Search results for: Bergman orthogonal polynomials

Authors: Tareq Hamadneh, Jochen Merker, Hassan Al-Zoubi

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Bernstein's expansion for exponentials in Taylor functions provides lower and upper optimization values for the range of its original function. these values converge to the original functions if the degree is elevated or the domain subdivided. Taylor polynomial can be applied so that the exponential is a polynomial of finite degree over a given domain. Bernstein's basis has two main properties: its sum equals 1, and positive for all x 2 (0; 1). In this work, we prove the existence of fixed points for exponential functions in a given domain using the optimization values of Bernstein. The Bernstein basis of finite degree T over a domain D is defined non-negatively. Any polynomial p of degree t can be expanded into the Bernstein form of maximum degree t ≤ T, where we only need to compute the coefficients of Bernstein in order to optimize the original polynomial. The main property is that p(x) is approximated by the minimum and maximum Bernstein coefficients (Bernstein bound). If the bound is contained in the given domain, then we say that p(x) has fixed points in the same domain.

Keywords: Bernstein polynomials, Stability of control functions, numerical optimization, Taylor function

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Authors: Mehdi Rashidi-Kouchi, Asghar Rahimi

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Sun introduced a generalization of frames and showed that this includes more other cases of generalizations of frame concept and proved that many basic properties can be derived within this more general context. Another generalization of frames is frames in Hilbert C*-module. It has been proved that every g-frame in Hilbert space H respect to Hilbert space K is a frame for B(H;K) as Hilbert C*-module. We show that every g-Riesz basis for Hilbert space H respect to K by add a condition is a Riesz basis for Hilbert B(K)-module B(H;K). Also, we investigate similar result for g-orthonormal and orthogonal bases.

Keywords: frame, g-frame, Riesz basis, g-Riesz basis, Hilbert C*-module

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Authors: Seung-Jun Yu, Hwan-Jun Choi, Hyoung-Kyu Song

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Among spatial diversity scheme, orthogonal space-time block code (OSTBC) and cyclic delay diversity (CDD) have been widely studied for the cooperative wireless relaying system. However, conventional OSTBC and CDD cannot cope with change in the number of relays owing to low throughput or error performance. In this paper, we propose a cooperative cyclic delay diversity (CDD) scheme that use hierarchical modulation at the source and adaptive modulation based on cyclic redundancy check (CRC) code at the relays.

Keywords: adaptive modulation, cooperative communication, CDD, OSTBC

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Authors: Dejin Chen, Bin Lin, Xiaohui LI, Haobin Tian

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In order to acquire stable impact performance of cover, the factors influencing the impact force of the cover were analyzed and researched. The influence of impact factors such as impact velocity, impact weight and fillet radius of warhead was studied by Orthogonal experiment. Through the range analysis and numerical simulation, the results show that the impact velocity has significant influences on impact force of cover. The impact force decreases with the increase of impact velocity and impact weight. The test results are similar to the numerical simulation. The cover broke up into four parts along the groove.

Keywords: fragile cover, numerical simulation, impact force, epoxy foam

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Authors: Prawal Sinha, Peeyush Singh, Pravir Dutt

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Problems in elastohydrodynamic lubrication have attracted a lot of attention in the last few decades. Solving a two-dimensional problem has always been a big challenge. In this paper, a new discontinuous finite volume method (DVM) for two-dimensional point contact Elastohydrodynamic Lubrication (EHL) problem has been developed and analyzed. A complete algorithm has been presented for solving such a problem. The method presented is robust and easily parallelized in MPI architecture. GMRES technique is implemented to solve the matrix obtained after the formulation. A new approach is followed in which discontinuous piecewise polynomials are used for the trail functions. It is natural to assume that the advantages of using discontinuous functions in finite element methods should also apply to finite volume methods. The nature of the discontinuity of the trail function is such that the elements in the corresponding dual partition have the smallest support as compared with the Classical finite volume methods. Film thickness calculation is done using singular quadrature approach. Results obtained have been presented graphically and discussed. This method is well suited for solving EHL point contact problem and can probably be used as commercial software.

