Kolesnikova, Andrey M. Gaponov, Sergey A. Roumiantsev, Tatiana V. Grigoryeva, Dilyara R. Khusnutdinova, Dilyara R. Kamaldinova, Alexander V. Shestopalov

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Background. Obese patients have unequal risks of metabolic disorders. It is accepted to distinguish between metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). MUHO patients have a high risk of metabolic disorders, insulin resistance, and diabetes mellitus. Among the other things, the gut microbiota also contributes to the development of metabolic disorders in obesity. Obesity is accompanied by significant changes in the gut microbial community. In turn, bacterial translocation from the intestine is the basis for the blood microbiome formation. The aim was to study the features of the blood microbiome in patients with various metabolic types of obesity. Patients, materials, methods. The study included 116 healthy donors and 101 obese patients. Depending on the metabolic type of obesity, the obese patients were divided into subgroups with MHO (n=36) and MUHO (n=53). Quantitative and qualitative assessment of the blood microbiome was based on metagenomic analysis. Blood samples were used to isolate DNA and perform sequencing of the variable v3-v4 region of the 16S rRNA gene. Alpha diversity indices (Simpson index, Shannon index, Chao1 index, phylogenetic diversity, the number of observed operational taxonomic units) were calculated. Moreover, we compared taxa (phyla, classes, orders, and families) in terms of isolation frequency and the taxon share in the total bacterial DNA pool between different patient groups. Results. In patients with MHO, the characteristics of the alpha-diversity of the blood microbiome were like those of healthy donors. However, MUHO was associated with an increase in all diversity indices. The main phyla of the blood microbiome were Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Cyanobacteria, TM7, Thermi, Verrucomicrobia, Chloroflexi, Acidobacteria, Planctomycetes, Gemmatimonadetes, and Tenericutes were found to be less significant phyla of the blood microbiome. Phyla Acidobacteria, TM7, and Verrucomicrobia were more often isolated in blood samples of patients with MUHO compared with healthy donors. Obese patients had a decrease in some taxonomic ranks (Bacilli, Caulobacteraceae, Barnesiellaceae, Rikenellaceae, Williamsiaceae). These changes appear to be related to the increased diversity of the blood microbiome observed in obesity. An increase of Lachnospiraceae, Succinivibrionaceae, Prevotellaceae, and S24-7 was noted for MUHO patients, which, apparently, is explained by a magnification in intestinal permeability. Conclusion. Blood microbiome differs in obese patients and healthy donors at class, order, and family levels. Moreover, the nature of the changes is determined by the metabolic type of obesity. MUHO linked to increased diversity of the blood microbiome. This appears to be due to increased microbial translocation from the intestine and non-intestinal sources.

Keywords: blood microbiome, blood bacterial DNA, obesity, metabolically healthy obesity, metabolically unhealthy obesity

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Authors: Irina Veselova, Maria Makedonskaya, Olga Eremina, Alexandr Sidorov, Eugene Goodilin, Tatyana Shekhovtsova

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Such catecholamines as dopamine, norepinephrine, and epinephrine are the principal neurotransmitters in the sympathetic nervous system. Catecholamines and their metabolites are considered to be important markers of socially significant diseases such as atherosclerosis, diabetes, coronary heart disease, carcinogenesis, Alzheimer's and Parkinson's diseases. Currently, neurotransmitters can be studied via electrochemical and chromatographic techniques that allow their characterizing and quantification, although these techniques can only provide crude spatial information. Besides, the difficulty of catecholamine determination in biological materials is associated with their low normal concentrations (~ 1 nM) in biomaterials, which may become even one more order lower because of some disorders. In addition, in blood they are rapidly oxidized by monoaminooxidases from thrombocytes and, for this reason, the determination of neurotransmitter metabolism indicators in an organism should be very rapid (15—30 min), especially in critical states. Unfortunately, modern instrumental analysis does not offer a complex solution of this problem: despite its high sensitivity and selectivity, HPLC-MS cannot provide sufficiently rapid analysis, while enzymatic biosensors and immunoassays for the determination of the considered analytes lack sufficient sensitivity and reproducibility. Fluorescent and SERS-sensors remain a compelling technology for approaching the general problem of selective neurotransmitter detection. In recent years, a number of catecholamine sensors have been reported including RNA aptamers, fluorescent ribonucleopeptide (RNP) complexes, and boronic acid based synthetic receptors and the sensor operated in a turn-off mode. In this work we present the fluorescent and SERS turn-on sensor systems based on the bio- or chemorecognizing nanostructured films {chitosan/collagen-Tb/Eu/Cu-nanoparticles-indicator reagents} that provide the selective recognition, visualization, and sensing of the above mentioned catecholamines on the level of nanomolar concentrations in biomaterials (cell cultures, tissue etc.). We have (1) developed optically transparent porous films and gels of chitosan/collagen; (2) ensured functionalization of the surface by molecules-'recognizers' (by impregnation and immobilization of components of the indicator systems: biorecognizing and auxiliary reagents); (3) performed computer simulation for theoretical prediction and interpretation of some properties of the developed materials and obtained analytical signals in biomaterials. We are grateful for the financial support of this research from Russian Foundation for Basic Research (grants no. 15-03-05064 a, and 15-29-01330 ofi_m).

