Search results for: Pavel Murat
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 205

Search results for: Pavel Murat

25 An Evaluation of Medical Waste in Health Facilities through Data Envelopment Analysis (DEA) Method: Turkey-Amasya Public Hospitals Union Model

Authors: Murat Iskender Aktaş, Sadi Ergin, Rasime Acar Aktaş

Abstract:

In the light of fast-paced changes and developments in the health sector, the Ministry of Health started a new structuring with decree law numbered 663 within the scope of the Project of Transformation in Health. Accordingly, hospitals should ensure patient satisfaction through more efficient, more effective use of resources and sustainable finance by placing patients in the centre and should operate to increase efficiency to its maximum level while doing these. Within this study, in order to find out how efficient the hospitals were in terms of medical waste management between the years 2011-2014, the data from six hospitals of Amasya Public Hospitals Union were evaluated separately through Data Envelopment Analysis (DEA) method. First of all, input variables were determined. Input variables were the number of patients admitted to polyclinics, the number of inpatients in clinics, the number of patients who were operated and the number of patients who applied to the laboratory. Output variable was the cost of medical wastes in Turkish liras. Each hospital’s total medical waste level before and after public hospitals union; the amounts of average medical waste per patient admitted to polyclinics, per inpatient in clinics, per patient admitted to laboratory and per operated patient were compared within each group. In addition, average medical waste levels and costs were compared for Turkey in general and Europe in general. Paired samples t-test was used to find out whether the changes (increase-decrease) after public hospitals union were statistically significant. The health facilities that were unsuccessful in terms of medical waste management before and after public hospital union and the factors that caused this failure were determined. Based on the results, for each health facility that was ineffective in terms of medical waste management, the level of improvement required for each input was determined. The results of the study showed that there was an improvement in medical waste management applications after the health facilities became a member of public hospitals union; their medical waste levels were lower than the average of Turkey and Europe while the averages of cost of disposal were the highest.

Keywords: medical waste management, cost of medical waste, public hospitals, data envelopment analysis

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24 Examination of Recreation Possibilities and Determination of Efficiency Zone in Bursa, Province Nilufer Creek

Authors: Zeynep Pirselimoglu Batman, Elvan Ender Altay, Murat Zencirkiran

Abstract:

Water and water resources are characteristic areas with their special ecosystems Their natural, cultural and economic value and recreation opportunities are high. Recreational activities differ according to the natural, cultural, socio-economic resource values of the areas. In this sense, water and water edge areas, which are important for their resource values, are also important landscape values for recreational activities. From these landscapes values, creeks and the surrounding areas have become a major source of daily life in the past, as well as a major attraction for people's leisure time. However, their qualities and quantities must be sufficient to enable these areas to be used effectively in a recreational sense and to be able to fulfill their recreational functions. The purpose of the study is to identify the recreational use of the water-based activities and identify effective service areas in dense urbanization zones along the creek and green spaces around them. For this purpose, the study was carried out in the vicinity of Nilufer Creek in Bursa. The study area and its immediate surroundings are in the boundaries of Osmangazi and Nilufer districts. The study was carried out in the green spaces along the creek with an individual interaction of 17.930m. These areas are Hudavendigar Urban Park, Atatürk Urban Forest, Bursa Zoo, Soganlı Botanical Park, Mihrapli Park, Nilufer Valley Park. In the first phase of the study, the efficiency zones of these locations were calculated according to international standards. 3200m of this locations are serving the city population and 800m are serving the district and neighborhood population. These calculations are processed on the digitized map by the AUTOCAD program using the satellite image. The efficiency zone of these green spaces in the city were calculated as 71.04 km². In the second phase of the study, water-based current activities were determined by evaluating the recreational potential of these green spaces, which are located along the Nilufer Creek, where efficiency zones have been identified. It has been determined that water-based activities are used intensively in Hudavendigar Urban Park and interacted with Nilufer Creek. Within the scope of effective zones for the study area, appropriate recreational planning proposals have been developed and water-based activities have been suggested.

Keywords: Bursa, efficiency zone, Nilufer Creek, recreation, water-based activities

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23 Integration Process and Analytic Interface of different Environmental Open Data Sets with Java/Oracle and R

Authors: Pavel H. Llamocca, Victoria Lopez

Abstract:

The main objective of our work is the comparative analysis of environmental data from Open Data bases, belonging to different governments. This means that you have to integrate data from various different sources. Nowadays, many governments have the intention of publishing thousands of data sets for people and organizations to use them. In this way, the quantity of applications based on Open Data is increasing. However each government has its own procedures to publish its data, and it causes a variety of formats of data sets because there are no international standards to specify the formats of the data sets from Open Data bases. Due to this variety of formats, we must build a data integration process that is able to put together all kind of formats. There are some software tools developed in order to give support to the integration process, e.g. Data Tamer, Data Wrangler. The problem with these tools is that they need data scientist interaction to take part in the integration process as a final step. In our case we don’t want to depend on a data scientist, because environmental data are usually similar and these processes can be automated by programming. The main idea of our tool is to build Hadoop procedures adapted to data sources per each government in order to achieve an automated integration. Our work focus in environment data like temperature, energy consumption, air quality, solar radiation, speeds of wind, etc. Since 2 years, the government of Madrid is publishing its Open Data bases relative to environment indicators in real time. In the same way, other governments have published Open Data sets relative to the environment (like Andalucia or Bilbao). But all of those data sets have different formats and our solution is able to integrate all of them, furthermore it allows the user to make and visualize some analysis over the real-time data. Once the integration task is done, all the data from any government has the same format and the analysis process can be initiated in a computational better way. So the tool presented in this work has two goals: 1. Integration process; and 2. Graphic and analytic interface. As a first approach, the integration process was developed using Java and Oracle and the graphic and analytic interface with Java (jsp). However, in order to open our software tool, as second approach, we also developed an implementation with R language as mature open source technology. R is a really powerful open source programming language that allows us to process and analyze a huge amount of data with high performance. There are also some R libraries for the building of a graphic interface like shiny. A performance comparison between both implementations was made and no significant differences were found. In addition, our work provides with an Official Real-Time Integrated Data Set about Environment Data in Spain to any developer in order that they can build their own applications.

Keywords: open data, R language, data integration, environmental data

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22 Effect of Carbide Precipitates in Tool Steel on Material Transfer: A Molecular Dynamics Study

Authors: Ahmed Tamer AlMotasem, Jens Bergström, Anders Gåård, Pavel Krakhmalev, Thijs Jan Holleboom

Abstract:

In sheet metal forming processes, accumulation and transfer of sheet material to tool surfaces, often referred to as galling, is the major cause of tool failure. Initiation of galling is assumed to occur due to local adhesive wear between two surfaces. Therefore, reducing adhesion between the tool and the work sheet has a great potential to improve the tool materials galling resistance. Experimental observations and theoretical studies show that the presence of primary micro-sized carbides and/or nitrides in alloyed steels may significantly improve galling resistance. Generally, decreased adhesion between the ceramic precipitates and the sheet material counter-surface are attributed as main reason to the latter observations. On the other hand, adhesion processes occur at an atomic scale and, hence, fundamental understanding of galling can be obtained via atomic scale simulations. In the present study, molecular dynamics simulations are used, with utilizing second nearest neighbor embedded atom method potential to investigate the influence of nano-sized cementite precipitates embedded in tool atoms. The main aim of the simulations is to gain new fundamental knowledge on galling initiation mechanisms. Two tool/work piece configurations, iron/iron and iron-cementite/iron, are studied under dry sliding conditions. We find that the average frictional force decreases whereas the normal force increases for the iron-cementite/iron system, in comparison to the iron/iron configuration. Moreover, the average friction coefficient between the tool/work-piece decreases by about 10 % for the iron-cementite/iron case. The increase of the normal force in the case of iron-cementite/iron system may be attributed to the high stiffness of cementite compared to bcc iron. In order to qualitatively explain the effect of cementite on adhesion, the adhesion force between self-mated iron/iron and cementite/iron surfaces has been determined and we found that iron/cementite surface exhibits lower adhesive force than that of iron-iron surface. The variation of adhesion force with temperature was investigated up to 600 K and we found that the adhesive force, generally, decreases with increasing temperature. Structural analyses show that plastic deformation is the main deformation mechanism of the work-piece, accompanied with dislocations generation.