Keywords: elastohydrodynamic, lubrication, discontinuous finite volume method, GMRES technique

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Authors: B. Makhlouf, O. Bouchhida, M. Nibouche, K. Laidi

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A variety of methods for selective harmonics elimination pulse width modulation have been developed, the most frequently used for real-time implementation based on look-up tables method. To address real-time requirements based in modified carrier signal is proposed in the presented work, with a general formulation to real-time harmonics control/elimination in switched inverters. Firstly, the proposed method has been demonstrated for a single value of the modulation index. However, in reality, this parameter is variable as a consequence of the voltage (amplitude) variability. In this context, a simple interpolation method for calculating the modified sine carrier signal is proposed. The method allows a continuous adjustment in both amplitude and frequency of the fundamental. To assess the performance of the proposed method, software simulations and hardware experiments have been carried out in the case of a single-phase inverter. Obtained results are very satisfactory.

Keywords: harmonic elimination, Particle Swarm Optimisation (PSO), polynomial interpolation, pulse width modulation, real-time harmonics control, voltage inverter

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Authors: Karim S. Hassan, Hisham M. Hamed, Yassmine A. Fahmy, Ahmed F. Shalash

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The mismatch between in-phase and quadrature signals in Orthogonal frequency division multiplexing (OFDM) systems, such as DVB-T2, results in a severe degradation in performance. Several general solutions have been proposed in the past, but these are largely computationally intensive, leading to complex implementations. In this paper, we propose a relatively simple iterative solution, which provides good results in relatively few iterations, using fixed precision arithmetic. An additional advantage is that complex digital blocks, such as dividers and square root, are not required. Thus, the proposed solution may be implemented in relatively simple hardware.

Keywords: OFDM, DVB-T2, I/Q imbalance, I/Q mismatch, iterative method, fixed point, reduced complexity

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Authors: Mohamed Sahli, David Bassir, Thierry Barriere, Xavier Roizard

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Predicting the behaviour of the Ti-6Al-4V alloy during the turning operation was very important in the choice of suitable cutting tools and also in the machining strategies. In this study, a 3D model with thermo-mechanical coupling has been proposed to study the influence of cutting parameters and also lubrication on the performance of cutting tools. The constants of the constitutive Johnson-Cook model of Ti-6Al-4V alloy were identified using inverse analysis based on the parameters of the orthogonal cutting process. Then, numerical simulations of the finishing machining operation were developed and experimentally validated for the cylindrical stock removal stage with the finishing cutting tool.

Keywords: titanium turning, cutting tools, FE simulation, chip

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Authors: Jalal Karam

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The methods of Fourier, Laplace, and Wavelet Transforms provide transfer functions and relationships between the input and the output signals in linear time invariant systems. This paper shows the equivalence among these three methods and in each case presenting an application of the appropriate (Fourier, Laplace or Wavelet) to the convolution theorem. In addition, it is shown that the same holds for a direct integration method. The Biorthogonal wavelets Bior3.5 and Bior3.9 are examined and the zeros distribution of their polynomials associated filters are located. This paper also presents the significance of utilizing wavelets as effective tools in processing speech signals for common multimedia applications in general, and for recognition and compression in particular. Theoretically and practically, wavelets have proved to be effective and competitive. The practical use of the Continuous Wavelet Transform (CWT) in processing and analysis of speech is then presented along with explanations of how the human ear can be thought of as a natural wavelet transformer of speech. This generates a variety of approaches for applying the (CWT) to many paradigms analysing speech, sound and music. For perception, the flexibility of implementation of this transform allows the construction of numerous scales and we include two of them. Results for speech recognition and speech compression are then included.

Keywords: continuous wavelet transform, biorthogonal wavelets, speech perception, recognition and compression

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Authors: Dmitry Dikarev, Ajit Nimbalker, Alexei Davydov

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Polar coding is a novel example of error correcting codes, which can achieve Shannon limit at block length N→∞ with log-linear complexity. Active research is being carried to adopt this theoretical concept for using in practical applications such as 5th generation wireless communication systems. Cyclic redundancy check (CRC) error detection code is broadly used in conjunction with successive cancellation list (SCL) decoding algorithm to improve finite-length polar code performance. However, there are two issues: increase of code block payload overhead by CRC bits and decrease of CRC error-detection capability. This paper proposes a method to control CRC overhead and false alarm rate of polar decoding. As shown in the computer simulations results, the proposed method provides the ability to use any set of CRC polynomials with any list size while maintaining the desired level of false alarm rate. This level of flexibility allows using polar codes in 5G New Radio standard.

