Search results for: safety stock optimization

Authors: Helen S. Ghali, Haidy S. Ghali, Salma Ibrahim, Ossama Hosny, Hatem S. Elbehairy

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Infrastructure systems are essential assets in any community; accordingly, authorities aim to maximize its life span while minimizing the life cycle cost. This requires studying the asset conditions throughout its operation and forming a cost-efficient maintenance strategy plan. The objective of this study is to develop a highway management system that provides medium-term maintenance plans with the minimum life cycle cost subject to budget constraints. The model is applied to data collected for the highway network in India with the aim to output a 5-year maintenance plan strategy from 2019 till 2023. The main element considered is the surface coarse, either rigid or flexible pavement. The model outputs a 5-year maintenance plan for each segment given the budget constraint while maximizing the new pavement condition rating and minimizing its life cycle cost.

Keywords: infrastructure, asset management, optimization, maintenance plan

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Authors: André Luís Brasil Cavalcante, Juan Felix Rodriguez Rebolledo, Lucas Parreira de Faria Borges

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A methodology for the probabilistic analysis of active earth pressure on retaining wall for c-Φ soil backfill is described in this paper. The Rosenblueth point estimate method is used to measure the failure probability of a gravity retaining wall. The basic principle of this methodology is to use two point estimates, i.e., the standard deviation and the mean value, to examine a variable in the safety analysis. The simplicity of this framework assures to its wide application. For the calculation is required 2ⁿ repetitions during the analysis, since the system is governed by n variables. In this study, a probabilistic model based on the Rosenblueth approach for the computation of the overturning probability of failure of a retaining wall is presented. The obtained results have shown the advantages of this kind of models in comparison with the deterministic solution. In a relatively easy way, the uncertainty on the wall and fill parameters are taken into account, and some practical results can be obtained for the retaining structure design.

Keywords: retaining wall, active earth pressure, backfill, probabilistic analysis

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Authors: Elisaveta Doncheva, Jelena Djokikj, Ognen Tuteski, Bojana Hadjieva

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In the past decade, additive manufacturing technology or 3D printing has been promoted as an efficient method for fabricating hybrid composite materials and structures with superior mechanical properties and complex shape and geometry. Fused deposition modeling (FDM) process is commonly used additive manufacturing technique for production of polymer products. Therefore, many studies and experiments are focused on investigating the possibilities for improving the obtained results on product properties as a key factor for expanding the spectrum of their application. This article provides an extensive review on recent research advances in FDM and reports on studies that cover the effects of process parameters, material, and design of the product properties. The paper conclusions provide a clear up-to date information for optimum efficiency and enhancement of the mechanical properties of 3D printed samples and recommends further research work and investigations.

Keywords: additive manufacturing, critical parameters, filament, print orientation, 3D printing

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Authors: Rana I. Abdulghani, Amera I. Melhum

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With the abnormal growth of the usage of computers over networks and under the consideration or agreement of most of the computer security experts who said that the goal of building a secure system is never achieved effectively, all these points led to the design of the intrusion detection systems(IDS). This research adopts a comparison between two techniques for network intrusion detection, The first one used the (Particles Swarm Optimization) that fall within the field (Swarm Intelligence). In this Act, the algorithm Enhanced for the purpose of obtaining the minimum error rate by amending the cluster centers when better fitness function is found through the training stages. Results show that this modification gives more efficient exploration of the original algorithm. The second algorithm used a (Back propagation NN) algorithm. Finally a comparison between the results of two methods used were based on (NSL_KDD) data sets for the construction and evaluation of intrusion detection systems. This research is only interested in clustering the two categories (Normal and Abnormal) for the given connection records. Practices experiments result in intrude detection rate (99.183818%) for EPSO and intrude detection rate (69.446416%) for BP neural network.