Keywords: biomaterials, fluorescent and SERS-recognition, neurotransmitters, solid-phase turn-on sensor system

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Authors: Areej K. Al-Jwaid, Dmitiry Berllio, Andrew Cundy, Irina Savina, Jonathan L. Caplin

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Phenol is a toxic compound that is widely distributed in the environment including the atmosphere, water and soil, due to the release of effluents from the petrochemical and pharmaceutical industries, coking plants and oil refineries. Moreover, a range of daily products, using phenol as a raw material, may find their way into the environment without prior treatment. The toxicity of phenol effects both human and environment health, and various physio-chemical methods to remediate phenol contamination have been used. While these techniques are effective, their complexity and high cost had led to search for alternative strategies to reduce and eliminate high concentrations of phenolic compounds in the environment. Biological treatments are preferable because they are environmentally friendly and cheaper than physico-chemical approaches. Some microorganisms such as Pseudomonas sp., Rhodococus sp., Acinetobacter sp. and Bacillus sp. have shown a high ability to degrade phenolic compounds to provide a sole source of energy. Immobilisation process utilising various materials have been used to protect and enhance the viability of cells, and to provide structural support for the bacterial cells. The aim of this study is to develop a new approach to the bioremediation of phenol based on an immobilisation strategy that can be used in wastewater. In this study, two bacterial species known to be phenol degrading bacteria (Pseudomonas mendocina and Rhodococus koreensis) were purchased from National Collection of Industrial, Food and Marine Bacteria (NCIMB). The two species and mixture of them were immobilised to produce macro porous crosslinked cell cryogels samples by using four types of cross-linker polymer solutions in a cryogelation process. The samples were used in a batch culture to degrade phenol at an initial concentration of 50mg/L at pH 7.5±0.3 and a temperature of 30°C. The four types of polymer solution - i. glutaraldehyde (GA), ii. Polyvinyl alcohol with glutaraldehyde (PVA+GA), iii. Polyvinyl alcohol–aldehyde (PVA-al) and iv. Polyetheleneimine–aldehyde (PEI-al), were used at different concentrations, ranging from 0.5 to 1.5% to crosslink the cells. The results of SEM and rheology analysis indicated that cell-cryogel samples crosslinked with the four cross-linker polymers formed monolithic macro porous cryogels. The samples were evaluated for their ability to degrade phenol. Macro porous cell–cryogels crosslinked with GA and PVA+GA showed an ability to degrade phenol for only one week, while the other samples crosslinked with a combination of PVA-al + PEI-al at two different concentrations have shown higher stability and viability to reuse to degrade phenol at concentration (50 mg/L) for five weeks. The initial results of using crosslinked cell cryogel samples to degrade phenol indicate that is a promising tool for bioremediation strategies especially to eliminate and remove the high concentration of phenol in wastewater.

Keywords: bioremediation, crosslinked cells, immobilisation, phenol degradation

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Authors: Irina P. Starodubtseva, Aleksandr N. Pavlenko

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Quenching is a term generally accepted for the process of rapid cooling of a solid that is overheated above the thermodynamic limit of the liquid superheat. The main objective of many previous studies on quenching is to find a way to reduce the total time of the transient process. Computational experiments were performed to simulate quenching by a falling liquid nitrogen film of an extremely overheated vertical copper plate with a structured capillary-porous coating. The coating was produced by directed plasma spraying. Due to the complexities in physical pattern of quenching from chaotic processes to phase transition, the mechanism of heat transfer during quenching is still not sufficiently understood. To our best knowledge, no information exists on when and how the first stable liquid-solid contact occurs and how the local contact area begins to expand. Here we have more models and hypotheses than authentically established facts. The peculiarities of the quench front dynamics and heat transfer in the transient process are studied. The created numerical model determines the quench front velocity and the temperature fields in the heater, varying in space and time. The dynamic pattern of the running quench front obtained numerically satisfactorily correlates with the pattern observed in experiments. Capillary-porous coatings with straight and reverse orientation of crests are investigated. The results show that the cooling rate is influenced by thermal properties of the coating as well as the structure and geometry of the protrusions. The presence of capillary-porous coating significantly affects the dynamics of quenching and reduces the total quenching time more than threefold. This effect is due to the fact that the initialization of a quench front on a plate with a capillary-porous coating occurs at a temperature significantly higher than the thermodynamic limit of the liquid superheat, when a stable solid-liquid contact is thermodynamically impossible. Waves present on the liquid-vapor interface and protrusions on the complex micro-structured surface cause destabilization of the vapor film and the appearance of local liquid-solid micro-contacts even though the average integral surface temperature is much higher than the liquid superheat limit. The reliability of the results is confirmed by direct comparison with experimental data on the quench front velocity, the quench front geometry, and the surface temperature change over time. Knowledge of the quench front velocity and total time of transition process is required for solving practically important problems of nuclear reactors safety.