Keywords: 5G New Radio, channel coding, cyclic redundancy check, list decoding, polar codes

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Authors: Shuaibu Hassan Usman, Ishaq Oyebisi Oyefolahan

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This study was aimed to explore the latent factors in the web 2.0 enabled knowledge sharing practices instrument. Seven latent factors were identified through a factor analysis with orthogonal rotation and interpreted based on simple structure convergence, item loadings, and analytical statistics. The number of factors retains was based on the analysis of Kaiser Normalization criteria and Scree plot. The reliability tests revealed a satisfactory reliability scores on each of the seven latent factors of the web 2.0 enabled knowledge sharing practices. Limitation, conclusion, and future work of this study were also discussed.

Keywords: factor analysis, latent factors, knowledge sharing practices, students, web 2.0 enabled

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Authors: Purnank Bhatt, Mit Shah, Pawan Nagda, Vimal Jasoliya

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The influence of parameters like velocity and depth of cut on cutting forces is investigated for the empirical relation of the coefficient of friction derived for CRS 1018 for different materials like AISI 4340 and Ti6Al4V. For this purpose, turning tests were carried out on the above materials using coated cemented carbide tool inserts for steel grade and uncoated cemented carbide cutting tool inserts for Titanium with different chip breaker geometries. The cutting forces were measured using a Kistler dynamometer where the multiplication factor taken is 200.The effect of cutting force variation was analyzed experimentally and are compared with the analytical results.

Keywords: cutting forces, coefficient of friction, carbide tool inserts, titanium

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Authors: Mahboobeh Eghtesad, Reza Mohseni

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We develop methods for detecting a target for orthogonal frequency division multiplexing (OFDM) based radars. As a preliminary step we introduce the target and Gaussian noise models in discrete–time form. Then, resorting to match filter (MF) we derive a detector for two different scenarios: a non-fluctuating target and a Rayleigh fluctuating target. It will be shown that a MF is not suitable for Rayleigh fluctuating targets. In this paper we propose a reduced-complexity method based on fast Fourier transfrom (FFT) for such a situation. The proposed method has better detection performance.

Keywords: constant false alarm rate (CFAR), match filter (MF), fast Fourier transform (FFT), OFDM radars, Rayleigh fluctuating target

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Authors: Keunhong Chae, Seokho Yoon

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This paper proposes frequency offset (FO) estimation schemes robust to the non-Gaussian noise for orthogonal frequency division multiplexing (OFDM) systems. A maximum-likelihood (ML) scheme and a low-complexity estimation scheme are proposed by applying the probability density function of the cyclic prefix of OFDM symbols to the ML criterion. From simulation results, it is confirmed that the proposed schemes offer a significant FO estimation performance improvement over the conventional estimation scheme in non-Gaussian noise environments.

Keywords: frequency offset, cyclic prefix, maximum-likelihood, non-Gaussian noise, OFDM

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Authors: Younghyun Jeon, Seungjoo Maeng

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In the Ad-hoc network, the great interests regarding MIMO scheme leads to their combination, which is also utilized into its applicable network. We manage the field of the problem into Reverse-link MIMO Ad-hoc Network (RMAN) and propose the methodology to maximize the data rate with its power consumption using Node-Cooperative beamforming technique. Based on the result of mathematical optimization formulation, we design the algorithm to construct optimal orthogonal weight vector according to channel feedback and control its transmission power according to QoS-pricing value level. In simulation results, we show the validity of the proposed mathematical optimization result and algorithm which mean that the sum-rate of each link is converged into some point.