Keywords: IDS, SI, BP, NSL_KDD, PSO

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Authors: Kamalendu Pal

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Supply chains are the spinal cord of trade and commerce. Their logistics use different transport corridors on regular basis for operational purpose. The international supply chain transport corridors include different infrastructure elements (e.g. weighbridge, package handling equipment, border clearance authorities, and so on) in supply chains. This paper presents the use of multi-agent systems (MAS) to model and simulate some aspects of transportation corridors, and in particular the area of weighbridge resource optimization for operational profit generation purpose. An underlying multi-agent model provides a means of modeling the relationships among stakeholders in order to enable coordination in a transport corridor environment. Simulations of the costs of container unloading, reloading, and waiting time for queuing up tracks have been carried out using data sets. Results of the simulation provide the potential guidance in making decisions about optimal service resource allocation in a trade corridor.

Keywords: multi-agent systems, simulation, supply chain, transport corridor, weighbridge

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Authors: Prafulla Kumar Choubey, Krishna Kishor Jha, S. B. Vaisakh Punnekkattu Chirayil

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In Graphics-display subsystem, frame buffers are shared between producer i.e. content rendering and consumer i.e. display. If a common buffer is operated by both producer and consumer simultaneously, their processing rates mismatch can cause tearing effect in displayed content. Therefore, Android OS employs triple buffered system, taking in to account an additional composition stage. Three stages-rendering, composition and display refresh, operate synchronously on three different buffers, which is achieved by using vsync pulses. This synchronization, however, brings in to the pipeline an additional latency of up to 26ms. The present study details about the existing synchronization mechanism of android graphics-display pipeline and discusses a new adaptive architecture which reduces the wait time to 5ms-16ms in all the use-cases. The proposed method uses two adaptive software vsyncs (PLL) for achieving the same result.

Keywords: Android graphics system, vertical synchronization, atrace, adaptive system

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Authors: Regita P. Permata, Ulfa S. Nuraini

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Traveling Salesman Problem (TSP) is the most studied problem in combinatorial optimization. In simple language, TSP can be described as a problem of finding a minimum distance tour to a city, starting and ending in the same city, and exactly visiting another city. In product distribution, companies often get problems in determining the minimum distance that affects the time allocation. In this research, we aim to apply TSP heuristic methods to simulate nodes as city coordinates in product distribution. The heuristics used are sub tour reversal, nearest neighbor, farthest insertion, cheapest insertion, nearest insertion, and arbitrary insertion. We have done simulation nodes using Euclidean distances to compare the number of cities and processing time, thus we get optimum heuristic method. The results show that the optimum heuristic methods are farthest insertion and nearest insertion. These two methods can be recommended to solve product distribution problems in certain companies.

Keywords: Euclidean, heuristics, simulation, TSP

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Authors: Rossella Arcucci, Luisa D'Amore, Simone Celestino, Giuseppe Scotti, Giuliano Laccetti

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This work is the first dowel in a rather wide research activity in collaboration with Euro Mediterranean Center for Climate Changes, aimed at introducing scalable approaches in Ocean Circulation Models. We discuss designing and implementation of a parallel algorithm for solving the Variational Data Assimilation (DA) problem on Graphics Processing Units (GPUs). The algorithm is based on the fully scalable 3DVar DA model, previously proposed by the authors, which uses a Domain Decomposition approach (we refer to this model as the DD-DA model). We proceed with an incremental porting process consisting of 3 distinct stages: requirements and source code analysis, incremental development of CUDA kernels, testing and optimization. Experiments confirm the theoretic performance analysis based on the so-called scale up factor demonstrating that the DD-DA model can be suitably mapped on GPU architectures.

Keywords: data assimilation, GPU architectures, ocean models, parallel algorithm

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Authors: Reza Karami, Ali Akbar Ebrahimi

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This paper discusses concurrent engineering of robot manipulators, based on the Holistic Concurrent Design (HCD) methodology and by using a hardware-in-the-loop simulation platform. The methodology allows for considering numerous design variables with different natures concurrently. It redefines the ultimate goal of design based on the notion of satisfaction, resulting in the simplification of the multi-objective constrained optimization process. It also formalizes the effect of designer’s subjective attitude in the process. To enhance modeling efficiency for both computation and accuracy, a hardware-in-the-loop simulation platform is used, which involves physical joint modules and the control unit in addition to the software modules. This platform is implemented in the HCD design architecture to reliably evaluate the design attributes and performance super criterion during the design process. The resulting overall architecture is applied to redesigning kinematic, dynamic and control parameters of an industrial robot manipulator.

