Search results for: hypercholesteraemic mice model

Authors: Nandita Ghosh, Shinjini Mitra, Ena Ray Banerjee

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Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish, and scaly lesions. It mainly affects children and has a high prevalence in developing countries. The AD may occur due to environmental or genetic factors. There is no permanent cure for the AD. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by the macrophage. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in the AD. To assess the wound healing capacity of the guar gum nanoparticle (GN), we first treated adherent NIH3T3 cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiment, Balb/c mice ear were topically treated with oxazolone (oxa) to induce AD and then were topically treated with GN. The ear thickness was increased significantly till day 28 on the treatment of Oxa. The GN application showed a significant decrease in the thickness as assessed on day 28. The total cell count of skin cells showed fold increase when treated with oxa, was again decreased on topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining was also increased when treated with oxa, GN application led to a significant decrease. The IgE level was assessed in the serum samples which showed that GN helped in restoring the alleviated IgE level. The T helper cells and the macrophage population showed increased percentage when treated with oxa, the GN application. This was examined by flow cytometry. The H&E staining of the ear tissue showed epidermal thickness in the oxa treated mice, GN application showed reduced cellular filtration followed by epidermal thickness. Thus our assays showed that GN was successful in alleviating the disease caused by Oxa when administered topically.

Keywords: allergen, inflammation, nanodrug, wound

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Authors: I. Behroyan, P. Ganesan, S. He, S. Sivasankaran

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This study compares the predictions of five types of Computational Fluid Dynamics (CFD) models, including two single-phase models (i.e. Newtonian and non-Newtonian) and three two-phase models (Eulerian-Eulerian, mixture and Eulerian-Lagrangian), to investigate turbulent forced convection of Cu-water nanofluid in a tube with a constant heat flux on the tube wall. The Reynolds (Re) number of the flow is between 10,000 and 25,000, while the volume fraction of Cu particles used is in the range of 0 to 2%. The commercial CFD package of ANSYS-Fluent is used. The results from the CFD models are compared with results from experimental investigations from literature. According to the results of this study, non-Newtonian single-phase model, in general, does not show a good agreement with Xuan and Li correlation in prediction of Nu number. Eulerian-Eulerian model gives inaccurate results expect for φ=0.5%. Mixture model gives a maximum error of 15%. Newtonian single-phase model and Eulerian-Lagrangian model, in overall, are the recommended models. This work can be used as a reference for selecting an appreciate model for future investigation. The study also gives a proper insight about the important factors such as Brownian motion, fluid behavior parameters and effective nanoparticle conductivity which should be considered or changed by the each model.

Keywords: heat transfer, nanofluid, single-phase models, two-phase models

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Authors: Yilei Song, Linlin Tian, Ning Zhao

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Turbulence energetics and structures in the wake of large-scale wind turbines under the stably-stratified atmospheric boundary layer (SABL) can be complicated due to the presence of low-level jets (LLJs), a region of higher wind speeds than the geostrophic wind speed. With a modified one-k-equation, eddy viscosity model specified for atmospheric flows as the sub-grid scale (SGS) model, a realistic atmospheric state of the stable ABL is well reproduced by large-eddy simulation (LES) techniques. Corresponding to the precursor stably stratification, the detailed wake properties of a standard 5-MW wind turbine represented as an actuator line model are provided. An engineering model is proposed for wake prediction based on the simulation statistics and gets validated. Results confirm that the proposed wake model can provide good predictions for wind turbines under the SABL.

Keywords: large-eddy simulation, stably-stratified atmospheric boundary layer, wake model, wind turbine wake

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Authors: Chen-Yin Kuo, Yung-Hsin Lee

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Previous studies applying residual income valuation (RIV) model generally use panel data and single-equation model to forecast stock prices. Unlike these, this paper uses Taiwan longitudinal data to estimate multi-equation time-series models such as Vector Autoregressive (VAR), Vector Error Correction Model (VECM), and conduct out-of-sample forecasting. Further, this work assesses their forecasting performance by two instruments. In favor of extant research, the major finding shows that VECM outperforms other three models in forecasting for three stock sectors over entire horizons. It implies that an error correction term containing long-run information contributes to improve forecasting accuracy. Moreover, the pattern of composite shows that at longer horizon, VECM produces the greater reduction in errors, and performs substantially better than VAR.

