Search results for: Munoz A. Tatiana

Authors: Tatiana S. Ogneva

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Aluminum and nickel-based intermetallic compounds have attracted the attention of scientific community as promising materials for heat-resistant and wear-resistant coatings in such manufacturing areas as microelectronics, aircraft and rocket building and chemical industries. Magnetron sputtering makes possible to coat materials without formation of liquid phase and improves the mechanical and functional properties of nickel aluminides due to the possibility of nanoscale structure formation. The purpose of the study is the investigation of structure and properties of intermetallic coatings produced by magnetron sputtering technique. The feature of this work is the using of composite targets for sputtering, which were consisted of two semicircular sectors of cp-Ni and cp-Al. Plates of alumina, silicon, titanium and steel alloys were used as substrates. To estimate sputtering conditions on structure of intermetallic coatings, a series of samples were produced and studied in detail using scanning and transition electron microcopy and X-Ray diffraction. Besides, nanohardness and scratching tests were carried out. The varying parameters were the distance from the substrate to the target, the duration and the power of the sputtering. The thickness of the obtained intermetallic coatings varied from 0.05 to 0.5 mm depending on the sputtering conditions. The X-ray diffraction data indicated that the formation of intermetallic compounds occurred after sputtering without additional heat treatment. Sputtering at a distance not closer than 120 mm led to the formation of NiAl phase. Increase in the power of magnetron from 300 to 900 W promoted the increase of heterogeneity of the phase composition and the appearance of intermetallic phases NiAl, Ni₂Al₃, NiAl₃, and Al under the aluminum side, and NiAl, Ni₃Al, and Ni under the nickel side of the target. A similar trend is observed with increasing the distance of sputtering from 100 to 60 mm. The change in the phase composition correlates with the changing of the atomic composition of the coatings. Scanning electron microscopy revealed that the coatings have a nanoscale grain structure. In this case, the substrate material and the distance from the substrate to the magnetron have a significant effect on the structure formation process. The size of nanograins differs from 10 to 83 nm and depends not only on the sputtering modes but also on material of a substrate. Nanostructure of the material influences the level of mechanical properties. The highest level of nanohardness of the coatings deposited during 30 minutes on metallic substrates at a distance of 100 mm reached 12 GPa. It was shown that nanohardness depends on the grain size of the intermetallic compound. Scratching tests of the coatings showed a high level of adhesion of the coating to substrate without any delamination and cracking. The results of the study showed that magnetron sputtering of composite targets consisting of nickel and aluminum semicircles makes it possible to form intermetallic coatings with good mechanical properties directly in the process of sputtering without additional heat treatment.

Keywords: intermetallic coatings, magnetron sputtering, mechanical properties, structure

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Authors: Tatiana L. Avalos-Rendon, Elias A. Pasten Chelala, Carlos J. Mendoza EScobedo, Ignacio A. Figueroa, Victor H. Lara, Luis M. Palacios-Romero

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The cement industry is facing cost increments in energy supply, requirements for reduction of CO₂, and insufficient supply of raw materials of good quality. According to all these environmental issues, cement industry must change its consumption patterns and reduce CO₂ emissions to the atmosphere. This can be achieved by generating environmental consciousness, which encourages the use of industrial by-products and/or recycling for the production of cement, as well as alternate, environment-friendly methods of synthesis which reduce CO₂. Calcination is the conventional method for the obtainment of Portland cement clinker. This method consists of grinding and mixing of raw materials (limestone, clay, etc.) in an adequate dosage. Resulting mix has a clinkerization temperature of 1450 °C so that the formation of the main component occur: alite (Ca₃SiO₅, C₃S). Considering that the energy required to produce C₃S is 1810 kJ kg -1, calcination method for the obtainment of clinker represents two major disadvantages: long thermal treatment and elevated temperatures of synthesis, both of which cause high emissions of carbon dioxide (CO₂) to the atmosphere. Belite Portland clinker is characterized by having a low content of calcium oxide (CaO), causing the presence of alite to diminish and favoring the formation of belite (β-Ca₂SiO₄, C₂S), so production of clinker requires a reduced energy consumption (1350 kJ kg-1), releasing less CO₂ to the atmosphere. Conventionally, β-Ca₂SiO₄ is synthetized by the calcination of calcium carbonate (CaCO₃) and silicon dioxide (SiO₂) through the reaction in solid state at temperatures greater than 1300 °C. Resulting belite shows low hydraulic reactivity. Therefore, this study concerns a new simple modified combustion method for the synthesis of two belite cements at low temperatures (1000 °C). Silica fume, as subproduct of metallurgic industry and commercial natural zeolite were utilized as raw materials. These are considered low-cost materials and were utilized with no additional purification process. Belite cements properties were characterized by XRD, SEM, EDS and BET techniques. Hydration capacity of belite cements was calculated while the mechanical strength was determined in ordinary Portland cement specimens (PC) with a 10% partial replacement of the belite cements obtained. Results showed belite cements presented relatively high surface áreas, at early ages mechanical strengths similar to those of alite cement and comparable to strengths of belite cements obtained by different synthesis methods. Cements obtained in this work present good hydraulic reactivity properties.

Keywords: belite, silica fume, zeolite, hydraulic reactivity

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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

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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: Tatiana Ponomarenko, Oksana Marinina, Marina Nevskaya

