Search results for: fault propagation fold
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1868

Search results for: fault propagation fold

1358 Utilization of an Object Oriented Tool to Perform Model-Based Safety Analysis According to Extended Failure System Models

Authors: Royia Soliman, Salma ElAnsary, Akram Amin Abdellatif, Florian Holzapfel

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Model-Based Safety Analysis (MBSA) is an approach in which the system and safety engineers share a common system model created using a model-based development process. The model can also be extended by the failure modes of the system components. There are two famous approaches for the addition of fault behaviors to system models. The first one is to enclose the failure into the system design directly. The second approach is to develop a fault model separately from the system model, thus combining both independent models for safety analysis. This paper introduces a hybrid approach of MBSA. The approach tries to use informal abstracted models to investigate failure behaviors. The approach will combine various concepts such as directed graph traversal, event lists and Constraint Satisfaction Problems (CSP). The approach is implemented using an Object Oriented programming language. The components are abstracted to its failure logic and relationships of connected components. The implemented approach is tested on various flight control systems, including electrical and multi-domain examples. The various tests are analyzed, and a comparison to different approaches is represented.

Keywords: flight control systems, model based safety analysis, safety assessment analysis, system modelling

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1357 Bio-Genetic Activities Associated with Resistant in Peppers to Phytophthora capsici

Authors: Mehdi Nasr-Esfahani, Leila Mohammad Bagheri, Ava Nasr-Esfahani

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Root and collar rot disease caused by Phytophthora capsici (Leonian) is one of the most serious diseases in pepper, Capsicum annuum L. In this study, a diverse collection of 37 commercial edible and ornamental pepper genotypes infected with P. capsici were investigated for biomass parameters and enzymatic activity of peroxidase or peroxide reductases (EC), superoxide dismutase (SOD), polyphenol oxidase (PPOs), catalase (CAT) and phenylalanine ammonia-lyase (PAL). Seven candidate DEG genes were also evaluated on resistant and susceptible pepper cultivars, through measuring product formation, using spectrophotometry and real-time polymerase chain reaction. All the five enzymes and seven defense-gene candidates were up-regulated in all inoculated pepper accessions to P. capsici. But, the enzymes and DEG genes were highly expressed in resistant cv. 19OrnP-PBI, 37ChillP-Paleo, and “23CherryP-Orsh". The expression level of enzymes were 1.5 to 5.6-fold higher in the resistant peppers, than the control non-inoculated genotypes. Also, the transcriptional levels of related candidate DEG genes were 3.16 to 5.90-fold higher in the resistant genotypes. There was a direct and high correlation coefficient between resistance, bio-mass parameters, enzymatic activity, and resistance gene expression. The related enzymes and candidate genes expressed herein will provide a basis for further gene cloning and functional verification studies, and also will aid in an understanding of the regulatory mechanism of pepper resistance to P. capsici.

Keywords: AP2/ERF, cDNA, enzymes, MIP gene, q-RTPCR, XLOC

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1356 Seismotectonics of Southern Haiti: A Faulting Model for the 12 January 2010 M7 Earthquake

Authors: Newdeskarl Saint Fleur, Nathalie Feuillet, Raphaël Grandin, Éric Jacques, Jennifer Weil-Accardo, Yann Klinger

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The prevailing consensus is that the 2010 Mw7.0 Haiti earthquake left the Enriquillo–Plantain Garden strike-slip Fault (EPGF) unruptured but broke unmapped blind north-dipping thrusts. Using high-resolution topography, aerial images, bathymetry and geology we identified previously unrecognized south-dipping NW-SE-striking active thrusts in southern Haiti. One of them, Lamentin thrust (LT), cuts across the crowded city of Carrefour, extends offshore into Port-au-Prince Bay and connects at depth with the EPGF. We propose that both faults broke in 2010. The rupture likely initiated on the thrust and propagated further along the EPGF due to unclamping. This scenario is consistent with geodetic, seismological and field data. The 2010 earthquake increased the stress toward failure on the unruptured segments of the EPGF and on neighboring thrusts, significantly increasing the seismic hazard in the Port-au-Prince urban area. The numerous active thrusts recognized in that area must be considered for future evaluation of the seismic hazard.

Keywords: active faulting, enriquillo-plantain garden fault, Haiti earthquake, seismic hazard

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1355 Serum 25-Hydroxyvitamin D Levels and Depression in Persons with Human Immunodeficiency Virus Infection: A Cross-Sectional and Prospective Study

Authors: Kalpana Poudel-Tandukar

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Background: Human Immunodeficiency Virus (HIV) infection has been frequently associated with vitamin D deficiency and depression. Vitamin D deficiency increases the risk of depression in people without HIV. We assessed the cross-sectional and prospective associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and depression in a HIV-positive people. Methods: A survey was conducted among 316 HIV-positive people aged 20-60 years residing in Kathmandu, Nepal for a cross-sectional association at baseline, and among 184 participants without depressive symptoms at baseline who responded to both baseline (2010) and follow-up (2011) surveys for prospective association. The competitive protein-binding assay was used to measure 25(OH)D levels and the Beck Depression Inventory-Ia method was used to measure depression, with cut off score 20 or higher. Relationships were assessed using multiple logistic regression analysis with adjustment of potential confounders. Results: The proportion of participants with 25(OH)D level of <20ng/mL, 20-30ng/mL, and >30ng/mL were 83.2%, 15.5%, and 1.3%, respectively. Only four participants with 25(OH)D level of >30ng/mL were excluded in the further analysis. The mean 25(OH)D level in men and women were 15.0ng/mL and 14.4ng/mL, respectively. Twenty six percent of participants (men:23%; women:29%) were depressed. Participants with 25(OH)D level of < 20 ng/mL had a 1.4 fold higher odds of depression in a cross-sectional and 1.3 fold higher odds of depression after 18 months of baseline compared to those with 25(OH)D level of 20-30ng/mL (p=0.40 and p=0.78, respectively). Conclusion: Vitamin D may not have significant impact against depression among HIV-positive people with 25(OH)D level below normal ( > 30ng/mL).