Keywords: residual income valuation model, vector error correction model, out of sample forecasting, forecasting accuracy

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Authors: M. J. Kang, Y. N. Jo, H. H. Yoo

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Pendulum tests were used to identify a stretch reflex and diagnose spasticity. Some researches tried to make a mathematical model to simulate the motions. Thighs are subject to compressive forces due to gravity during a pendulum test. Therefore, it affects knee trajectories. However, the most studies on the pendulum tests did not consider that conditions. We used Kelvin-Voight model as compression model of skin and muscles. In this study, we investigated viscoelastic behaviors of skin and muscles using gelatin blocks from experiments of the vibration of the compliantly supported beam. Then we calculated a dynamic stiffness and loss factors from the experiment and estimated a damping coefficient of the model. We also did pendulum tests of human lower limbs to validate the stiffness and damping coefficient of a skin model. To simulate the pendulum motion, we derive equations of motion. We used stretch reflex activation model to estimate muscle forces induced by the stretch reflex. To validate the results, we compared the activation with electromyography signals during experiments. The compression behavior of skin and muscles in this study can be applied to analyze sitting posture as wee as developing surgical techniques.

Keywords: Kelvin-Voight model, pendulum test, skin and muscles under compression, stretch reflex

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Authors: Y. S. Yusoff, G. Streftaris, H. R Waters

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Death within 30 days is an important factor to be looked into, as there is a significant risk of deaths immediately following or soon after, Myocardial Infarction (MI) or stroke. In this paper, we will model the deaths within 30 days following a Myocardial Infarction (MI) or stroke in the UK. We will see how the probabilities of sudden deaths from MI or stroke have changed over the period 1981-2000. We will model the sudden deaths using a Generalized Linear Model (GLM), fitted using the R statistical package, under a Binomial distribution for the number of sudden deaths. We parameterize our model using the extensive and detailed data from the Framingham Heart Study, adjusted to match UK rates. The results show that there is a reduction for the sudden deaths following a MI over time but no significant improvement for sudden deaths following a stroke.

Keywords: sudden deaths, myocardial infarction, stroke, ischemic heart disease

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Authors: C. Castro-Egler, A. Durán-Escalante, A. García-González

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This paper presents a method to generate a finite element model of the human auditory inner ear system. The geometric model has been realized using 2D images from a virtual model of temporal bones. A point cloud has been gotten manually from those images to construct a whole mesh with hexahedral elements. The main difference with the predecessor models is the spiral shape of the cochlea with its three scales completely defined: scala tympani, scala media and scala vestibuli; which are separate by basilar membrane and Reissner membrane. To validate this model, numerical simulations have been realised with two models: an isolated inner ear and a whole model of human auditory system. Ideal conditions of displacement are applied over the oval window in the isolated Inner Ear model. The whole model is made up of the outer auditory channel, the tympani, the ossicular chain, and the inner ear. The boundary condition for the whole model is 1Pa over the auditory channel entrance. The numerical simulations by FEM have been done using a harmonic analysis with a frequency range between 100-10.000 Hz with an interval of 100Hz. The following results have been carried out: basilar membrane displacement; the scala media pressure according to the cochlea length and the transfer function of the middle ear normalized with the pressure in the tympanic membrane. The basilar membrane displacements and the pressure in the scala media make it possible to validate the response in frequency of the basilar membrane.

Keywords: finite elements method, human auditory system model, numerical analysis, 3D modelling cochlea

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Authors: John Lorenzo Bautista, Yoon-Joong Kim

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This paper presents the development of a Filipino speech recognition tool using the HTK System. The system was trained from a subset of the Filipino Speech Corpus developed by the DSP Laboratory of the University of the Philippines-Diliman. The speech corpus was both used in training and testing the system by estimating the parameters for phonetic HMM-based (Hidden-Markov Model) acoustic models. Experiments on different mixture-weights were incorporated in the study. The phoneme-level word-based recognition of a 5-state HMM resulted in an average accuracy rate of 80.13 for a single-Gaussian mixture model, 81.13 after implementing a phoneme-alignment, and 87.19 for the increased Gaussian-mixture weight model. The highest accuracy rate of 88.70% was obtained from a 5-state model with 6 Gaussian mixtures.