Keywords: adhesion, cementite, galling, molecular dynamics

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21 Advantages of Computer Navigation in Knee Arthroplasty

Authors: Mohammad Ali Al Qatawneh, Bespalchuk Pavel Ivanovich

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Computer navigation has been introduced in total knee arthroplasty to improve the accuracy of the procedure. Computer navigation improves the accuracy of bone resection in the coronal and sagittal planes. It was also noted that it normalizes the rotational alignment of the femoral component and fully assesses and balances the deformation of soft tissues in the coronal plane. The work is devoted to the advantages of using computer navigation technology in total knee arthroplasty in 62 patients (11 men and 51 women) suffering from gonarthrosis, aged 51 to 83 years, operated using a computer navigation system, followed up to 3 years from the moment of surgery. During the examination, the deformity variant was determined, and radiometric parameters of the knee joints were measured using the Knee Society Score (KSS), Functional Knee Society Score (FKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) scales. Also, functional stress tests were performed to assess the stability of the knee joint in the frontal plane and functional indicators of the range of motion. After surgery, improvement was observed in all scales; firstly, the WOMAC values decreased by 5.90 times, and the median value to 11 points (p < 0.001), secondly KSS increased by 3.91 times and reached 86 points (p < 0.001), and the third one is that FKSS data increased by 2.08 times and reached 94 points (p < 0.001). After TKA, the axis deviation of the lower limbs of more than 3 degrees was observed in 4 patients at 6.5% and frontal instability of the knee joint just in 2 cases at 3.2%., The lower incidence of sagittal instability of the knee joint after the operation was 9.6%. The range of motion increased by 1.25 times; the volume of movement averaged 125 degrees (p < 0.001). Computer navigation increases the accuracy of the spatial orientation of the endoprosthesis components in all planes, reduces the variability of the axis of the lower limbs within ± 3 °, allows you to achieve the best results of surgical interventions, and can be used to solve most basic tasks, allowing you to achieve excellent and good outcomes of operations in 100% of cases according to the WOMAC scale. With diaphyseal deformities of the femur and/or tibia, as well as with obstruction of their medullary canal, the use of computer navigation is the method of choice. The use of computer navigation prevents the occurrence of flexion contracture and hyperextension of the knee joint during the distal sawing of the femur. Using the navigation system achieves high-precision implantation for the endoprosthesis; in addition, it achieves an adequate balance of the ligaments, which contributes to the stability of the joint, reduces pain, and allows for the achievement of a good functional result of the treatment.

Keywords: knee joint, arthroplasty, computer navigation, advantages

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20 Double Wishbone Pushrod Suspension Systems Co-Simulation for Racing Applications

Authors: Suleyman Ogul Ertugrul, Mustafa Turgut, Serkan Inandı, Mustafa Gorkem Coban, Mustafa Kıgılı, Ali Mert, Oguzhan Kesmez, Murat Ozancı, Caglar Uyulan

Abstract:

In high-performance automotive engineering, the realistic simulation of suspension systems is crucial for enhancing vehicle dynamics and handling. This study focuses on the double wishbone suspension system, prevalent in racing vehicles due to its superior control and stability characteristics. Utilizing MATLAB and Adams Car simulation software, we conduct a comprehensive analysis of displacement behaviors and damper sizing under various dynamic conditions. The initial phase involves using MATLAB to simulate the entire suspension system, allowing for the preliminary determination of damper size based on the system's response under simulated conditions. Following this, manual calculations of wheel loads are performed to assess the forces acting on the front and rear suspensions during scenarios such as braking, cornering, maximum vertical loads, and acceleration. Further dynamic force analysis is carried out using MATLAB Simulink, focusing on the interactions between suspension components during key movements such as bumps and rebounds. This simulation helps in formulating precise force equations and in calculating the stiffness of the suspension springs. To enhance the accuracy of our findings, we focus on a detailed kinematic and dynamic analysis. This includes the creation of kinematic loops, derivation of relevant equations, and computation of Jacobian matrices to accurately determine damper travel and compression metrics. The calculated spring stiffness is crucial in selecting appropriate springs to ensure optimal suspension performance. To validate and refine our results, we replicate the analyses using the Adams Car software, renowned for its detailed handling of vehicular dynamics. The goal is to achieve a robust, reliable suspension setup that maximizes performance under the extreme conditions encountered in racing scenarios. This study exemplifies the integration of theoretical mechanics with advanced simulation tools to achieve a high-performance suspension setup that can significantly improve race car performance, providing a methodology that can be adapted for different types of racing vehicles.

Keywords: FSAE, suspension system, Adams Car, kinematic

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19 Design of Photonic Crystal with Defect Layer to Eliminate Interface Corrugations for Obtaining Unidirectional and Bidirectional Beam Splitting under Normal Incidence

Authors: Evrim Colak, Andriy E. Serebryannikov, Pavel V. Usik, Ekmel Ozbay

Abstract:

Working with a dielectric photonic crystal (PC) structure which does not include surface corrugations, unidirectional transmission and dual-beam splitting are observed under normal incidence as a result of the strong diffractions caused by the embedded defect layer. The defect layer has twice the period of the regular PC segments which sandwich the defect layer. Although the PC has even number of rows, the structural symmetry is broken due to the asymmetric placement of the defect layer with respect to the symmetry axis of the regular PC. The simulations verify that efficient splitting and occurrence of strong diffractions are related to the dispersion properties of the Floquet-Bloch modes of the photonic crystal. Unidirectional and bi-directional splitting, which are associated with asymmetric transmission, arise due to the dominant contribution of the first positive and first negative diffraction orders. The effect of the depth of the defect layer is examined by placing single defect layer in varying rows, preserving the asymmetry of PC. Even for deeply buried defect layer, asymmetric transmission is still valid even if the zeroth order is not coupled. This transmission is due to evanescent waves which reach to the deeply embedded defect layer and couple to higher order modes. In an additional selected performance, whichever surface is illuminated, i.e., in both upper and lower surface illumination cases, incident beam is split into two beams of equal intensity at the output surface where the intensity of the out-going beams are equal for both illumination cases. That is, although the structure is asymmetric, symmetric bidirectional transmission with equal transmission values is demonstrated and the structure mimics the behavior of symmetric structures. Finally, simulation studies including the examination of a coupled-cavity defect for two different permittivity values (close to the permittivity values of GaAs or Si and alumina) reveal unidirectional splitting for a wider band of operation in comparison to the bandwidth obtained in the case of a single embedded defect layer. Since the dielectric materials that are utilized are low-loss and weakly dispersive in a wide frequency range including microwave and optical frequencies, the studied structures should be scalable to the mentioned ranges.