Keywords: capillary-porous coating, heat transfer, Leidenfrost phenomenon, numerical simulation, quenching

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Authors: Dorottya Guban, Irina Borbath, Istvan Bakos, Peter Nemeth, Andras Tompos

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One of the greatest challenges of the implementation of polymer electrolyte membrane fuel cells (PEMFCs) is to find active and durable electrocatalysts. The cell performance is always limited by the oxygen reduction reaction (ORR) on the cathode since it is at least 6 orders of magnitude slower than the hydrogen oxidation on the anode. Therefore high loading of Pt is required. Catalyst corrosion is also more significant on the cathode, especially in case of mobile applications, where rapid changes of loading have to be tolerated. Pt-Sn bulk alloys and SnO2-decorated Pt3Sn nanostructures are among the most studied bimetallic systems for fuel cell applications. Exclusive formation of supported Sn-Pt alloy phases with different Pt/Sn ratios can be achieved by using controlled surface reactions (CSRs) between hydrogen adsorbed on Pt sites and tetraethyl tin. In this contribution our results for commercial and a home-made 20 wt.% Pt/C catalysts modified by tin anchoring via CSRs are presented. The parent Pt/C catalysts were synthesized by modified NaBH4-assisted ethylene-glycol reduction method using ethanol as a solvent, which resulted either in dispersed and highly stable Pt nanoparticles or evenly distributed raspberry-like agglomerates according to the chosen synthesis parameters. The 20 wt.% Pt/C catalysts prepared that way showed improved electrocatalytic performance in the ORR and stability in comparison to the commercial 20 wt.% Pt/C catalysts. Then, in order to obtain Sn-Pt/C catalysts with Pt/Sn= 3 ratio, the Pt/C catalysts were modified with tetraethyl tin (SnEt4) using three and five consecutive tin anchoring periods. According to in situ XPS studies in case of catalysts with highly dispersed Pt nanoparticles, pre-treatment in hydrogen even at 170°C resulted in complete reduction of the ionic tin to Sn0. No evidence of the presence of SnO2 phase was found by means of the XRD and EDS analysis. These results demonstrate that the method of CSRs is a powerful tool to create Pt-Sn bimetallic nanoparticles exclusively, without tin deposition onto the carbon support. On the contrary, the XPS results revealed that the tin-modified catalysts with raspberry-like Pt agglomerates always contained a fraction of non-reducible tin oxide. At the same time, they showed increased activity and long-term stability in the ORR than Pt/C, which was assigned to the presence of SnO2 in close proximity/contact with Pt-Sn alloy phase. It has been demonstrated that the content and dispersion of the fcc Pt3Sn phase within the electrocatalysts can be controlled by tuning the reaction conditions of CSRs. The bimetallic catalysts displayed an outstanding performance in the ORR. The preparation of a highly dispersed 20Pt/C catalyst permits to decrease the Pt content without relevant decline in the electrocatalytic performance of the catalysts.

Keywords: anode catalyst, cathode catalyst, controlled surface reactions, oxygen reduction reaction, PtSn/C electrocatalyst

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Authors: Elizaveta Startseva, Elena Notina, Irina Bykova, Valentina Ulyumdzhieva, Natallia Zhabo

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With the various existing models of intercultural communication that contain a vast number of stages for foreign language acquisition, there is a need for conscious perception of the foreign culture. Such a process is associated with the emergence of linguistic conflict with the consistent students’ desire to solve the problem of the language differences, along with cultural discrepancies. The aim of this study is to present the modern ways and methods of removing psycholinguistic conflict through skills development in professional translation and intercultural communication. The study was conducted in groups of 1-4-year students of Medical Institute and Agro-Technological Institute RUDN university. In the course of training, students got knowledge in such disciplines as basic grammar and vocabulary of the English language, phonetics, lexicology, introduction to linguistics, theory of translation, annotating and referencing media texts and texts in specialty. The students learned to present their research work, participated in the University and exit conferences with their reports and presentations. Common strategies of removing linguistic and cultural conflict can be attributed to the development of such abilities of a language personality as a commitment to communication and cooperation, the formation of cultural awareness and empathy of other cultures of the individual, realistic self-esteem, emotional stability, tolerance, etc. The process of mastering a foreign language and culture of the target language leads to a reduplication of linguistic identity, which leads to successive formation of the so-called 'secondary linguistic personality.' In our study, we tried to approach the problem comprehensively, focusing on the translation gaps for technical and non-technical language still missing such a typology which could classify all of the lacunas on the same principle. When obtaining the background knowledge, students learn to overcome the difficulties posed by the national-specific and linguistic differences of cultures in contact, i.e., to eliminate the gaps (to fill in and compensate). Compensation gaps is a means of fixing it, the initial phase of elimination, followed in some cases and some not is filling semantic voids (plenus). The concept of plenus occurs in most cases of translation gaps, for example in the transcription and transliteration of (intercultural and exoticism), the replication (reproduction of the morphemic structure of words or idioms. In all the above cases the task of the translator is to ensure an identical response of the receptors of the original and translated texts, since any statement is created with the goal of obtaining communicative effect, and hence pragmatic potential is the most important part of its contents. The practical value of our work lies in improving the methodology of teaching English for specific purposes on the basis of psycholinguistic concept of the secondary language personality.