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Modern corporate social responsibility (CSR) is a sphere of multilevel responsibility of a company toward society represented by various stakeholders. The relevance of CSR management grows due to the active development of socially responsible investing (principles for responsible investment) taking into account factors of environmental, social and corporate governance (ESG), growing attention of the investment community in general to the long-term stability of companies and the quality of control of nonfinancial risks. The modern approach to CSR strategic management is aimed at the creation of trustful relationships with stakeholders, on the basis of which a contribution to the sustainable development of companies, regions, and national economics is insured. However, the practical concepts of social responsibility in mining companies are different, which leads to various degrees of application of CSR. A number of companies implement CSR using a traditional (limited) understanding of responsibility toward employees and counteragents, the others understand CSR much wider and try to use leverages of efficient cooperation. As in large mining companies the scope of CSR measures is diverse and characterized by different indices, the study was aimed at evaluating CSR efficiency on the basis of a proprietary methodology and determining the level of development of CSR management in terms of anti-crisis, reactive and proactive development. The methodology of the research includes analysis of integrated global reporting initiative (GRI) reports of large mining companies; choice of most representative sectoral agents by a criterion of the regularity of issuance and publication of reports; calculation of indices of evaluation of CSR level of the selected companies in dynamics. The methodology of evaluation of CSR level is based on a rating score of changes in standard indices of GRI reports by economic, environmental, and social directions. Result. By the results of the analysis, companies of fuel and energy and metallurgic complexes, in overwhelming majority, reflecting three indices out of a wide range of possible indicators of SDGs (Sustainable Development Goals), were selected for the study. The evaluation of the scopes of CSR of the companies Gazprom, LUKOIL, Metalloinvest, Nornikel, Rosneft, Severstal, SIBUR, SUEK corresponds to the reactive type of development according to a scale of CSR strategic management, which is the average value out of the possible values. The chief drawback is that companies, in the process of analyzing global goals, often choose the goals which relate to their own activities, paying insufficient attention to the interests of the stakeholders inside the country. This fact evidences the necessity of searching for more effective mechanisms of CSR control. Acknowledgment: This article is prepared within grant support of the RFBR, project 19-510-44013 'Development of the concept of mineral resources value formation in the context of sustainable development in resource-oriented economies'.

Keywords: sustainable development, corporate social responsibility, development strategies, efficiency assessment

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Authors: Natalia V. Minaeva, Natalia A. Zorina, Marina N. Khorobrikh, Philipp S. Sherstnev, Tatiana V. Krivokorytova, Alexander S. Luchinin, Maksim S. Minaev, Igor V. Paramonov

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Background. Over the last few decades, the Center for International Blood and Marrow Transplant Research (CIBMTR) and the World Marrow Donor Association (WMDA) have been actively working to ensure the safety of the hematopoietic stem cell (HSC) donation process. Registration of adverse events that may occur during the donation period and establishing a relationship between donation and side effects are included in the WMDA international standards. The level of blood serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is an early marker of myocardial stress. Due to the high analytical sensitivity and specificity, laboratory assessment of NT-proBNP makes it possible to objectively diagnose myocardial dysfunction. It is well known that the main stimulus for proBNP synthesis and secretion from atrial and ventricular cardiac myocytes is myocyte stretch and increasement of myocardial extensibility and pressure in the heart chambers. Аim. The aim of the study was to assess the dynamic changes in the levels of blood serum N-terminal pro-brain natriuretic peptide of unrelated donors at various stages of hematopoietic stem cell mobilization. Materials. We have examined 133 unrelated donors, including 92 men and 41 women, that have been included into the study. The NT-proBNP levels were measured before the start of mobilization, then on the day of apheresis, and after the donation of allogeneic HSC. The relationship between NT-proBNP levels and body mass index (BMI), ferritin, hemoglobin, and white blood cells (WBC) levels was assessed on the day of apheresis. The median age of donors was 34 years. Mobilization of HSCs was managed with filgrastim administration at a dose of 10 μg/kg daily for 4-5 days. The first leukocytapheresis was performed on day 4 from the start of filgrastim administration. Quantitative values of the blood serum NT-proBNP level are presented as a median (Me), first and third quartiles (Q1-Q3). Comparative analysis was carried out using the t-test and correlation analysis as well by Spearman method. Results. The baseline blood serum NT-proBNP levels in all 133 donors were within the reference values (<125 pg/ml) and equaled 21,6 (10,0; 43,3) pg/ml. At the same time, the level of NT-proBNP in women was significantly higher than that of men. On the day of the HSC apheresis, a significant increase of blood serum NT-proBNP levels was detected and equald 131,2 (72,6; 165,3) pg/ml (p<0,001), with higher rates in female donors. A statistically significant weak inverse correleation was established between the level of NT-proBNP and the BMI of donors (-0.18, p = 0,03), as well as the level of hemoglobin (-0.33, p <0,001), and ferritin levels (-0.19, p = 0,03). No relationship has been established between the magnitude of WBC levels achieved as a result of the mobilization of HSC on the day of leukocytapheresis. A day after the apheresis, the blood serum NT-proBNP levels still exceeded the reference values, but there was a decreasing tendency. Conclusion. An increase of the blood serum NT-proBNP level in unrelated donors during the mobilization of HSC was established. Future studies should clarify the reason for this phenomenon, as well as its effects on donors' long-term health.

Keywords: unrelated donors, mobilization, hematopoietic stem cells, N-terminal pro-brain natriuretic peptide

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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

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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: Willian C. De Brito, Hernan D. C. Munoz, Erlan V. C. Carvalho, Helder L. C. De Oliveira

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In order to improve commute time for small distance trips and relieve large cities traffic, a new transport category has been the subject of research and new designs worldwide. The air taxi travel market promises to change the way people live and commute by using the concept of vehicles with the ability to take-off and land vertically and to provide passenger’s transport equivalent to a car, with mobility within large cities and between cities. Today’s civil air transport remains costly and accounts for 2% of the man-made CO₂ emissions. Taking advantage of this scenario, many companies have developed their own Vertical Take Off and Landing (VTOL) design, seeking to meet comfort, safety, low cost and flight time requirements in a sustainable way. Thus, the use of green power supplies, especially batteries, and fully electric power plants is the most common choice for these arising aircrafts. However, it is still a challenge finding a feasible way to handle with the use of batteries rather than conventional petroleum-based fuels. The batteries are heavy and have an energy density still below from those of gasoline, diesel or kerosene. Therefore, despite all the clear advantages, all electric aircrafts (AEA) still have low flight autonomy and high operational cost, since the batteries must be recharged or replaced. In this sense, this paper addresses a way to optimize the energy consumption in a typical mission of an aerial taxi aircraft. The approach and landing procedure was chosen to be the subject of an optimization genetic algorithm, while final programming can be adapted for take-off and flight level changes as well. A real tilt rotor aircraft with fully electric power plant data was used to fit the derived dynamic equations of motion. Although a tilt rotor design is used as a proof of concept, it is possible to change the optimization to be applied for other design concepts, even those with independent motors for hover and cruise flight phases. For a given trajectory, the best set of control variables are calculated to provide the time history response for aircraft´s attitude, rotors RPM and thrust direction (or vertical and horizontal thrust, for independent motors designs) that, if followed, results in the minimum electric power consumption through that landing path. Safety, comfort and design constraints are assumed to give representativeness to the solution. Results are highly dependent on these constraints. For the tested cases, performance improvement ranged from 5 to 10% changing initial airspeed, altitude, flight path angle, and attitude.