Keywords: ad-hoc network, MIMO, cooperative beamforming, transmit power

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Authors: I Made Gatot Karohika, Shigeyuki Haruyama, Ken Kaminishi

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In this study, we proposed a three-layer metal gasket with Al, Cu, and SUS304 as the material, respectively. A finite element method was employed to develop simulation solution and design of experiment (DOE). Taguchi method was used to analysis the effect of each parameter design and predicts optimal design of new 25A-size three layer corrugated metal gasket. The L18 orthogonal array of Taguchi method was applied to design experiment matrix for eight factors with three levels. Based on elastic mode and plastic mode, optimum design gasket is gasket with core metal SUS304, surface layer aluminum, p1 = 4.5 mm, p2 = 4.5 mm, p3 = 4 mm, Tg = 1.2 mm, R = 3.5 mm, h = 0.4 mm and Ts = 0.3 mm.

Keywords: contact width, contact stress, layer, metal gasket, corrugated, simulation

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Authors: Ravinder Kataria, Jatinder Kumar, B. S. Pabla

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Ultrasonic machining is one of the most widely used non-traditional machining processes for machining of materials that are relatively brittle, hard, and fragile such as advanced ceramics, refractories, crystals, quartz etc. Present article has been targeted at investigating the impact of different experimental conditions (power rating, cobalt content, tool material, thickness of work piece, tool geometry, and abrasive grit size) on over cut in ultrasonic drilling of WC-Co composite material. Taguchi’s L-36 orthogonal array has been employed for conducting the experiments. Significant factors have been identified using analysis of variance (ANOVA) test. The experimental results revealed that abrasive grit size and tool material are most significant factors for over cut.

Keywords: ANOVA, abrasive grit size, Taguchi, WC-Co, ultrasonic machining

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Authors: Alexander P. Vazhenin, Mikhail M. Lavrentiev, Alexey A. Romanenko, Pavel V. Tatarintsev

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One of the problems obstructing effective tsunami modelling is the lack of information about initial wave shape at source. The existing methods; geological, sea radars, satellite images, contain an important part of uncertainty. Therefore, direct measurement of tsunami waves obtained at the deep water bottom peruse recorders is also used. In this paper we propose a new method to reconstruct the initial sea surface displacement at tsunami source by the measured signal (marigram) approximation with the help of linear combination of synthetic marigrams from the selected set of unit sources, calculated in advance. This method has demonstrated good precision and very high performance. The mathematical model and results of numerical tests are here described.

Keywords: numerical tests, orthogonal decomposition, Tsunami Initial Sea Surface Displacement

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Authors: Zhenming Wang, Jun Zhu, Yuchen Yang, Ning Zhao

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In the present paper, an alternative framework is proposed to construct a class of finite difference multi-resolution nested weighted essentially non-oscillatory (WENO) schemes with an increasingly higher order of accuracy for solving inviscid Euler equations. These WENO schemes firstly obtain a set of reconstruction polynomials by a hierarchy of nested central spatial stencils, and then recursively achieve a higher order approximation through the lower-order precision WENO schemes. The linear weights of such WENO schemes can be set as any positive numbers with a requirement that their sum equals one and they will not pollute the optimal order of accuracy in smooth regions and could simultaneously suppress spurious oscillations near discontinuities. Numerical results obtained indicate that these alternative finite-difference multi-resolution nested WENO schemes with different accuracies are very robust with low dissipation and use as few reconstruction stencils as possible while maintaining the same efficiency, achieving the high-resolution property without any equivalent multi-resolution representation. Besides, its finite volume form is easier to implement in unstructured grids.

Keywords: finite-difference, WENO schemes, high order, inviscid Euler equations, multi-resolution

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Authors: Chirine Aouichaoui, Mohamed Tounsi, Ines Mrizak, Zouhair Tabka, Yassine Trabelsi

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The aim of this study was to provide percentile values for vertical jumping performances and anthropometric characteristics for athletic Tunisian children. One thousand and fifty-five athletic Tunisian children and adolescents (643 boys and 412 girls) aged 7-18 years were randomly selected to participate in our study. They were asked to perform squat jumps and countermovement jumps. For each measurement, a least square regression model with high order polynomials was fitted to predict mean and standard deviation of vertical jumping parameters and anthropometric variables. Smoothed percentile curves and percentile values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles are presented for boys and girls. In conclusion, percentiles values of vertical jumping performances and anthropometric characteristics are provided. The new Tunisian reference charts obtained can be used as a screening tool to determine growth disorders and to estimate the proportion of adolescents with high or low muscular strength levels. This study may help in verifying the effectiveness of a specific training program and detecting highly talented athletes.