Keywords: asymmetric transmission, beam deflection, blazing, bi-directional splitting, defect layer, dual beam splitting, Floquet-Bloch modes, isofrequency contours, line defect, oblique incidence, photonic crystal, unidirectionality

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18 Risk Assessment of Lead Element in Red Peppers Collected from Marketplaces in Antalya, Southern Turkey

Authors: Serpil Kilic, Ihsan Burak Cam, Murat Kilic, Timur Tongur

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Interest in the lead (Pb) has considerably increased due to knowledge about the potential toxic effects of this element, recently. Exposure to heavy metals above the acceptable limit affects human health. Indeed, Pb is accumulated through food chains up to toxic concentrations; therefore, it can pose an adverse potential threat to human health. A sensitive and reliable method for determination of Pb element in red pepper were improved in the present study. Samples (33 red pepper products having different brands) were purchased from different markets in Turkey. The selected method validation criteria (linearity, Limit of Detection, Limit of Quantification, recovery, and trueness) demonstrated. Recovery values close to 100% showed adequate precision and accuracy for analysis. According to the results of red pepper analysis, all of the tested lead element in the samples was determined at various concentrations. A Perkin- Elmer ELAN DRC-e model ICP-MS system was used for detection of Pb. Organic red pepper was used to obtain a matrix for all method validation studies. The certified reference material, Fapas chili powder, was digested and analyzed, together with the different sample batches. Three replicates from each sample were digested and analyzed. The results of the exposure levels of the elements were discussed considering the scientific opinions of the European Food Safety Authority (EFSA), which is the European Union’s (EU) risk assessment source associated with food safety. The Target Hazard Quotient (THQ) was described by the United States Environmental Protection Agency (USEPA) for the calculation of potential health risks associated with long-term exposure to chemical pollutants. THQ value contains intake of elements, exposure frequency and duration, body weight and the oral reference dose (RfD). If the THQ value is lower than one, it means that the exposed population is assumed to be safe and 1 < THQ < 5 means that the exposed population is in a level of concern interval. In this study, the THQ of Pb was obtained as < 1. The results of THQ calculations showed that the values were below one for all the tested, meaning the samples did not pose a health risk to the local population. This work was supported by The Scientific Research Projects Coordination Unit of Akdeniz University. Project Number: FBA-2017-2494.

Keywords: lead analyses, red pepper, risk assessment, daily exposure

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17 Modeling of Anisotropic Hardening Based on Crystal Plasticity Theory and Virtual Experiments

Authors: Bekim Berisha, Sebastian Hirsiger, Pavel Hora

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Advanced material models involving several sets of model parameters require a big experimental effort. As models are getting more and more complex like e.g. the so called “Homogeneous Anisotropic Hardening - HAH” model for description of the yielding behavior in the 2D/3D stress space, the number and complexity of the required experiments are also increasing continuously. In the context of sheet metal forming, these requirements are even more pronounced, because of the anisotropic behavior or sheet materials. In addition, some of the experiments are very difficult to perform e.g. the plane stress biaxial compression test. Accordingly, tensile tests in at least three directions, biaxial tests and tension-compression or shear-reverse shear experiments are performed to determine the parameters of the macroscopic models. Therefore, determination of the macroscopic model parameters based on virtual experiments is a very promising strategy to overcome these difficulties. For this purpose, in the framework of multiscale material modeling, a dislocation density based crystal plasticity model in combination with a FFT-based spectral solver is applied to perform virtual experiments. Modeling of the plastic behavior of metals based on crystal plasticity theory is a well-established methodology. However, in general, the computation time is very high and therefore, the computations are restricted to simplified microstructures as well as simple polycrystal models. In this study, a dislocation density based crystal plasticity model – including an implementation of the backstress – is used in a spectral solver framework to generate virtual experiments for three deep drawing materials, DC05-steel, AA6111-T4 and AA4045 aluminum alloys. For this purpose, uniaxial as well as multiaxial loading cases, including various pre-strain histories, has been computed and validated with real experiments. These investigations showed that crystal plasticity modeling in the framework of Representative Volume Elements (RVEs) can be used to replace most of the expensive real experiments. Further, model parameters of advanced macroscopic models like the HAH model can be determined from virtual experiments, even for multiaxial deformation histories. It was also found that crystal plasticity modeling can be used to model anisotropic hardening more accurately by considering the backstress, similar to well-established macroscopic kinematic hardening models. It can be concluded that an efficient coupling of crystal plasticity models and the spectral solver leads to a significant reduction of the amount of real experiments needed to calibrate macroscopic models. This advantage leads also to a significant reduction of computational effort needed for the optimization of metal forming process. Further, due to the time efficient spectral solver used in the computation of the RVE models, detailed modeling of the microstructure are possible.

Keywords: anisotropic hardening, crystal plasticity, micro structure, spectral solver

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16 Transducers for Measuring Displacements of Rotating Blades in Turbomachines

Authors: Pavel Prochazka

Abstract:

The study deals with transducers for measuring vibration displacements of rotating blade tips in turbomachines. In order to prevent major accidents with extensive economic consequences, it shows an urgent need for every low-pressure steam turbine stage being equipped with modern non-contact measuring system providing information on blade loading, damage and residual lifetime under operation. The requirement of measuring vibration and static characteristics of steam turbine blades, therefore, calls for the development and operational verification of both new types of sensors and measuring principles and methods. The task is really demanding: to measure displacements of blade tips with a resolution of the order of 10 μm by speeds up to 750 m/s, humidity 100% and temperatures up to 200 °C. While in gas turbines are used primarily capacitive and optical transducers, these transducers cannot be used in steam turbines. The reason is moisture vapor, droplets of condensing water and dirt, which disable the function of sensors. Therefore, the most feasible approach was to focus on research of electromagnetic sensors featuring promising characteristics for given blade materials in a steam environment. Following types of sensors have been developed and both experimentally and theoretically studied in the Institute of Thermodynamics, Academy of Sciences of the Czech Republic: eddy-current, Hall effect, inductive and magnetoresistive. Eddy-current transducers demand a small distance of 1 to 2 mm and change properties in the harsh environment of steam turbines. Hall effect sensors have relatively low sensitivity, high values of offset, drift, and especially noise. Induction sensors do not require any supply current and have a simple construction. The magnitude of the sensors output voltage is dependent on the velocity of the measured body and concurrently on the varying magnetic induction, and they cannot be used statically. Magnetoresistive sensors are formed by magnetoresistors arranged into a Wheatstone bridge. Supplying the sensor from a current source provides better linearity. The MR sensors can be used permanently for temperatures up to 200 °C at lower values of the supply current of about 1 mA. The frequency range of 0 to 300 kHz is by an order higher comparing to the Hall effect and induction sensors. The frequency band starts at zero frequency, which is very important because the sensors can be calibrated statically. The MR sensors feature high sensitivity and low noise. The symmetry of the bridge arrangement leads to a high common mode rejection ratio and suppressing disturbances, which is important, especially in industrial applications. The MR sensors feature high sensitivity, high common mode rejection ratio, and low noise, which is important, especially in industrial applications. Magnetoresistive transducers provide a range of excellent properties indicating their priority for displacement measurements of rotating blades in turbomachines.