Keywords: lacuna, language barrier, plenus, secondary language personality

Procedia PDF Downloads 258

Authors: Dmitriy Babenko, Sergey Yegorov, Ilya Korshukov, Aidana Sultanbekova, Valentina Barkhanskaya, Tatiana Bashirova, Yerzhan Zhunusov, Yevgeniya Li, Viktoriya Parakhina, Svetlana Kolesnichenko, Yeldar Baiken, Aruzhan Pralieva, Zhibek Zhumadilova, Matthew S. Miller, Gonzalo H. Hortelano, Anar Turmuhambetova, Antonella E. Chesca, Irina Kadyrova

Abstract:

Introduction: The rapidly evolving COVID-19 pandemic, along with the re-emergence of pathogens causing acute respiratory infections (ARI), has necessitated the development of novel diagnostic tools to differentiate various causes of ARI. MALDI-MS, due to its wide usage and affordability, has been proposed as a potential instrument for diagnosing SARS-CoV-2 versus non-SARS-CoV-2 ARI. The aim of this study was to investigate the potential of MALDI-MS in conjunction with a machine learning model to accurately distinguish between symptomatic infections caused by SARS-CoV-2 and non-SARS-CoV-2 during both the early and later phases of the pandemic. Furthermore, this study aimed to analyze mass spectrometry (MS) data obtained from nasal swabs of healthy individuals. Methods: We gathered mass spectra from 252 samples, comprising 108 SARS-CoV-2-positive samples obtained in 2020 (Covid 2020), 7 SARS-CoV- 2-positive samples obtained in 2023 (Covid 2023), 71 samples from symptomatic individuals without SARS-CoV-2 (Control non-Covid ARVI), and 66 samples from healthy individuals (Control healthy). All the samples were subjected to RT-PCR testing. For data analysis, we employed the caret R package to train and test seven machine-learning algorithms: C5.0, KNN, NB, RF, SVM-L, SVM-R, and XGBoost. We conducted a training process using a five-fold (outer) nested repeated (five times) ten-fold (inner) cross-validation with a randomized stratified splitting approach. Results: In this study, we utilized the Covid 2020 dataset as a case group and the non-Covid ARVI dataset as a control group to train and test various machine learning (ML) models. Among these models, XGBoost and SVM-R demonstrated the highest performance, with accuracy values of 0.97 [0.93, 0.97] and 0.95 [0.95; 0.97], specificity values of 0.86 [0.71; 0.93] and 0.86 [0.79; 0.87], and sensitivity values of 0.984 [0.984; 1.000] and 1.000 [0.968; 1.000], respectively. When examining the Covid 2023 dataset, the Naive Bayes model achieved the highest classification accuracy of 43%, while XGBoost and SVM-R achieved accuracies of 14%. For the healthy control dataset, the accuracy of the models ranged from 0.27 [0.24; 0.32] for k-nearest neighbors to 0.44 [0.41; 0.45] for the Support Vector Machine with a radial basis function kernel. Conclusion: Therefore, ML models trained on MALDI MS of nasopharyngeal swabs obtained from patients with Covid during the initial phase of the pandemic, as well as symptomatic non-Covid individuals, showed excellent classification performance, which aligns with the results of previous studies. However, when applied to swabs from healthy individuals and a limited sample of patients with Covid in the late phase of the pandemic, ML models exhibited lower classification accuracy.