Keywords: percentile values, jump height, leg muscle power, athletes, anthropometry

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Authors: Fatima Akhmedova, Simon Liao

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One of the most critical decision points in the design of a face recognition system is the choice of an appropriate face representation. Effective feature descriptors are expected to convey sufficient, invariant and non-redundant facial information. In this work, we propose a set of Hahn moments as a new approach for feature description. Hahn moments have been widely used in image analysis due to their invariance, non-redundancy and the ability to extract features either globally and locally. To assess the applicability of Hahn moments to Face Recognition we conduct two experiments on the Olivetti Research Laboratory (ORL) database and University of Notre-Dame (UND) X1 biometric collection. Fusion of the global features along with the features from local facial regions are used as an input for the conventional k-NN classifier. The method reaches an accuracy of 93% of correctly recognized subjects for the ORL database and 94% for the UND database.

Keywords: face recognition, Hahn moments, recognition-by-parts, time-lapse

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Authors: Alina Mirza, Sumrin M. Kabir, Shahzad A. Sheikh

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The Orthogonal Frequency Division Multiplexing (OFDM) with high data rate, high spectral efficiency and its ability to mitigate the effects of multipath makes them most suitable in wireless application. Impulsive noise distorts the OFDM transmission and therefore methods must be investigated to suppress this noise. In this paper, a State Space Recursive Least Square (SSRLS) algorithm based adaptive impulsive noise suppressor for OFDM communication system is proposed. And a comparison with another adaptive algorithm is conducted. The state space model-dependent recursive parameters of proposed scheme enables to achieve steady state mean squared error (MSE), low bit error rate (BER), and faster convergence than that of some of existing algorithm.

Keywords: OFDM, impulsive noise, SSRLS, BER

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Authors: Mohamed Ben Amar, Najib Souissi, Chedly Bradai

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A Taguchi design investigation has been made into the relationship between the ductility and process variables in a squeeze cast 2017A wrought aluminium alloy. The considered process parameters were: squeeze pressure, melt temperature and die preheating temperature. An orthogonal array (OA), main effect, signal-to-noise (S/N) ratio, and the analysis of variance (ANOVA) are employed to analyze the effect of casting parameters. The results have shown that the selected parameters significantly affect the ductility of 2017A wrought Al alloy castings. Optimal squeeze cast process parameters were provided to illustrate the proposed approach and the results were proven to be trustworthy through practical experiments.

Keywords: Taguchi method, squeeze casting, process parameters, ductility, microstructure

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Authors: Mahbube Eghtesad

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For a number of years, the problem of simultaneous detection and tracking of a target has been one of the most relevant and challenging issues in a wide variety of military and civilian systems. We develop methods for detecting and tracking a target using an orthogonal frequency division multiplexing (OFDM) based radar. As a preliminary step we introduce the target trajectory and Gaussian noise model in discrete time form. Then resorting to match filter and Kalman filter we derive a detector and target tracker. After that we propose an OFDM radar in order to achieve further improvement in tracking performance. The motivation for employing multiple frequencies is that the different scattering centers of a target resonate differently at each frequency. Numerical examples illustrate our analytical results, demonstrating the achieved performance improvement due to the OFDM signaling method.

Keywords: matched filter, target trashing, OFDM radar, Kalman filter

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Authors: Khosrow Maleknejad, Yaser Rostami

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In this paper, semi-orthogonal B-spline scaling functions and wavelets and their dual functions are presented to approximate the solutions of integro-differential equations.The B-spline scaling functions and wavelets, their properties and the operational matrices of derivative for this function are presented to reduce the solution of integro-differential equations to the solution of algebraic equations. Here we compute B-spline scaling functions of degree 4 and their dual, then we will show that by using them we have better approximation results for the solution of integro-differential equations in comparison with less degrees of scaling functions.