Keywords: air taxi travel, all electric aircraft, batteries, energy consumption, genetic algorithm, landing performance, optimization, performance improvement, tilt rotor, VTOL design

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Authors: Tatiana G. Smirnova, Stan G. Benjamin

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Rapid Update Cycle (RUC) land surface model (LSM) was a land-surface component in several generations of operational weather prediction models at the National Center for Environment Prediction (NCEP) at the National Oceanic and Atmospheric Administration (NOAA). It was designed for short-range weather predictions with an emphasis on severe weather and originally was intentionally simple to avoid uncertainties from poorly known parameters. Nevertheless, the RUC LSM, when coupled with the hourly-assimilating atmospheric model, can produce a realistic evolution of time-varying soil moisture and temperature, as well as the evolution of snow cover on the ground surface. This result is possible only if the soil/vegetation/snow component of the coupled weather prediction model has sufficient skill to avoid long-term drift. RUC LSM was first implemented in the operational NCEP Rapid Update Cycle (RUC) weather model in 1998 and later in the Weather Research Forecasting Model (WRF)-based Rapid Refresh (RAP) and High-resolution Rapid Refresh (HRRR). Being available to the international WRF community, it was implemented in operational weather models in Austria, New Zealand, and Switzerland. Based on the feedback from the US weather service offices and the international WRF community and also based on our own validation, RUC LSM has matured over the years. Also, a sea-ice module was added to RUC LSM for surface predictions over the Arctic sea-ice. Other modifications include refinements to the snow model and a more accurate specification of albedo, roughness length, and other surface properties. At present, RUC LSM is being tested in the regional application of the Unified Forecast System (UFS). The next generation UFS-based regional Rapid Refresh FV3 Standalone (RRFS) model will replace operational RAP and HRRR at NCEP. Over time, RUC LSM participated in several international model intercomparison projects to verify its skill using observed atmospheric forcing. The ESM-SnowMIP was the last of these experiments focused on the verification of snow models for open and forested regions. The simulations were performed for ten sites located in different climatic zones of the world forced with observed atmospheric conditions. While most of the 26 participating models have more sophisticated snow parameterizations than in RUC, RUC LSM got a high ranking in simulations of both snow water equivalent and surface temperature. However, ESM-SnowMIP experiment also revealed some issues in the RUC snow model, which will be addressed in this paper. One of them is the treatment of grid cells partially covered with snow. RUC snow module computes energy and moisture budgets of snow-covered and snow-free areas separately by aggregating the solutions at the end of each time step. Such treatment elevates the importance of computing in the model snow cover fraction. Improvements to the original simplistic threshold-based approach have been implemented and tested both offline and in the coupled weather model. The detailed description of changes to the snow cover fraction and other modifications to RUC soil and snow parameterizations will be described in this paper.

Keywords: land-surface models, weather prediction, hydrology, boundary-layer processes

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Authors: Yulia V. Krasavtseva, Tatiana V. Kornilova

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Risk-taking behaviors are not only dictated by cognitive components but also involve emotional aspects. Anticipatory emotions, involving both cognitive and affective mechanisms, are involved in decision-making in general, and risk-taking in particular. Affective reactions are prompted when an expectation or prediction is either validated or invalidated in the achieved result. This study aimed to combine predictions, anticipatory emotions, affective reactions, and personality traits in the context of risk-taking behaviors. An experimental online method Emotion and Prediction In a Casino (EPIC) was used, based on a casino-like roulette game. In a series of choices, the participant is presented with progressively riskier roulette combinations, where the potential sums of wins and losses increase with each choice and the participant is given a choice: to 'walk away' with the current sum of money or to 'play' the displayed roulette, thus accepting the implicit risk. Before and after the result is displayed, participants also rate their emotions, using the Self-Assessment Mannequin [Bradley, Lang, 1994], picking a picture, representing the intensity of pleasure, arousal, and dominance. The following personality measures were used: 1) Personal Decision-Making Factors [Kornilova, 2003] assessing risk and rationality; 2) I7 – Impulsivity Questionnaire [Kornilova, 1995] assessing impulsiveness, risk readiness, and empathy and 3) Subjective Risk Intelligence Scale [Craparo et al., 2018] assessing negative attitude toward uncertainty, emotional stress vulnerability, imaginative capability, and problem-solving self-efficacy. Two groups of participants took part in the study: 1) 98 university students (Mage=19.71, SD=3.25; 72% female) and 2) 94 online participants (Mage=28.25, SD=8.25; 89% female). Online participants were recruited via social media. Students with high rationality rated their pleasure and dominance before and after choices as lower (ρ from -2.6 to -2.7, p < 0.05). Those with high levels of impulsivity rated their arousal lower before finding out their result (ρ from 2.5 - 3.7, p < 0.05), while also rating their dominance as low (ρ from -3 to -3.7, p < 0.05). Students prone to risk-rated their pleasure and arousal before and after higher (ρ from 2.5 - 3.6, p < 0.05). High empathy was positively correlated with arousal after learning the result. High emotional stress vulnerability positively correlates with arousal and pleasure after the choice (ρ from 3.9 - 5.7, p < 0.05). Negative attitude to uncertainty is correlated with high anticipatory and reactive arousal (ρ from 2.7 - 5.7, p < 0.05). High imaginative capability correlates negatively with anticipatory and reactive dominance (ρ from - 3.4 to - 4.3, p < 0.05). Pleasure (.492), arousal (.590), and dominance (.551) before and after the result were positively correlated. Higher predictions positively correlated with reactive pleasure and arousal. In a riskier scenario (6/8 chances to win), anticipatory arousal was negatively correlated with the pleasure emotion (-.326) and vice versa (-.265). Correlations occur regardless of the roulette outcome. In conclusion, risk-taking behaviors are linked not only to personality traits but also to anticipatory emotions and affect in a modeled casino setting. Acknowledgment: The study was supported by the Russian Foundation for Basic Research, project 19-29-07069.