Keywords: Filipino language, Hidden Markov Model, HTK system, speech recognition

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Authors: Seyed Mohammadbagher Jafari, Elahe Mahdizadeh, Masomeh Ghahremani

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Nowadays almost all organizations depend on information systems to run their businesses. Investment on information systems and their maintenance to keep them always in best situation to support firm business is one of the main issues for every organization. The new concept of cloud computing was developed as a technical and economic model to address this issue. In cloud computing the computing resources, including networks, applications, hardwares and services are configured as needed and are available at the moment of request. However, migration to cloud is not an easy task and there are many issues that should be taken into account. This study tries to provide a comprehensive model to assess a firm readiness to implement cloud computing. By conducting a systematic literature review, four dimensions of readiness were extracted which include technological, human, organizational and environmental dimensions. Every dimension has various criteria that have been discussed in details. This model provides a framework for cloud computing readiness assessment. Organizations that intend to migrate to cloud can use this model as a tool to assess their firm readiness before making any decision on cloud implementation.

Keywords: cloud computing, human readiness, organizational readiness, readiness assessment model

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Authors: Aref Ghafouri, Mohammad javad Mollakazemi, Farhad Asadi

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In this paper, model order reduction method is used for approximation in linear and nonlinearity aspects in some experimental data. This method can be used for obtaining offline reduced model for approximation of experimental data and can produce and follow the data and order of system and also it can match to experimental data in some frequency ratios. In this study, the method is compared in different experimental data and influence of choosing of order of the model reduction for obtaining the best and sufficient matching condition for following the data is investigated in format of imaginary and reality part of the frequency response curve and finally the effect and important parameter of number of order reduction in nonlinear experimental data is explained further.

Keywords: frequency response, order of model reduction, frequency matching condition, nonlinear experimental data

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Authors: Shan-Jen Cheng, Te-Jen Chang, Kuang-Hsiung Tan, Shou-Ling Kuo

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Polymer Electrolyte Membrane Fuel Cell (PEMFC) is such a time-vary nonlinear dynamic system. The traditional linear modeling approach is hard to estimate structure correctly of PEMFC system. From this reason, this paper presents a nonlinear modeling of the PEMFC using Neural Network Auto-regressive model with eXogenous inputs (NNARX) approach. The multilayer perception (MLP) network is applied to evaluate the structure of the NNARX model of PEMFC. The validity and accuracy of NNARX model are tested by one step ahead relating output voltage to input current from measured experimental of PEMFC. The results show that the obtained nonlinear NNARX model can efficiently approximate the dynamic mode of the PEMFC and model output and system measured output consistently.

Keywords: PEMFC, neural network, nonlinear modeling, NNARX

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Authors: Amir Mohammad Fathollahi Fard, Mostafa Hajiaghaei-Keshteli, Mohammad Mahdi Paydar

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With increasing life expectancy in developed countries, the role of home care services is highlighted by both academia and industrial contributors in Home Health Care Supply Chain (HHCSC) companies. The main decisions in such supply chain systems are the location of pharmacies, the allocation of patients to these pharmacies and also the routing and scheduling decisions of nurses to visit their patients. In this study, for the first time, an integrated model is proposed to consist of all preliminary and necessary decisions in these companies, namely, location-allocation-routing model. This model is a type of NP-hard one. Therefore, an Imperialist Competitive Algorithm (ICA) is utilized to solve the model, especially in large sizes. Results confirm the efficiency of the developed model for HHCSC companies as well as the performance of employed ICA.

