Search results for: target receptor

Authors: Mohamed Noureldin, Jinkoo Kim

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In this study, a genetic algorithm was used to find out the optimum locations of the slit dampers satisfying a target displacement. A seismic retrofit scheme for a building structure was presented using steel plate slit dampers. A cyclic loading test was used to verify the energy dissipation capacity of the slit damper. The seismic retrofit of the model structure using the slit dampers was compared with the retrofit with enlarging shear walls. The capacity spectrum method was used to propose a simple damper distribution scheme proportional to the inter-story drifts. The validity of the simple story-wise damper distribution procedure was verified by comparing the results of the genetic algorithm. It was observed that the proposed simple damper distribution pattern was in a good agreement with the optimum distribution obtained from the genetic algorithm. Acknowledgment: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03032809).

Keywords: slit dampers, seismic retrofit, genetic algorithm, optimum design

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Authors: Eli Avraham

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The Arab Spring was widely covered in the global media and the number of Western tourists traveling to the area began to fall. The goal of this study was to analyze which media strategies marketers in Middle Eastern countries chose to employ in their attempts to repair the negative image of the area in the wake of the Arab Spring. Several studies were published concerning image-restoration strategies of destinations during crises around the globe; however, these strategies were not part of an overarching theory, conceptual framework or model from the fields of crisis communication and image repair. The conceptual framework used in the current study was the ‘multi-step model for altering place image’, which offers three types of strategies: source, message and audience. Three research questions were used: 1.What public relations crisis techniques and advertising campaign components were used? 2. What media policies and relationships with the international media were adopted by Arab officials? 3. Which marketing initiatives (such as cultural and sports events) were promoted? This study is based on qualitative content analysis of four types of data: 1) advertising components (slogans, visuals and text); (2) press interviews with Middle Eastern officials and marketers; (3) official media policy adopted by government decision-maker (e.g. boycotting or arresting newspeople); and (4) marketing initiatives (e.g. organizing heritage festivals and cultural events). The data was located in three channels from December 2010, when the events started, to September 31, 2013: (1) Internet and video-sharing websites: YouTube and Middle Eastern countries' national tourism board websites; (2) News reports from two international media outlets, The New York Times and Ha’aretz; these are considered quality newspapers that focus on foreign news and tend to criticize institutions; (3) Global tourism news websites: eTurbo news and ‘Cities and countries branding’. Using the ‘multi-step model for altering place image,’ the analysis reveals that Middle Eastern marketers and officials used three kinds of strategies to repair their countries' negative image: 1. Source (cooperation and media relations; complying, threatening and blocking the media; and finding alternatives to the traditional media) 2. Message (ignoring, limiting, narrowing or reducing the scale of the crisis; acknowledging the negative effect of an event’s coverage and assuring a better future; promotion of multiple facets, exhibitions and softening the ‘hard’ image; hosting spotlight sporting and cultural events; spinning liabilities into assets; geographic dissociation from the Middle East region; ridicule the existing stereotype) and 3. Audience (changing the target audience by addressing others; emphasizing similarities and relevance to specific target audience). It appears that dealing with their image problems will continue to be a challenge for officials and marketers of Middle Eastern countries until the region stabilizes and its regional conflicts are resolved.

Keywords: Arab spring, cultural events, image repair, Middle East, tourism marketing

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Authors: Ting Hsiang Chang, Cheng Zuo Tsai

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In recent years, sports culture dominated in Taiwan, which spurred the rapid development of the sports industry. More innovative and high-tech sporting goods were developed to provide choices for consumers. Nowadays, Taiwan has gradually entered the aging society where people pay more attention to health promotion, delay of aging and other related issues among senior. However, it is an undeniable fact that moderate exercise is a great help to delay aging. Therefore, how senior select the appropriate sporting goods, including sports shoes, sportswear, sports equipment, and even the sports brands when engaged in various kinds of sports, are explored in this research. Therefore, this study sets the reference indicators by exploring the brands of sporting goods, that senior aged 50-70 choose in a fog peak district, the Taichung City, as the subjects of study by answering a questionnaire. Also, this study offers recommendations in terms of the design, marketing or selling of sporting goods for the senior, and how owners of sports brands or related sports industries should target them.

Keywords: senior, aging, sporting goods, sports brand

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Authors: Nikhil Verma, Akshay Kant Mishra, Rishabh Rastogi, Bikarama Prasad Yadav

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Emerging fire incidents are the protuberant contributor out turning into life loss, property damage and importantly firefighters. It insinuates that a firefighting and rescue operation of the existing equipment or apparatus and their proficiency is limited, particularly in annihilating firefighting environments. The proposed methodology will help in developing a technology which can be useful in minimizing the risks and losses due to fire. In this paper, design and development of combat mini vehicle comprising of multi-purpose nozzle system is proposed which can target diverse fires simultaneously at distinct time and location. Basically, the system is semi-automated type protection system which can be manoeuvred by controller. Designing of robust vehicle based on semi-automated protection type system is consummated using SolidWorks platform. Concept of developing a robust vehicle will help to fight fires in multiple directions reducing the time required to douse multiple fires.