Keywords: turbines, blade vibration, blade tip timing, non-contact sensors, magnetoresistive sensors

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15 Preliminary Studies on Poloxamer-Based Hydrogels with Oregano Essential Oil as Potential Topical Treatment of Cutaneous Papillomas

Authors: Ana Maria Muț, Georgeta Coneac, Ioana Olariu, Ștefana Avram, Ioana Zinuca Pavel, Ionela Daliana Minda, Lavinia Vlaia, Cristina Adriana Dehelean, Corina Danciu

Abstract:

Oregano essential oil is obtained from different parts of the plant Origanum vulgare (fam. Lamiaceae) and carvacrol and thymol are primary components, widely recognized for their antimicrobial activity, as well as their antiviral and antifungal properties. Poloxamers are triblock copolymers (Pluronic®), formed of three non-ionic blocks with a hydrophobic polyoxypropylene central chain flanked by two polyoxyethylene hydrophilic chains. They are known for their biocompatibility, sensitivity to temperature changes (sol-to-gel transition of aqueous solution with temperature increase), but also for their amphiphilic and surface active nature determining the formation of micelles, useful for solubilization of different hydrophobic compounds such as the terpenes and terpenoids contained in essential oils. Thus, these polymers, listed in European and US Pharmacopoeia and approved by FDA, are widely used as solubilizers and gelling agents for various pharmaceutical preparations, including topical hydrogels. The aim of this study was to investigate the posibility of solubilizing oregano essential oil (OEO) in polymeric micelles using polyoxypropylene (PPO)-polyoxyethylene (PEO)-polyoxypropylene (PPO) triblock polymers to obtain semisolid systems suitable for topical application. A formulation screening was performed, using Pluronic® F-127 in concentration of 20%, Pluronic® L-31, Pluronic® L-61 and Pluronic® L-62 in concentration of 0.5%, 0.8% respectively 1% to obtain the polymeric micelles-based systems. Then, to each selected system, with or without 10% absolute ethanol, 5% or 8% OEO was added. The obtained transparent poloxamer-based hydrogels containing solubilized OEO were further evaluated for pH, rheological characteristics (flow behaviour, viscosity, consistency and spreadability), using consacrated techniques like potentiometric titration, stationary shear flow test, penetrometric method and parallel plate method. Also, in vitro release and permeation of carvacrol from the hydrogels was carried out, using vertical diffusion cells and synthetic hydrophilic membrane and porcine skin respectively. The pH values and rheological features of all tested formulations were in accordance with official requirements for semisolid cutaneous preparations. But, the formulation containing 0.8% Pluronic® L-31, 10% absolute ethanol, 8% OEO and water and the formulation with 1% Pluronic® L-31, 5% OEO and water, produced the highest cumulative amounts of carvacrol released/permeated through the membrane. The present study demonstrated that oregano essential oil can be successfully solubilized in the investigated poloxamer-based hydrogels. These systems can be further investigated as potential topical therapy for cutaneous papillomas. Funding: This research was funded by Project PN-III-P1-1.1-TE2019-0130, Contract number TE47, Romania.

Keywords: oregano essential oil, carvacrol, poloxamer, topical hydrogels

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14 Gold-Mediated Modification of Apoferritin Surface with Targeting Antibodies

Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Protein apoferritin seems to be a very promising structure for use as a nanocarrier. It is prepared from intracellular ferritin protein naturally found in most organisms. The role of ferritin proteins is to store and transport ferrous ions. Apoferritin is a hollow protein cage without ferrous ions that can be prepared from ferritin by reduction with thioglycolic acid or dithionite. The structure of apoferritin is composed of 24 protein subunits, creating a sphere with 12 nm in diameter. The inner cavity has a diameter of 8 nm. The drug encapsulation process is based on the response of apoferritin structure to the pH changes of surrounding solution. In low pH, apoferritin is disassembled into individual subunits and its structure is “opened”. It can then be mixed with any desired cytotoxic drug and after adjustment of pH back to neutral the subunits are reconnected again and the drug is encapsulated within the apoferritin particles. Excess drug molecules can be removed by dialysis. The receptors for apoferritin, SCARA5 and TfR1 can be found in the membrane of both healthy and cancer cells. To enhance the specific targeting of apoferritin nanocarrier, it is possible to modify its surface with targeting moieties, such as antibodies. To ensure sterically correct complex, we used a a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (ApoDox) was coated either with gold nanoparticles (ApoDox-Nano) or gold (III) chloride hydrate reduced with sodium borohydride (ApoDox-HAu). The applied amount of gold in form of gold (III) chloride hydrate was 10 times higher than in the case of gold nanoparticles. However, after removal of the excess unbound ions by electrophoretic separation, the concentration of gold on the surface of apoferritin was only 6 times higher for ApoDox-HAu in comparison with ApoDox-Nano. Moreover, the reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties (excitation maximum at 480 nm with emission maximum at 600 nm) and thus its biological activity. Fluorescent properties of ApoDox-Nano were similar to the unmodified ApoDox, therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, we used ELISA-like method with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, we applied ApoDox without targeting antibodies and ApoDox-Nano modified with targeting antibodies (human IgG antibodies). The amount of unmodified ApoDox on antigen after incubation and subsequent rinsing with water was 5 times lower than in the case of ApoDox-Nano modified with targeting antibodies. The modification of non-gold ApoDox with antibodies caused no change in its targeting properties. It can therefore be concluded that the demonstrated procedure allows us to create nanocarrier with enhanced targeting properties, suitable for nanomedicine.

Keywords: apoferritin, doxorubicin, nanocarrier, targeting antibodies

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13 Gender Differences in Morbid Obese Children: Clinical Significance of Two Diagnostic Obesity Notation Model Assessment Indices

Authors: Mustafa M. Donma, Orkide Donma, Murat Aydin, Muhammet Demirkol, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

Abstract:

Childhood obesity is an ever increasing global health problem, affecting both developed and developing countries. Accurate evaluation of obesity in children requires difficult and detailed investigation. In our study, obesity in children was evaluated using new body fat ratios and indices. Assessment of anthropometric measurements, as well as some ratios, is important because of the evaluation of gender differences particularly during the late periods of obesity. A total of 239 children; 168 morbid obese (MO) (81 girls and 87 boys) and 71 normal weight (NW) (40 girls and 31 boys) children, participated in the study. Informed consent forms signed by the parents were obtained. Ethics Committee approved the study protocol. Mean ages (years)±SD calculated for MO group were 10.8±2.9 years in girls and 10.1±2.4 years in boys. The corresponding values for NW group were 9.0±2.0 years in girls and 9.2±2.1 years in boys. Mean body mass index (BMI)±SD values for MO group were 29.1±5.4 kg/m2 and 27.2±3.9 kg/m2 in girls and boys, respectively. These values for NW group were calculated as 15.5±1.0 kg/m2 in girls and 15.9±1.1 kg/m2 in boys. Groups were constituted based upon BMI percentiles for age-and-sex values recommended by WHO. Children with percentiles >99 were grouped as MO and children with percentiles between 85 and 15 were considered NW. The anthropometric measurements were recorded and evaluated along with the new ratios such as trunk-to-appendicular fat ratio, as well as indices such as Index-I and Index-II. The body fat percent values were obtained by bio-electrical impedance analysis. Data were entered into a database for analysis using SPSS/PASW 18 Statistics for Windows statistical software. Increased waist-to-hip circumference (C) ratios, decreased head-to-neck C, height ‘to’ ‘two’-‘to’-waist C and height ‘to’ ‘two’-‘to’-hip C ratios were observed in parallel with the development of obesity (p≤0.001). Reference value for height ‘to’ ‘two’-‘to’-hip ratio was detected as approximately 1.0. Index-II, based upon total body fat mass, showed much more significant differences between the groups than Index-I based upon weight. There was not any difference between trunk-to-appendicular fat ratios of NW girls and NW boys (p≥0.05). However, significantly increased values for MO girls in comparison with MO boys were observed (p≤0.05). This parameter showed no difference between NW and MO states in boys (p≥0.05). However, statistically significant increase was noted in MO girls compared to their NW states (p≤0.001). Trunk-to-appendicular fat ratio was the only fat-based parameter, which showed gender difference between NW and MO groups. This study has revealed that body ratios and formula based upon body fat tissue are more valuable parameters than those based on weight and height values for the evaluation of morbid obesity in children.

