Search results for: Mehmet Ozturk

Authors: Mehmet Savsar

Abstract:

This paper presents a practical case application of simulation modeling and analysis in a specific industrial setting. Various maintenance related parameters of the equipment in the system under consideration are determined and a simulation model is developed to study system behavior. System performance is determined based on established parameters and operational policies, which included system operation with and without preventive maintenance implementation. The results show that preventive maintenance practice has significant effects on improving system productivity. The simulation procedures outlined in this paper can be used by operation managers to perform production line analysis under different maintenance policies in various industrial settings.

Keywords: simulation, production line, machine failures, maintenance, industrial bakery

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Authors: Eyyup Murat Karakurt, Yan Huang, Mehmet Kaya, Huseyin Demirtas

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In this study, the effect of the porosity effect of Ti-20Zr alloy produced by powder metallurgy as a biomaterial was investigated experimentally. The Ti based alloys (Ti-20%Zr (at.) were produced under 300 MPa, for 6 h at 1200 °C. Afterward, the microstructure of the Ti-based alloys was analyzed by optical analysis, scanning electron microscopy, energy dispersive spectrometry. Moreover, compression tests were applied to determine the mechanical behaviour of samples. As a result, highly porous Ti-20Zr alloys exhibited an elastic modulus close to human bone. The results later were compared theoretically and experimentally.

Keywords: porosity effect, Ti based alloys, elastic modulus, compression test

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Authors: Arda Ozturk, Turgay Ozgur, Mursit Aksoy, Bahar O. Ozgur, Ozan Yilmaz

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The purpose of this study was to investigate the effect of 8 weeks of basic basketball and volleyball exercises to Bodily-Kinesthetic Intelligence (BKI) levels in 245 (92 girls and 154 boys) adolescents aged between 12 and 14 years. Data collected via Bodily-Kinesthetic Intelligence scale as a subdimension of Multiple Intelligences Inventory. BKI levels were not different between basketball and volleyball groups. Statistical analyses were made based on gender, age groups (12, 13, 14 years) and exercise type. Independent samples t-test revealed that there was no significant difference between boy’s and girl’s BKI levels. One way ANOVA test revealed that there was significant difference between age group’s (12, 13, 14) BKI levels in post-test. However, Paired samples t-test revealed no significant differences between pre-post test results of adolescent’s BKI levels. In conclusion, despite the relatively long-term (8 weeks) physical activity. BKI levels have not shown significant differences.

Keywords: bodily-kinesthetic intelligence, adolescent, basketball, volleyball

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Authors: Esra Öztürk, Erkul Karacaoglu

Abstract:

Pyrochlores, having compounds of the general formula, A2B2O7 (A and B are metals/rare earths) are important class of materials thanks to having technological applications like in luminescence, ionic conductivity, nuclear waste immobilization etc. The rare earths included pyrochlore compounds have also potential photoluminescence characteristics. In this context, Er3+-activated Lu2Ti2O7 pyrochlore was chosen and synthesized through a high-temperature solid-state reaction route that was sintered under the open atmosphere in this study. The optimal reaction conditions to obtain expected single phase system, the thermal analysis (DTA/TG) were carried out. The X-ray powder diffraction (XRD) was used to determine phase properties of the sample. The photoluminescence (PL) results were done to obtain excitation, emission and decay time properties by a PL spectrometer under room temperature. According to the PL, there are excitation bands at 352 nm, 388 nm, 423 nm and 453 nm that are due to 4I15/2 → 2G7/2, 4I15/2 → 4G11/2 and 4I15/2 → 4F5/2 transitions of Er3+ ions, respectively. The emission bands are placed at 582 nm, 677 nm and 762 nm that are associated with 2H11/2, 4S3/2 → 4I15/2, 4F9/2 → 4I15/2, 4I9/2 → 4I15/2 transitions of Er3+ ions, respectively.

Keywords: Er3+, Lu2Ti2O7, photoluminescence, pyrochlore, rare-earths

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Authors: Aslı Günay Bulutsuz, Mehmet Emin Yurci

Abstract:

Severe plastic deformation techniques are top-down deformation methods which enable superior mechanical properties by decreasing grain size. Different kind severe plastic deformation methods have been widely being used at various process temperature and geometries. Besides manufacturing advantages of severe plastic deformation technique, most of the types are being used only at the laboratory level. They cannot be adapted to industrial usage due to their continuous manufacturability and manufacturing costs. In order to enhance these manufacturing difficulties and enable widespread usage, different kinds of methods have been developed. In this review, a comprehensive literature research was fulfilled in order to highlight continuous severe plastic deformation methods.