Keywords: fire douse vehicle, multiple fires, multi-purpose nozzle, semi-automated system

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Authors: Yuanhao Gao, Ping Lin, Kees Weijer

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An optimal control system model is proposed for the cell flow in the process of chick embryo gastrulation in this paper. The target is to determine the cellular interaction forces which are hard to measure. This paper will take an approach to investigate the forces with the idea of the inverse problem. By choosing the forces as the control variable and regarding the cell flow as Stokes fluid, an objective functional will be established to match the numerical result of cell velocity with the experimental data. So that the forces could be determined by minimizing the objective functional. The Lagrange multiplier method is utilized to derive the state and adjoint equations consisting the optimal control system, which specifies the first-order necessary conditions. Finite element method is used to discretize and approximate equations. A conjugate gradient algorithm is given for solving the minimum solution of the system and determine the forces.

Keywords: optimal control model, Stokes equation, conjugate gradient method, finite element method, chick embryo gastrulation

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Authors: Maki Mizogami, Hironori Tsuchiya, Yoshiroh Hayabuchi, Kenji Shigemi

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Since drugs exhibit significant structure-dependent differences in activity and toxicity, their differentiation based on the mechanism of action should have implications for comparative drug efficacy and safety. We aimed to differentiate drug stereoisomers by their stereostructure-selective membrane interactions underlying pharmacological and toxicological effects. Biomimetic lipid bilayer membranes were prepared with phospholipids and sterols (either cholesterol or epicholesterol) to mimic the lipid compositions of neuronal and cardiomyocyte membranes and to provide these membranes with the chirality. The membrane preparations were treated with different classes of stereoisomers at clinically- and pharmacologically-relevant concentrations (25-200 μM), followed by measuring fluorescence polarization to determine the membrane interactivity of drugs to change the physicochemical property of membranes. All the tested drugs acted on lipid bilayers to increase or decrease the membrane fluidity. Drug stereoisomers could not be differentiated when interacting with the membranes consisting of phospholipids alone. However, they stereostructure-selectively interacted with neuro-mimetic and cardio-mimetic membranes containing 40 mol% cholesterol ((3β)-cholest-5-en-3-ol) to show the relative potencies being local anesthetic R(+)-bupivacaine > rac-bupivacaine > S(‒)-bupivacaine, α2-adrenergic agonistic D-medetomidine > rac-medetomidine > L-medetomidine, β-adrenergic antagonistic R(+)-propranolol > rac-propranolol > S(–)-propranolol, NMDA receptor antagonistic S(+)-ketamine > rac-ketamine, analgesic monoterpenoid (+)-menthol > (‒)-menthol, non-steroidal anti-inflammatory S(+)-ibuprofen > rac-ibuprofen > R(‒)-ibuprofen, and bioactive flavonoid (+)-epicatechin > (‒)-epicatechin. All of the order of membrane interactivity were correlated to those of beneficial and adverse effects of the tested stereoisomers. In contrast, the membranes prepared with epicholesterol ((3α)-chotest-5-en-3-ol), an epimeric form of cholesterol, reversed the rank order of membrane interactivity to be S(‒)-enantiomeric > racemic > R(+)-enantiomeric bupivacaine, L-enantiomeric > racemic > D-enantiomeric medetomidine, S(–)-enantiomeric > racemic > R(+)-enantiomeric propranolol, racemic > S(+)-enantiomeric ketamine, (‒)-enantiomeric > (+)-enantiomeric menthol, R(‒)-enantiomeric > racemic > S(+)-enantiomeric ibuprofen, and (‒)-enantiomeric > (+)-enantiomeric epicatechin. The opposite configuration allows drug molecules to interact with chiral sterol membranes enantiomer-selectively. From the comparative results, it is speculated that a 3β-hydroxyl group in cholesterol is responsible for the enantioselective interactions of drugs. In conclusion, the differentiation of drug stereoisomers by their stereostructure-selective membrane interactions would be useful for designing and predicting drugs with higher activity and/or lower toxicity.

Keywords: chiral membrane, differentiation, drug stereoisomer, enantioselective membrane interaction

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: S. Holly, R. Schnitzer, P. Haslberger, D. Zügner

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The development of new filler consumables necessitates a high effort regarding samples and experiments to achieve the required mechanical properties and chemistry. In the scope of the development of a metal-cored wire with the target tensile strength of 1150 MPa and acceptable impact toughness, thermodynamic and kinetic calculations via MatCalc were used to reduce the experimental work and the resources required. Micro alloying elements were used to reach the high strength as an alternative approach compared to the conventional solid solution hardening. In order to understand the influence of different micro alloying elements in more detail, the influence of different elements on the precipitation behavior in the weld metal was evaluated. Investigations of the microstructure were made via atom probe and EBSD to understand the effect of micro alloying elements. The calculated results are in accordance with the results obtained by experiments and can be explained by the microstructural investigations. On the example of aluminium, the approach is exemplified and clarifies the efficient way of development.