Keywords: anticipatory emotions, casino game, risk taking, impulsiveness

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Authors: Puzanova Zhanna Vasilyevna, Larina Tatiana Igorevna, Tertyshnikova Anastasia Gennadyevna

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In this day and age, extremism in various forms of its manifestation is a real threat to the world community, the national security of a state and its territorial integrity, as well as to the constitutional rights and freedoms of citizens. Extremism, as it is known, in general terms described as a commitment to extreme views and actions, radically denying the existing social norms and rules. Supporters of extremism in the ideological and political struggles often adopt methods and means of psychological warfare, appeal not to reason and logical arguments, but to emotions and instincts of the people, to prejudices, biases, and a variety of mythological designs. They are dissatisfied with the established order and aim at increasing this dissatisfaction among the masses. Youth extremism holds a specific place among the existing forms and types of extremism. In this context in 2015, we conducted a survey among Moscow college and high school students. The aim of this study was to determine how great or small is the difference in understanding and attitudes towards extremism manifestations, inclination and readiness to take part in extremist activities and what causes this predisposition, if it exists. We performed multivariate analysis and found the Russian college and high school students' opinion about the extremism and terrorism situation in our country and also their cognition on these topics. Among other things, we showed, that the level of aggressiveness of young people were not above the average for the whole population. The survey was conducted using the questionnaire method. The sample included college and high school students in Moscow (642 and 382, respectively) by method of random selection. The questionnaire was developed by specialists of RUDN University Sociological Laboratory and included both original questions (projective questions, the technique of incomplete sentences), and the standard test Dayhoff S. to determine the level of internal aggressiveness. It is also used as an experiment, the technique of study option using of FACS and SPAFF to determine the psychotypes and determination of non-verbal manifestations of emotions. The study confirmed the hypothesis that in respondents’ opinion, the level of aggression is higher today than a few years ago. Differences were found in the understanding of and respect for such social phenomena as extremism, terrorism, and their danger and appeal for the two age groups of young people. Theory of psychotypes, SPAFF (specific affect cording system) and FACS (facial action cording system) are considered as additional techniques for the diagnosis of a tendency to extreme views. Thus, it is established that diagnostics of acceptance of extreme views among young people is possible thanks to simultaneous use of knowledge from the different fields of socio-humanistic sciences. The results of the research can be used in a comparative context with other countries and as a starting point for further research in the field, taking into account its extreme relevance.

Keywords: extremism, youth extremism, diagnostics of extremist manifestations, forecast of behavior, sociological polls, theory of psychotypes, FACS, SPAFF

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Authors: Tatiana Butkova, Nikolai Kibrik, Kristina Malsagova, Alexander Izotov, Alexander Stepanov, Anna Kaysheva

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Relevance. The genetic risk of developing schizophrenia is determined by two factors: single nucleotide polymorphisms and gene copy number variations. The search for serological markers for early diagnosis of schizophrenia is driven by the fact that the first five years of the disease are accompanied by significant biological, psychological, and social changes. It is during this period that pathological processes are most amenable to correction. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) that are hypothesized to potentially influence the onset and development of the endogenous process. Materials and Methods It was analyzed 73 single nucleotide polymorphism variants. The study included 48 patients undergoing inpatient treatment at "Psychiatric Clinical Hospital No. 1" in Moscow, comprising 23 females and 25 males. Inclusion criteria: - Patients aged 18 and above. - Diagnosis according to ICD-10: F20.0, F20.2, F20.8, F21.8, F25.1, F25.2. - Voluntary informed consent from patients. Exclusion criteria included: - The presence of concurrent somatic or neurological pathology, neuroinfections, epilepsy, organic central nervous system damage of any etiology, and regular use of medication. - Substance abuse and alcohol dependence. - Women who were pregnant or breastfeeding. Clinical and psychopathological assessment was complemented by psychometric evaluation using the PANSS scale at the beginning and end of treatment. The duration of observation during therapy was 4-6 weeks. Total DNA extraction was performed using QIAamp DNA. Blood samples were processed on Illumina HiScan and genotyped for 652,297 markers on the Infinium Global Chips Screening Array-24v2.0 using the IMPUTE2 program with parameters Ne=20,000 and k=90. Additional filtration was performed based on INFO>0.5 and genotype probability>0.5. Quality control of the obtained DNA was conducted using agarose gel electrophoresis, with each tested sample having a volume of 100 µL. Results. It was observed that several SNPs exhibited gender dependence. We identified groups of single nucleotide polymorphisms with a membership of 80% or more in either the female or male gender. These SNPs included rs2661319, rs2842030, rs4606, rs11868035, rs518147, rs5993883, and rs6269.Another noteworthy finding was the limited combination of SNPs sufficient to manifest clinical symptoms leading to hospitalization. Among all 48 patients, each of whom was analyzed for deviations in 73 SNPs, it was discovered that the combination of involved SNPs in the manifestation of pronounced clinical symptoms of schizophrenia was 19±3 out of 73 possible. In study, the frequency of occurrence of single nucleotide polymorphisms also varied. The most frequently observed SNPs were rs4849127 (in 90% of cases), rs1150226 (86%), rs1414334 (75%), rs10170310 (73%), rs2857657, and rs4436578 (71%). Conclusion. Thus, the results of this study provide additional evidence that these genes may be associated with the development of schizophrenia spectrum disorders. However, it's impossible cannot rule out the hypothesis that these polymorphisms may be in linkage disequilibrium with other functionally significant polymorphisms that may actually be involved in schizophrenia spectrum disorders. It has been shown that missense SNPs by themselves are likely not causative of the disease but are in strong linkage disequilibrium with non-functional SNPs that may indeed contribute to disease predisposition.

Keywords: gene polymorphisms, genotyping, single nucleotide polymorphisms, schizophrenia.