Keywords: anthropometry, childhood obesity, gender, morbid obesity

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12 Nanocomplexes on the Base of Triterpene Saponins Isolated from Glycyrrhiza glabra and Saponaria officinalis Plants as an Efficient Adjuvants for Influenza Vaccine Use

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

Abstract:

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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11 Oxidative Dehydrogenation and Hydrogenation of Malic Acid over Transition Metal Oxides

Authors: Gheorghiţa Mitran, Adriana Urdă, Mihaela Florea, Octavian Dumitru Pavel, Florentina Neaţu

Abstract:

Oxidative dehydrogenation and hydrogenation reactions of L-malic acid are interesting ways for its transformation into valuable products, including oxaloacetic, pyruvic and malonic acids but also 1,4-butanediol and 1,2,4-butanetriol. Keto acids have a range of applicationsin many chemical syntheses as pharmaceuticals, food additives and cosmetics. 3-Hydroxybutyrolactone and 1,2,4-butanetriol are used for the synthesis of chiral pharmaceuticals and other fine chemicals, while 1,4-butanediol can be used for organic syntheses, such as polybutylene succinate (PBS), polybutylene terephthalate (PBT), and for production of tetrahydrofuran (THF). L-malic acid is a non-toxic and natural organic acid present in fruits, and it is the main component of wine alongside tartaric acid representing about 90% of the wine total acidity. Iron oxides dopped with cobalt (CoxFe3-xO4; x= 0; 0.05; 0.1; 0.15) were studied as catalysts in these reactions. There is no mention in the literature of non-noble transition metal catalysts for these reactions. The method used for catalysts preparation was coprecipitation, whileBET XRD, XPS, FTIR and UV-VIS spectroscopy were used for the physicochemical properties evaluation.TheXRD patterns revealed the presence of α-Fe2O3 rhombohedral hematite structure, with cobalt atoms well dispersed and embedded in this structure. The studied samples are highly crystalline, with a crystallite size ranged from 58 to 65 nm. The optical absorption properties were investigated using UV-Vis spectroscopy, emphasizing the presence of bands that correspond with the reported hematite nanoparticle. Likewise, the presence of bands corresponding to lattice vibration of hexagonal hematite structurehas been evidenced in DRIFT spectra. Oxidative dehydrogenation of malic acid was studied using as solvents for malic acid ethanol or water(2, 5 and 10% malic acid in 5 mL solvent)at room temperature, while the hydrogenation reaction was evaluated in water as solvent (5%), in the presence of 1% catalyst. The oxidation of malic acid into oxaloacetic acid is the first step, after that, oxaloacetic acid is rapidly decarboxylated to malonic acid or pyruvic acid, depending on the active site. The concentration of malic acid in solution, it, in turn, has an influence on conversionthis decreases when the concentration of malic acid in the solution is high. The spent catalysts after the oxidative dehydrogenation of malic acid in ethanol were characterized by DRIFT spectroscopy and the presence of oxaloacetic, pyruvic and malonicacids, along with unreacted malic acidwere observed on the surface. The increase of the ratio of Co/Fe on the surface has an influence on the malic acid conversion and on the pyruvic acid yield, while the yield of malonic acid is influenced by the percentage of iron on the surface (determined from XPS). Oxaloacetic acid yield reaches a maximumat one hour of reaction, being higher when ethanol is used as a solvent, after which it suddenly decreases. The hydrogenation of malic acid occurs by consecutive reactions with the production of 3-hydroxy-butyrolactone, 1,2,4-butanetriol and 1,4-butanediol. Malic acid conversion increases with cobalt loading increasing up to Co/Fe ratio of 0.1, after which it has a slight decrease, while the yield in 1,4-butanediol is directly proportional to the cobalt content.

Keywords: malic acid, oxidative dehydrogenation, hydrogenation, oxaloacetic acid

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10 Evaluation of Nanoparticle Application to Control Formation Damage in Porous Media: Laboratory and Mathematical Modelling

Authors: Gabriel Malgaresi, Sara Borazjani, Hadi Madani, Pavel Bedrikovetsky

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Suspension-Colloidal flow in porous media occurs in numerous engineering fields, such as industrial water treatment, the disposal of industrial wastes into aquifers with the propagation of contaminants and low salinity water injection into petroleum reservoirs. The main effects are particle mobilization and captured by the porous rock, which can cause pore plugging and permeability reduction which is known as formation damage. Various factors such as fluid salinity, pH, temperature, and rock properties affect particle detachment. Formation damage is unfavorable specifically near injection and production wells. One way to control formation damage is pre-treatment of the rock with nanoparticles. Adsorption of nanoparticles on fines and rock surfaces alters zeta-potential of the surfaces and enhances the attachment force between the rock and fine particles. The main objective of this study is to develop a two-stage mathematical model for (1) flow and adsorption of nanoparticles on the rock in the pre-treatment stage and (2) fines migration and permeability reduction during the water production after the pre-treatment. The model accounts for adsorption and desorption of nanoparticles, fines migration, and kinetics of particle capture. The system of equations allows for the exact solution. The non-self-similar wave-interaction problem was solved by the Method of Characteristics. The analytical model is new in two ways: First, it accounts for the specific boundary and initial condition describing the injection of nanoparticle and production from the pre-treated porous media; second, it contains the effect of nanoparticle sorption hysteresis. The derived analytical model contains explicit formulae for the concentration fronts along with pressure drop. The solution is used to determine the optimal injection concentration of nanoparticle to avoid formation damage. The mathematical model was validated via an innovative laboratory program. The laboratory study includes two sets of core-flood experiments: (1) production of water without nanoparticle pre-treatment; (2) pre-treatment of a similar core with nanoparticles followed by water production. Positively-charged Alumina nanoparticles with the average particle size of 100 nm were used for the rock pre-treatment. The core was saturated with the nanoparticles and then flushed with low salinity water; pressure drop across the core and the outlet fine concentration was monitored and used for model validation. The results of the analytical modeling showed a significant reduction in the fine outlet concentration and formation damage. This observation was in great agreement with the results of core-flood data. The exact solution accurately describes fines particle breakthroughs and evaluates the positive effect of nanoparticles in formation damage. We show that the adsorbed concentration of nanoparticle highly affects the permeability of the porous media. For the laboratory case presented, the reduction of permeability after 1 PVI production in the pre-treated scenario is 50% lower than the reference case. The main outcome of this study is to provide a validated mathematical model to evaluate the effect of nanoparticles on formation damage.