Keywords: alloy development, high strength steel, MatCalc, metal-cored wire

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Authors: Ana B. Vivas, Antonia Ypsilanti, Aristea I. Ladas, Angeles F. Estevez

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Mild Cognitive Impairment (MCI) is considered an intermediate stage between normal and pathological aging, as a substantial percentage of people diagnosed with MCI converts later to dementia of the Alzheimer’s type. Memory is of the first cognitive processes to deteriorate in this condition. In the present study we employed the differential outcomes procedure (DOP) to improve visuospatial memory in a group of participants with MCI. The DOP requires the structure of a conditional discriminative learning task in which a correct choice response to a specific stimulus-stimulus association is reinforced with a particular reinforcer or outcome. A group of 10 participants with MCI, and a matched control group had to learn and keep in working memory four target locations out of eight possible locations where a shape could be presented. Results showed that participants with MCI had a statistically significant better terminal accuracy when a unique outcome was paired with a location (76% accuracy) as compared to a non differential outcome condition (64%). This finding suggests that the DOP is useful in improving working memory in MCI patients, which may delay their conversion to dementia.

Keywords: mild cognitive impairment, working memory, differential outcomes, cognitive process

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Authors: Anita Kéri

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Higher education marketing has been a widely researched field in recent years. Due to the increasing competition among higher education institutions worldwide, it has become crucial to target foreign students with effective marketing tools. Online marketing tools became central to attracting, retaining, and satisfying the needs of foreign students. Therefore, the aim of the current study is to reveal how the online marketing tools of a Hungarian university are perceived visually by its first-year foreign students, with special emphasis on the university webpage content. Eye-camera tracking and retrospective think-aloud interviews were used to measure visual perceptions. Results show that freshmen students remember those online marketing content more that has familiar content on them. Pictures of real-life students and their experiences attract students’ attention more, and they also remember information on these webpage elements more, compared to designs with stock photos. This research is novel in the sense that it uses eye-camera tracking in the field of higher education marketing, thereby providing insight into the perception of online higher education marketing for foreign students.

Keywords: higher education, marketing, eye-camera, visual perceptions

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Authors: Tannaz Alizadeh Ashrafi

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Seasonal variability in biological and ecological factors together with relevant socio-economic determinants affect the choice of fishing gear, frequency of its usage and decision about gear conversion under multi-species situation. In order to deal with the complex dynamics of fisheries, fishers, constantly, have to make decisions about how long to fish, when to go fishing, what species to target, and which gear to deploy. In this regard, the purpose of this study is to examine the dynamics of gear/ species combination in Norwegian fishery. A comprehensive vessel-level set of data for the main economically important species including: cod, haddock, saithe, shrimp and mixed catch have been obtained from the Norwegian Directorate of Fisheries covering the daily data in 2010. The present study further analyzes the level of flexibility and rationality of the fishers operating in the trawl fishery. The results show the disproportion between intention of the trawl fishers to maximize profitability of each fishing trip and their harvesting behavior in reality. Discussion is based on so-called maximizing behavior.

Keywords: trawl fishery, gear substitution, rationality, profit maximizing behavior

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Authors: Ahmed Elkholy

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Most power transmission cases use gearing in general, and worm gearing, in particular for energy utilization. Therefore, designing gears for minimum weight and maximum power transmission is the main target of this study. In this regard, a new approach has been developed to estimate the load share and stress distribution of worm gear sets. The approach is based upon considering the instantaneous tooth meshing stiffness where the worm gear drive was modelled as a series of spur gear slices, and each slice was analyzed separately using a well-established criteria. By combining the results obtained for all slices, the entire worm gear set loading and stressing was determined. The geometric modelling method presented, allows tooth elastic deformation and tooth root stresses of worm gear drives under different load conditions to be investigated. On the basis of the method introduced in this study, the instantaneous meshing stiffness and load share were obtained. In comparison with existing methods, this approach has both good analytical accuracy and less computing time.

Keywords: gear, load/stress distribution, worm, wheel, tooth stiffness, contact line

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Authors: Asha Dukkipati

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Cognitive neuroscience explores neural functioning and aberrant brain activity during cognitive and perceptual tasks. Neurocinematics is a subfield of cognitive neuroscience that observes neural responses of individuals watching a film to see similarities and differences between individuals. This method is typically used for commercial use, allowing directors and filmmakers to produce better visuals and increasing their results in the box office. However, neurocinematics is increasingly becoming a common tool for neuroscientists interested in studying similar patterns of brain activity across viewers outside of the film industry. In this review, it argue that neurocinematics provides an easy, naturalistic approach for studying and diagnosing learning disorders. While the neural underpinnings of developmental learning disorders are traditionally assessed with well-established methods like EEG and fMRI that target particular cognitive domains, such as simple visual and attention tasks, there is initial evidence and theoretical background in support of neurocinematics as a biomarker for learning differences. By using ADHD, dyslexia, and autism as case studies, this literature review discusses the potential advantages of neurocinematics as a new tool for learning disorders research.