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Authors: Denise De Fátima Fernandes Barbosa, Tyane Mayara Ferreira Oliveira, Diego Jorge Maia Lima, Paula Renata Amorim Lessa, Ana Karina Bezerra Pinheiro, Cintia Gondim Pereira Calou, Glauberto Da Silva Quirino, Hellen Lívia Oliveira Catunda, Tatiana Gomes Guedes, Nicolau Da Costa

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The aim of this study is to evaluate the use of Digital Cervicography (DC) in the diagnosis of precancerous lesions related to Human Papillomavirus (HPV). Cross-sectional study with a quantitative approach, of evaluative type, held in a health unit linked to the Pro Dean of Extension of the Federal University of Ceará, in the period of July to August 2015 with a sample of 33 women. Data collecting was conducted through interviews with enforcement tool. Franco (2005) standardized the technique used for DC. Polymerase Chain Reaction (PCR) was performed to identify high-risk HPV genotypes. DC were evaluated and classified by 3 judges. The results of DC and PCR were classified as positive, negative or inconclusive. The data of the collecting instruments were compiled and analyzed by the software Statistical Package for Social Sciences (SPSS) with descriptive statistics and cross-references. Sociodemographic, sexual and reproductive variables were analyzed through absolute frequencies (N) and their respective percentage (%). Kappa coefficient (κ) was applied to determine the existence of agreement between the DC of reports among evaluators with PCR and also among the judges about the DC results. The Pearson's chi-square test was used for analysis of sociodemographic, sexual and reproductive variables with the PCR reports. It was considered statistically significant (p<0.05). Ethical aspects of research involving human beings were respected, according to 466/2012 Resolution. Regarding the socio-demographic profile, the most prevalent ages and equally were those belonging to the groups 21-30 and 41-50 years old (24.2%). The brown color was reported in excess (84.8%) and 96.9% out of them had completed primary and secondary school or studying. 51.5% were married, 72.7% Catholic, 54.5% employed and 48.5% with income between one and two minimum wages. As for the sexual and reproductive characteristics, prevailed heterosexual (93.9%) who did not use condoms during sexual intercourse (72.7%). 51.5% had a previous history of Sexually Transmitted Infection (STI), and HPV the most prevalent STI (76.5%). 57.6% did not use contraception, 78.8% underwent examination Cancer Prevention Uterus (PCCU) with shorter time interval or equal to one year, 72.7% had no cases of Cervical Cancer in the family, 63.6% were multiparous and 97% were not vaccinated against HPV. DC identified good level of agreement between raters (κ=0.542), had a specificity of 77.8% and sensitivity of 25% when compared their results with PCR. Only the variable race showed a statistically significant association with CRP (p=0.042). DC had 100% acceptance amongst women in the sample, revealing the possibility of other experiments in using this method so that it proves as a viable technique. The DC positivity criteria were developed by nurses and these professionals also perform PCCU in Brazil, which means that DC can be an important complementary diagnostic method for the appreciation of these professional’s quality of examinations.

Keywords: gynecological examination, human papillomavirus, nursing, papillomavirus infections, uterine lasmsneop

Procedia PDF Downloads 274

Authors: Álvaro Ramírez Vidal, Martín Muñoz Morales, Francisco Jesús Fernández Morales, Luis Rodríguez Romero, José Villaseñor Camacho, Javier Llanos López

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In recent times, environmental problems have led to the extensive use of biological systems to solve them. Among the different types of biological systems, the use of plants such as aquatic macrophytes in constructed wetlands and terrestrial plant species for treating polluted soils and sludge has gained importance. Though the use of constructed wetlands for wastewater treatment is a well-researched domain, the slowness of pollutant degradation and high biomass production pose some challenges. Plants used in CW participate in different mechanisms for the capture and degradation of pollutants that also can retain some pharmaceutical and personal care products (PPCPs) that are very persistent in the environment. Thus, these systems present advantages in line with the guidelines published for the transition towards friendly and ecological procedures as they are environmentally friendly systems, consume low energy, or capture atmospheric CO₂. However, the use of CW presents some drawbacks, as the slowness of pollutant degradation or the production of important amounts of plant biomass, which need to be harvested and managed periodically. Taking this opportunity in mind, it is important to highlight that this residual biomass (of lignocellulosic nature) could be used as the feedstock for the generation of carbonaceous materials using thermochemical transformations such as slow pyrolysis or hydrothermal carbonization to produce high-value biomass-derived carbons through sustainable processes as adsorbents, catalysts…, thereby improving the circular carbon economy. Thus, this work carried out the analysis of some PPCPs commonly found in urban wastewater, as salicylic acid or ibuprofen, to evaluate the remediation carried out for the Phragmites Australis. Then, after the harvesting, this biomass can be used to synthesize electrodes through hydrothermal carbonization (HTC) and produce high-value biomass-derived carbons with electrocatalytic activity to remove heavy metals and persistent pollutants, promoting circular economy concepts. To do this, it was chosen biomass derived from the natural environment in high environmental risk as the Daimiel Wetlands National Park in the center of Spain, and the rest of the biomass developed in a CW specifically designed to remove pollutants. The research emphasizes the impact of the composition of the biomass waste and the synthetic parameters applied during HTC on the electrocatalytic activity. Additionally, this parameter can be related to the physicochemical properties, as porosity, surface functionalization, conductivity, and mass transfer of the electrodes lytic inks. Data revealed that carbon materials synthesized have good surface properties (good conductivities and high specific surface area) that enhance the electro-oxidants generated and promote the removal of PPCPs and the chemical oxygen demand of polluted waters.

Keywords: constructed wetlands, carbon materials, heavy metals, pharmaceutical and personal care products, hydrothermal carbonization

Procedia PDF Downloads 54

Authors: Javier E. García-Gallo, Nelson J. Fonseca-Ruiz, John F. Duitama-Munoz

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Sepsis is a syndrome that occurs with physiological and biochemical abnormalities induced by severe infection and carries a high mortality and morbidity, therefore the severity of its condition must be interpreted quickly. After patient admission in an intensive care unit (ICU), it is necessary to synthesize the large volume of information that is collected from patients in a value that represents the severity of their condition. Traditional severity of illness scores seeks to be applicable to all patient populations, and usually assess in-hospital mortality. However, the use of machine learning techniques and the data of a population that shares a common characteristic could lead to the development of customized mortality prediction scores with better performance. This study presents the development of a score for the one-year mortality prediction of the patients that are admitted to an ICU with a sepsis diagnosis. 5650 ICU admissions extracted from the MIMICIII database were evaluated, divided into two groups: 70% to develop the score and 30% to validate it. Comorbidities, demographics and clinical information of the first 24 hours after the ICU admission were used to develop a mortality prediction score. LASSO (least absolute shrinkage and selection operator) and SGB (Stochastic Gradient Boosting) variable importance methodologies were used to select the set of variables that make up the developed score; each of this variables was dichotomized and a cut-off point that divides the population into two groups with different mean mortalities was found; if the patient is in the group that presents a higher mortality a one is assigned to the particular variable, otherwise a zero is assigned. These binary variables are used in a logistic regression (LR) model, and its coefficients were rounded to the nearest integer. The resulting integers are the point values that make up the score when multiplied with each binary variables and summed. The one-year mortality probability was estimated using the score as the only variable in a LR model. Predictive power of the score, was evaluated using the 1695 admissions of the validation subset obtaining an area under the receiver operating characteristic curve of 0.7528, which outperforms the results obtained with Sequential Organ Failure Assessment (SOFA), Oxford Acute Severity of Illness Score (OASIS) and Simplified Acute Physiology Score II (SAPSII) scores on the same validation subset. Observed and predicted mortality rates within estimated probabilities deciles were compared graphically and found to be similar, indicating that the risk estimate obtained with the score is close to the observed mortality, it is also observed that the number of events (deaths) is indeed increasing as the outcome go from the decile with the lowest probabilities to the decile with the highest probabilities. Sepsis is a syndrome that carries a high mortality, 43.3% for the patients included in this study; therefore, tools that help clinicians to quickly and accurately predict a worse prognosis are needed. This work demonstrates the importance of customization of mortality prediction scores since the developed score provides better performance than traditional scoring systems.