Keywords: depression, HIV, Nepal, vitamin D

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1354 Current-Based Multiple Faults Detection in Electrical Motors

Authors: Moftah BinHasan

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Induction motors (IM) are vital components in industrial processes whose failure may yield to an unexpected interruption at the industrial plant, with highly incurred consequences in costs, product quality, and safety. Among different detection approaches proposed in the literature, that based on stator current monitoring termed as Motor Current Signature Analysis (MCSA) is the most preferred. MCSA is advantageous due to its non-invasive properties. The popularity of motor current signature analysis comes from being that the current consists of motor harmonics, around the supply frequency, which show some properties related to different situations of healthy and faulty conditions. One of the techniques used with machine line current resorts to spectrum analysis. Besides discussing the fundamentals of MCSA and its applications in the condition monitoring arena, this paper shows a summary of the most frequent faults and their consequence signatures on the stator current spectrum of an induction motor. In addition, this article presents different case studies of induction motor fault diagnosis. These faults were seeded in the machine which was run for more than an hour for each test before the results were recorded for the faulty situations. These results are then compared with those for the healthy cases that were recorded earlier.

Keywords: induction motor, condition monitoring, fault diagnosis, MCSA, rotor, stator, bearing, eccentricity

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1353 Numerical Modelling of 3-D Fracture Propagation and Damage Evolution of an Isotropic Heterogeneous Rock with a Pre-Existing Surface Flaw under Uniaxial Compression

Authors: S. Mondal, L. M. Olsen-Kettle, L. Gross

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Fracture propagation and damage evolution are extremely important for many industrial applications including mining industry, composite materials, earthquake simulations, hydraulic fracturing. The influence of pre-existing flaws and rock heterogeneity on the processes and mechanisms of rock fracture has important ramifications in many mining and reservoir engineering applications. We simulate the damage evolution and fracture propagation in an isotropic sandstone specimen containing a pre-existing 3-D surface flaw in different configurations under uniaxial compression. We apply a damage model based on the unified strength theory and solve the solid deformation and damage evolution equations using the Finite Element Method (FEM) with tetrahedron elements on unstructured meshes through the simulation software, eScript. Unstructured meshes provide higher geometrical flexibility and allow a more accurate way to model the varying flaw depth, angle, and length through locally adapted FEM meshes. The heterogeneity of rock is considered by initializing material properties using a Weibull distribution sampled over a cubic grid. In our model, we introduce a length scale related to the rock heterogeneity which is independent of the mesh size. We investigate the effect of parameters including the heterogeneity of the elastic moduli and geometry of the single flaw in the stress strain response. The generation of three typical surface cracking patterns, called wing cracks, anti-wing cracks and far-field cracks were identified, and these depend on the geometry of the pre-existing surface flaw. This model results help to advance our understanding of fracture and damage growth in heterogeneous rock with the aim to develop fracture simulators for different industry applications.

Keywords: finite element method, heterogeneity, isotropic damage, uniaxial compression

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1352 Geological Structure Identification in Semilir Formation: An Correlated Geological and Geophysical (Very Low Frequency) Data for Zonation Disaster with Current Density Parameters and Geological Surface Information

Authors: E. M. Rifqi Wilda Pradana, Bagus Bayu Prabowo, Meida Riski Pujiyati, Efraim Maykhel Hagana Ginting, Virgiawan Arya Hangga Reksa

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The VLF (Very Low Frequency) method is an electromagnetic method that uses low frequencies between 10-30 KHz which results in a fairly deep penetration. In this study, the VLF method was used for zonation of disaster-prone areas by identifying geological structures in the form of faults. Data acquisition was carried out in Trimulyo Region, Jetis District, Bantul Regency, Special Region of Yogyakarta, Indonesia with 8 measurement paths. This study uses wave transmitters from Japan and Australia to obtain Tilt and Elipt values that can be used to create RAE (Rapat Arus Ekuivalen or Current Density) sections that can be used to identify areas that are easily crossed by electric current. This section will indicate the existence of a geological structure in the form of faults in the study area which is characterized by a high RAE value. In data processing of VLF method, it is obtained Tilt vs Elliptical graph and Moving Average (MA) Tilt vs Moving Average (MA) Elipt graph of each path that shows a fluctuating pattern and does not show any intersection at all. Data processing uses Matlab software and obtained areas with low RAE values that are 0%-6% which shows medium with low conductivity and high resistivity and can be interpreted as sandstone, claystone, and tuff lithology which is part of the Semilir Formation. Whereas a high RAE value of 10% -16% which shows a medium with high conductivity and low resistivity can be interpreted as a fault zone filled with fluid. The existence of the fault zone is strengthened by the discovery of a normal fault on the surface with strike N550W and dip 630E at coordinates X= 433256 and Y= 9127722 so that the activities of residents in the zone such as housing, mining activities and other activities can be avoided to reduce the risk of natural disasters.

Keywords: current density, faults, very low frequency, zonation

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1351 Microseismicity of the Tehran Region Based on Three Seismic Networks

Authors: Jamileh Vasheghani Farahani

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The main purpose of this research is to show the current active faults and active tectonic of the area by three seismic networks in Tehran region: 1-Tehran Disaster Mitigation and Management Organization (TDMMO), 2-Broadband Iranian National Seismic Network Center (BIN), 3-Iranian Seismological Center (IRSC). In this study, we analyzed microearthquakes happened in Tehran city and its surroundings using the Tehran networks from 1996 to 2015. We found some active faults and trends in the region. There is a 200-year history of historical earthquakes in Tehran. Historical and instrumental seismicity show that the east of Tehran is more active than the west. The Mosha fault in the North of Tehran is one of the active faults of the central Alborz. Moreover, other major faults in the region are Kahrizak, Eyvanakey, Parchin and North Tehran faults. An important seismicity region is an intersection of the Mosha and North Tehran fault systems (Kalan village in Lavasan). This region shows a cluster of microearthquakes. According to the historical and microseismic events analyzed in this research, there is a seismic gap in SE of Tehran. The empirical relationship is used to assess the Mmax based on the rupture length. There is a probability of occurrence of a strong motion of 7.0 to 7.5 magnitudes in the region (based on the assessed capability of the major faults such as Parchin and Eyvanekey faults and historical earthquakes).