Keywords: behavioral and social sciences, neuroscience, neurocinematics, biomarkers, neurobehavioral disorders

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Authors: Z. Sakka, I. Assakkaf, T. Al-Yaqoub, J. Parol

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A reliability-based methodology for the analysis assessment and evaluation of reinforced concrete structural elements of concrete structures is presented herein. The results of the reliability analysis and assessment for structural elements are verified by the results obtained from the deterministic methods. The analysis outcomes of reliability-based analysis are compared against the safety limits of the required reliability index β according to international standards and codes. The methodology is based on probabilistic analysis using reliability concepts and statistics of the main random variables that are relevant to the subject matter, and for which they are to be used in the performance-function equation(s) related to the structural elements under study. These methodology techniques can result in reliability index β, which is commonly known as the reliability index or reliability measure value that can be utilized to assess and evaluate the safety, human risk, and functionality of the structural component. Also, these methods can result in revised partial safety factor values for certain target reliability indices that can be used for the purpose of redesigning the reinforced concrete elements of the building and in which they could assist in considering some other remedial actions to improve the safety and functionality of the member.

Keywords: structural reliability, concrete structures, FORM, Monte Carlo simulation

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Authors: Virendra Nath, Vipin Kumar

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Background: TypeII Diabetes mellitus is a foremost health problem worldwide, predisposing to increased mortality and morbidity. Undesirable effects of the current medications have prompted the researcher to develop more potential drug(s) against the disease. The peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors family and take part in a vital role in the regulation of metabolic equilibrium. They can induce or repress genes associated with adipogenesis, lipid, and glucose metabolism. Aims: Investigation of PPARα/γ agonistic hits were screened by hierarchical virtual screening followed by molecular dynamics simulation and knowledge-based structure-activity relation (SAR) analysis using approved PPAR α/γ dual agonist. Methods: The PPARα/γ agonistic activity of compounds was searched by using Maestro through structure-based virtual screening and molecular dynamics (MD) simulation application. Virtual screening of nuclear-receptor ligands was done, and the binding modes with protein-ligand interactions of newer entity(s) were investigated. Further, binding energy prediction, Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit along with the structural comparative analysis of approved PPARα/γ agonists with screened hit was done for knowledge-based SAR. Results and Discussion: The silicone chip-based approach recognized the most capable nine hits and had better predictive binding energy as compared to the reference drug compound (Tesaglitazar). In this study, the key amino acid residues of binding pockets of both targets PPARα/γ were acknowledged as essential and were found to be associated in the key interactions with the most potential dual hit (ChemDiv-3269-0443). Stability studies using molecular dynamics (MD) simulation of PPARα and γ complex was performed with the most promising hit and found root mean square deviation (RMSD) stabile around 2Å and 2.1Å, respectively. Frequency distribution data also revealed that the key residues of both proteins showed maximum contacts with a potent hit during the MD simulation of 20 nanoseconds (ns). The knowledge-based SAR studies of PPARα/γ agonists were studied using 2D structures of approved drugs like aleglitazar, tesaglitazar, etc. for successful designing and synthesis of compounds PPARγ agonistic candidates with anti-hyperlipidimic potential.

Keywords: computational, diabetes, PPAR, simulation

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Authors: Shelly Sharma, Pooja Chadha

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Humans are exposed to pesticides and insecticides either directly or indirectly. Exposure to these pesticides may lead to acute toxicity to mammals and non-target organisms. Chlorpyrifos (CPF) is a broad spectrum organophosphate pesticide widely used in various countries of the world. The aim of the present study was to assess the toxicity associated with chlorpyrifos exposure and possible mitigating effect of cow urine against genotoxic and toxic effects in rat brain induced by chlorpyrifos. For this purpose LD50 was determined and rats were orally administered with 1/8th of LD50 (19mg/kg b.wt). Brain samples were taken after 24hrs, 48hrs and 72hrs of treatment. A significant increase in the % tail DNA was observed along with the increase in MDA levels of brain tissues in chlorpyrifos treated groups as compared to control. Cow urine treated groups show decrease in DNA damage and MDA levels as compared to CPF treated group. The study indicates that cow urine has ameliorative potential against neurotoxicity and genotoxicity induced by CPF. Cow urine is considered rich in vitamin A, E and volatile fatty acids which provide antioxidant potential to it. Thus, it can be used as a genoprotective agent.