Keywords: intensive care, logistic regression model, mortality prediction, sepsis, severity of illness, stochastic gradient boosting

Procedia PDF Downloads 187

Authors: Óscar Muñoz Garrigós, José Manuel Bernabeu Aubán

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Time-sensitive services are the base of the cloud services industry. Keeping low service saturation is essential for controlling response time. All auto-scalable services make use of reactive auto-scaling. However, reactive auto-scaling has few in-depth studies. This presentation shows a model for reactive auto-scaling methodologies with a MAPE-k architecture. Queuing theory can compute different properties of static services but lacks some parameters related to the transition between models. Our model uses queuing theory parameters to relate the transition between models. It associates MAPE-k related times, the sampling frequency, the cooldown period, the number of requests that an instance can handle per unit of time, the number of incoming requests at a time instant, and a function that describes the acceleration in the service's ability to handle more requests. This model is later used as a solution to horizontally auto-scale time-sensitive services composed of microservices, reevaluating the model’s parameters periodically to allocate resources. The solution requires limiting the acceleration of the growth in the number of incoming requests to keep a constrained response time. Business benefits determine such limits. The solution can add a dynamic number of instances and remains valid under different system sizes. The study includes performance recommendations to improve results according to the incoming load shape and business benefits. The exposed methodology is tested in a simulation. The simulator contains a load generator and a service composed of two microservices, where the frontend microservice depends on a backend microservice with a 1:1 request relation ratio. A common request takes 2.3 seconds to be computed by the service and is discarded if it takes more than 7 seconds. Both microservices contain a load balancer that assigns requests to the less loaded instance and preemptively discards requests if they are not finished in time to prevent resource saturation. When load decreases, instances with lower load are kept in the backlog where no more requests are assigned. If the load grows and an instance in the backlog is required, it returns to the running state, but if it finishes the computation of all requests and is no longer required, it is permanently deallocated. A few load patterns are required to represent the worst-case scenario for reactive systems: the following scenarios test response times, resource consumption and business costs. The first scenario is a burst-load scenario. All methodologies will discard requests if the rapidness of the burst is high enough. This scenario focuses on the number of discarded requests and the variance of the response time. The second scenario contains sudden load drops followed by bursts to observe how the methodology behaves when releasing resources that are lately required. The third scenario contains diverse growth accelerations in the number of incoming requests to observe how approaches that add a different number of instances can handle the load with less business cost. The exposed methodology is compared against a multiple threshold CPU methodology allocating/deallocating 10 or 20 instances, outperforming the competitor in all studied metrics.

Keywords: reactive auto-scaling, auto-scaling, microservices, cloud computing

Procedia PDF Downloads 68

Authors: Damien Mouratille, Antonio R. Hidalgo-Muñoz, Nadine Matton, Yves Rouillard, Mickael Causse, Radouane El Yagoubi

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Background: The monitoring of the physiological activity related to mental workload (MW) on pilots will be useful to improve aviation safety by anticipating human performance degradation. The electrocardiogram (ECG) can reveal MW fluctuations due to either cognitive workload or/and emotional state since this measure exhibits autonomic nervous system modulations. Arguably, heart rate (HR) is one of its most intuitive and reliable parameters. It would be particularly interesting to analyze the interaction between cognitive requirements and emotion in ecologic sets such as a flight simulator. This study aims to explore by means of HR the relation between cognitive demands and emotional activation. Presumably, the effects of cognition and emotion overloads are not necessarily cumulative. Methodology: Eight healthy volunteers in possession of the Private Pilot License were recruited (male; 20.8±3.2 years). ECG signal was recorded along the whole experiment by placing two electrodes on the clavicle and left pectoral of the participants. The HR was computed within 4 minutes segments. NASA-TLX and Big Five inventories were used to assess subjective workload and to consider the influence of individual personality differences. The experiment consisted in completing two dual-tasks of approximately 30 minutes of duration into a flight simulator AL50. Each dual-task required the simultaneous accomplishment of both a pre-established flight plan and an additional task based on target stimulus discrimination inserted between Air Traffic Control instructions. This secondary task allowed us to vary the cognitive workload from low (LC) to high (HC) levels, by combining auditory and visual numerical stimuli to respond to meeting specific criteria. Regarding emotional condition, the two dual-tasks were designed to assure analogous difficulty in terms of solicited cognitive demands. The former was realized by the pilot alone, i.e. Low Arousal (LA) condition. In contrast, the latter generates a high arousal (HA), since the pilot was supervised by two evaluators, filmed and involved into a mock competition with the rest of the participants. Results: Performance for the secondary task showed significant faster reaction times (RT) for HA compared to LA condition (p=.003). Moreover, faster RT was found for LC compared to HC (p < .001) condition. No interaction was found. Concerning HR measure, despite the lack of main effects an interaction between emotion and cognition is evidenced (p=.028). Post hoc analysis showed smaller HR for HA compared to LA condition only for LC (p=.049). Conclusion. The control of an aircraft is a very complex task including strong cognitive demands and depends on the emotional state of pilots. According to the behavioral data, the experimental set has permitted to generate satisfactorily different emotional and cognitive levels. As suggested by the interaction found in HR measure, these two factors do not seem to have a cumulative impact on the sympathetic nervous system. Apparently, low cognitive workload makes pilots more sensitive to emotional variations. These results hint the independency between data processing and emotional regulation. Further physiological data are necessary to confirm and disentangle this relation. This procedure may be useful for monitoring objectively pilot’s mental workload.