Keywords: concurrent engineering, hardware-in-the-loop simulation, robot manipulator, multidisciplinary systems, mechatronics

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Authors: Pavan K. Rallabandi, Kailash C. Patidar

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In this paper, we present an optimization technique or a learning algorithm using the hybrid architecture by combining the most popular sequence recognition models such as Recurrent Neural Networks (RNNs) and Hidden Markov models (HMMs). In order to improve the sequence or pattern recognition/ classification performance by applying a hybrid/neural symbolic approach, a gradient descent learning algorithm is developed using the Real Time Recurrent Learning of Recurrent Neural Network for processing the knowledge represented in trained Hidden Markov Models. The developed hybrid algorithm is implemented on automata theory as a sample test beds and the performance of the designed algorithm is demonstrated and evaluated on learning the deterministic finite state automata.

Keywords: hybrid systems, hidden markov models, recurrent neural networks, deterministic finite state automata

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Authors: Henri Champliaud, Zhengkun Feng, Ngan Van Lê, Javad Gholipour

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In this article, a method is presented to effectively estimate the deformed shape of a thick plate due to line heating. The method uses a fifth order spline interpolation, with up to C3 continuity at specific points to compute the shape of the deformed geometry. First and second order derivatives over a surface are the resulting parameters of a given heating line on a plate. These parameters are determined through experiments and/or finite element simulations. Very accurate kriging models are fitted to real or virtual surfaces to build-up a database of maps. Maps of first and second order derivatives are then applied on numerical plate models to evaluate their evolving shapes through a sequence of heating lines. Adding an optimization process to this approach would allow determining the trajectories of heating lines needed to shape complex geometries, such as Francis turbine blades.

Keywords: deformation, kriging, fifth order spline interpolation, first, second and third order derivatives, C3 continuity, line heating, plate forming, thermal forming

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Authors: hadi kargar, bahador shabani

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In this article, 16 cylinder motor combustion CFD modeling with a diameter of 165 mm and 195 mm along the way to help the FIRE software to optimize its function to work. A three-dimensional model of the processes that formed inside the cylinder made that involves mixing the fuel and air, ignition and spraying. In this three-dimensional model, all chemical species, density of air fuel spraying and spray with full profile intended to detailed results from mixing the fuel and air, igniting the ignition advance, spray, and mixed media in different times and get fit by moving the piston. Optimal selection of the model for the shape of the piston and spraying fuel specifications (including the management of spraying, the number of azhneh hole, start time of spraying and spraying angle) to achieve the best fuel consumption and minimal pollution. The spray hole 6 and 7 in three different configurations with five spraying and gives the best geometry and various performances in the simulation. 6 hole spray angle, finally spraying 72.5 degrees and two forms of spraying a better performance in comparison with other items of their own.

Keywords: spray, FIRE, CFD, optimize, diesel engine

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Authors: Hyun-Woo Cho

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Detection of incipient abnormal events in production processes is important to improve safety and reliability of manufacturing operations and reduce losses caused by failures. The construction of calibration models for predicting faulty conditions is quite essential in making decisions on when to perform preventive maintenance. This paper presents a multivariate calibration monitoring approach based on the statistical analysis of process measurement data. The calibration model is used to predict faulty conditions from historical reference data. This approach utilizes variable selection techniques, and the predictive performance of several prediction methods are evaluated using real data. The results shows that the calibration model based on supervised probabilistic model yielded best performance in this work. By adopting a proper variable selection scheme in calibration models, the prediction performance can be improved by excluding non-informative variables from their model building steps.