Keywords: home health care supply chain, location-allocation-routing problem, imperialist competitive algorithm, optimization

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Authors: Hamdi Sana, Emna Bouazizi, Sami Faiz

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In recent years, there is a huge increase in the use of spatio-temporal applications where data and queries are continuously moving. As a result, the need to process real-time spatio-temporal data seems clear and real-time stream data management becomes a hot topic. Sliding window model and frequent itemset mining over dynamic data are the most important problems in the context of data mining. Thus, sliding window model for frequent itemset mining is a widely used model for data stream mining due to its emphasis on recent data and its bounded memory requirement. These methods use the traditional transaction-based sliding window model where the window size is based on a fixed number of transactions. Actually, this model supposes that all transactions have a constant rate which is not suited for real-time applications. And the use of this model in such applications endangers their performance. Based on these observations, this paper relaxes the notion of window size and proposes the use of a timestamp-based sliding window model. In our proposed frequent itemset mining algorithm, support conditions are used to differentiate frequents and infrequent patterns. Thereafter, a tree is developed to incrementally maintain the essential information. We evaluate our contribution. The preliminary results are quite promising.

Keywords: real-time spatial big data, frequent itemset, transaction-based sliding window model, timestamp-based sliding window model, weighted frequent patterns, tree, stream query

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Authors: Ling Qi, Matloob Khushi, Josiah Poon

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This paper introduces a pre-trained Masked Candlestick Model (MCM) for trading time-series data. The pre-trained model is based on three core designs. First, we convert trading price data at each data point as a set of normalized elements and produce embeddings of each element. Second, we generate a masked sequence of such embedded elements as inputs for self-supervised learning. Third, we use the encoder mechanism from the transformer to train the inputs. The masked model learns the contextual relations among the sequence of embedded elements, which can aid downstream classification tasks. To evaluate the performance of the pre-trained model, we fine-tune MCM for three different downstream classification tasks to predict future price trends. The fine-tuned models achieved better accuracy rates for all three tasks than the baseline models. To better analyze the effectiveness of MCM, we test the same architecture for three currency pairs, namely EUR/GBP, AUD/USD, and EUR/JPY. The experimentation results demonstrate MCM’s effectiveness on all three currency pairs and indicate the MCM’s capability for signal extraction from trading data.

Keywords: masked language model, transformer, time series prediction, trading prediction, embedding, transfer learning, self-supervised learning

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Authors: Jung–Min Yang

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Solvability of the model matching problem for input/output switched asynchronous sequential machines is discussed in this paper. The control objective is to determine the existence condition and design algorithm for a corrective controller that can match the stable-state behavior of the closed-loop system to that of a reference model. Switching operations and correction procedures are incorporated using output feedback so that the controlled switched machine can show the desired input/output behavior. A matrix expression is presented to address reachability of switched asynchronous sequential machines with output equivalence with respect to a model. The presented reachability condition for the controller design is validated in a simple example.

Keywords: asynchronous sequential machines, corrective control, model matching, input/output control

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Authors: Hycham Aboutaleb, Bruno Monsuez

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Current systems complexity has reached a degree that requires addressing conception and design issues while taking into account all the necessary aspects. Therefore, one of the main challenges is the way complex systems are specified and designed. The exponential growing effort, cost and time investment of complex systems in modeling phase emphasize the need for a paradigm, a framework and a environment to handle the system model complexity. For that, it is necessary to understand the expectations of the human user of the model and his limits. This paper presents a generic framework for designing complex systems, highlights the requirements a system model needs to fulfill to meet human user expectations, and defines the refined functional as well as non functional requirements modeling tools needs to meet to be useful in model-based system engineering.

Keywords: system modeling, modeling language, modeling requirements, framework

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Authors: Hussain Syed Asad, Richard Kwok Kit Yuen, Gongsheng Huang

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Real-time optimization has been considered an effective approach for improving energy efficient operation of heating, ventilation, and air-conditioning (HVAC) systems. In model-based real-time optimization, model mismatches cannot be avoided. When model mismatches are significant, the performance of the real-time optimization will be impaired and hence the expected energy saving will be reduced. In this paper, the model mismatches for chiller plant on real-time optimization are considered. In the real-time optimization of the chiller plant, simplified semi-physical or grey box model of chiller is always used, which should be identified using available operation data. To overcome the model mismatches associated with the chiller model, hybrid Genetic Algorithms (HGAs) method is used for online real-time training of the chiller model. HGAs combines Genetic Algorithms (GAs) method (for global search) and traditional optimization method (i.e. faster and more efficient for local search) to avoid conventional hit and trial process of GAs. The identification of model parameters is synthesized as an optimization problem; and the objective function is the Least Square Error between the output from the model and the actual output from the chiller plant. A case study is used to illustrate the implementation of the proposed method. It has been shown that the proposed approach is able to provide reliability in decision making, enhance the robustness of the real-time optimization strategy and improve on energy performance.