Keywords: continuous manufacturing, severe plastic deformation, ultrafine grains, grain size refinement

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Authors: Mehmet Ekici

Abstract:

In this study, the fading time affecting the mechanical properties and microstructures of vermicular cast iron were studied. Pig iron and steel scrap weighing about 12 kg were charged into the high-frequency induction furnace crucible and completely melted for production of vermicular cast iron. The slag was skimmed using a common flux. After fading time was set at 1. 3 and 5 minutes. In this way, three vermicular cast iron was produced that same composition but different phase structures. The microstructure of specimens was investigated, and uni-axial tensile test and the Charpy impact test were performed, and their micro-hardness measurements were done in order to characterize the mechanical behaviours of vermicular cast iron.

Keywords: vermicular cast iron, fading time, hardness, tensile test and impact test

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Authors: Tugrul Oktay, Mehmet Konar, Mustafa Soylak, Firat Sal, Murat Onay, Orhan Kizilkaya

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In this paper, autonomous performance of a small manufactured unmanned helicopter is tried to be increased. For this purpose, a small unmanned helicopter is manufactured in Erciyes University, Faculty of Aeronautics and Astronautics. It is called as ZANKA-Heli-I. For performance maximization, autopilot parameters are determined via minimizing a cost function consisting of flight performance parameters such as settling time, rise time, overshoot during trajectory tracking. For this purpose, a stochastic optimization method named as simultaneous perturbation stochastic approximation is benefited. Using this approach, considerable autonomous performance increase (around %23) is obtained.

Keywords: small helicopters, hierarchical control, stochastic optimization, autonomous performance maximization, autopilots

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Authors: Aydin Teymourifar, Gurkan Ozturk

Abstract:

In this paper, a new hybrid particle swarm optimization algorithm is proposed for the multi-objective flexible job shop scheduling problem that is very important and hard combinatorial problem. The Pareto approach is used for solving the multi-objective problem. Several new local search heuristics are integrated into an algorithm based on the critical block concept to enhance the performance of the algorithm. The algorithm is compared with the recently published multi-objective algorithms based on benchmarks selected from the literature. Several metrics are used for quantifying performance and comparison of the achieved solutions. The algorithms are also compared based on the Weighting summation of objectives approach. The proposed algorithm can find the Pareto solutions more efficiently than the compared algorithms in less computational time.

Keywords: swarm-based optimization, local search, Pareto optimality, flexible job shop scheduling, multi-objective optimization

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Authors: Abdullah Bilal Ozturk, Nil Acarali, Hediye Irem Ozgunduz, Hava Gizem Kandilci, Hanifi Sarac

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In this study, zeolite, shellac and different boron chemicals were used as additive to dye and effects were comprehensively investigated. Considering previous studies additive materials that had not used before were determined for produce dye with physical properties. Literature research about the materials provides determining easily sufficient amount of additive materials. Accessible of additives or yearly production amounts are become important issue at selection of materials. Zeolite and boron chemicals are suitable selection in that easy access and has large amount of production in our country. Previous research about boron chemicals shows they have flame retardant effect on textile materials besides numerous usage areas. Also, from previous research, shellac was used widely for protection and insulation of metallic materials. Zeolite added to dye to increase adhesive effect of dye. In this study, corrosion tests were applied to find out if there are positive effects of zeolite, shellac, and boron chemicals to dye’s physical properties.

Keywords: dye, corrosion, zeolite, shellac, boron

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Authors: Selcuk Aslan, Dervis Karaboga, Celal Ozturk

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Artificial Bee Colony (ABC) algorithm is one of the most successful swarm intelligence based metaheuristics. It has been applied to a number of constrained or unconstrained numerical and combinatorial optimization problems. In this paper, we presented a parallelized version of ABC algorithm by adapting employed and onlooker bee phases to the Compute Unified Device Architecture (CUDA) platform which is a graphical processing unit (GPU) programming environment by NVIDIA. The execution speed and obtained results of the proposed approach and sequential version of ABC algorithm are compared on functions that are typically used as benchmarks for optimization algorithms. Tests on standard benchmark functions with different colony size and number of parameters showed that proposed parallelization approach for ABC algorithm decreases the execution time consumed by the employed and onlooker bee phases in total and achieved similar or better quality of the results compared to the standard sequential implementation of the ABC algorithm.