Keywords: ıntegro-differential equations, quartic B-spline wavelet, operational matrices, dual functions

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Authors: Balwinder Singh, Veerpaul Kaur Mann

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A composite material is formed by the combination of two or more phases or materials. Natural minerals-derived Basalt fiber is a kind of fiber being introduced in the polymer composite industry due to its good mechanical properties similar to synthetic fibers and low cost, environment friendly. Also, there is a rising trend towards the use of industrial wastes as fillers in polymer composites with the aim of improving the properties of the composites. The mechanical properties of the fiber-reinforced polymer composites are influenced by various factors like fiber length, fiber weight %, filler weight %, filler size, etc. Thus, a detailed study has been done on the characterization of short-chopped Basalt fiber-reinforced polymer matrix composites using fly ash as filler. Taguchi’s L9 orthogonal array has been used to develop the composites by considering fiber length (6, 9 and 12 mm), fiber weight % (25, 30 and 35 %) and filler weight % (0, 5 and 10%) as input parameters with their respective levels and a thorough analysis on the mechanical characteristics (tensile strength and impact strength) has been done using ANOVA analysis with the help of MINITAB14 software. The investigation revealed that fiber weight is the most significant parameter affecting tensile strength, followed by fiber length and fiber weight %, respectively, while impact characterization showed that fiber length is the most significant factor, followed by fly ash weight, respectively. Introduction of fly ash proved to be beneficial in both the characterization with enhanced values upto 5% fly ash weight. The present study on the natural fibres reinforced epoxy composites using fly ash as filler material to study the effect of input parameters on the tensile strength in order to maximize tensile strength of the composites. Fabrication of composites based on Taguchi L9 orthogonal array design of experiments by using three factors fibre type, fibre weight % and fly ash % with three levels of each factor. The Optimization of composition of natural fibre reinforces composites using ANOVA for obtaining maximum tensile strength on fabricated composites revealed that the natural fibres along with fly ash can be successfully used with epoxy resin to prepare polymer matrix composites with good mechanical properties. Paddy- Paddy fibre gives high elasticity to the fibre composite due to presence of approximately hexagonal structure of cellulose present in paddy fibre. Coir- Coir fibre gives less tensile strength than paddy fibre as Coir fibre is brittle in nature when it pulls breakage occurs showing less tensile strength. Banana- Banana fibre has the least tensile strength in comparison to the paddy & coir fibre due to less cellulose content. Higher fibre weight leads to reduction in tensile strength due to increased nuclei of air pockets. Increasing fly ash content reduces tensile strength due to nonbonding of fly ash particles with natural fibre. Fly ash is also not very strong as compared to the epoxy resin leading to reduction in tensile strength.

Keywords: tensile strength and epoxy resin. basalt Fiber, taguchi, polymer matrix, natural fiber

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Authors: Alan C. Lin, Tran Anh Son

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This study proposes an approach to determine the undercut regions and their releasing directions for slider design of complex parts represented by the file format of STL (STereoLithography). In order to delineate the border of undercut regions, orthogonal cutting planes are firstly employed to automatically find the inner loops of a part model. To discover the facets belonging to undercut regions, attributes are then assigned to the facets of the part model based on the topological relationship of adjacent facets of each inner loop. After that, the undercut regions are separated from other facets in the model. Through the recognized facets of the undercut regions, the concept of 'visibility map (V-map)' is further applied to determine feasible releasing directions for each of the undercut regions. The undercut regions having the same releasing direction are finally grouped to form a slider in the injection mold.

Keywords: solid model, STL data, injection mold design, visibility map

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Authors: C. C. Lv, Y. L. Sun, D. W. Zuo

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Cemented carbide balls are usually implemented in industry under the environment of high speed, high temperature, corrosiveness and strong collisions. However, its application is limited due to high fabrication cost, processing efficiency and quality. A novel eccentric lapping method with two rotatable lapping plates was proposed in this paper. A mathematical model was constructed to analyze the influence of each design parameter on this lapping method. To validate this new lapping method, an orthogonal experiment was conducted with cemented carbide balls (YG6). The simulation model was verified and the optimal lapping parameters were derived. The results show that the surface roundness of the balls reaches to 0.65um from 2um in 1 hour using this lapping method. So, using this novel lapping method, it can effectively improve the machining precision and efficiency of cemented carbide balls.