Keywords: energy performance, hybrid adaptive modeling, hybrid genetic algorithms, real-time optimization, heating, ventilation, and air-conditioning

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Authors: Mohammad Reza Oftadeh

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The purpose of the article is to describe project objective structure (POS) concept that was developed on research activities and experiences about project management, Balanced Scorecard (BSC) and European Foundation Quality Management Excellence Model (EFQM Excellence Model). Furthermore, this paper tries to define a balanced, systematic, and integrated measurement approach to meet project objectives and project strategic goals based on a process-oriented model. In this paper, POS is suggested in order to measure project performance in the project life cycle. After using the POS model, the project manager can ensure in order to achieve the project objectives on the project charter. This concept can help project managers to implement integrated and balanced monitoring and control project work.

Keywords: project objectives, project performance management, PMBOK, key performance indicators, integration management

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Authors: Rupinder Pal Kaur, Vishal Goyal

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In this research, a systematic and quantitative engineering-based approach is followed by applying well-known international standards and guidelines to develop a web quality model (PH.WQT- Punjabi and Hindi Website Quality Tester) to measure external quality for websites of government domain that are developed in Punjabi and Hindi. Correspondingly, the model can be used for websites developed in other languages also. The research is valuable to researchers and practitioners interested in designing, implementing and managing websites of government domain Also, by implementing PH.WQT analysis and comparisons among web sites of government domain can be performed in a consistent way.

Keywords: external quality, PH.WQT, indian languages, punjabi and hindi, quality model, websites of government

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Authors: Chattrarat Hotrawaisaya

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This research aims to formulate the logistics collaborative model which is the management tool for orchid flower exporter. The researchers study logistics activities in orchid supply chain that stakeholders can collaborate and develop, including demand forecasting, inventory management, warehouse and storage, order-processing, and transportation management. The research also explores logistics collaboration implementation into orchid’s stakeholders. The researcher collected data before implementation and after model implementation. Consequently, the costs and efficiency were calculated and compared between pre and post period of implementation. The research found that the results of applying the logistics collaborative model to orchid exporter reduces inventory cost and transport cost. The model also improves forecasting accuracy, and synchronizes supply chain of exporter. This research paper contributes the uniqueness logistics collaborative model which value to orchid industry in Thailand. The orchid exporters may use this model as their management tool which aims in competitive advantage.

Keywords: logistics, orchid, supply chain, collaboration

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Authors: Jitendra Singh, Vivek Kumar

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In this paper, a susceptible infective susceptible mathematical model is proposed and analyzed where the migration of human population is given by migration function. It is assumed that the disease is transmitted by direct contact of susceptible and infective populations with constant contact rate. The equilibria and their stability are studied by using the stability theory of ordinary differential equations and computer simulation. The model analysis shows that the spread of infectious disease increases when human population immigration increases in the habitat but it decreases if emigration increases.

Keywords: SIS (Susceptible Infective Susceptible) model, migration function, susceptible, stability

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Authors: Satoshi Nishimura

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Although much information has been garnered from the genomes of humans and mice, it remains difficult to extend that information to explain physiological and pathological phenomena. This is because the processes underlying life are by nature stochastic and fluctuate with time. Thus, we developed novel "in vivo molecular imaging" method based on single and two-photon microscopy. We visualized and analyzed many life phenomena, including common adult diseases. We integrated the knowledge obtained, and established new models that will serve as the basis for new minimally invasive therapeutic approaches.

Keywords: two photon microscope, intravital visualization, thrombus, artery

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Authors: Tarek Sayed Taha Ali

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The dependence of the axial-vector coupling constant gA on the quark masses has been investigated in the frame work of the extended linear sigma model. The field equations have been solved in the mean-field approximation. Our study shows a better fitting to the experimental data compared with the existing models.