Keywords: Iran, major faults, microseismicity, Tehran

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1350 In Vitro Propagation of Aloe vera and Aloe littoralis Plants: Gamma Radiation, Biochemical and Genetic Changes

Authors: Z. Nourmohammadi, F. Farahani, M. Shaker

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Aloe is an important commercial crop available in a wide range of species and varieties in international markets. The applications of this plant have been recorded in the ancient cultures of India, Egypt, Greece, Rome and China. Aloe has been used for centuries and is currently being actively studied for medicinal purposes. Aloe is propagated through lateral buds, which is slow, very expensive and low income practice. Nowadays, it has been cultured by in vitro propagation for rapid multiplication of plants, genetic improvement of crops, obtaining disease-free clones and for progressive valuable germplasm. The present study focused on the influence of different phytohormones on rapid in vitro propagation of Aloe plants. We also investigated the effect of gamma radiation on biochemical characters as well as genetic changes. Shoot tip of 2-3 cm were collected from offshoot of Aloe barbadensis and Aloe littoralis, and were inoculated with MS medium containing various concentrations of BA (0.5, 1, 2 mg/l), IAA (0.5, 1 mg/l). The best treatment for a highest shoot number and bud proliferation was MS medium containing 2 mg/l BAP and 0.5 mg/l IAA in A. barbadensis and A. littoralis. Maximum percentage of proliferated shoot buds (90% and 95%) from a single explant were obtained in MS medium after 4-5 weeks of the second and the first subcultures, respectively. Different genome sizes were also indicated among treatments and subcultures. The mixoploids identified in flow cytometery histograms in different treatments. The effect of gamma radiation on A. littoralis showed that by increasing the dose of gamma radiation, amounts of chlorophyll A, B, carotenoids, total protein content and superoxide dismutase were significantly increased compared to control plants. Genetic variation analysis also revealed significant genetic differences between control and gamma radiation treated regenerated plants by AMOVA test. Higher genetic heterozygocity was observed in radiation treated plants. Our findings may provide useful method for improving of Aloe plant proliferation with increasing of useful material such as antioxidant enzymes.

Keywords: aloe, antioxidant enzyme, micropropagation, gamma radiation, genetic variation

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1349 An Innovative Auditory Impulsed EEG and Neural Network Based Biometric Identification System

Authors: Ritesh Kumar, Gitanjali Chhetri, Mandira Bhatia, Mohit Mishra, Abhijith Bailur, Abhinav

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The prevalence of the internet and technology in our day to day lives is creating more security issues than ever. The need for protecting and providing a secure access to private and business data has led to the development of many security systems. One of the potential solutions is to employ the bio-metric authentication technique. In this paper we present an innovative biometric authentication method that utilizes a person’s EEG signal, which is acquired in response to an auditory stimulus,and transferred wirelessly to a computer that has the necessary ANN algorithm-Multi layer perceptrol neural network because of is its ability to differentiate between information which is not linearly separable.In order to determine the weights of the hidden layer we use Gaussian random weight initialization. MLP utilizes a supervised learning technique called Back propagation for training the network. The complex algorithm used for EEG classification reduces the chances of intrusion into the protected public or private data.

Keywords: EEG signal, auditory evoked potential, biometrics, multilayer perceptron neural network, back propagation rule, Gaussian random weight initialization

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1348 A Distributed Mobile Agent Based on Intrusion Detection System for MANET

Authors: Maad Kamal Al-Anni

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This study is about an algorithmic dependence of Artificial Neural Network on Multilayer Perceptron (MPL) pertaining to the classification and clustering presentations for Mobile Adhoc Network vulnerabilities. Moreover, mobile ad hoc network (MANET) is ubiquitous intelligent internetworking devices in which it has the ability to detect their environment using an autonomous system of mobile nodes that are connected via wireless links. Security affairs are the most important subject in MANET due to the easy penetrative scenarios occurred in such an auto configuration network. One of the powerful techniques used for inspecting the network packets is Intrusion Detection System (IDS); in this article, we are going to show the effectiveness of artificial neural networks used as a machine learning along with stochastic approach (information gain) to classify the malicious behaviors in simulated network with respect to different IDS techniques. The monitoring agent is responsible for detection inference engine, the audit data is collected from collecting agent by simulating the node attack and contrasted outputs with normal behaviors of the framework, whenever. In the event that there is any deviation from the ordinary behaviors then the monitoring agent is considered this event as an attack , in this article we are going to demonstrate the  signature-based IDS approach in a MANET by implementing the back propagation algorithm over ensemble-based Traffic Table (TT), thus the signature of malicious behaviors or undesirable activities are often significantly prognosticated and efficiently figured out, by increasing the parametric set-up of Back propagation algorithm during the experimental results which empirically shown its effectiveness  for the ratio of detection index up to 98.6 percentage. Consequently it is proved in empirical results in this article, the performance matrices are also being included in this article with Xgraph screen show by different through puts like Packet Delivery Ratio (PDR), Through Put(TP), and Average Delay(AD).

Keywords: Intrusion Detection System (IDS), Mobile Adhoc Networks (MANET), Back Propagation Algorithm (BPA), Neural Networks (NN)

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1347 Modeling of Long Wave Generation and Propagation via Seabed Deformation

Authors: Chih-Hua Chang

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This study uses a three-dimensional (3D) fully nonlinear model to simulate the wave generation problem caused by the movement of the seabed. The numerical model is first simplified into two dimensions and then compared with the existing two-dimensional (2D) experimental data and the 2D numerical results of other shallow-water wave models. Results show that this model is different from the earlier shallow-water wave models, with the phase being closer to the experimental results of wave propagation. The results of this study are also compared with those of the 3D experimental results of other researchers. Satisfactory results can be obtained in both the waveform and the flow field. This study assesses the application of the model to simulate the wave caused by the circular (radius r0) terrain rising or falling (moving distance bm). The influence of wave-making parameters r0 and bm are discussed. This study determines that small-range (e.g., r0 = 2, normalized by the static water depth), rising, or sinking terrain will produce significant wave groups in the far field. For large-scale moving terrain (e.g., r0 = 10), uplift and deformation will potentially generate the leading solitary-like waves in the far field.

Keywords: seismic wave, wave generation, far-field waves, seabed deformation

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1346 An Efficient and Low Cost Protocol for Rapid and Mass in vitro Propagation of Hyssopus officinalis L.