Keywords: comet assay, brain, cow urine, genotoxicity, toxicity

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: A. Bhatt, C. Bassi, H. Farragher, J. Musk

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Background: All medicines placed on the EU market are legally required to be accompanied by labeling and package leaflet, which provide comprehensive information, enabling its safe and appropriate use. Mock-ups with results of assessments using a target patient group must be submitted for a marketing authorisation application. Consumers need confidence in non-prescription, OTC medicines in order to manage their minor ailments and umbrella brands assist purchasing decisions by assisting easy identification within a particular therapeutic area. A number of regulatory agencies have risk management tools and guidelines to assist in developing umbrella brands for OTC medicines, however assessment and decision making is subjective and inconsistent. This study presents an evaluation in the UK following the US FDA warning concerning methaemoglobinaemia following 21 reported cases (11 children under 2 years) caused by OTC oral analgesics containing benzocaine. METHODS: A standard face to face, 25 structured task based user interview testing methodology using a standard questionnaire and rating scale in consumers aged 15-91 years, was conducted independently between June and October 2015 in their homes. Whether individuals could discriminate between the labelling, safety information and warnings on cartons and PILs between 3 different OTC medicines packs with the same umbrella name was evaluated. Each pack was presented with differing information hierarchy using, different coloured cartons, containing the 3 different active ingredients, benzocaine (oromucosal spray) and two lozenges containing 2, 4, dichlorobenzyl alcohol, amylmetacresol and hexylresorcinol respectively (for the symptomatic relief of sore throat pain). The test was designed to determine whether warnings on the carton and leaflet were prominent, accessible to alert users that one product contained benzocaine, risk of methaemoglobinaemia, and refer to the leaflet for the signs of the condition and what to do should this occur. Results: Two consumers did not locate the warnings on the side of the pack, eventually found them on the back and two suggestions to further improve accessibility of the methaemoglobinaemia warning. Using a gold pack design for the oromucosal spray, all consumers could differentiate between the 3 drugs, minimum age particulars, pharmaceutical form and the risk factor methaemoglobinaemia. The warnings for benzocaine were deemed to be clear or very clear; appearance of the 3 packs were either very well differentiated or quite well differentiated. The PIL test passed on all criteria. All consumers could use the product correctly, identify risk factors ensuring the critical information necessary for the safe use was legible and easily accessible so that confusion and errors were minimised. Conclusion: Patients with known methaemoglobinaemia are likely to be vigilant in checking for benzocaine containing products, despite similar umbrella brand names across a range of active ingredients. Despite these findings, the package design and spray format were not deemed to be sufficient to mitigate potential safety risks associated with differences in target populations and contraindications when submitted to the Regulatory Agency. Although risk management tools are increasingly being used by agencies to assist in providing objective assurance of package safety, further transparency, reduction in subjectivity and proportionate risk should be demonstrated.

Keywords: labelling, OTC, risk, user testing

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Authors: Alex J. Summers, Jasmine P. Devadhasan, Douglas Montgomery, Brittany Fischer, Jian Gu, Frederic Zenhausern

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Immunoassays have been utilized for several applications, including the detection of pathogens. Our laboratory is in the development of a tier 1 biothreat panel utilizing Vertical Flow Assay (VFA) technology for simultaneous detection of pathogens and toxins. One method of manufacturing VFA membranes is with non-contact piezoelectric dispensing, which provides advantages, such as low-volume and rapid dispensing without compromising the structural integrity of antibody or substrate. Challenges of this processinclude premature discontinuation of dispensing and misaligned spotting. Preliminary data revealed the Yp 11C7 mAb (11C7)reagent to exhibit a large angle of failure during printing which may have contributed to variable printing outputs. A Design of Experiment (DOE) was executed using this reagent to investigate the effects of hydrostatic pressure and reagent concentration on microarray printing outputs. A Nano-plotter 2.1 (GeSIM, Germany) was used for printing antibody reagents ontonitrocellulose membrane sheets in a clean room environment. A spotting plan was executed using Spot-Front-End software to dispense volumes of 11C7 reagent (20-50 droplets; 1.5-5 mg/mL) in a 6-test spot array at 50 target membrane locations. Hydrostatic pressure was controlled by raising the Pressure Compensation Vessel (PCV) above or lowering it below our current working level. It was hypothesized that raising or lowering the PCV 6 inches would be sufficient to cause either liquid accumulation at the tip or discontinue droplet formation. After aspirating 11C7 reagent, we tested this hypothesis under stroboscope.75% of the effective raised PCV height and of our hypothesized lowered PCV height were used. Humidity (55%) was maintained using an Airwin BO-CT1 humidifier. The number and quality of membranes was assessed after staining printed membranes with dye. The droplet angle of failure was recorded before and after printing to determine a “stroboscope score” for each run. The DOE set was analyzed using JMP software. Hydrostatic pressure and reagent concentration had a significant effect on the number of membranes output. As hydrostatic pressure was increased by raising the PCV 3.75 inches or decreased by lowering the PCV -4.5 inches, membrane output decreased. However, with the hydrostatic pressure closest to equilibrium, our current working level, membrane output, reached the 50-membrane target. As the reagent concentration increased from 1.5 to 5 mg/mL, the membrane output also increased. Reagent concentration likely effected the number of membrane output due to the associated dispensing volume needed to saturate the membranes. However, only hydrostatic pressure had a significant effect on stroboscope score, which could be due to discontinuation of dispensing, and thus the stroboscope check could not find a droplet to record. Our JMP predictive model had a high degree of agreement with our observed results. The JMP model predicted that dispensing the highest concentration of 11C7 at our current PCV working level would yield the highest number of quality membranes, which correlated with our results. Acknowledgements: This work was supported by the Chemical Biological Technologies Directorate (Contract # HDTRA1-16-C-0026) and the Advanced Technology International (Contract # MCDC-18-04-09-002) from the Department of Defense Chemical and Biological Defense program through the Defense Threat Reduction Agency (DTRA).