Keywords: extended linear sigma model, nucleon properties, axial coupling constant, physic

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Authors: Hanjong Kim, Changwan Han, Seonghun Park

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Heat exchanger manifolds in aircraft play an important role in evenly distributing the fluid entering through the inlet to the heat transfer unit. In order to achieve this requirement, the manifold should be designed to have a light weight by withstanding high internal pressure. Therefore, this study aims at minimizing the weight of the heat exchanger manifold through topology optimization. For topology optimization, the initial design space was created with the inner surface extracted from the currently used manifold model and with the outer surface having a dimension of 243.42 mm of X 74.09 mm X 65 mm. This design space solid model was transformed into a finite element model with a maximum tetrahedron mesh size of 2 mm using ANSYS Workbench. Then, topology optimization was performed under the boundary conditions of an internal pressure of 5.5 MPa and the fixed support for rectangular inlet boundaries by SIMULIA TOSCA. This topology optimization produced the minimized finial volume of the manifold (i.e., 7.3% of the initial volume) based on the given constraints (i.e., 6% of the initial volume) and the objective function (i.e., maximizing manifold stiffness). Weight of the optimized model was 6.7% lighter than the currently used manifold, but after smoothing the topology optimized model, this difference would be bigger. The current optimized model has uneven thickness and skeleton-shaped outer surface to reduce stress concentration. We are currently simplifying the optimized model shape with spline interpolations by reflecting the design characteristics in thickness and skeletal structures from the optimized model. This simplified model will be validated again by calculating both stress distributions and weight reduction and then the validated model will be manufactured using 3D printing processes.

Keywords: topology optimization, manifold, heat exchanger, 3D printing

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Authors: H. Hosseini, B. V. Berdyshev, I. Iskopintsev

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This paper presents a rheological model for producing shape-memory thermoplastic polymers. Shape-memory occurs as a result of internal rearrangement of the structural elements of a polymer. A non-linear viscoelastic model was developed that allows qualitative and quantitative prediction of the stress-strain behavior of shape-memory polymers during heating. This research was done to develop a technique to determine the maximum possible change in size of heat-shrinkable products during heating. The rheological model used in this work was particularly suitable for defining process parameters and constructive parameters of the processing equipment.

Keywords: elastic deformation, heating, shape-memory polymers, stress-strain behavior, viscoelastic model

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Authors: Zuodong Liang, Dong-Sheng Jeng

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Seabed instability around an offshore pipeline is one of key factors that need to be considered in the design of offshore infrastructures. Unlike previous investigations, a three-dimensional numerical model for the wave-induced soil response around an offshore pipeline is proposed in this paper. The numerical model was first validated with 2-D experimental data available in the literature. Then, a parametric study will be carried out to examine the effects of wave, seabed characteristics and confirmation of pipeline. Numerical examples demonstrate significant influence of wave obliquity on the wave-induced pore pressures and the resultant seabed liquefaction around the pipeline, which cannot be observed in 2-D numerical simulation.

Keywords: pore pressure, 3D wave model, seabed liquefaction, pipeline

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Authors: S. F. Wong, W. I. Ho, B. Lin, Q. Huang

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ERP has been used in many enterprises for management, the accuracy of the production forecasting module is vital to the decision making of the enterprise, and the profit is affected directly. Therefore, enhancing the accuracy of the production forecasting module can also increase the efficiency and profitability. To deal with a lot of data, a suitable, reliable and accurate statistics model is necessary. LSSVM and Grey System are two main models to be studied in this paper, and a case study is used to demonstrate how the combination model is effective to the result of forecasting.

Keywords: ERP, grey system, LSSVM, production forecasting

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Nisha Budhwar, Sunita Daniel

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In this paper, we analyse the stability of the SEIR model of malaria with infective immigrants which was recently formulated by the authors. The model consists of an SEIR model for the human population and SI Model for the mosquitoes. Susceptible humans become infected after they are bitten by infectious mosquitoes and move on to the Exposed, Infected and Recovered classes respectively. The susceptible mosquito becomes infected after biting an infected person and remains infected till death. We calculate the reproduction number R0 using the next generation method and then discuss about the stability of the equilibrium points. We use the Lyapunov function to show the global stability of the equilibrium points.

Keywords: equilibrium points, exposed, global stability, infective immigrants, Lyapunov function, recovered, reproduction number, susceptible

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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