Keywords: SARS-CoV-2, MALDI-TOF MS, ML models, nasopharyngeal swabs, classification

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Authors: Valentina V. Goftman, Vladislav A. Pankratov, Alexey V. Markin, Tangi Aubert, Zeger Hens, Sarah De Saeger, Irina Yu. Goryacheva

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The most important requirements for biochemical applicability of quantum dots (QDs) are: 1) the surface cap should render intact or improved optical properties; 2) mono-dispersion and good stability in aqueous phase in a wide range of pH and ionic strength values; 3) presence of functional groups, available for bioconjugation; 4) minimal impact from the environment on the QDs’ properties and, vice versa, minimal influence of the QDs’ components on the environment; and 5) stability against chemical/biochemical/physical influence. The latter is especially important for in vitro and in vivo applications. For example, some physical intracellular delivery strategies (e.g., electroporation) imply a rapid high-voltage electric field impulse in order to temporarily generate hydrophilic pores in the cell plasma membrane, necessary for the passive transportation of QDs into the cell. In this regard, it is interesting to investigate how different capping layers, which can provide high stability and sufficient fluorescent properties of QDs in a water solution, behave under these abnormal conditions. In this contribution, hydrophobic core-shell CdSe/CdS/CdZnS/ZnS QDs (λem=600 nm), produced by means of the Successive Ion Layer Adsorption and Reaction (SILAR) technique, were transferred to a water solution using two of the most commonly used methods: (i) encapsulation in an amphiphilic brush polymer based on poly(maleic anhydride-alt-1-octadecene) (PMAO) modified with polyethylene glycol (PEG) chains and (ii) silica covering. Polymer encapsulation preserves the initial ligands on the QDs’ surface owing to the hydrophobic attraction between the hydrophobic groups of the amphiphilic molecules and the surface hydrophobic groups of the QDs. This covering process allows maintaining the initial fluorescent properties, but it leads to a considerable increase of the QDs’ size. However, covering with a silica shell, by means of the reverse microemulsion method, allows maintaining both size and fluorescent properties of the initial QDs. The obtained water solutions of polymer covered and silica-coated QDs in three different concentrations were exposed to a low-voltage electric field for a short time and the fluorescent properties were investigated. It is shown that the PMAO-PEG polymer acquires some additional charges in the presence of the electric field, which causes repulsion between the polymer and the QDs’ surface. This process destroys the homogeneity of the whole amphiphilic shell and it dramatically decreases the fluorescent properties (dropping to 10% from its initial value) because of the direct contact of the QDs with the strongly oxidative environment (water). In contrast, a silica shell possesses dielectric properties which allow retaining 90% of its initial fluorescence intensity, even after a longer electric impact. Thus, silica shells are clearly a preferable covering for bio-application of QDs, because – besides the high uniform morphology, controlled size and biocompatibility – it allows protecting QDs from oxidation, even under the influence of an electric field.

Keywords: electric field, polymer coating, quantum dots, silica covering, stability

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Authors: Vladimir Berezin, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Aizhan Turmagambetova, Irina Zaitseva, Nadezhda Sokolova, Elmira Omirtaeva

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Introduction: Triterpene saponins of plant origin are one of the most promising candidates for elaboration of novel adjuvants. Due to the combination of immunostimulating activity and the capacity interact with amphipathic molecules with formation of highly immunogenic nanocomplexes, triterpene saponins could serve as a good adjuvant/delivery system for vaccine use. In the research presented adjuvants on the base of nanocomplexes contained triterpene saponins isolated from Glycyrrhiza glabra and Saponaria officinalis plants indigenous to Kazakhstan were elaborated for influenza vaccine use. Methods: Purified triterpene saponins 'Glabilox' and 'SO1' with low toxicity and high immunostimulatory activity were isolated from plants Glycyrrhiza glabra L. and Saponaria officinalis L. by high-performance liquid chromatography (HPLC) and identified using electrospray ionization mass spectrometry (ESI-MS). Influenza virus A/St-Petersburg/5/09 (H1N1) propagated in 9-days old chicken embryos was concentrated and purified by centrifugation in sucrose gradient. Nanocomplexes contained lipids, and triterpene saponins Glabilox or SO1 were prepared by dialysis technique. Immunostimulating activity of experimental vaccine preparations was studied in vaccination/challenge experiments in mice. Results: Humoral and cellular immune responses and protection against influenza virus infection were examined after single subcutaneous and intranasal immunization. Mice were immunized subunit influenza vaccine (HA+NA) or whole virus inactivated influenza vaccine in doses 3.0/5.0/10.0 µg antigen/animal mixed with adjuvant in dose 15.0 µg/animal. Sera were taken 14-21 days following single immunization and mice challenged by A/St-Petersburg/5/09 influenza virus in dose 100 EID₅₀. Study of experimental influenza vaccine preparations in animal immunization experiments has shown that subcutaneous and intranasal immunization with subunit influenza vaccine mixed with nanocomplexes contained Glabilox or SO1 saponins stimulated high levels of humoral immune response (IgM, IgA, IgG1, IgG2a, and IgG2b antibody) and cellular immune response (IL-2, IL-4, IL-10, and IFN-γ cytokines) and resulted 80-90% protection against lethal influenza infection. Also, single intranasal and single subcutaneous immunization with whole virus inactivated influenza vaccine mixed with nanoparticulated adjuvants stimulated high levels of humoral and cellular immune responses and provided 100% protection against lethal influenza infection. Conclusion: The results of study have shown that nanocomplexes contained purified triterpene saponins Glabilox and SO1 isolated from plants indigenous to Kazakhstan can stimulate a broad spectrum of humoral and cellular immune responses and induce protection against lethal influenza infection. Both elaborated adjuvants are promising for incorporation to influenza vaccine intended for subcutaneous and intranasal routes of immunization.