Keywords: cognitive demands, emotion, flight simulator, heart rate, mental workload

Procedia PDF Downloads 250

Authors: Tatiana Rizova

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The migrant crisis, which peaked in 2015-2016, posed an unprecedented challenge to the European Union’s (EU) newest member states, including Bulgaria and Hungary. Their governments had to formulate sound migration policies with expediency and sensitivity to the needs of millions of people fleeing violent conflicts in the Middle East and failed states in North Africa. Political leaders in post-communist countries had to carefully coordinate with other EU member states on joint policies and solutions while minimizing the risk of alienating their increasingly anti-migrant domestic constituents. Post-communist member states’ governments chose distinct policy responses to the crisis, which were dictated by factors such as their governments’ partisan stances on migration, their views of the European Union, and the decision to frame the crisis as a security or a humanitarian issue. This paper explores how two Bulgarian governments (Boyko Borisov’s second and third government formed during the 43rd and 44th Bulgarian National Assembly, respectively) navigated the processes of EU migration policy making and managing the expectations of their electorates. Based on a comparative analysis of refugee policies in Bulgaria and Hungary during the height of the crisis (2015-2016) and a temporal analysis of refugee policies in Bulgaria (2015-2018), the paper advances the following conclusions. Drawing on insights of the Copenhagen school of security studies, the paper argues that cultural concerns dominated domestic debates in both Bulgaria and Hungary; both governments framed the issue predominantly as a matter of security rather than humanitarian disaster. Regardless of the similarities in issue framing, however, the two governments sought different paths of tackling the crisis. While the Bulgarian government demonstrated its willingness to comply with EU decisions (such as the proposal for mandatory quotas for refugee relocation), the Hungarian government defied EU directives and became a leading voice of dissent inside the EU. The current Bulgarian government (April 2017 - present) appears to be committed to complying with EU decisions and accepts the strategy of EU burden-sharing, while the Hungarian government has continually snubbed the EU’s appeals for cooperation despite the risk of hefty financial penalties. Hungary’s refugee policies have been influenced by the parliamentary representation of the far right-wing party Movement for a Better Hungary (Jobbik), which has encouraged the majority party (FIDESZ) to adopt harsher anti-migrant rhetoric and more hostile policies toward refugees. Bulgaria’s current government is a coalition of the center-right Citizens for a European Development of Bulgaria (GERB) and its far right-wing junior partners – the United Patriots (comprised of three nationalist political parties). The parliamentary presence of Jobbik in Hungary’s parliament has magnified the anti-migrant stance, rhetoric, and policies of Mr. Orbán’s Civic Alliance; we have yet to observe a substantial increase in the anti-migrant rhetoric and policies in Bulgaria’s case. Analyzing responses to the migrant/refugee crisis is a critical opportunity to understand how issues of cultural identity and belonging, inclusion and exclusion, regional integration and disintegration are debated and molded into policy in Europe’s youngest member states in the broader EU context.

Keywords: Copenhagen School, migrant crisis, refugees, security

Procedia PDF Downloads 101

Authors: Emilio Galdeano-Gómez, Juan C. Pérez-Mesa, Laura Piedra-Muñoz, María C. García-Barranco, Jesús Hernández-Rubio

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The situation in which firms engage in simultaneous cooperation and competition with each other is a phenomenon known as co-opetition. This scenario has received increasing attention in business economics and management analyses. In the domain of supply chain networks and for small and medium-sized enterprises, SMEs, these strategies are of greater relevance given the complex environment of globalization and competition in open markets. These firms face greater challenges regarding technology and access to specific resources due to their limited capabilities and limited market presence. Consequently, alliances and collaborations with both buyers and suppliers prove to be key elements in overcoming these constraints. However, rivalry and competition are also regarded as major factors in successful internationalization processes, as they are drivers for firms to attain a greater degree of specialization and to improve efficiency, for example enabling them to allocate scarce resources optimally and providing incentives for innovation and entrepreneurship. The present work aims to contribute to the literature on SMEs’ internationalization strategies. The sample is constituted by a panel data of marketing firms from the Andalusian food sector and a multivariate regression analysis is developed, measuring variables of co-opetition and international activity. The hierarchical regression equations method has been followed, thus resulting in three estimated models: the first one excluding the variables indicative of channel type, while the latter two include the international retailer chain and wholesaler variable. The findings show that the combination of several factors leads to a complex scenario of inter-organizational relationships of cooperation and competition. In supply chain management analyses, these relationships tend to be classified as either buyer-supplier (vertical level) or supplier-supplier relationships (horizontal level). Several buyers and suppliers tend to participate in supply chain networks, and in which the form of governance (hierarchical and non-hierarchical) influences cooperation and competition strategies. For instance, due to their market power and/or their closeness to the end consumer, some buyers (e.g. large retailers in food markets) can exert an influence on the selection and interaction of several of their intermediate suppliers, thus endowing certain networks in the supply chain with greater stability. This hierarchical influence may in turn allow these suppliers to develop their capabilities (e.g. specialization) to a greater extent. On the other hand, for those suppliers that are outside these networks, this environment of hierarchy, characterized by a “hub firm” or “channel master”, may provide an incentive for developing their co-opetition relationships. These results prove that the analyzed firms have experienced considerable growth in sales to new foreign markets, mainly in Europe, dealing with large retail chains and wholesalers as main buyers. This supply industry is predominantly made up of numerous SMEs, which has implied a certain disadvantage when dealing with the buyers, as negotiations have traditionally been held on an individual basis and in the face of high competition among suppliers. Over recent years, however, cooperation among these marketing firms has become more common, for example regarding R&D, promotion, scheduling of production and sales.