Keywords: immunoassay, microarray, design of experiment, piezoelectric dispensing

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Authors: Achiron Anat, Mathilda Mandel, Mayust Sue, Achiron Reuven, Gurevich Michael

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Introduction: As coronavirus disease 2019 (COVID-19) vaccination is currently spreading around the world, it is of importance to assess the ability of multiple sclerosis (MS) patients to mount an appropriate immune response to the vaccine in the context of disease-modifying treatments (DMT’s). Objectives: Evaluate immunity generated following COVID-19 vaccination in MS patients, and assess factors contributing to protective humoral and cellular immune responses in MS patients vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus infection. Methods: Review our recent data related to (1) the safety of PfizerBNT162b2 COVID-19 mRNA vaccine in adult MS patients; (2) the humoral post-vaccination SARS-CoV2 IgG response in MS vaccinees using anti-spike protein-based serology; and (3) the cellular immune response of memory B-cells specific for SARS-CoV-2 receptor-binding domain (RBD) and memory T-cells secreting IFN-g and/or IL-2 in response to SARS-CoV2 peptides using ELISpot/Fluorospot assays in MS patients either untreated or under treatment with fingolimod, cladribine, or ocrelizumab; (4) covariate parameters related to mounting protective immune responses. Results: COVID-19 vaccine proved safe in MS patients, and the adverse event profile was mainly characterised by pain at the injection site, fatigue, and headache. Not any increased risk of relapse activity was noted and the rate of patients with acute relapse was comparable to the relapse rate in non-vaccinated patients during the corresponding follow-up period. A mild increase in the rate of adverse events was noted in younger MS patients, among patients with lower disability, and in patients treated with DMTs. Following COVID-19 vaccination protective humoral immune response was significantly decreased in fingolimod- and ocrelizumab- treated MS patients. SARS-CoV2 specific B-cell and T-cell cellular responses were respectively decreased. Untreated MS patients and patients treated with cladribine demonstrated protective humoral and cellular immune responses, similar to healthy vaccinated subjects. Conclusions: COVID-19 BNT162b2 vaccine proved as safe for MS patients. No increased risk of relapse activity was noted post-vaccination. Although COVID-19 vaccination is new, accumulated data demonstrate differences in immune responses under various DMT’s. This knowledge can help to construct appropriate COVID-19 vaccine guidelines to ensure proper immune responses for MS patients.

Keywords: covid-19, vaccination, multiple sclerosis, IgG

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Authors: Diana Santiago, Tania Lisboa, Sophie Lee, Alexander P. Demos, Monica C. S. Vasconcelos

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Memorization has long been recognized as an arduous and anxiety-evoking task for musicians, and yet, it is an essential aspect of performance. Research shows that musicians are often not taught how to memorize. While memorization and practice strategies of professionals have been studied, little research has been done to examine how student musicians learn to practice and memorize music in different cultural settings. We present the process of developing and testing a questionnaire of music memorization and musical practice for student musicians in the UK and Brazil. A survey was developed for a cross-cultural research project aiming at examining how young orchestral musicians (aged 7–18 years) in different learning environments and cultures engage in instrumental practice and memorization. The questionnaire development included members of a UK/US/Brazil research team of music educators and performance science researchers. A pool of items was developed for each aspect of practice and memorization identified, based on literature, personal experiences, and adapted from existing questionnaires. Item development took the varying levels of cognitive and social development of the target populations into consideration. It also considered the diverse target learning environments. Items were initially grouped in accordance with a single underlying construct/behavior. The questionnaire comprised three sections: a demographics section, a section on practice (containing 29 items), and a section on memorization (containing 40 items). Next, the response process was considered and a 5-point Likert scale ranging from ‘always’ to ‘never’ with a verbal label and an image assigned to each response option was selected, following effective questionnaire design for children and youths. Finally, a pilot study was conducted with young orchestral musicians from diverse learning environments in Brazil and the United Kingdom. Data collection took place in either one-to-one or group settings to facilitate the participants. Cognitive interviews were utilized to establish response process validity by confirming the readability and accurate comprehension of the questionnaire items or highlighting the need for item revision. Internal reliability was investigated by measuring the consistency of the item groups using the statistical test Cronbach’s alpha. The pilot study successfully relied on the questionnaire to generate data about the engagement of young musicians of different levels and instruments, across different learning and cultural environments, in instrumental practice and memorization. Interaction analysis of the cognitive interviews undertaken with these participants, however, exposed the fact that certain items, and the response scale, could be interpreted in multiple ways. The questionnaire text was, therefore, revised accordingly. The low Cronbach’s Alpha scores of many item groups indicated another issue with the original questionnaire: its low level of internal reliability. Several reasons for each poor reliability can be suggested, including the issues with item interpretation revealed through interaction analysis of the cognitive interviews, the small number of participants (34), and the elusive nature of the construct in question. The revised questionnaire measures 78 specific behaviors or opinions. It can be seen to provide an efficient means of gathering information about the engagement of young musicians in practice and memorization on a large scale.