Keywords: calibration model, monitoring, quality improvement, feature selection

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Authors: Dimitrie Marinceu, Alan Murchison

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The Canadian Used Fuel Container (UFC) is a mid-size hemispherical headed copper coated steel container measuring 2.5 meters in length and 0.5 meters in diameter containing 48 used fuel bundles. The contained used fuel produces significant gamma radiation requiring automated assembly processes to complete the assembly. The design throughput of 2,500 UFCs per year places constraints on equipment and hot cell design for repeatability, speed of processing, robustness and recovery from upset conditions. After UFC assembly, the UFC is inserted into a Buffer Box (BB). The BB is made from adequately pre-shaped blocks (lower and upper block) and Highly Compacted Bentonite (HCB) material. The blocks are practically ‘sandwiching’ the UFC between them after assembly. This paper identifies one possible approach for the BB automatic assembly cell and processes. Automation of the BB assembly will have a significant positive impact on nuclear safety, quality, productivity, and reliability.

Keywords: used fuel packing plant, automatic assembly cell, used fuel container, buffer box, deep geological repository

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Authors: Amrita Anil Agashe, Sumant Tapas, Ajay Verma Yogesh Sonavane, Sourabh Yeravar

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Due to advancement in MEMS technology today wireless sensors network has gained a lot of importance. The wide range of its applications includes environmental and habitat monitoring, object localization, target tracking, security surveillance etc. Wireless sensor networks consist of tiny sensor devices called as motes. The constrained computation power, battery power, storage capacity and communication bandwidth of the tiny motes pose challenging problems in the design and deployment of such systems. In this paper, we propose a ubiquitous framework for Real-Time Tracking, Sensing and Management System using IITH motes. Also, we explain the algorithm that we have developed for location management in wireless sensor networks with the aspect of mobility. Our developed framework and algorithm can be used to detect emergency events and safety threats and provides warning signals to handle the emergency.

Keywords: mobility management, motes, multihop, wireless sensor networks

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Authors: A. Hilsana, Vinay U. Rao, M. Sudhakar

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Even though a number of non-steroidal anti-inflammatory drugs (NSAIDS) are available with different chemistries, they share a common solubility characteristic that is they are relatively more soluble in alkaline environment and practically insoluble in acidic environment. This work deals with developing a wax matrix drug delivery platform for controlled delivery of three model NSAIDS, Diclofenac sodium (DNa), Mefenamic acid (MA) and Naproxen (NPX) using the melt granulation technique. The aim of developing the platform was to have a general understanding on how an erodible matrix system modulates drug delivery rate and extent and how it can be optimized to give a delivery system which shall release the drug as per a common target product profile (TPP). Commonly used waxes like Cetostearyl alcohol and stearic acid were used singly an in combination to achieve a TPP of not 15 to 35% in 1 hour and not less than 80% Q in 24 hours. Full factorial design of experiments was followed for optimization of the formulation.

Keywords: NSAIDs, controlled delivery, target product profile, melt granulation

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Authors: Veerpaul Maan, Gaurav Mishra

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The evolution of omnichannel has revolutionized the supply chain of the organizations by enhancing customer shopping experience. For these organizations need to develop well-integrated multiple distribution channels to leverage the benefits of omnichannel. To adopt an omnichannel system in the supply chain has resulted in structuring and reconfiguring the practices of the traditional supply chain distribution network. In this paper a multiple distribution supply chain network (MDSCN) have been proposed which integrates online giants with a local retailers distribution network in uncertain environment followed by sustainability. To incorporate sustainability, an additional objective function is added to reduce the carbon content through minimizing the travel distance of the product. Through this proposed model, customers are free to access product and services as per their choice of channels which increases their convenience, reach and satisfaction. Further, a numerical illustration is being shown along with interpretation of results to validate the proposed model.

Keywords: sustainable supply chain network, omnichannel, multiple distribution supply chain network, integrate multiple distribution channels

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Authors: Leandro Moura da Silva

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The international community has strived to create legal mechanisms to protect their biodiversity, but this can represent, sometimes, particularly in the case of regulatory regime on access to genetic resources, an excessive nationalism which transforms itself into a significant obstacle to scientific progress causing damages to the country and to local farmers. Although it has been poorly publicized in the media, the international legal system was marked, in 2014, by the entry into force of the Nagoya Protocol, which regulates the access and benefit sharing of genetic resources of the States Party to that legal instrument. However, it’s not reasonable to think of regulating access to genetic resources without reflecting on the links of this important subject with other related issues, such as family farming and agribusiness, food safety, food security, intellectual property rights (on seeds, genetic material, new plant varieties, etc.), environmental sustainability, biodiversity, and biosafety.