Keywords: nano-particles, formation damage, permeability, fines migration

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9 Phenolic Acids of Plant Origin as Promising Compounds for Elaboration of Antiviral Drugs against Influenza

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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8 The Stable Isotopic Composition of Pedogenic Carbonate in the Minusinsk Basin, South Siberia

Authors: Jessica Vasil'chuk, Elena Ivanova, Pavel Krechetov, Vladimir Litvinsky, Nadine Budantseva, Julia Chizhova, Yurij Vasil'chuk

Abstract:

Carbonate minerals’ isotopic composition is widely used as a proxy for environmental parameters of the past. Pedogenic carbonate coatings on lower surfaces of coarse rock fragments are studied in order to indicate the climatic conditions and predominant vegetation under which they were formed. The purpose of the research is to characterize the isotopic composition of carbonate pedofeatures in soils of Minusink Hollow and estimate its correlation with isotopic composition of soil pore water, precipitation, vegetation and parent material. The samples of pedogenic carbonates, vegetation, carbonate parent material, soil water and precipitation water were analyzed using the Delta-V mass spectrometer with options of a gas bench and element analyser. The soils we studied are mainly Kastanozems that are poorly moisturized, therefore soil pore water was extracted by ethanol. Oxygen and carbon isotopic composition of pedogenic carbonates was analyzed in 3 key sites. Kazanovka Khakass state national reserve, Hankul salt lake, region of Sayanogorsk aluminum smelter. Vegetation photosynthetic pathway in the region is mainly C3. δ18O values of carbonate coatings in soils of Kazanovka vary in a range from −7.49 to −10.5‰ (vs V-PDB), and the smallest value −13.9‰ corresponds the coatings found between two buried soil horizons which 14C dates are 4.6 and 5.2 kyr BP. That may indicate cooler conditions of late Holocene than nowadays. In Sayanogorsk carbonates’ δ18O range is from −8.3 to −11.1‰ and near the Hankul Lake is from −9.0 to −10.2‰ all ranges are quite similar and may indicate coatings’ uniform formation conditions. δ13C values of carbonate coatings in Kazanovka vary from −2.5 to −6.7‰, the highest values correspond to the soils of Askiz and Syglygkug rivers former floodplains. For Sayanogorsk the range is from −4.9 to −6.8‰ and for Hankul from −2.3 to −5.7‰, where the highest value is for the modern salt crust. δ13C values of coatings strongly decrease from inner (older) to outer (younger) layers of coatings, that can indicate differences connected with the diffusion of organic material. Carbonate parent material δ18O value in the region vary from −11.1 to −12.0‰ and δ13C values vary from −4.9 to −5.7‰. Soil pore water δ18O values that determine the oxygen isotope composition of carbonates vary due to the processes of transpiration and mixing in the studied sites in a wide range of −2.0 to −13.5‰ (vs V-SMOW). Precipitation waters show δ18O values from -6.6‰ in May and -19.0‰ in January (snow) due to the temperature difference. The main conclusions are as follows: pedogenic carbonates δ13C values (−7…−2,5‰) show no correlation with modern C3 vegetation δ13C values (−30…−26‰), expected values under such vegetation are (−19…−15‰) but are closer to C4 vegetation. Late Holocene climate for the Minusinsk Hollow according to obtained data on isotope composition of carbonates and soil pore water chemical composition was dryer and cooler than present, that does not contradict with paleocarpology data obtained for the region. The research was supported by Russian Science Foundation (grant №14-27-00083).

Keywords: carbon, oxygen, pedogenic carbonates, South Siberia, stable isotopes

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7 Bio-Psycho-Social Consequences and Effects in Fall-Efficacy Scale in Seniors Using Exercise Intervention of Motor Learning According to Yoga Techniques

Authors: Milada Krejci, Martin Hill, Vaclav Hosek, Dobroslava Jandova, Jiri Kajzar, Pavel Blaha

Abstract:

The paper declares effects of exercise intervention of the research project “Basic research of balance changes in seniors”, granted by the Czech Science Foundation. The objective of the presented study is to define predictors, which influence bio-psycho-social consequences and effects of balance ability in senior 65 years old and above. We focused on the Fall-Efficacy Scale changes evaluation in seniors. Comprehensive hypothesis of the project declares, that motion uncertainty (dyskinesia) can negatively affect the well-being of a senior in bio-psycho-social context. In total, random selection and testing of 100 seniors (30 males, 70 females) from Prague and Central Bohemian region was provided. The sample was divided by stratified random selection into experimental and control groups, who underwent input and output testing. For diagnostics the methods of Medical Anamnesis, Functional anthropological examinations, Tinetti Balance Assessment Tool, SF-36 Health Survey, Anamnestic comparative self-assessment scale were used. Intervention method called "Life in Balance" based on yoga techniques was applied in four-week cycle. Results of multivariate regression were verified by repeated measures ANOVA: subject factor, phase of intervention (between-subject factor), body fluid (within-subject factor) and phase of intervention × body fluid interaction). ANOVA was performed with a repetition involving the factors of subjects, experimental/control group, phase of intervention (independent variable), and x phase interaction followed by Bonferroni multiple comparison assays with a test strength of at least 0.8 on the probability level p < 0.05. In the paper results of the first-year investigation of the three years running project are analysed. Results of balance tests confirmed no significant difference between females and males in pre-test. Significant improvements in balance and walking ability were observed in experimental group in females comparing to males (F = 128.4, p < 0.001). In the females control group, there was no significant change in post- test, while in the female experimental group positive changes in posture and spine flexibility in post-tests were found. It seems that females even in senior age react better to incentives of intervention in balance and spine flexibility. On the base of results analyses, we can declare the significant improvement in social balance markers after intervention in the experimental group (F = 10.5, p < 0.001). In average, seniors are used to take four drugs daily. Number of drugs can contribute to allergy symptoms and balance problems. It can be concluded that static balance and walking ability of seniors according Tinetti Balance scale correlate significantly with psychic and social monitored markers.

Keywords: exercises, balance, seniors 65+, health, mental and social balance

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6 Computer Based Identification of Possible Molecular Targets for Induction of Drug Resistance Reversion in Multidrug Resistant Mycobacterium Tuberculosis

Authors: Oleg Reva, Ilya Korotetskiy, Marina Lankina, Murat Kulmanov, Aleksandr Ilin