Authors: Ira V. Stancheva, Ely G. Zayova, Maria P. Geneva, Marieta G. Hristozkova, Lyudmila I. Dimitrova, Maria I. Petrova

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The study describes a highly efficient and low-cost protocol for rapid and mass in vitro propagation of medicinal and aromatic plant species (Hyssopus officinalis L., Lamiaceae). Hyssop is an important aromatic herb used for its medicinal values because of its antioxidant, anti-inflammatory and antimicrobial properties. The protocol for large-scale multiplication of this aromatic plant was developed using young stem tips explants. The explants were sterilized with 0.04% mercuric chloride (HgCl₂) solution for 20 minutes and washing three times with sterile distilled water in 15 minutes. The cultural media was full and half strength Murashige and Skoog medium containing indole-3-butyric acid. Full and ½ Murashige and Skoog media without auxin were used as controls. For each variant 20 glass tubes with two plants were used. In each tube two tip and nodal explants were inoculated. Maximum shoot and root number were obtained on ½ Murashige and Skoog medium supplemented with 0.1 mg L-1 indole-3-butyric acid at the same time after four weeks of culture. The number of shoots per explant and shoot height were considered. The data on rooting percentage, the number of roots per plant and root length were collected after the same cultural period. The highest percentage of survival 85% for this medicinal plant was recorded in mixture of soil, sand and perlite (2:1:1 v/v/v). This mixture was most suitable for acclimatization of all propagated plants. Ex vitro acclimatization was carried out at 24±1 °C and 70% relative humidity under 16 h illuminations (50 μmol m⁻²s⁻¹). After adaptation period, the all plants were transferred to the field. The plants flowered within three months after transplantation. Phenotypic variations in the acclimatized plants were not observed. An average of 90% of the acclimatized plants survived after transferring into the field. All the in vitro propagated plants displayed normal development under the field conditions. Developed in vitro techniques could provide a promising alternative tool for large-scale propagation that increases the number of homologous plants for field cultivation. Acknowledgments: This study was conducted with financial support from National Science Fund at the Bulgarian Ministry of Education and Science, Project DN06/7 17.12.16.

Keywords: Hyssopus officinalis L., in vitro culture, micro propagation, acclimatization

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1345 Uncertainty Quantification of Crack Widths and Crack Spacing in Reinforced Concrete

Authors: Marcel Meinhardt, Manfred Keuser, Thomas Braml

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Cracking of reinforced concrete is a complex phenomenon induced by direct loads or restraints affecting reinforced concrete structures as soon as the tensile strength of the concrete is exceeded. Hence it is important to predict where cracks will be located and how they will propagate. The bond theory and the crack formulas in the actual design codes, for example, DIN EN 1992-1-1, are all based on the assumption that the reinforcement bars are embedded in homogeneous concrete without taking into account the influence of transverse reinforcement and the real stress situation. However, it can often be observed that real structures such as walls, slabs or beams show a crack spacing that is orientated to the transverse reinforcement bars or to the stirrups. In most Finite Element Analysis studies, the smeared crack approach is used for crack prediction. The disadvantage of this model is that the typical strain localization of a crack on element level can’t be seen. The crack propagation in concrete is a discontinuous process characterized by different factors such as the initial random distribution of defects or the scatter of material properties. Such behavior presupposes the elaboration of adequate models and methods of simulation because traditional mechanical approaches deal mainly with average material parameters. This paper concerned with the modelling of the initiation and the propagation of cracks in reinforced concrete structures considering the influence of transverse reinforcement and the real stress distribution in reinforced concrete (R/C) beams/plates in bending action. Therefore, a parameter study was carried out to investigate: (I) the influence of the transversal reinforcement to the stress distribution in concrete in bending mode and (II) the crack initiation in dependence of the diameter and distance of the transversal reinforcement to each other. The numerical investigations on the crack initiation and propagation were carried out with a 2D reinforced concrete structure subjected to quasi static loading and given boundary conditions. To model the uncertainty in the tensile strength of concrete in the Finite Element Analysis correlated normally and lognormally distributed random filed with different correlation lengths were generated. The paper also presents and discuss different methods to generate random fields, e.g. the Covariance Matrix Decomposition Method. For all computations, a plastic constitutive law with softening was used to model the crack initiation and the damage of the concrete in tension. It was found that the distributions of crack spacing and crack widths are highly dependent of the used random field. These distributions are validated to experimental studies on R/C panels which were carried out at the Laboratory for Structural Engineering at the University of the German Armed Forces in Munich. Also, a recommendation for parameters of the random field for realistic modelling the uncertainty of the tensile strength is given. The aim of this research was to show a method in which the localization of strains and cracks as well as the influence of transverse reinforcement on the crack initiation and propagation in Finite Element Analysis can be seen.

Keywords: crack initiation, crack modelling, crack propagation, cracks, numerical simulation, random fields, reinforced concrete, stochastic

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1344 Investigation of the Litho-Structure of Ilesa Using High Resolution Aeromagnetic Data

Authors: Oladejo Olagoke Peter, Adagunodo T. A., Ogunkoya C. O.

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The research investigated the arrangement of some geological features under Ilesa employing aeromagnetic data. The obtained data was subjected to various data filtering and processing techniques, which are Total Horizontal Derivative (THD), Depth Continuation and Analytical Signal Amplitude using Geosoft Oasis Montaj 6.4.2 software. The Reduced to the Equator –Total Magnetic Intensity (TRE-TMI) outcomes reveal significant magnetic anomalies, with high magnitude (55.1 to 155 nT) predominantly at the Northwest half of the area. Intermediate magnetic susceptibility, ranging between 6.0 to 55.1 nT, dominates the eastern part, separated by depressions and uplifts. The southern part of the area exhibits a magnetic field of low intensity, ranging from -76.6 to 6.0 nT. The lineaments exhibit varying lengths ranging from 2.5 and 16.0 km. Analyzing the Rose Diagram and the analytical signal amplitude indicates structural styles mainly of E-W and NE-SW orientations, particularly evident in the western, SW and NE regions with an amplitude of 0.0318nT/m. The identified faults in the area demonstrate orientations of NNW-SSE, NNE-SSW and WNW-ESE, situated at depths ranging from 500 to 750 m. Considering the divergence magnetic susceptibility, structural style or orientation of the lineaments, identified fault and their depth, these lithological features could serve as a valuable foundation for assessing ground motion, particularly in the presence of sufficient seismic energy.