Keywords: Artificial Bee Colony algorithm, GPU computing, swarm intelligence, parallelization

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Authors: Hakan Erol, Altan Elibol, Ömer Eryılmaz, Mehmet Şimşek

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Organizations aim to manage information in a most possible effective way for sustainment and development. In doing so, they apply various procedures and methods. The very same situation is valid for each service of Armed Forces. During long-lasting endeavors such as shaping and maintaining security environment, supporting and securing peace, knowledge management is a crucial asset. Optimum Balance Model aims to promote the system from a decisive point to a higher decisive point. In this context, this paper analyses the application of optimum balance model to knowledge management in Armed Forces and tries to find answer to the question how Optimum Balance Model is integrated in knowledge management.

Keywords: optimum balance model, knowledge management, security environment, supporting peace

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Authors: Eyup Ozkan, Ozkan U. Nalbantoglu, Aycan Gundogdu, Mehmet Hora, A. Emre Onuk

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The human microbiome has been associated with cardiological conditions and this relationship is becoming to be defined beyond the gastrointestinal track. In this study, we investigate the alteration in circulatory microbiota in the context of Coronary Artery Disease (CAD). We received circulatory blood samples from suspected CAD patients and maintain 16S ribosomal RNA sequencing to identify each patient’s microbiome. It was found that Corynebacterium and Methanobacteria genera show statistically significant differences between healthy and CAD patients. The overall biodiversities between the groups were observed to be different revealed by machine learning classification models. We also achieve and demonstrate the performance of a diagnostic method using circulatory blood microbiome-based estimation.

Keywords: coronary artery disease, blood microbiome, machine learning, angiography, next-generation sequencing

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Authors: Z. Funda Türkmenoğlu, Mehmet Türkmenoglu, Demet Yavuz,

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In this study, the effects of waste marbles as aggregate material on workability and hardened concrete characteristics of self compacting lightweight concrete are investigated. For this purpose, self compacting light weight concrete are produced by waste marble aggregates are replaced with fine aggregate at 5%, 7.5%, and 10% ratios. Fresh concrete properties, slump flow, T₅₀ time, V funnel, compressive strength and ultrasonic pulse velocity of self compacting lightweight concrete are determined. It is concluded from the test results that using waste marbles as aggregate material by replacement with fine aggregate slightly affects fresh and hardened concrete characteristics of self compacting lightweight concretes.

Keywords: hardened concrete characteristics, self compacting lightweight concrete, waste marble, workability

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Authors: Gizem Akcan, Erdinc Ozturk

Abstract:

The purpose of the study was to determine some psychosocial variables that predict dissociation in university students. These psychosocial variables were perceived childhood trauma, alexithymia, and gender. 150 (75 males, 75 females) university students (bachelor, master and postgraduate) were enrolled in this study. They were chosen from universities in Istanbul at the education year of 2016-2017. Dissociative Experiences Scale (DES), Childhood Trauma Questionnaire (CTQ) and Toronto Alexithymia Scale were used to assess related variables. Demographic Information Form was given to students in order to have their demographic information. Frequency Distribution, Linear Regression Analysis, and t-test analysis were used for statistical analysis. Childhood trauma and alexithymia were found to have predictive value on dissociation among university students. However, physical abuse, physical neglect and emotional neglect sub dimensions of childhood trauma and externally-oriented thinking sub dimension of alexithymia did not have predictive value on dissociation. Moreover, there was no significant difference between males and females in terms of dissociation scores of participants.

Keywords: childhood trauma, dissociation, alexithymia, gender

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Authors: Gokhan Dok, Hakan Ozturk, Aydin Demir

Abstract:

The behavior of reinforced concrete (RC) members is quite important in RC structures. When evaluating the performance of structures, the nonlinear properties are defined according to the cross sectional behavior of RC members. To be able to determine the behavior of RC members, its cross sectional behavior should be known well. The moment-curvature (MC) relationship is used to represent cross sectional behavior. The MC relationship of RC cross section can be best determined both experimentally and numerically. But, experimental study on RC members is very difficult. The aim of the study is to obtain the MC relationship of RC shear walls. Additionally, it is aimed to determine the parameters which affect MC relationship. While obtaining MC relationship of RC members, XTRACT which can represent robustly the MC relationship is used. Concrete quality, longitudinal and transverse reinforcing ratios, are selected as parameters which affect MC relationship. As a result of the study, curvature ductility and effective flexural stiffness are determined using this parameter. Effective flexural stiffness is compared with the values defined in design codes.