Keywords: international law, regulation on agriculture, agronomy techniques, sustainability, genetic resources and new crop varieties, CBD, Nagoya Protocol, ITPGRFA

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Authors: Draou Azeddine, Mazin Alahmadi, Abdulrahmane Alkassem, Alamri Abdullah

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The demand for electric power in Saudi Arabia is steadily increasing with economic growth. More power plants should be installed to increase generation capacity and meet demand. Electricity in Saudi Arabia is mainly dependent on fossil fuels, which are a major problem as they deplete natural resources and increase CO₂ emissions. In this research work, performance and techno-economic analyzes are conducted to evaluate a microgrid system based on hybrid PV/wind diesel power sources as a stand-alone system for rural electrification in Saudi Arabia. The total power flow, maximum power point tracking (MPPT) efficiency, effectiveness of the proposed control strategy, and total harmonic distortion (THD) are analyzed in MATLAB/Simulink environment. Various simulation studies have been carried out under different irradiation conditions. The sizing, optimization, and economic feasibility analysis were performed using Homer energy software.

Keywords: WIND, solar, microgrid, energy

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Authors: Rayhana Begum, HongBin Wang, Nur Alam Siddiquee, Md.Yasin Ahmed

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Biotin treatment has significant effects on blood glucose, and pharmacological doses of biotin improve hyperglycemia. The present study was aimed to investigate the efficacy and safety of biotin in combination with canagliflozin in improving glycemic control on High Fat Diet-induced diabetes in Rats. Thirty male rats were divided into five groups (six rats /group): control, high fat diet (HFD), canagliflozin (CAG), biotin (BIO), and CAG + BIO. The treatments with CAG and /or BIO significantly reduced the body weight gain, blood glucose and HbA1c levels, whereas CAG in combination with BIO revealed greater glycemic improvement than CAG monotherapy. The treatment with CAG and /or BIO causes significant change in lipid profile and CK level while the treatment with CAG in combination with BIO showed better results as compared with CAG monotherapy. Furthermore, combination of biotin with CAG improved the pancreatic and cardiac damage when compared with other treated groups.

Keywords: canagliflozin, biotin, HbA1c, lipid profile

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Authors: M. Erol Genevois, D. Celik, H. Z. Ulukan

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Automated teller machines (ATMs) can be considered among one of the most important service facilities in the banking industry. The investment in ATMs and the impact on the banking industry is growing steadily in every part of the world. The banks take into consideration many factors like safety, convenience, visibility, cost in order to determine the optimum locations of ATMs. Today, ATMs are not only available in bank branches but also at retail locations. Another important factor is the cash management in ATMs. A cash demand model for every ATM is needed in order to have an efficient cash management system. This forecasting model is based on historical cash demand data which is highly related to the ATMs location. So, the location and the cash management problem should be considered together. Although the literature survey on facility location models is quite large, it is surprising that there are only few studies which handle together ATMs location and cash management problem. In order to fulfill the gap, this paper provides a general review on studies, efforts and development in ATMs location and cash management problem.

Keywords: ATM location problem, cash management problem, ATM cash replenishment problem, literature review in ATMs

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Authors: Tobias Beyer, Christoph Friedrich

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Modern simulation methodology using finite element models is nowadays a recognized tool for product design/optimization. Likewise, manufacturing process design is increasingly becoming the focus of simulation methodology in order to enable sustainable results based on reduced real-life tests here as well. In this article, two process simulations -radial riveting and roller burnishing- used for mechanical joining of components are explained. In the first step, the required boundary conditions are developed and implemented in the respective simulation models. This is followed by process space validation. With the help of the validated models, the interdependencies of the input parameters are investigated and evaluated by means of sensitivity analyses. Limit case investigations are carried out and evaluated with the aid of the process simulations. Likewise, a comparison of the two joining methods to each other becomes possible.