Keywords: cross-cultural, memorization, practice, questionnaire, young musicians

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Authors: Khaled Karim

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Although a large number of studies have examined the effectiveness of written corrective feedback (WCF) in L2 writing, very few studies have investigated students’ attitudes towards the feedback and their perspectives regarding the usefulness of different types of feedback. Using prompted stimulated recall interviews, this study investigated ESL students’ perceptions and attitudes towards the CF they received as well as their preferences and reactions to the corrections. 24 ESL students first received direct (e.g., providing target forms after crossing out erroneous forms) and indirect (e.g., underlining and underline+metalinguistic) CF on four written tasks and then participated in an interview with the researcher. The analysis revealed that both direct and indirect CF were judged to be useful strategies for correction but in different ways. Underline only CF helped them think about the nature and type of the errors they made while metalinguistic CF was useful as it provided clues about the nature and type of the errors. Most participants indicated that indirect correction needed sufficient prior knowledge of the form to be effective. The majority of the students found the combination of underlining with metalinguistic information as the most effective method of providing feedback. Detailed findings will be presented, and pedagogical implications of the study will be discussed.

Keywords: ESL writing, error correction, feedback, written corrective feedback

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Authors: Radha Rajamma, Susheela Palanisamy

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The use of chemical fertilizers and pesticides has posed a serious threat to the environment, cause disturbance to the soil ecosystem, pollute the water causing serious health problems. The indigenous practices such as herbal spray, phyto-alternatives, etc. offer harmless alternatives in integrated pest management. The use of plant materials has become an integral part of insect pest management because of their cheap and non-toxic nature. Hence an investigation has been made to determine the bio-efficacy of vermiwash and two leaf extracts, Azadirachta indica and Vitex negundo against mealy bug, Paracoccus marginatus. The results on the effect of vermitechnologies on the activity of mealy bug indicated the effectiveness of vermiwash foliar application in suppressing the pest activity. Accumulative mortality of mealy bug increased gradually with the increase of exposure intervals. The combined treatment of vermiwash with Azadirachta indica reported the highest mortality percentage of 96% followed by the individual treatment of leaf extracts. Hence vermiwash was proved to be the most effective in enhancing the potency of mealy bug and decreased LC50 of the target insect.

Keywords: Azadirachta indica, Paracoccus marginatus, vermiwash, Vitex negundo

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Authors: Khalid S. Hashim, Andy Shaw, Rafid Al-Khaddar, Montserrat Ortoneda Pedrola

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In spite of the acknowledged advantages of the electrocoagulation (EC) method to remove a wide range of pollutants from waters and wastewaters, its efficiency is limited by several operational parameters (such as electrolysis time, current density, electrode material, distance between electrodes, and water temperature). Hence, optimizing these key operating parameters is considered a vital step to remove a pollutant efficiently. In this context, the present study has been carried out to explore the influence of electrodes spacing on energy consumption, temperature of the water being treated, and iron removal from water. To achieve this target, iron containing synthetic water samples were electrolysed for 20 min, using a new flow column electrocoagulation reactor (FCER), at three different gaps between electrodes (5, 10, and 20 mm). These batch experiments were commenced at a constant current density of 1.5 mA/cm² and initial pH of 6. The obtained results demonstrated that increasing gap between electrodes negatively influenced the performance of the EC method. It was found that increasing the gap between electrodes from 5 to 20 mm increased the energy consumption from about 3.3 to 7.3 kW.h/m³, and water temperature from 20.2 to 22 °C, respectively. In addition, it has been found, after 20 min of electrolysing, that increasing the gap between electrodes from 5 to 20 mm increased the residual iron concentration from 0.05 to 1.01 mg/L, respectively.

Keywords: electrocoagulation, water, electrodes, iron

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Authors: Geoffrey J. Blanford, Christoph Weissbart

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The prospects for the European power sector indicate that it has to almost fully decarbonize in order to reach the economy-wide target of CO₂-emission reduction. We apply the EU-REGEN model to explain the penetration of RES from an economic perspective, their spatial distribution, and the complementary role of conventional generation technologies. Furthermore, we identify economic consequences of national energy and climate targets. Our study shows that onshore wind power will be the most crucial generation technology for the future European power sector. Its geographic distribution is driven by resource quality. Gas power will be the major conventional generation technology for backing-up wind power. Moreover, a complete phase out of coal power proves to be not economically optimal. The paper demonstrates that existing national targets have a negative impact, especially on the German region with higher prices and lower revenues. The remaining regions profit are hardly affected. We encourage an EU-wide coordination on the expansion of wind power with harmonized policies. Yet, this requires profitable market structures for both, RES and conventional generation technologies.