Keywords: lineament, aeromagnetic, anomaly, fault, magnetic

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1343 Nanorods Based Dielectrophoresis for Protein Concentration and Immunoassay

Authors: Zhen Cao, Yu Zhu, Junxue Fu

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Immunoassay, i.e., antigen-antibody reaction, is crucial for disease diagnostics. To achieve the adequate signal of the antigen protein detection, a large amount of sample and long incubation time is needed. However, the amount of protein is usually small at the early stage, which makes it difficult to detect. Unlike cells and DNAs, no valid chemical method exists for protein amplification. Thus, an alternative way to improve the signal is through particle manipulation techniques to concentrate proteins, among which dielectrophoresis (DEP) is an effective one. DEP is a technique that concentrates particles to the designated region through a force created by the gradient in a non-uniform electric field. Since DEP force is proportional to the cube of particle size and square of electric field gradient, it is relatively easy to capture larger particles such as cells. For smaller ones like proteins, a super high gradient is then required. In this work, three-dimensional Ag/SiO2 nanorods arrays, fabricated by an easy physical vapor deposition technique called as oblique angle deposition, have been integrated with a DEP device and created the field gradient as high as of 2.6×10²⁴ V²/m³. The nanorods based DEP device is able to enrich bovine serum albumin (BSA) protein by 1800-fold and the rate has reached 180-fold/s when only applying 5 V electric potential. Based on the above nanorods integrated DEP platform, an immunoassay of mouse immunoglobulin G (IgG) proteins has been performed. Briefly, specific antibodies are immobilized onto nanorods, then IgG proteins are concentrated and captured, and finally, the signal from fluorescence-labelled antibodies are detected. The limit of detection (LoD) is measured as 275.3 fg/mL (~1.8 fM), which is a 20,000-fold enhancement compared with identical assays performed on blank glass plates. Further, prostate-specific antigen (PSA), which is a cancer biomarker for diagnosis of prostate cancer after radical prostatectomy, is also quantified with a LoD as low as 2.6 pg/mL. The time to signal saturation has been significantly reduced to one minute. In summary, together with an easy nanorod fabrication and integration method, this nanorods based DEP platform has demonstrated highly sensitive immunoassay performance and thus poses great potentials in applications for early point-of-care diagnostics.

Keywords: dielectrophoresis, immunoassay, oblique angle deposition, protein concentration

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1342 Application of Artificial Neural Network for Single Horizontal Bare Tube and Bare Tube Bundles (Staggered) of Large Particles: Heat Transfer Prediction

Authors: G. Ravindranath, S. Savitha

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This paper presents heat transfer analysis of single horizontal bare tube and heat transfer analysis of staggered arrangement of bare tube bundles bare tube bundles in gas-solid (air-solid) fluidized bed and predictions are done by using Artificial Neural Network (ANN) based on experimental data. Fluidized bed provide nearly isothermal environment with high heat transfer rate to submerged objects i.e. due to through mixing and large contact area between the gas and the particle, a fully fluidized bed has little temperature variation and gas leaves at a temperature which is close to that of the bed. Measurement of average heat transfer coefficient was made by local thermal simulation technique in a cold bubbling air-fluidized bed of size 0.305 m. x 0.305 m. Studies were conducted for single horizontal Bare Tube of length 305mm and 28.6mm outer diameter and for bare tube bundles of staggered arrangement using beds of large (average particle diameter greater than 1 mm) particle (raagi and mustard). Within the range of experimental conditions influence of bed particle diameter ( Dp), Fluidizing Velocity (U) were studied, which are significant parameters affecting heat transfer. Artificial Neural Networks (ANNs) have been receiving an increasing attention for simulating engineering systems due to some interesting characteristics such as learning capability, fault tolerance, and non-linearity. Here, feed-forward architecture and trained by back-propagation technique is adopted to predict heat transfer analysis found from experimental results. The ANN is designed to suit the present system which has 3 inputs and 2 out puts. The network predictions are found to be in very good agreement with the experimental observed values of bare heat transfer coefficient (hb) and nusselt number of bare tube (Nub).

Keywords: fluidized bed, large particles, particle diameter, ANN

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1341 Hg Anomalies and Soil Temperature Distribution to Delineate Upflow and Outflow Zone in Bittuang Geothermal Prospect Area, south Sulawesi, Indonesia

Authors: Adhitya Mangala, Yobel

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Bittuang geothermal prospect area located at Tana Toraja district, South Sulawesi. The geothermal system of the area related to Karua Volcano eruption product. This area has surface manifestation such as fumarole, hot springs, sinter silica and mineral alteration. Those prove that there are hydrothermal activities in the subsurface. However, the project and development of the area have not implemented yet. One of the important elements in geothermal exploration is to determine upflow and outflow zone. This information very useful to identify the target for geothermal wells and development which it is a risky task. The methods used in this research were Mercury (Hg) anomalies in soil, soil and manifestation temperature distribution and fault fracture density from 93 km² research area. Hg anomalies performed to determine the distribution of hydrothermal alteration. Soil and manifestation temperature distribution were conducted to estimate heat distribution. Fault fracture density (FFD) useful to determine fracture intensity and trend from surface observation. Those deliver Hg anomaly map, soil and manifestation temperature map that combined overlayed to fault fracture density map and geological map. Then, the conceptual model made from north – south, and east – west cross section to delineate upflow and outflow zone in this area. The result shows that upflow zone located in northern – northeastern of the research area with the increase of elevation and decrease of Hg anomalies and soil temperature. The outflow zone located in southern - southeastern of the research area which characterized by chloride, chloride - bicarbonate geothermal fluid type, higher soil temperature, and Hg anomalies. The range of soil temperature distribution from 16 – 19 °C in upflow and 19 – 26.5 °C in the outflow. The range of Hg from 0 – 200 ppb in upflow and 200 – 520 ppb in the outflow. Structural control of the area show northwest – southeast trend. The boundary between upflow and outflow zone in 1550 – 1650 m elevation. This research delivers the conceptual model with innovative methods that useful to identify a target for geothermal wells, project, and development in Bittuang geothermal prospect area.