Keywords: influenza vaccine, adjuvants, triterpene saponins, immunostimulating activity

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Authors: Mona Mihailescu, Rebeca Tudor, Irina A. Paun, Cristian Kusko, Eugen I. Scarlat, Mihai Kusko

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Specific intensity distributions in the laser beams are required in many fields: optical communications, material processing, microscopy, optical tweezers. In optical communications, the information embedded in specific beams and the superposition of multiple beams can be used to increase the capacity of the communication channels, employing spatial modulation as an additional degree of freedom, besides already available polarization and wavelength multiplexing. In this regard, optical vortices present interest due to their potential to carry independent data which can be multiplexed at the transmitter and demultiplexed at the receiver. Also, in the literature were studied their combinations: 1) axial or perpendicular superposition of multiple optical vortices or 2) with other laser beam types: Bessel, Airy. Optical vortices, characterized by stationary ring-shape intensity and rotating phase, are achieved using computer generated holograms (CGH) obtained by simulating the interference between a tilted plane wave and a wave passing through a helical phase object. Here, we propose a method to combine information through the reunion of two CGHs. One is obtained using the helical phase distribution, characterized by its topological charge, m. The other is obtained using conical phase distribution, characterized by its radial factor, r0. Each CGH is obtained using plane wave with different tilts: km and kr for CGH generated from helical phase object and from conical phase object, respectively. These reunions of two CGHs are calculated to be phase optical elements, addressed on the liquid crystal display of a spatial light modulator, to optically process the incident beam for investigations of the diffracted intensity pattern in far field. For parallel reunion of two CGHs and high values of the ratio between km and kr, the bright ring from the first diffraction order, specific for optical vortices, is changed in an asymmetric intensity pattern: a number of circle arcs. Both diffraction orders (+1 and -1) are asymmetrical relative to each other. In different planes along the optical axis, it is observed that this asymmetric intensity pattern rotates around its centre: in the +1 diffraction order the rotation is anticlockwise and in the -1 diffraction order, the rotation is clockwise. The relation between m and r0 controls the diameter of the circle arcs and the ratio between km and kr controls the number of arcs. For perpendicular reunion of the two CGHs and low values of the ratio between km and kr, the optical vortices are multiplied and focalized in different planes, depending on the radial parameter. The first diffraction order contains information about both phase objects. It is incident on the phase masks placed at the receiver, computed using the opposite values for topological charge or for the radial parameter and displayed successively. In all, the proposed method is exploited in terms of constructive parameters, for the possibility offered by the combination of different types of beams which can be used in robust optical communications.

Keywords: asymmetrical diffraction orders, computer generated holograms, conical phase distribution, optical vortices, spatial light modulator

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Authors: Olga Kruzhkova, Irina Vorobyeva, Roman Porozov

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Vandalism is a common phenomenon, but its definition is still not clearly defined. In the public sense, vandalism is the blatant cases of pogroms in cemeteries, destruction of public places (regardless of whether these actions are authorized), damage to significant objects of culture and history (monuments, religious buildings). From a legal point of view, only such an act can be called vandalism, which is aimed at 'desecrating buildings or other structures, damaging property on public transport or in other public places'. The key here is the notion of public property that is being damaged. In addition, the principal is the semantics of messages, expressed in a kind of sign system (drawing, inscription, symbol), which initially threatens public order, the calmness of citizens, public morality. Because of this, the legal qualification of vandalism doesn’t include a sufficiently wide layer of environmental destructions that are common in modern urban space (graffiti and other damage to private property, broken shop windows, damage to entrances and elevator cabins), which in ordinary consciousness are seen as obvious facts of vandalism. At the same time, the understanding of vandalism from the position of psychology implies an appeal to the question of the limits of the activity of the subject of vandalism and his motivational basis. Also recently, the discourse on the positive meaning of some forms of vandalism (graffiti, street-art, etc.) has been activated. But there is no discussion of the role and significance of vandalism in public and individual life, although, like any socio-cultural and socio-psychological phenomenon, vandalism is not groundless and meaningless. Our aim of the study was to identify and describe the functions of vandalism as a socio-cultural and socio-psychological phenomenon of the life of the urban community, as well as personal determinants of its manifestations. The study was conducted in the spatial environment of the Russian megalopolis (Ekaterinburg) by photographing visual results of vandal acts (6217 photos) with subsequent trace-assessment and image content analysis, as well as diagnostics of personal characteristics and motivational basis of vandal activity of possible subjects of vandalism among youth. The results of the study allowed to identify the functions of vandalism at the socio-environmental and individual-subjective levels. The socio-environmental functions of vandalism include the signaling function, the function of preparing of social changes, the constructing function, and the function of managing public moods. The demonstrative-protest function, the response function, the refund function, and the self-expression function are assigned to the individual-subjective functions of vandalism. A two-dimensional model of vandal functions has been formed, where functions are distributed in the spaces 'construction reconstruction', 'emotional regulation/moral regulation'. It is noted that any function of vandal activity at the individual level becomes a kind of marker of 'points of tension' at the social and environmental level. Acknowledgment: The research was supported financially by Russian Science Foundation, (Project No. 17-18-01278).