Keywords: European, policy evaluation, power sector investment, technology choices

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Authors: Mina Jafari, Kobra Hamraee, Saied Hossein Hosseini

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The prediction of breast cancer disease is one of the challenges in medicine. In this paper we collected 528 records of women’s information who live in Kabul including demographic, life style, diet and pregnancy data. There are many classification algorithm in breast cancer prediction and tried to find the best model with most accurate result and lowest error rate. We evaluated some other common supervised algorithms in data mining to find the best model in prediction of breast cancer disease among afghan women living in Kabul regarding to momography result as target variable. For evaluating these algorithms we used Cross Validation which is an assured method for measuring the performance of models. After comparing error rate and accuracy of three models: Decision Tree, Naive Bays and Rule Induction, Decision Tree with accuracy of 94.06% and error rate of %15 is found the best model to predicting breast cancer disease based on the health care records.

Keywords: decision tree, breast cancer, probability, data mining

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Authors: Ali Murat Guler

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A variety of experiments have been developed over the past decades, aiming at the detection of Weakly Interactive Massive Particles (WIMPs) via their scattering in an instrumented medium. The sensitivity of these experiments has improved with a tremendous speed, thanks to a constant development of detectors and analysis methods. Detectors capable of reconstructing the direction of the nuclear recoil induced by the WIMP scattering are opening a new frontier to possibly extend Dark Matter searches beyond the neutrino background. Measurement of WIMP’s direction will allow us to detect the galactic origin of dark matter and, therefore to have a clear signal-background separation. The NEWSdm experiment, based on nuclear emulsions, is intended to measure the direction of WIMP-induced nuclear coils with a solid-state detector, thus with high sensitivity. We discuss the discovery potential of a directional experiment based on the use of a solid target made of newly developed nuclear emulsions and novel read-out systems achieving nanometric resolution. We also report results of a technical test conducted in Gran Sasso.

Keywords: dark matter, direct detection, nuclear emulsion, WIMPS

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Authors: Vani Singhal, Jitendra Parmar, Satyendra Singh Chouhan

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Unseen class discovery has now become an important part of a machine-learning algorithm to judge new classes. Unseen classes are the classes on which the machine learning model is not trained on. With the advancement in technology and AI replacing humans, the amount of data has increased to the next level. So while implementing a model on real-world examples, we come across unseen new classes. Our aim is to find the number of unseen classes by using a hierarchical-based active learning algorithm. The algorithm is based on hierarchical clustering as well as active sampling. The number of clusters that we will get in the end will give the number of unseen classes. The total clusters will also contain some clusters that have unseen classes. Instead of first discovering unseen classes and then finding their number, we directly calculated the number by applying the algorithm. The dataset used is for intent classification. The target data is the intent of the corresponding query. We conclude that when the machine learning model will encounter real-world data, it will automatically find the number of unseen classes. In the future, our next work would be to label these unseen classes correctly.

Keywords: active sampling, hierarchical clustering, open world learning, unseen class discovery

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Authors: Rashmi D. G., Aishwarya G., Niharika M. K.

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Purpose: Free recall tasks target cognitive and linguistic processes like episodic memory, lexical access and retrieval. Consequently, the free recall paradigm is suitable for assessing memory deterioration caused by aging; this also depends on linguistic factors, including the use of first and second languages and their relative ability. Hence, the present study aimed to determine if aging has an effect on visual and auditory recall abilities. Method: Twenty young adults (mean age: 25.4±0.99) and older adults (mean age: 63.3±3.51) participated in the study. Participants performed a free recall task under two conditions – related and unrelated and two modalities - visual and auditory where they were instructed to recall as many items as possible with no specific order and time limit. Results: Free recall performance was calculated as the mean number of correctly recalled items. Although younger participants recalled a higher number of items, the performance across conditions and modality was variable. Conclusion: In summary, the findings of the present study revealed an age-related decline in the efficiency of episodic memory, which is crucial to remember recent events.

Keywords: recall, episodic memory, aging, modality

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Authors: Mehrdad Shahrbanozadeh, Gholam Abbas Barani, Saeed Shojaee

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In this study, a finite element (Seep3D model) and an artificial neural network (ANN) model were developed to simulate flow through dam foundation. Seep3D model is capable of simulating three-dimensional flow through a heterogeneous and anisotropic, saturated and unsaturated porous media. Flow through the Shahid Abbaspour dam foundation has been used as a case study. The FEM with 24960 triangular elements and 28707 nodes applied to model flow through foundation of this dam. The FEM being made denser in the neighborhood of the curtain screen. The ANN model developed for Shahid Abbaspour dam is a feedforward four layer network employing the sigmoid function as an activator and the back-propagation algorithm for the network learning. The water level elevations of the upstream and downstream of the dam have been used as input variables and the piezometric heads as the target outputs in the ANN model. The two models are calibrated and verified using the Shahid Abbaspour’s dam piezometric data. Results of the models were compared with those measured by the piezometers which are in good agreement. The model results also revealed that the ANN model performed as good as and in some cases better than the FEM.

Keywords: seepage, dam foundation, finite element method, neural network, seep 3D model

Procedia PDF Downloads 461