Keywords: moment-curvature, reinforced concrete, shear wall, numerical

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Authors: Mehmet Savsar

Abstract:

Several factors affect productivity of Food Processing Assembly Lines (FPAL). Engineers and line managers usually do not recognize some of these factors and underutilize their production/assembly lines. In this paper, a special food processing assembly line is studied in detail, and procedures are presented to illustrate how productivity and efficiency of such lines can be increased. The assembly line considered produces ten different types of freshly prepared salads on the same line, which is called mixed model assembly line. Problems causing delays and inefficiencies on the line are identified. Line balancing and related tools are used to increase line efficiency and minimize balance delays. The procedure and the approach utilized in this paper can be useful for the operation managers and industrial engineers dealing with similar assembly lines in food processing industry.

Keywords: assembly lines, line balancing, production efficiency, bottleneck

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Authors: Rahile Ozturk, Esra Maltas

Abstract:

This study aimed to determine the effect of vinclozolin on some biochemical characteristics of Galleria mellonella (Lepidoptera: Pyralidae) which is an economically harmful species damaging the honeycomb in beekeeping. For experimental groups, the eggs obtained from stock were dropped into the mixed feed of vinclozolin at different doses (20, 40 and 60 ppm) and had the larvae fed with this feed. As result of the addition of vinclozolin at concentrations of 20, 40 and 60 ppm, glycogen contents of G. mellonella were determined and a significant reduction in the amount of glycogen was observed with increasing concentration of vinclozolin. In this study, activity of catalase enzyme, particularly effective in defense mechanism, activity of xanthine oxidase involved in nucleotide metabolism and activity of glucose oxidase in the metabolism of carbohydrates were measured. When compared with the results from control groups, the enzyme activities of the larvaes fed with the feed including 20, 40 and 60 ppm of vinclozolin were observed to vary or remain constant. Accordingly, glucose oxidase and catalase activities increased with the increase in amount of vinclozolin in the feed and the activity of xanthine oxidase remained stable.

Keywords: Catalase, Galleria mellonella, glucose oxidase, vinclozolin, xanthine oxidase.

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Authors: İmren Öztürk Yılmaz, Abdullah Yasin Bilici, Yasin Atalay Candemir

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The system consists of 4 main elements: motion system, image acquisition system, image processing software, and control interface. The parts coming out of the production line to enter the image processing system with the conveyor belt at the end of the line. The 3D scanning of the produced part is performed with the laser scanning system integrated into the system entry side. With the 3D scanning method, it is determined at what position and angle the parts enter the system, and according to the data obtained, parameters such as part origin and conveyor speed are calculated with the designed software, and the robot is informed about the position where it will take part. The robot, which receives the information, takes the produced part on the belt conveyor and shows it to high-resolution cameras for quality control. Measurement processes are carried out with a maximum error of 20 microns determined by the experiments.

Keywords: quality control, industry 4.0, image processing, automated fault detection, digital visual inspection

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Authors: Murat Toren, Mehmet Çelebi

Abstract:

Reducing the weight of transformers while providing good performance, cost reduction and increased efficiency is important. Weight is one of the most significant factors in all electrical machines, and as such, many transformer design parameters are related to weight calculations. This study presents a comparison of the weight of oil type transformers and dry type transformer weight. Oil type transformers are mainly used in industry; however, dry type transformers are becoming more widespread in recent years. MATLAB is typically used for designing transformers and design parameters (rated voltages, core loss, etc.) along with design in ANSYS Maxwell. Similar to other studies, this study presented that the dry type transformer option is limited. Moreover, the commonly-used 50 kVA distribution transformers in the industry are oil type and dry type transformers are designed and considered in terms of weight. Currently, the preference for low-cost oil-type transformers would change if costs for dry-type transformer were more competitive. The aim of this study was to compare the weight of transformers, which is a substantial cost factor, and to provide an evaluation about increasing the use of dry type transformers.