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Molecular docking approaches are widely used for design of new antibiotics and modeling of antibacterial activities of numerous ligands which bind specifically to active centers of indispensable enzymes and/or key signaling proteins of pathogens. Widespread drug resistance among pathogenic microorganisms calls for development of new antibiotics specifically targeting important metabolic and information pathways. A generally recognized problem is that almost all molecular targets have been identified already and it is getting more and more difficult to design innovative antibacterial compounds to combat the drug resistance. A promising way to overcome the drug resistance problem is an induction of reversion of drug resistance by supplementary medicines to improve the efficacy of the conventional antibiotics. In contrast to well established computer-based drug design, modeling of drug resistance reversion still is in its infancy. In this work, we proposed an approach to identification of compensatory genetic variants reducing the fitness cost associated with the acquisition of drug resistance by pathogenic bacteria. The approach was based on an analysis of the population genetic of Mycobacterium tuberculosis and on results of experimental modeling of the drug resistance reversion induced by a new anti-tuberculosis drug FS-1. The latter drug is an iodine-containing nanomolecular complex that passed clinical trials and was admitted as a new medicine against MDR-TB in Kazakhstan. Isolates of M. tuberculosis obtained on different stages of the clinical trials and also from laboratory animals infected with MDR-TB strain were characterized by antibiotic resistance, and their genomes were sequenced by the paired-end Illumina HiSeq 2000 technology. A steady increase in sensitivity to conventional anti-tuberculosis antibiotics in series of isolated treated with FS-1 was registered despite the fact that the canonical drug resistance mutations identified in the genomes of these isolates remained intact. It was hypothesized that the drug resistance phenotype in M. tuberculosis requires an adjustment of activities of many genes to compensate the fitness cost of the drug resistance mutations. FS-1 cased an aggravation of the fitness cost and removal of the drug-resistant variants of M. tuberculosis from the population. This process caused a significant increase in genetic heterogeneity of the Mtb population that was not observed in the positive and negative controls (infected laboratory animals left untreated and treated solely with the antibiotics). A large-scale search for linkage disequilibrium associations between the drug resistance mutations and genetic variants in other genomic loci allowed identification of target proteins, which could be influenced by supplementary drugs to increase the fitness cost of the drug resistance and deprive the drug-resistant bacterial variants of their competitiveness in the population. The approach will be used to improve the efficacy of FS-1 and also for computer-based design of new drugs to combat drug-resistant infections.

Keywords: complete genome sequencing, computational modeling, drug resistance reversion, Mycobacterium tuberculosis

Procedia PDF Downloads 243
5 Benefits of High Power Impulse Magnetron Sputtering (HiPIMS) Method for Preparation of Transparent Indium Gallium Zinc Oxide (IGZO) Thin Films

Authors: Pavel Baroch, Jiri Rezek, Michal Prochazka, Tomas Kozak, Jiri Houska

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Transparent semiconducting amorphous IGZO films have attracted great attention due to their excellent electrical properties and possible utilization in thin film transistors or in photovoltaic applications as they show 20-50 times higher mobility than that of amorphous silicon. It is also known that the properties of IGZO films are highly sensitive to process parameters, especially to oxygen partial pressure. In this study we have focused on the comparison of properties of transparent semiconducting amorphous indium gallium zinc oxide (IGZO) thin films prepared by conventional sputtering methods and those prepared by high power impulse magnetron sputtering (HiPIMS) method. Furthermore we tried to optimize electrical and optical properties of the IGZO thin films and to investigate possibility to apply these coatings on thermally sensitive flexible substrates. We employed dc, pulsed dc, mid frequency sine wave and HiPIMS power supplies for magnetron deposition. Magnetrons were equipped with sintered ceramic InGaZnO targets. As oxygen vacancies are considered to be the main source of the carriers in IGZO films, it is expected that with the increase of oxygen partial pressure number of oxygen vacancies decreases which results in the increase of film resistivity. Therefore in all experiments we focused on the effect of oxygen partial pressure, discharge power and pulsed power mode on the electrical, optical and mechanical properties of IGZO thin films and also on the thermal load deposited to the substrate. As expected, we have observed a very fast transition between low- and high-resistivity films depending on oxygen partial pressure when deposition using conventional sputtering methods/power supplies have been utilized. Therefore we established and utilized HiPIMS sputtering system for enlargement of operation window for better control of IGZO thin film properties. It is shown that with this system we are able to effectively eliminate steep transition between low and high resistivity films exhibited by DC mode of sputtering and the electrical resistivity can be effectively controlled in the wide resistivity range of 10-² to 10⁵ Ω.cm. The highest mobility of charge carriers (up to 50 cm2/V.s) was obtained at very low oxygen partial pressures. Utilization of HiPIMS also led to significant decrease in thermal load deposited to the substrate which is beneficial for deposition on the thermally sensitive and flexible polymer substrates. Deposition rate as a function of discharge power and oxygen partial pressure was also systematically investigated and the results from optical, electrical and structure analysis will be discussed in detail. Most important result which we have obtained demonstrates almost linear control of IGZO thin films resistivity with increasing of oxygen partial pressure utilizing HiPIMS mode of sputtering and highly transparent films with low resistivity were prepared already at low pO2. It was also found that utilization of HiPIMS technique resulted in significant improvement of surface smoothness in reactive mode of sputtering (with increasing of oxygen partial pressure).

Keywords: charge carrier mobility, HiPIMS, IGZO, resistivity

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4 Laboratory Indices in Late Childhood Obesity: The Importance of DONMA Indices

Authors: Orkide Donma, Mustafa M. Donma, Muhammet Demirkol, Murat Aydin, Tuba Gokkus, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

Abstract:

Obesity in childhood establishes a ground for adulthood obesity. Especially morbid obesity is an important problem for the children because of the associated diseases such as diabetes mellitus, cancer and cardiovascular diseases. In this study, body mass index (BMI), body fat ratios, anthropometric measurements and ratios were evaluated together with different laboratory indices upon evaluation of obesity in morbidly obese (MO) children. Children with nutritional problems participated in the study. Written informed consent was obtained from the parents. Study protocol was approved by the Ethics Committee. Sixty-two MO girls aged 129.5±35.8 months and 75 MO boys aged 120.1±26.6 months were included into the scope of the study. WHO-BMI percentiles for age-and-sex were used to assess the children with those higher than 99th as morbid obesity. Anthropometric measurements of the children were recorded after their physical examination. Bio-electrical impedance analysis was performed to measure fat distribution. Anthropometric ratios, body fat ratios, Index-I and Index-II as well as insulin sensitivity indices (ISIs) were calculated. Girls as well as boys were binary grouped according to homeostasis model assessment-insulin resistance (HOMA-IR) index of <2.5 and >2.5, fasting glucose to insulin ratio (FGIR) of <6 and >6 and quantitative insulin sensitivity check index (QUICKI) of <0.33 and >0.33 as the frequently used cut-off points. They were evaluated based upon their BMIs, arms, legs, trunk, whole body fat percentages, body fat ratios such as fat mass index (FMI), trunk-to-appendicular fat ratio (TAFR), whole body fat ratio (WBFR), anthropometric measures and ratios [waist-to-hip, head-to-neck, thigh-to-arm, thigh-to-ankle, height/2-to-waist, height/2-to-hip circumference (C)]. SPSS/PASW 18 program was used for statistical analyses. p≤0.05 was accepted as statistically significance level. All of the fat percentages showed differences between below and above the specified cut-off points in girls when evaluated with HOMA-IR and QUICKI. Differences were observed only in arms fat percent for HOMA-IR and legs fat percent for QUICKI in boys (p≤ 0.05). FGIR was unable to detect any differences for the fat percentages of boys. Head-to-neck C was the only anthropometric ratio recommended to be used for all ISIs (p≤0.001 for both girls and boys in HOMA-IR, p≤0.001 for girls and p≤0.05 for boys in FGIR and QUICKI). Indices which are recommended for use in both genders were Index-I, Index-II, HOMA/BMI and log HOMA (p≤0.001). FMI was also a valuable index when evaluated with HOMA-IR and QUICKI (p≤0.001). The important point was the detection of the severe significance for HOMA/BMI and log HOMA while they were evaluated also with the other indices, FGIR and QUICKI (p≤0.001). These parameters along with Index-I were unique at this level of significance for all children. In conclusion, well-accepted ratios or indices may not be valid for the evaluation of both genders. This study has emphasized the limiting properties for boys. This is particularly important for the selection process of some ratios and/or indices during the clinical studies. Gender difference should be taken into consideration for the evaluation of the ratios or indices, which will be recommended to be used particularly within the scope of obesity studies.