Keywords: FEM, model-based process development, process simulation, radial riveting, roller burnishing, sensitivity analysis

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Authors: Md Fazle Alam, Amaj Ahmed Laskar, Hina Younus

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Melamine toxicity which causes renal failure and death of humans and animals have recently attracted worldwide attention. Developing an easy, fast and sensitive method for the routine melamine detection is the need of the hour. Herein, we have developed a rapid, sensitive, one step and selective colorimetric method for the detection of melamine in milk samples based upon in-situ formation of silver nanoparticles (AgNPs) via tannic acid at room temperature. These AgNPs thus formed were characterized by UV-VIS spectrophotometer, transmission electron microscope (TEM), zetasizer and dynamic light scattering (DLS). Under optimal conditions, melamine could be selectively detected within the concentration range of 0.05-1.4 µM with a limit of detection (LOD) of 10.1 nM, which is lower than the strictest melamine safety requirement of 1 ppm. This assay does not utilize organic cosolvents, enzymatic reactions, light sensitive dye molecules and sophisticated instrumentation, thereby overcoming some of the limitations of conventional methods.

Keywords: milk adulteration, melamine, silver nanoparticles, tannic acid

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Authors: M. Karimpour, N. Elkhoury, L. Hitihamillage, S. Moridpour, R. Hesami

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There is a necessity among rail transportation authorities for a superior understanding of the rail track degradation overtime and the factors influencing rail degradation. They need an accurate technique to identify the time when rail tracks fail or need maintenance. In turn, this will help to increase the level of safety and comfort of the passengers and the vehicles as well as improve the cost effectiveness of maintenance activities. An accurate model can play a key role in prediction of the long-term behaviour of railroad tracks. An accurate model can decrease the cost of maintenance. In this research, the rail track degradation is predicted using an autoregressive moving average with exogenous input (ARMAX). An ARMAX has been implemented on Melbourne tram data to estimate the values for the tram track degradation. Gauge values and rail usage in Million Gross Tone (MGT) are the main parameters used in the model. The developed model can accurately predict the future status of the tram tracks.

Keywords: ARMAX, dynamic systems, MGT, prediction, rail degradation

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Authors: Samira Alvandi

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In the context of the circular economy, production planning aims to eliminate waste and emissions and maximize resource efficiency. Historically production planning is challenged through arrays of uncertainty and complexity arising from the interdependence and variability of products, processes, and systems. Manufacturers worldwide are facing new challenges in tackling various environmental issues such as climate change, resource depletion, and land degradation. In managing the inherited complexity and uncertainty and yet maintaining profitability, the manufacturing sector is in need of a holistic framework that supports energy efficiency and carbon emission reduction schemes. The proposed framework addresses the current challenges and integrates simulation modeling with optimization for finding optimal machine-job allocation to maximize throughput and total energy consumption while minimizing lead time. The aluminium refinery facility in western Sydney, Australia, is used as an exemplar to validate the proposed framework.

Keywords: smart production planning, simulation-optimisation, energy aware capacity planning, energy intensive industries

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Authors: Mehmet Karahan, Nevin Karahan

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Water and air permeability and thermal resistance of fabrics are the important attributes which strongly influence the thermo-physiological comfort properties of sportswear fabrics in different environmental conditions. In this work, terry and fleece fabrics were developed by varying the fiber content and areal density of fabrics. Further, the thermo-physical properties, including air permeability, water vapor permeability, and thermal resistance, of the developed fabrics were analyzed before and after washing. The multi-response optimization of thermo-physiological comfort properties was done by using principal component analysis (PCA) and Taguchi signal to noise ratio (PCA-S/N ratio) for optimal properties. It was found that the selected parameters resulted in a significant effect on thermo-physiological comfort properties of knitted fabrics. The PCA analysis showed that before wash, 100% cotton fabric with an aerial weight of 220 g.m⁻² gave optimum values of thermo-physiological comfort.