Keywords: weight, optimization, oil-type transformers, dry-type transformers

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Authors: Nuran Bahar, Mehmet A. Akcayol

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In the aviation industry, many faults may occur frequently during the maintenance processes and assembly operations of complex structured aircrafts because of their high dependencies of components. These faults affect the quality of aircraft parts or developed modules adversely. Technical employee requires long time and high labor force while checking the correctness of each component. In addition, the person must be trained regularly because of the ever-growing and changing technology. Generally, the cost of this training is very high. Augmented Reality (AR) technology reduces the cost of training radically and improves the effectiveness of the training. In this study, the usage of AR technology in the aviation industry has been investigated and the effectiveness of AR with heads-up display glasses has been examined. An application has been developed for comparison of production process with AR and manual one.

Keywords: aerospace, assembly quality, augmented reality, heads-up display

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Authors: Cafer Görkem Pınar, İlker Coşar, Serkan Uzun, Atahan Çelebi, Mehmet Ali Ersoy, Ali Pınarbaşı

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In this study, it was numerically investigated that a 1:1 scale model of the Renault Clio MK4 SW brand vehicle aerodynamic analysis was performed in the commercial computational fluid dynamics (CFD) package program of ANSYS CFX 2021 R1 under steady, subsonic, and 3-D conditions. The model of vehicle used for the analysis was made independent of the number of mesh elements, and the k-epsilon turbulence model was applied during the analysis. Results were interpreted as streamlines, pressure gradient, and turbulent kinetic energy contours around the vehicle at 50 km/h and 100 km/h speeds. In addition, the validity of the analysis was decided by comparing the drag coefficient of the vehicle with the values in the literature. As a result, the pressure gradient contours of the taillight of the Renault Clio MK4 SW vehicle were examined, and the behavior of the total force at speeds of 50 km/h and 100 km/h was interpreted.

Keywords: CFD, k-epsilon, aerodynamics, drag coefficient, taillight

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Authors: Mehmet Hakan Karaata, Ali Hamdan, Omer Yusuf Adam Mohamed

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Consider a distributed system that delivers messages from a process to another. Such a system is often required to deliver each message to its destination regardless of whether or not the system components experience arbitrary forms of faults. In addition, each message received by the destination must be a message sent by a system process. In this paper, we first identify the necessary and sufficient conditions to detect some restricted form of Byzantine faults referred to as modifying Byzantine faults. An observable form of a Byzantine fault whose effect is limited to the modification of a message metadata or content, timing and omission faults, and message replay is referred to as a modifying Byzantine fault. We then present a distributed protocol to detect modifying Byzantine faults using optimal number of messages over node-disjoint paths.

Keywords: Byzantine faults, distributed systems, fault detection, network protocols, node-disjoint paths

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Authors: Haci Mehmet Guzey, Levent Acar

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In this paper, a novel decentralized controller is developed for linear systems with nonlinear unknown interconnections. A model linear decoupled system is assigned for each system. By using the difference actual and model state dynamics, the problem is formulated as inverse problem. Then, the interconnected dynamics are approximated by using Galerkin’s expansion method for inverse problems. Two different sets of orthogonal basis functions are utilized to approximate the interconnected dynamics. Approximated interconnections are utilized in the controller to cancel the interconnections and decouple the systems. Subsequently, the interconnected systems behave as a collection of decoupled systems.

Keywords: decentralized control, inverse problems, large scale systems, nonlinear interconnections, basis functions, system identification

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Authors: Tutku Ak, Abdullah Kelkit, Cihad Öztürk

Abstract:

An increase has been witnessed with the number of multinational environmental agreements in the past decade, particularly in Europe. Success with implementation, however, shows variation. While many countries are willing to join these agreements, they do not always fully honor their obligations to put their commitments into practice. One reason for this is that countries have different legal and administrative systems. One example of an international multilateral environmental agreement is the European Landscape Convention (ELC). ELC expresses a concern to achieve sustainable development based on a balanced and harmonious relationship between social needs, economic activity, and the environment. Member states are required to implement the convention in accordance with their own administrative structure, respecting subsidiarity. In particular, the importance of cooperation in the protection, management, and planning of the resources is expressed through the convention. In this paper, it is intended to give a broad view of ELC’s implementation process in Turkey and what factors have influenced by the process. Under this context, the paper will focus on the objectives of the convention for addressing the issue of the loss of European landscapes, and the justification and tools used to accomplish these objectives. The degree to which these objectives have been implemented in Turkey and the opportunities and constraints that have been faced during this process have been discussed.