Keywords: destruction, urban environment, vandal behavior, vandalism, vandalism functions

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Authors: Vladimir Berezin, Aizhan Turmagambetova, Andrey Bogoyavlenskiy, Pavel Alexyuk, Madina Alexyuk, Irina Zaitceva, Nadezhda Sokolova

Abstract:

Introduction: Influenza viruses could infect approximately 5% to 10% of the global human population annually, resulting in serious social and economic damage. Vaccination and etiotropic antiviral drugs are used for the prevention and treatment of influenza. Vaccination is important; however, antiviral drugs represent the second line of defense against new emerging influenza virus strains for which vaccines may be unsuccessful. However, the significant drawback of commercial synthetic anti-flu drugs is the appearance of drug-resistant influenza virus strains. Therefore, the search and development of new anti-flu drugs efficient against drug-resistant strains is an important medical problem for today. The aim of this work was a study of four phenolic acids of plant origin (Gallic, Syringic, Vanillic, and Protocatechuic acids) as a possible tool for treatment against influenza virus. Methods: Phenolic acids; gallic, syringic, vanillic, and protocatechuic have been prepared by extraction from plant tissues and purified using high-performance liquid chromatography fractionation. Avian influenza virus, strain A/Tern/South Africa/1/1961 (H5N3) and human epidemic influenza virus, strain A/Almaty/8/98 (H3N2) resistant to commercial anti-flu drugs (Rimantadine, Oseltamivir) were used for testing antiviral activity. Viruses were grown in the allantoic cavity of 10 days old chicken embryos. The chemotherapeutic index (CTI), determined as the ratio of an average toxic concentration of the tested compound (TC₅₀) to the average effective virus-inhibition concentration (EC₅₀), has been used as a criteria of specific antiviral action. Results: The results of study have shown that the structure of phenolic acids significantly affected their ability to suppress the reproduction of tested influenza virus strains. The highest antiviral activity among tested phenolic acids was detected for gallic acid, which contains three hydroxyl groups in the molecule at C3, C4, and C5 positions. Antiviral activity of gallic acid against A/H5N3 and A/H3N2 influenza virus strains was higher than antiviral activity of Oseltamivir and Rimantadine. gallic acid inhibited almost 100% of the infection activity of both tested viruses. Protocatechuic acid, which possesses 2 hydroxyl groups (C3 and C4) have shown weaker antiviral activity in comparison with gallic acid and inhibited less than 10% of virus infection activity. Syringic acid, which contains two hydroxyl groups (C3 and C5), was able to suppress up to 12% of infection activity. Substitution of two hydroxyl groups by methoxy groups resulted in the complete loss of antiviral activity. Vanillic acid, which is different from protocatechuic acid by replacing of C3 hydroxyl group to methoxy group, was able to suppress about 30% of infection activity of tested influenza viruses. Conclusion: For pronounced antiviral activity, the molecular of phenolic acid must have at least two hydroxyl groups. Replacement of hydroxyl groups to methoxy group leads to a reduction of antiviral properties. Gallic acid demonstrated high antiviral activity against influenza viruses, including Rimantadine and Oseltamivir resistant strains, and could be used as a potential candidate for the development of antiviral drug against influenza virus.

Keywords: antiviral activity, influenza virus, drug resistance, phenolic acids

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Authors: Irina-Emily Hansen, Ola Jon Mork