Keywords: thermo-physiological comfort, fleece knitted fabric, air permeability, water vapor transmission, cotton/polyester

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Authors: Ioannis Manikas

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The increased consumer demand for environmentally friendly production and distribution practices and the stricter environmental regulations turned environmental aspects into important criteria in business decision-making. On the other hand, Food and Nutrition Security (FNS) has evolved dramatically during the last decades in theory and practice serving as a reference point for exchanging experiences among all agents involved in programs and projects to fostering policy and strategy development. Global pressures make it more important than ever to gain a better understanding of the contribution that agrifood businesses make to FNS and to examine ways to make them more resilient in an increasingly globalized and uncertain world. This study extends the standard three-dimensional model of sustainability to include two more dimensions: A technological dimension and a policy/political dimension. Apart from the economic, environmental and social dimensions regularly used in sustainability literature, the extended model will accurately represent the measures and policies addressing food and nutrition security.

Keywords: food and nutrition security, sustainability, food safety, resilience

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Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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Authors: Osiris Terry, Kenneth Hopkinson, Laura Humphrey

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Systematic resampling is the most popularly used resampling method in particle filters. This paper seeks to further the understanding of systematic resampling by defining a formula made up of variables from the sampling equation and the particle weights. The formula is then verified via SPARK, a software verification language. The verified systematic resampling formula states that the minimum/maximum number of possible samples taken of a particle is equal to the floor/ceiling value of particle weight divided by the sampling interval, respectively. This allows for the creation of a randomness spectrum that each resampling method can fall within. Methods on the lower end, e.g., systematic resampling, have less randomness and, thus, are quicker to reach an estimate. Although lower randomness allows for error by having a larger bias towards the size of the weight, having this bias creates vulnerabilities to the noise in the environment, e.g., jamming. Conclusively, this is the first step in characterizing each resampling method. This will allow target-tracking engineers to pick the best resampling method for their environment instead of choosing the most popularly used one.

Keywords: SPARK, software verification, resampling, systematic resampling, particle filter, tracking

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Authors: Pavel Porubiak, Lukas Kudlacek

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Introduction Transplant tourism is a controversial method of obtaining an organ, and that goes all the more for a country such as China, where sources of evidence point out to the possibility of organs being harvested illegally. This research aimed at listing the individual countries these tourists come from, or which medical companies sell transplant related products in there, with China being used as an example. Materials and methods The methodology of scoping study was used for both parts of the research. The countries from which transplant tourists come to China were identified by a search through existing medical studies in the NCBI PubMed database, listed under the keyword ‘transplantation in China’. The search was not limited by any other criteria, but only the studies available for free – directly on PubMed or a linked source – were used. Other research studies on this topic were considered as well. The companies were identified through multiple methods. The first was an online search focused on medical companies and their products. The Bloomberg Service, used by stock brokers worldwide, was then used to identify the revenue of these companies in individual countries – if data were available – as well as their business presence in China. A search through the U.S. Securities and Exchange Commission was done in the same way. Also a search on the Chinese internet was done, and to obtain more results, a second online search was done as well. The results and discussion The extensive search has identified 14 countries with transplant tourists to China. The search for a similar studies or reports resulted in finding additional six countries. The companies identified by our research also amounted to 20. Eight of them are sourcing China with organ preservation products – of which one is just trying to enter the Chinese market, six with immunosuppressive drugs, four with transplant diagnostics, one with medical robots which Chinese doctors use for transplantation as well, and another one trying to enter the Chinese market with a consumable-type product also related to transplantation. The conclusion The question of the ethicality of transplant tourism may be very pressing, since as the research shows, just the sheer amount of participating countries, sourcing transplant tourists to another one, amounts to 20. The identified companies are facing risks due to the nature of transplantation business in China, as officially executed prisoners are used as sources, and widely cited pieces of evidence point out to illegal organ harvesting. Similar risks and ethical questions are also relevant to the countries sourcing the transplant tourists to China.

Keywords: China, illegal organ harvesting, transplant tourism, organ harvesting technology

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