Keywords: European landscape convention, implementation, multinational environmental agreements, policy tools

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Authors: Duygu Kan, Mehmet Cayoren

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Sommerfeld-integrals (SIs) are commonly encountered in electromagnetics problems involving analysis of antennas and scatterers embedded in planar multilayered media. Generally speaking, the analytical solution of SIs is unavailable, and it is well known that numerical evaluation of SIs is very time consuming and computationally expensive due to the highly oscillating and slowly decaying nature of the integrands. Therefore, fast computation of SIs has a paramount importance. In this paper, a parallel code has been developed to speed up the computation of SI in the framework of calculation of dyadic Green’s function in multilayered media. OpenMP shared memory approach is used to parallelize the SI algorithm and resulted in significant time savings. Moreover accelerating the computation of dyadic Green’s function is discussed based on the parallel SI algorithm developed.

Keywords: Sommerfeld-integrals, multilayer dyadic Green’s function, OpenMP, shared memory parallel programming

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Authors: Mehmet Ekici

Abstract:

The objective of this research is to investigate the effect of pouring temperature on the microstructure of the cast iron. The pattern was designed with 300 mm of width, and the thickness variations are 1.25 mm and poured at five different temperatures; 1300, 1325, 1350, 1375 and 1400°C. Several cast irons, prepared with different chemical compositions and microstructures (three lamellar and three spheroidal structures) have been examined by extensive mechanical testing and optical microscopy. The fluidity of spheroidal and lamellar graphite in cast iron increases with the pouring temperature. The numbers of nodules were decreased by increasing pouring temperature for spheroidal structures. Whereas, the numbers of flakes of lamellar structures changed by both pouring temperature and chemical composition. In general, with increasing pouring temperature, the amount of pearlite in the internal structure of both lamellar and spheroidal graphite cast iron materials were increased.

Keywords: spheroidal graphite cast iron, lamellar graphite in cast iron, pouring temperature, tensile test and impact test

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Authors: Esma Gizem Daskiran, Mehmet Mustafa Daskiran

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This paper investigates the effectiveness of two natural zeolites in reducing expansion of concrete due to alkali-silica reaction. These natural zeolites have different reactive silica content. Three aggregates; two natural sand and one crushed stone aggregate were used while preparing mortar bars in accordance with accelerated mortar bar test method, ASTM C1260. Performance of natural zeolites are compared by examining the expansions due to alkali silica reaction. Natural zeolites added to the mixtures at %10 and %20 replacement levels by weight of cement. Natural zeolite with high reactive silica content had better performance on reducing expansions due to ASR. In this research, using high reactive zeolite at %20 replacement level was effective in mitigating expansions.

Keywords: alkali silica reaction, natural zeolite, durability, expansion

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Authors: Aydin Teymourifar, Gurkan Ozturk, Ozan Bahadir

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In this paper, a new neural network based variable neighborhood search is proposed for the multi-objective dynamic, flexible job shop scheduling problems. The neural network controls the problems' constraints to prevent infeasible solutions, while the Variable Neighborhood Search (VNS) applies moves, based on the critical block concept to improve the solutions. Two approaches are used for managing the constraints, in the first approach, infeasible solutions are modified according to the constraints, after the moves application, while in the second one, infeasible moves are prevented. Several neighborhood structures from the literature with some modifications, also new structures are used in the VNS. The suggested neighborhoods are more systematically defined and easy to implement. Comparison is done based on a multi-objective flexible job shop scheduling problem that is dynamic because of the jobs different release time and machines breakdowns. The results show that the presented method has better performance than the compared VNSs selected from the literature.

Keywords: constrained optimization, neural network, variable neighborhood search, flexible job shop scheduling, dynamic multi-objective optimization

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Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Mehmet Hakan Karaata, Ali Hamdan, Omer Yusuf Adam Mohamed

Abstract:

Consider a distributed system that delivers messages from a process to another. Such a system is often required to deliver each message to its destination regardless of whether or not the system components experience arbitrary forms of faults. In addition, each message received by the destination must be a message sent by a system process. In this paper, we first identify the necessary and sufficient conditions to detect some restricted form of Byzantine faults referred to as modifying Byzantine faults. An observable form of a Byzantine fault whose effect is limited to the modification of a message metadata or content, timing and omission faults, and message replay is referred to as a modifying Byzantine fault. We then present a distributed protocol to detect modifying Byzantine faults using optimal number of messages over node-disjoint paths.

Keywords: Byzantine faults, distributed systems, fault detection, network pro- tocols, node-disjoint paths

Procedia PDF Downloads 548