Keywords: co-petition networks, international supply chain, maketing agrifood firms, SMEs strategies

Procedia PDF Downloads 54

Authors: Adriana Muñoz-Talavera, Ana Rosa Rincón-Sánchez, Abraham Escobedo-Moratilla, María Cristina Islas-Carbajal, Miguel Ángel Gómez-Lim

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The highest rates of diabetes incidence and prevalence worldwide will increase the number of diabetic patients requiring insulin or insulin analogues. Then, current production systems would not be sufficient to meet the future market demands. Therefore, developing efficient expression systems for insulin and insulin analogues are needed. In addition, insulin analogues with better pharmacokinetics and pharmacodynamics properties and without mitogenic potential will be required. SCI-57 (single chain insulin-57) is an insulin analogue having 10 times greater affinity to the insulin receptor, higher resistance to thermal degradation than insulin, native mitogenicity and biological effect. Plants as expression platforms have been used to produce recombinant proteins because of their advantages such as cost-effectiveness, posttranslational modifications, absence of human pathogens and high quality. Immunoglobulin production with a yield of 50% has been achieved by transient expression in Nicotiana benthamiana (Nb). The aim of this study is to produce SCI-57 by transient expression in Nb. Methodology: DNA sequence encoding SCI-57 was cloned in pICH31070. This construction was introduced into Agrobacterium tumefaciens by electroporation. The resulting strain was used to infiltrate leaves of Nb. In order to isolate SCI-57, leaves from transformed plants were incubated 3 hours with the extraction buffer therefore filtrated to remove solid material. The resultant protein solution was subjected to anion exchange chromatography on an FPLC system and ultrafiltration to purify SCI-57. Detection of SCI-57 was made by electrophoresis pattern (SDS-PAGE). Protein band was digested with trypsin and the peptides were analyzed by Liquid chromatography tandem-mass spectrometry (LC-MS/MS). A purified protein sample (20µM) was analyzed by ESI-Q-TOF-MS to obtain the ionization pattern and the exact molecular weight determination. Chromatography pattern and impurities detection were performed using RP-HPLC using recombinant insulin as standard. The identity of the SCI-57 was confirmed by anti-insulin ELISA. The total soluble protein concentration was quantified by Bradford assay. Results: The expression cassette was verified by restriction mapping (5393 bp fragment). The SDS-PAGE of crude leaf extract (CLE) of transformed plants, revealed a protein of about 6.4 kDa, non-present in CLE of untransformed plants. The LC-MS/MS results displayed one peptide with a high score that matches SCI-57 amino acid sequence in the sample, confirming the identity of SCI-57. From the purified SCI-57 sample (PSCI-57) the most intense charge state was 1069 m/z (+6) on the displayed ionization pattern corresponding to the molecular weight of SCI-57 (6412.6554 Da). The RP-HPLC of the PSCI-57 shows the presence of a peak with similar retention time (rt) and UV spectroscopic profile to the insulin standard (SCI-57 rt=12.96 and insulin rt=12.70 min). The collected SCI-57 peak had ELISA signal. The total protein amount in CLE from transformed plants was higher compared to untransformed plants. Conclusions: Our results suggest the feasibility to produce insulin analogue SCI-57 by transient expression in Nicotiana benthamiana. Further work is being undertaken to evaluate the biological activity by glucose uptake by insulin-sensitive and insulin-resistant murine and human cultured adipocytes.

Keywords: insulin analogue, mass spectrometry, Nicotiana benthamiana, transient expression

Procedia PDF Downloads 321

Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

Procedia PDF Downloads 189

Authors: B.L. España-Sánchez, E. Luna-Hernández, R.A. Mauricio-Sánchez, M.E. Cruz-Soto, F. Padilla-Vaca, R. Muñoz, L. Granados-López, L.R. Ovalle-Flores, J.L. Menchaca-Arredondo, G. Luna-Bárcenas

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Treatment of burn injured has been considered an important clinical problem due to the fluid control and the presence of microorganisms during the healing process. Conventional treatment includes antiseptic techniques, topical medication and surgical removal of damaged skin, to avoid bacterial growth. In order to accelerate this process, different alternatives for tissue regeneration have been explored, including artificial skin, polymers, hydrogels and hybrid materials. Some requirements consider a nonreactive organic polymer with high biocompatibility and skin adherence, avoiding bacterial infections. Chitin-derivative biopolymer such as chitosan (CS) has been used in skin regeneration following third-degree burns. The biological interest of CS is associated with the improvement of tissue cell stimulation, biocompatibility and antibacterial properties. In particular, antimicrobial properties of CS can be significantly increased when is blended with nanostructured materials. Silver-based nanocomposites have gained attention in medicine due to their high antibacterial properties against pathogens, related to their high surface area/volume ratio at nanomolar concentrations. Silver nanocomposites can be blended or synthesized with chitin-derivative biopolymers in order to obtain a biodegradable/antimicrobial hybrid with improved physic-mechanical properties. In this study, nanocomposites based on chitosan/silver nanoparticles (CS/nAg) were synthesized by the in situ chemical reduction method, improving their antibacterial properties against pathogenic bacteria and enhancing the healing process in thermal burn injuries produced in an animal model. CS/nAg was prepared in solution by the chemical reduction method, using AgNO₃ as precursor. CS was dissolved in acetic acid and mixed with different molar concentrations of AgNO₃: 0.01, 0.025, 0.05 and 0.1 M. Solutions were stirred at 95°C during 20 hours, in order to promote the nAg formation. CS/nAg solutions were placed in Petri dishes and dried, to obtain films. Structural analyses confirm the synthesis of silver nanoparticles (nAg) by means of UV-Vis and TEM, with an average size of 7.5 nm and spherical morphology. FTIR analyses showed the complex formation by the interaction of hydroxyl and amine groups with metallic nanoparticles, and surface chemical analysis (XPS) shows low concentration of Ag⁰/Ag⁺ species. Topography surface analyses by means of AFM shown that hydrated CS form a mesh with an average diameter of 10 µm. Antibacterial activity against S. aureus and P. aeruginosa was improved in all evaluated conditions, such as nAg loading and interaction time. CS/nAg nanocomposites films did not show Ag⁰/Ag⁺ release in saline buffer and rat serum after exposition during 7 days. Healing process was significantly enhanced by the presence of CS/nAg nanocomposites, inducing the production of myofibloblasts, collagen remodelation, blood vessels neoformation and epidermis regeneration after 7 days of injury treatment, by means of histological and immunohistochemistry assays. The present work suggests that hydrated CS/nAg nanocomposites can be formed a mesh, improving the bacterial penetration and the contact with embedded nAg, producing complete growth inhibition after 1.5 hours. Furthermore, CS/nAg nanocomposites improve the cell tissue regeneration in thermal burn injuries induced in rats. Synthesis of antibacterial, non-toxic, and biocompatible nanocomposites can be an important issue in tissue engineering and health care applications.

Keywords: antibacterial, chitosan, healing process, nanocomposites, silver

Procedia PDF Downloads 264

Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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