Keywords: Bittuang geothermal prospect area, Hg anomalies, soil temperature, upflow and outflow zone

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1340 Shear Surface and Localized Waves in Functionally Graded Piezoactive Electro-Magneto-Elastic Media

Authors: Karen B. Ghazaryan

Abstract:

Recently, the propagation of coupled electromagnetic and elastic waves in magneto-electro-elastic (MEE) structures attracted much attention due to the wide range of application of these materials in smart structures. MEE materials are a class of new artificial composites that consist of simultaneous piezoelectric and piezomagnetic phases. Magneto-electro-elastic composites are built up by combining piezoelectric and piezomagnetic phases to obtain a smart composite that presents not only the electromechanical and magneto-mechanical coupling but also a strong magnetoelectric coupling, which makes such materials highly valuable in technological usage. In the framework of quasi-static approach shear surface and localized waves are considered in magneto-electro-elastic piezo-active structure consisting of functionally graded 6mm hexagonal symmetry group crystals. Assuming that in a functionally graded material the elastic and electromagnetic properties vary in the same proportion in direction perpendicular to the MEE polling direction, special classes of inhomogeneity functions were found, admitting exact solutions for coupled electromagnetic and elastic wave fields. Based on these exact solutions, defining the coupled shear wave field in magneto-electro-elastic composites several modal problems are considered: shear surface waves propagation along surface of a MEE half-space, interfacial wave propagation in a MEE oppositely polarized bi-layer, Love type waves in a functionally graded MEE layer overlying a homogeneous elastic half-space. For the problems under consideration corresponding dispersion equations are deduced analytically in an explicit form and for the BaTiO₃–CoFe₂O₄ crystal numerical results estimating effects of inhomogeneity and piezo effect are carried out.

Keywords: surface shear waves, magneto-electro-elastic composites, piezoactive crystals, functionally graded elastic materials

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1339 Introduction, Establishment, and Transformation: An Initial Exploration of the Cultural Shifts and Influence of Fa Yi Chong De, Yi-Kuan-Tao in Malaysian Chinese Community

Authors: Lim Pey Huan

Abstract:

Yi-Kuan-Tao has been developing in Malaysia for nearly 60 years. It was initially introduced from mainland China and later from Taiwan starting from the 1970s. Yi-Kuan-Tao was considered a 'new religion' for the local Chinese community in Malaysia in its early stages, as Chinese immigrants primarily practiced Taoism, Buddhism, Christianity, or Catholicism upon settling in the region. The overseas propagation and development of Yi-Kuan-Tao today primarily occur through Taiwanese temples, which began spreading abroad as early as 1949. Particularly since the 1970s, with the rapid economic growth of Taiwan, various branches of Taiwanese Yi-Kuan-Tao have gained economic strength to propagate abroad, further expanding the influence of Yi-Kuan-Tao overseas. Southeast Asia is the region out from Taiwan where the propagation and development of Yi-Kuan-Tao are fastest and most concentrated. With approximately over 6 million Chinese inhabitants, Malaysia's pursuit of traditional Chinese culture has led to a flourishing interest in Yi-Kuan-Tao, particularly its advocacy of the unity of Confucianism, Buddhism, and Taoism, with an emphasis on promoting Confucian thought. Moreover, Taiwan's rapid economic development since the 1970s has enabled Yi-Kuan-Tao to allocate significant human and financial resources for external propagation efforts. Additionally, Malaysia's government has adopted a relatively tolerant policy towards religion since that time, further fostering the flourishing development of Yi-Kuan-Tao in Malaysia. Furthermore, this thesis aims to strengthen the lineage and continuity of the Yi-Kuan-Tao tradition, particularly the branch of Fa Yi Chong De, through the perspective of Heavenly Mandate (天命). By examining the different origins and ethnic backgrounds, it investigates how the Malaysian Chinese community has experienced different changes through the cultural baptism of religion, thus delving into the religious influence of Yi-Kuan-Tao. Given that the Fa Yi Chong De Academy in Taiwan is currently in an active development and construction phase, academic works related to Yi-Kuan-Tao will lay a more solid academic foundation for the future establishment of the academy.

Keywords: initial exploration, cultural shifts, Yi-Kuan-Tao, Malaysian Chinese community

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1338 Temporary Ureteric Catheterization after Ureteropyeloscopy: Experience from Regional Australia

Authors: Jake Tempo, Jack Crozier, Huay Ann Chia, Philip Tan

Abstract:

Purpose: A prospective study was performed to determine whether temporary ureteric catheterization should be eliminated as a prophylactic method for preventing ureteric obstruction after uncomplicated ureteropyeloscopic lithotripsy. Material and Methods: From 2010 to 2014, 227 patients underwent uncomplicated ureteroscopic and/or pyeloscopic lithotripsy. Three patient-groups based on postoperative drainage method were analysed: temporary uretericcatheter (TUC), -ureteric JJ stent, and no-stent groups. Exclusion criteria included urosepsis, ureteric injury, and non-surgical complications delaying hospital-discharge. Outcome measures included parenteral analgesic requirements, prolonged hospitalization ≥2 days due to postoperative-pain, and readmissions rate. Results: Delayed discharge was reported in 14.5%(9 of 62) patients in the TUC group compared to 3.4%(4 of 119) in theureteric JJ stent group and 8.7%(4 of 46) in the no-drainage-group (p=0.02). Odds ratio for delayed-discharge between catheter- versus-ureteric JJ stent is 4.9 (95% CI = 1.6-15.0; p < 0.01). Parenteral analgesic requirements in the TUC group (12.9%) was also significantly higher than theureteric JJ stent group (1.7%; p=0.003). Readmissions were negligible between groups. Conclusions: Patients with ureteric catheters after uncomplicated ureteroscopy have a prolonged hospital stay with increased pain and parenteral analgesic requirements. There is a 7.6-fold increased requirement for parenteral analgesia and a 4.2-fold increased risk of delayed-discharge compared to a patient with a ureteric JJ stent.

Keywords: ureteric catheter, ureteric stent, ureteroscopy, pyeloscopy

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1337 Gene Expression Profiling of Iron-Related Genes of Pasteurella multocida Serotype A Strain PMTB2.1

Authors: Shagufta Jabeen, Faez Jesse Firdaus Abdullah, Zunita Zakaria, Nurulfiza Mat Isa, Yung Chie Tan, Wai Yan Yee, Abdul Rahman Omar

Abstract:

Pasteurella multocida is associated with acute, as well as, chronic infections in avian and bovine such as pasteurellosis and hemorrhagic septicemia (HS) in cattle and buffaloes. Iron is one of the most important nutrients for pathogenic bacteria including Pasteurella and acts as a cofactor or prosthetic group in several essential enzymes and is needed for amino acid, pyrimidine, and DNA biosynthesis. In our recent study, we showed that 2% of Pasteurella multocida serotype A strain PMTB2.1 encode for iron regulating genes (Accession number CP007205.1). Genome sequencing of other Pasteurella multocida serotypes namely PM70 and HB01 also indicated up to 2.5% of the respective genome encode for iron regulating genes, suggesting that Pasteurella multocida genome comprises of multiple systems for iron uptake. Since P. multocida PMTB2.1 has more than 40 CDs out of 2097 CDs (approximately 2%), encode for iron-regulated. The gene expression profiling of four iron-regulating genes namely fbpb, yfea, fece and fur were characterized under iron-restricted environment. The P. multocida strain PMTB2.1 was grown in broth with and without iron chelating agent and samples were collected at different time points. Relative mRNA expression profile of these genes was determined using Taqman probe based real-time PCR assay. The data analysis, normalization with two house-keeping genes and the quantification of fold changes were carried out using Bio-Rad CFX manager software version 3.1. Results of this study reflect that iron reduced environment has significant effect on expression profile of iron regulating genes (p < 0.05) when compared to control (normal broth) and all evaluated genes act differently with response to iron reduction in media. The highest relative fold change of fece gene was observed at early stage of treatment indicating that PMTB2.1 may utilize its periplasmic protein at early stage to acquire iron. Furthermore, down-regulation expression of fece with the elevated expression of other genes at later time points suggests that PMTB2.1 control their iron requirements in response to iron availability by down-regulating the expression of iron proteins. Moreover, significantly high relative fold change (p ≤ 0.05) of fbpb gene is probably associated with the ability of P. multocida to directly use host iron complex such as hem, hemoglobin. In addition, the significant increase (p ≤ 0.05) in fbpb and yfea expressions also reflects the utilization of multiple iron systems in P. multocida strain PMTB2.1. The findings of this study are very much important as relative scarcity of free iron within hosts creates a major barrier to microbial growth inside host and utilization of outer-membrane proteins system in iron acquisition probably occurred at early stage of infection with P. multocida. In conclusion, the presence and utilization of multiple iron system in P. multocida strain PMTB2.1 revealed the importance of iron in the survival of P. multocida.

Keywords: iron-related genes, real-time PCR, gene expression profiling, fold changes

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1336 CFD Modeling of Mixing Enhancement in a Pitted Micromixer by High Frequency Ultrasound Waves

Authors: Faezeh Mohammadi, Ebrahim Ebrahimi, Neda Azimi

Abstract:

Use of ultrasound waves is one of the techniques for increasing the mixing and mass transfer in the microdevices. Ultrasound propagation into liquid medium leads to stimulation of the fluid, creates turbulence and so increases the mixing performance. In this study, CFD modeling of two-phase flow in a pitted micromixer equipped with a piezoelectric with frequency of 1.7 MHz has been studied. CFD modeling of micromixer at different velocity of fluid flow in the absence of ultrasound waves and with ultrasound application has been performed. The hydrodynamic of fluid flow and mixing efficiency for using ultrasound has been compared with the layout of no ultrasound application. The result of CFD modeling shows well agreements with the experimental results. The results showed that the flow pattern inside the micromixer in the absence of ultrasound waves is parallel, while when ultrasound has been applied, it is not parallel. In fact, propagation of ultrasound energy into the fluid flow in the studied micromixer changed the hydrodynamic and the forms of the flow pattern and caused to mixing enhancement. In general, from the CFD modeling results, it can be concluded that the applying ultrasound energy into the liquid medium causes an increase in the turbulences and mixing and consequently, improves the mass transfer rate within the micromixer.

Keywords: CFD modeling, ultrasound, mixing, mass transfer

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1335 Hyaluronic Acid as Potential Excipient for Buccal Delivery

Authors: Flavia Laffleur

Abstract:

Summary: Biomaterials have gained immense interest in the pharmaceutical research in the last decades. Hyaluronic acid a carbohydrate and mucopolysaccharide was chemically modified in order to achieve and establish a promising platform for buccal drug delivery. Aim: Novel biomaterial was tested for its potential for buccal drug delivery. Background: Polysaccharide hyaluronic acid (HA) was chemically modified with cysteine ethyl ether (CYS). By immobilization of the thiol-bearing ligand on the polymeric backbone the thiolated bioconjugate HA-CYS was obtained. Methodology: Mucoadhesive, permeation enhancing and stability potential as well as mechanical, physicochemical properties further mucoadhesive strength, swelling index and residence time were investigated. The developed thiolated bioconjugate displayed enhanced mucoadhesiveness on buccal mucosa as well as permeation behavior and polymer stability. The near neutral pH and negative cytotoxicity studies indicated their non-irritability and biocompatible nature with biological tissues. Further, the model drug sulforhodamine 101 was incorporated to determine its drug release profiles. Results: The synthesized thiomer showed no toxicity. The mucoadhesion of thiolated hyaluronic acid on buccal mucosa was significantly improved in comparison to unmodified one. The biomaterial showed 2.5-fold higher stability in polymer structure. The release of sulforhodamine in the presence of thiolated hyaluronic acid was 2.3-fold increased compared to hyaluronic acid. Conclusion: Thus, the promising results encourage further investigations and exploitation of this versatile polysaccharide. So far, hyaluronic acid was not evaluated for buccal drug delivery.

Keywords: buccal delivery, hyaluronic acid, mucoadhesion, thiomers

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1334 Is Brain Death Reversal Possible in Near Future: Intrathecal Sodium Nitroprusside (SNP) Superfusion in Brain Death Patients=The 10,000 Fold Effect

Authors: Vinod Kumar Tewari, Mazhar Husain, Hari Kishan Das Gupta

Abstract:

Background: Primary or secondary brain death is also accompanied with vasospasm of the perforators other than tissue disruption & further exaggerates the anoxic damage, in the form of neuropraxia. In normal conditions the excitatory impulse propagates as anterograde neurotransmission (ANT) and at the level of synapse, glutamate activates NMDA receptors on postsynaptic membrane. Nitric oxide (NO) is produced by Nitric oxide Synthetase (NOS) in postsynaptic dendride or cell body and travels backwards across a chemical synapse to bind to the axon terminal of a presynaptic neuron for regulation of ANT this process is called as the retrograde neurotransmission (RNT). Thus the primary function of NO is RNT and the purpose of RNT is regulation of chemical neurotransmission at synapse. For this reason, RNT allows neural circuits to create feedback loops. The haem is the ligand binding site of NO receptor (sGC) at presynaptic membrane. The affinity of haem exhibits > 10,000-fold excess for NO than Oxygen (THE 10,000 FOLD EFFECT). In pathological conditions ANT, normal synaptic activity including RNT is absent. NO donors like sodium nitroprusside (SNP) releases NO by activating NOS at the level of postsynaptic area. NO now travels backwards across a chemical synapse to bind to the haem of NO receptor at axon terminal of a presynaptic neuron as in normal condition. NO now acts as impulse generator (at presynaptic membrane) thus bypasses the normal ANT. Also the arteriolar perforators are having Nitric Oxide Synthetase (NOS) at the adventitial side (outer border) on which sodium nitroprusside (SNP) acts; causing release of Nitric Oxide (NO) which vasodilates the perforators causing gush of blood in brain’s tissue and reversal of brain death. Objective: In brain death cases we only think for various transplantations but this study being a pilot study reverses some criteria of brain death by vasodilating the arteriolar perforators. To study the effect of intrathecal sodium nitroprusside (IT SNP) in cases of brain death in which: 1. Retrograde transmission = assessed by the hyperacute timings of reversal 2. The arteriolar perforator vasodilatation caused by NO and the maintenance of reversal of brain death reversal. Methods: 35 year old male, who became brain death after head injury and has not shown any signs of improvement after every maneuver for 6 hours, a single superfusion done by SNP via transoptic canal route for quadrigeminal cistern and cisternal puncture for IV ventricular with SNP done. Results: He showed spontaneous respiration (7 bouts) with TCD studies showing start of pulsations of various branches of common carotid arteries. Conclusions: In future we can give this SNP via transoptic canal route and in IV ventricle before declaring the body to be utilized for transplantations or dead or in broader way we can say that in near future it is possible to revert back from brain death or we have to modify our criterion.

Keywords: brain death, intrathecal sodium nitroprusside, TCD studies, perforators, vasodilatations, retrograde transmission, 10, 000 fold effect

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1333 The Impact of Distributed Epistemologies on Software Engineering

Authors: Thomas Smith

Abstract:

Many hackers worldwide would agree that, had it not been for linear-time theory, the refinement of Byzantine fault tolerance might never have occurred. After years of significant research into extreme programming, we validate the refinement of simulated annealing. Maw, our new framework for unstable theory, is the solution to all of these issues.

Keywords: distributed, software engineering, DNS, DHCP

Procedia PDF Downloads 354
1332 Two Fold Dimensional Analysis of Post-Employment Dissonance in Employer Branding Framework of it SMES

Authors: J. Janani, S. Gomathi

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Despite the new economy is embodied with the ample size of talent pool, the corporate world is facing the hardship in the mismatch of talent demand supply. Therefore to combat with this fallout crisis, here depicts the relevance of Employer Branding. Employer branding is gaining its popularity in Large sized companies especially IT companies but less employer branding awareness among IT SMEs (Small and Medium size Enterprises). There are N range of analysis has been dole out on employer branding from different perspectives and in different industries. The hidden factor behind the employer branding namely the post employment dissonance was not given a lot of importance into the research picture. The present study examines the employer branding as the employer image and the organizational identity. It focuses on the two fold dimensional branding initiatives namely job offer attributes and organizational attractiveness. The study will depict the dissonance level and their variations among the foresaid initiatives from the former employees and the post-employment dissonance from the present employees in IT SMEs and it will also examine the employer perception from the prospective employees towards the stated branding initiatives. The demographic factors such as generational factors (gen X and gen Y) and the career stages are majorly focused in the study. The study will promote the IT SMEs to strengthen their employer branding effectively and efficiently through implementing varied strategies and this will help them to enhance the talent pool at their best. This will eventually result in talent attraction and talent retention.

Keywords: employer image, organizational identity, post-employment dissonance, job offer attributes, organizational attractiveness, talent pool, career stages, generational factors, information technology, SMEs

Procedia PDF Downloads 496
1331 Improvement of Model for SIMMER Code for SFR Corium Relocation Studies

Authors: A. Bachrata, N. Marie, F. Bertrand, J. B. Droin

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The in-depth understanding of severe accident propagation in Generation IV of nuclear reactors is important so that appropriate risk management can be undertaken early in their design process. This paper is focused on model improvements in the SIMMER code in order to perform studies of severe accident mitigation of Sodium Fast Reactor. During the design process of the mitigation devices dedicated to extraction of molten fuel from the core region, the molten fuel propagation from the core up to the core catcher has to be studied. In this aim, analytical as well as the complex thermo-hydraulic simulations with SIMMER-III code are performed. The studies presented in this paper focus on physical phenomena and associated physical models that influence the corium relocation. Firstly, the molten pool heat exchange with surrounding structures is analysed since it influences directly the instant of rupture of the dedicated tubes favouring the corium relocation for mitigation purpose. After the corium penetration into mitigation tubes, the fuel-coolant interactions result in formation of debris bed. Analyses of debris bed fluidization as well as sinking into a fluid are presented in this paper.

Keywords: corium, mitigation tubes, SIMMER-III, sodium fast reactor

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1330 Fault Detection and Diagnosis of Broken Bar Problem in Induction Motors Base Wavelet Analysis and EMD Method: Case Study of Mobarakeh Steel Company in Iran

Authors: M. Ahmadi, M. Kafil, H. Ebrahimi

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Nowadays, induction motors have a significant role in industries. Condition monitoring (CM) of this equipment has gained a remarkable importance during recent years due to huge production losses, substantial imposed costs and increases in vulnerability, risk, and uncertainty levels. Motor current signature analysis (MCSA) is one of the most important techniques in CM. This method can be used for rotor broken bars detection. Signal processing methods such as Fast Fourier transformation (FFT), Wavelet transformation and Empirical Mode Decomposition (EMD) are used for analyzing MCSA output data. In this study, these signal processing methods are used for broken bar problem detection of Mobarakeh steel company induction motors. Based on wavelet transformation method, an index for fault detection, CF, is introduced which is the variation of maximum to the mean of wavelet transformation coefficients. We find that, in the broken bar condition, the amount of CF factor is greater than the healthy condition. Based on EMD method, the energy of intrinsic mode functions (IMF) is calculated and finds that when motor bars become broken the energy of IMFs increases.

Keywords: broken bar, condition monitoring, diagnostics, empirical mode decomposition, fourier transform, wavelet transform

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1329 MicroRNA-1246 Expression Associated with Resistance to Oncogenic BRAF Inhibitors in Mutant BRAF Melanoma Cells

Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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