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The European economic growth strategy and supporting it framework for research and innovation highlight the importance of nurturing new open innovation in order to strengthen Europe’s competitiveness. One of the main approaches to enhance innovation in European society is the Triple Helix model that centres on science- industry collaboration where the universities are assigned the managerial role. In spite of the defined collaboration strategy, the collaboration between academics and in-dustry in Europe has still many challenges. Many of them are explained by culture difference: academic culture aims towards scientific knowledge, while businesses are oriented towards pro-duction and profitable results; also execution of collaborative projects is seen differently by part-ners involved. That proves that traditional management strategies applied to collaboration between researchers and businesses are not effective. There is a need for dynamic strategies that can support the interaction between researchers and industry intensifying knowledge co-creation and contributing to development of national innovation system (NIS) by incorporating individual, organizational and inter-organizational learning. In order to find a good subject to follow, the researchers of a given paper have investigated one of the most rapidly developing knowledge-based, innovation society, Singapore. Singapore does not dispose much land- or sea- resources that normally provide income for any country. Therefore, Singapore was forced to think differently and build society on resources that are available: talented people and knowledge. Singapore has during the last twenty years developed attracting high rated university camps, research institutions and leading industrial companies from all over the world. This article elucidates and elaborates Singapore’s national innovation strategies from Knowledge Management perspective. The research is done on the variety of organizations that enable and support knowledge development in this state: governmental research and development (R&D) centers in universities, private talent incubators for entrepreneurs, and industrial companies with own R&D departments. The research methods are based on presentations, documents, and visits at a number of universities, research institutes, innovation parks, governmental institutions, industrial companies and innovation exhibitions in Singapore. In addition, a literature review of science articles is made regarding the topic. The first finding is that objectives of collaboration between researchers, entrepreneurs and industry in Singapore correspond primary goals of the state: knowledge- and economy growth. There are common objectives for all stakeholders on all national levels. The second finding is that Singapore has enabled system on a national level that supports innovation the entire way from fostering or capturing the new knowledge, providing knowledge exchange and co-creation to application of it in real-life. The conclusion is that innovation means not only new idea, but also the enabling mechanism for its execution and the marked-oriented approach in order that new knowledge can be absorbed in society. The future research can be done with regards to application of Singapore knowledge management strategy in innovation to European countries.

Keywords: knowledge management strategy, national innovation system, research industry and business collaboration, knowledge enabling

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Authors: Sonia Boscenco, Zihan Wang, Euclides José de Mendoça Filho, João Paulo Hoppe, Irina Pokhvisneva, Geoffrey B.C. Hall, Michael J. Meaney, Patricia Pelufo Silveira

Abstract:

Entropy can be described as a measure of the number of states of a system, and when used in the context of physiological time-based signals, it serves as a measure of complexity. In functional connectivity data, entropy can account for the moment-to-moment variability that is neglected in traditional functional magnetic resonance imaging (fMRI) analyses. While brain fMRI resting state entropy has been associated with some pathological conditions like schizophrenia, no investigations have explored the association between brain entropy measures and individual differences in child behavior in healthy children. We describe a novel exploratory approach to evaluate brain fMRI resting state data in two child cohorts, and MAVAN (N=54, 4.5 years, 48% males) and GUSTO (N = 206, 4.5 years, 48% males) and its associations to child behavior, that can be used in future research in the context of child exposures and long-term health. Following rs-fMRI data pre-processing and Shannon entropy calculation across 32 network regions of interest to acquire 496 unique functional connections, partial correlation coefficient analysis adjusted for sex was performed to identify associations between entropy data and Strengths and Difficulties questionnaire in MAVAN and Child Behavior Checklist domains in GUSTO. Significance was set at p < 0.01, and we found eight significant associations in GUSTO. Negative associations were found between two frontoparietal regions and cerebellar posterior and oppositional defiant problems, (r = -0.212, p = 0.006) and (r = -0.200, p = 0.009). Positive associations were identified between somatic complaints and four default mode connections: salience insula (r = 0.202, p < 0.01), dorsal attention intraparietal sulcus (r = 0.231, p = 0.003), language inferior frontal gyrus (r = 0.207, p = 0.008) and language posterior superior temporal gyrus (r = 0.210, p = 0.008). Positive associations were also found between insula and frontoparietal connection and attention deficit / hyperactivity problems (r = 0.200, p < 0.01), and insula – default mode connection and pervasive developmental problems (r = 0.210, p = 0.007). In MAVAN, ten significant associations were identified. Two positive associations were found = with prosocial scores: the salience prefrontal cortex and dorsal attention connection (r = 0.474, p = 0.005) and the salience supramarginal gyrus and dorsal attention intraparietal sulcus (r = 0.447, p = 0.008). The insula and prefrontal connection were negatively associated with peer problems (r = -0.437, p < 0.01). Conduct problems were negatively associated with six separate connections, the left salience insula and right salience insula (r = -0.449, p = 0.008), left salience insula and right salience supramarginal gyrus (r = -0.512, p = 0.002), the default mode and visual network (r = -0.444, p = 0.009), dorsal attention and language network (r = -0.490, p = 0.003), and default mode and posterior parietal cortex (r = -0.546, p = 0.001). Entropy measures of resting state functional connectivity can be used to identify individual differences in brain function that are correlated with variation in behavioral problems in healthy children. Further studies applying this marker into the context of environmental exposures are warranted.

Keywords: child behaviour, functional connectivity, imaging, Shannon entropy

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

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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

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