Keywords: cemented carbide balls, eccentric lapping, high precision, lapping tracks, V-groove

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Authors: Nihar Ranjan, Derrick Watkins, Dev P. Arya

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Current methods in the study of antibiotic activity of ribosome targeted antibiotics are dependent on cell based bacterial inhibition assays or various forms of ribosomal binding assays. These assays are typically independent of each other and little direct correlation between the ribosomal binding and bacterial inhibition is established with the complementary assay. We have developed novel high-throughput capable assays for ribosome targeted drug discovery. One such assay examines the compounds ability to bind to a model ribosomal RNA A-site. We have also coupled this assay to other functional orthogonal assays. Such analysis can provide valuable understanding of the relationships between two complementary drug screening methods and could be used as standard analysis to correlate the affinity of a compound for its target and the effect the compound has on a cell.

Keywords: bacterial resistance, aminoglycosides, screening, drugs

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Authors: Aizati N. A. Daud, Jorieke E. H. Bergman, Wilhelmina S. Kerstjens-Frederikse, Pieter Van Der Vlies, Eelko Hak, Rolf M. F. Berger, Henk Groen, Bob Wilffert

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Prenatal use of SRIs was previously associated with Congenital Heart Anomalies (CHA). The aim of the study is to explore whether pharmacogenetics plays a role in this teratogenicity using a gene-environment interaction study. A total of 33 case-mother dyads and 2 mother-only (children deceased) registered in EUROCAT Northern Netherlands were included in a case-only study. Five case-mother dyads and two mothers-only were exposed to SRIs (paroxetine=3, fluoxetine=2, venlafaxine=1, paroxetine and venlafaxine=1) in the first trimester of pregnancy. The remaining 28 case-mother dyads were not exposed to SRIs. Ten genes that encode the enzymes or proteins important in determining fetal exposure to SRIs or its mechanism of action were selected: CYPs (CYP1A2, CYP2C9, CYP2C19, CYP2D6), ABCB1 (placental P-glycoprotein), SLC6A4 (serotonin transporter) and serotonin receptor genes (HTR1A, HTR1B, HTR2A, and HTR3B). All included subjects were genotyped for 58 genetic variations in these ten genes. Logistic regression analyses were performed to determine the interaction odds ratio (OR) between genetic variations and SRIs exposure on the risk of CHA. Due to low phenotype frequencies of CYP450 poor metabolizers among exposed cases, the OR cannot be calculated. For ABCB1, there was no indication of changes in the risk of CHA with any of the ABCB1 SNPs in the children and their mothers. Several genetic variations of the serotonin transporter and receptors (SLC6A4 5-HTTLPR and 5-HTTVNTR, HTR1A rs1364043, HTR1B rs6296 & rs6298, HTR3B rs1176744) were associated with an increased risk of CHA, but with too limited sample size to reach statistical significance. For SLC6A4 genetic variations, the mean genetic scores of the exposed case-mothers tended to be higher than the unexposed mothers (2.5 ± 0.8 and 1.88 ± 0.7, respectively; p=0.061). For SNPs of the serotonin receptors, the mean genetic score for exposed cases (children) tended to be higher than the unexposed cases (3.4 ± 2.2, and 1.9 ± 1.6, respectively; p=0.065). This study might be among the first to explore the potential gene-environment interaction between pharmacogenetic determinants and SRIs use on the risk of CHA. With small sample sizes, it was not possible to find a significant interaction. However, there were indications for a role of serotonin receptor polymorphisms in fetuses exposed to SRIs on fetal risk of CHA which warrants further investigation.

Keywords: gene-environment interaction, heart defects, pharmacogenetics, serotonin reuptake inhibitors, teratogenicity

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