Keywords: anthropometry, childhood obesity, gender, insulin sensitivity index

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3 Post-Exercise Recovery Tracking Based on Electrocardiography-Derived Features

Authors: Pavel Bulai, Taras Pitlik, Tatsiana Kulahava, Timofei Lipski

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The method of Electrocardiography (ECG) interpretation for post-exercise recovery tracking was developed. Metabolic indices (aerobic and anaerobic) were designed using ECG-derived features. This study reports the associations between aerobic and anaerobic indices and classical parameters of the person’s physiological state, including blood biochemistry, glycogen concentration and VO2max changes. During the study 9 participants, healthy, physically active medium trained men and women, which trained 2-4 times per week for at least 9 weeks, fulfilled (i) ECG monitoring using Apple Watch Series 4 (AWS4); (ii) blood biochemical analysis; (iii) maximal oxygen consumption (VO2max) test, (iv) bioimpedance analysis (BIA). ECG signals from a single-lead wrist-wearable device were processed with detection of QRS-complex. Aerobic index (AI) was derived as the normalized slope of QR segment. Anaerobic index (ANI) was derived as the normalized slope of SJ segment. Biochemical parameters, glycogen content and VO2max were evaluated eight times within 3-60 hours after training. ECGs were recorded 5 times per day, plus before and after training, cycloergometry and BIA. The negative correlation between AI and blood markers of the muscles functional status including creatine phosphokinase (r=-0.238, p < 0.008), aspartate aminotransferase (r=-0.249, p < 0.004) and uric acid (r = -0.293, p<0.004) were observed. ANI was also correlated with creatine phosphokinase (r= -0.265, p < 0.003), aspartate aminotransferase (r = -0.292, p < 0.001), lactate dehydrogenase (LDH) (r = -0.190, p < 0.050). So, when the level of muscular enzymes increases during post-exercise fatigue, AI and ANI decrease. During recovery, the level of metabolites is restored, and metabolic indices rising is registered. It can be concluded that AI and ANI adequately reflect the physiology of the muscles during recovery. One of the markers of an athlete’s physiological state is the ratio between testosterone and cortisol (TCR). TCR provides a relative indication of anabolic-catabolic balance and is considered to be more sensitive to training stress than measuring testosterone and cortisol separately. AI shows a strong negative correlation with TCR (r=-0.437, p < 0.001) and correctly represents post-exercise physiology. In order to reveal the relation between the ECG-derived metabolic indices and the state of the cardiorespiratory system, direct measurements of VO2max were carried out at various time points after training sessions. The negative correlation between AI and VO2max (r = -0.342, p < 0.001) was obtained. These data testifying VO2max rising during fatigue are controversial. However, some studies have revealed increased stroke volume after training, that agrees with findings. It is important to note that post-exercise increase in VO2max does not mean an athlete’s readiness for the next training session, because the recovery of the cardiovascular system occurs over a substantially longer period. Negative correlations registered for ANI with glycogen (r = -0.303, p < 0.001), albumin (r = -0.205, p < 0.021) and creatinine (r = -0.268, p < 0.002) reflect the dehydration status of participants after training. Correlations between designed metabolic indices and physiological parameters revealed in this study can be considered as the sufficient evidence to use these indices for assessing the state of person’s aerobic and anaerobic metabolic systems after training during fatigue, recovery and supercompensation.

Keywords: aerobic index, anaerobic index, electrocardiography, supercompensation

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2 Rheological Properties of Thermoresponsive Poly(N-Vinylcaprolactam)-g-Collagen Hydrogel

Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

Abstract:

Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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1 Evaluation of Academic Research Projects Using the AHP and TOPSIS Methods

Authors: Murat Arıbaş, Uğur Özcan

Abstract:

Due to the increasing number of universities and academics, the fund of the universities for research activities and grants/supports given by government institutions have increased number and quality of academic research projects. Although every academic research project has a specific purpose and importance, limited resources (money, time, manpower etc.) require choosing the best ones from all (Amiri, 2010). It is a pretty hard process to compare and determine which project is better such that the projects serve different purposes. In addition, the evaluation process has become complicated since there are more than one evaluator and multiple criteria for the evaluation (Dodangeh, Mojahed and Yusuff, 2009). Mehrez and Sinuany-Stern (1983) determined project selection problem as a Multi Criteria Decision Making (MCDM) problem. If a decision problem involves multiple criteria and objectives, it is called as a Multi Attribute Decision Making problem (Ömürbek & Kınay, 2013). There are many MCDM methods in the literature for the solution of such problems. These methods are AHP (Analytic Hierarchy Process), ANP (Analytic Network Process), TOPSIS (Technique for Order Preference by Similarity to Ideal Solution), PROMETHEE (Preference Ranking Organization Method for Enrichment Evaluation), UTADIS (Utilities Additives Discriminantes), ELECTRE (Elimination et Choix Traduisant la Realite), MAUT (Multiattribute Utility Theory), GRA (Grey Relational Analysis) etc. Teach method has some advantages compared with others (Ömürbek, Blacksmith & Akalın, 2013). Hence, to decide which MCDM method will be used for solution of the problem, factors like the nature of the problem, types of choices, measurement scales, type of uncertainty, dependency among the attributes, expectations of decision maker, and quantity and quality of the data should be considered (Tavana & Hatami-Marbini, 2011). By this study, it is aimed to develop a systematic decision process for the grant support applications that are expected to be evaluated according to their scientific adequacy by multiple evaluators under certain criteria. In this context, project evaluation process applied by The Scientific and Technological Research Council of Turkey (TÜBİTAK) the leading institutions in our country, was investigated. Firstly in the study, criteria that will be used on the project evaluation were decided. The main criteria were selected among TÜBİTAK evaluation criteria. These criteria were originality of project, methodology, project management/team and research opportunities and extensive impact of project. Moreover, for each main criteria, 2-4 sub criteria were defined, hence it was decided to evaluate projects over 13 sub-criterion in total. Due to superiority of determination criteria weights AHP method and provided opportunity ranking great number of alternatives TOPSIS method, they are used together. AHP method, developed by Saaty (1977), is based on selection by pairwise comparisons. Because of its simple structure and being easy to understand, AHP is the very popular method in the literature for determining criteria weights in MCDM problems. Besides, the TOPSIS method developed by Hwang and Yoon (1981) as a MCDM technique is an alternative to ELECTRE method and it is used in many areas. In the method, distance from each decision point to ideal and to negative ideal solution point was calculated by using Euclidian Distance Approach. In the study, main criteria and sub-criteria were compared on their own merits by using questionnaires that were developed based on an importance scale by four relative groups of people (i.e. TUBITAK specialists, TUBITAK managers, academics and individuals from business world ) After these pairwise comparisons, weight of the each main criteria and sub-criteria were calculated by using AHP method. Then these calculated criteria’ weights used as an input in TOPSİS method, a sample consisting 200 projects were ranked on their own merits. This new system supported to opportunity to get views of the people that take part of project process including preparation, evaluation and implementation on the evaluation of academic research projects. Moreover, instead of using four main criteria in equal weight to evaluate projects, by using weighted 13 sub-criteria and decision point’s distance from the ideal solution, systematic decision making process was developed. By this evaluation process, new approach was created to determine importance of academic research projects.

Keywords: Academic projects, Ahp method, Research projects evaluation, Topsis method.

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