Search results for: predicted mean vote
461 Investigations of Bergy Bits and Ship Interactions in Extreme Waves Using Smoothed Particle Hydrodynamics
Authors: Mohammed Islam, Jungyong Wang, Dong Cheol Seo
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The Smoothed Particle Hydrodynamics (SPH) method is a novel, meshless, and Lagrangian technique based numerical method that has shown promises to accurately predict the hydrodynamics of water and structure interactions in violent flow conditions. The main goal of this study is to build confidence on the versatility of the Smoothed Particle Hydrodynamics (SPH) based tool, to use it as a complementary tool to the physical model testing capabilities and support research need for the performance evaluation of ships and offshore platforms exposed to an extreme and harsh environment. In the current endeavor, an open-sourced SPH-based tool was used and validated for modeling and predictions of the hydrodynamic interactions of a 6-DOF ship and bergy bits. The study involved the modeling of a modern generic drillship and simplified bergy bits in floating and towing scenarios and in regular and irregular wave conditions. The predictions were validated using the model-scale measurements on a moored ship towed at multiple oblique angles approaching a floating bergy bit in waves. Overall, this study results in a thorough comparison between the model scale measurements and the prediction outcomes from the SPH tool for performance and accuracy. The SPH predicted ship motions and forces were primarily within ±5% of the measurements. The velocity and pressure distribution and wave characteristics over the free surface depicts realistic interactions of the wave, ship, and the bergy bit. This work identifies and presents several challenges in preparing the input file, particularly while defining the mass properties of complex geometry, the computational requirements, and the post-processing of the outcomes.Keywords: SPH, ship and bergy bit, hydrodynamic interactions, model validation, physical model testing
Procedia PDF Downloads 132460 Identification of Promiscuous Epitopes for Cellular Immune Responses in the Major Antigenic Protein Rv3873 Encoded by Region of Difference 1 of Mycobacterium tuberculosis
Authors: Abu Salim Mustafa
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Rv3873 is a relatively large size protein (371 amino acids in length) and its gene is located in the immunodominant genomic region of difference (RD)1 that is present in the genome of Mycobacterium tuberculosis but deleted from the genomes of all the vaccine strains of Bacillus Calmette Guerin (BCG) and most other mycobacteria. However, when tested for cellular immune responses using peripheral blood mononuclear cells from tuberculosis patients and BCG-vaccinated healthy subjects, this protein was found to be a major stimulator of cell mediated immune responses in both groups of subjects. In order to further identify the sequence of immunodominant epitopes and explore their Human Leukocyte Antigen (HLA)-restriction for epitope recognition, 24 peptides (25-mers overlapping with the neighboring peptides by 10 residues) covering the sequence of Rv3873 were synthesized chemically using fluorenylmethyloxycarbonyl chemistry and tested in cell mediated immune responses. The results of these experiments helped in the identification of an immunodominant peptide P9 that was recognized by people expressing varying HLA-DR types. Furthermore, it was also predicted to be a promiscuous binder with multiple epitopes for binding to HLA-DR, HLA-DP and HLA-DQ alleles of HLA-class II molecules that present antigens to T helper cells, and to HLA-class I molecules that present antigens to T cytotoxic cells. In addition, the evaluation of peptide P9 using an immunogenicity predictor server yielded a high score (0.94), which indicated a greater probability of this peptide to elicit a protective cellular immune response. In conclusion, P9, a peptide with multiple epitopes and ability to bind several HLA class I and class II molecules for presentation to cells of the cellular immune response, may be useful as a peptide-based vaccine against tuberculosis.Keywords: mycobacterium tuberculosis, PPE68, peptides, vaccine
Procedia PDF Downloads 135459 Metabolic Profiling of Populus trichocarpa Family 1 UDP-Glycosyltransferases
Authors: Patricia M. B. Saint-Vincent, Anna Furches, Stephanie Galanie, Erica Teixeira Prates, Piet Jones, Nancy Engle, David Kainer, Wellington Muchero, Daniel Jacobson, Timothy J. Tschaplinski
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Uridine diphosphate-glycosyltransferases (UGTs) are enzymes that catalyze sugar transfer to a variety of plant metabolites. UGT substrates, which include plant secondary metabolites involved in lignification, demonstrate new activities and incorporation when glycosylated. Knowledge of UGT function, substrate specificity, and enzyme products is important for plant engineering efforts, especially related to increasing plant biomass through lignification. UGTs in Populus trichocarpa, a biofuel feedstock, and model woody plant, were selected from a pool of gene candidates using rapid prioritization strategies. A functional genomics workflow, consisting of a metabolite genome-wide association study (mGWAS), expression of synthetic codon-optimized genes, and high-throughput biochemical assays with mass spectrometry-based analysis, was developed for determining the substrates and products of previously-uncharacterized enzymes. A total of 40 UGTs from P. trichocarpa were profiled, and the biochemical assay results were compared to predicted mGWAS connections. Assay results confirmed seven of 11 leaf mGWAS associations and demonstrated varying levels of substrate specificity among candidate UGTs. P. trichocarpa UGT substrate processing confirms the role of these newly-characterized enzymes in lignan, flavonoid, and phytohormone metabolism, with potential implications for cell wall biosynthesis, nitrogen uptake, and biotic and abiotic stress responses.Keywords: Populus, metabolite-gene associations, GWAS, bio feedstocks, glycosyltransferase
Procedia PDF Downloads 114458 Suggested Role for Neutrophil Extracellular Traps Formation in Ewing Sarcoma Immune Microenvironment
Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid
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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis
Procedia PDF Downloads 64457 Design of Sustainable Concrete Pavement by Incorporating RAP Aggregates
Authors: Selvam M., Vadthya Poornachandar, Surender Singh
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These Reclaimed Asphalt Pavement (RAP) aggregates are generally dumped in the open area after the demolition of Asphalt Pavements. The utilization of RAP aggregates in cement concrete pavements may provide several socio-economic-environmental benefits and could embrace the circular economy. The cross recycling of RAP aggregates in the concrete pavement could reduce the consumption of virgin aggregates and saves the fertile land. However, the structural, as well as functional properties of RAP-concrete could be significantly lower than the conventional Pavement Quality Control (PQC) pavements. This warrants judicious selection of RAP fraction (coarse and fine aggregates) along with the accurate proportion of the same for PQC highways. Also, the selection of the RAP fraction and its proportion shall not be solely based on the mechanical properties of RAP-concrete specimens but also governed by the structural and functional behavior of the pavement system. In this study, an effort has been made to predict the optimum RAP fraction and its corresponding proportion for cement concrete pavements by considering the low-volume and high-volume roads. Initially, the effect of inclusions of RAP on the fresh and mechanical properties of concrete pavement mixes is mapped through an extensive literature survey. Almost all the studies available to date are considered for this study. Generally, Indian Roads Congress (IRC) methods are the most widely used design method in India for the analysis of concrete pavements, and the same has been considered for this study. Subsequently, fatigue damage analysis is performed to evaluate the required safe thickness of pavement slab for different fractions of RAP (coarse RAP). Consequently, the performance of RAP-concrete is predicted by employing the AASHTO-1993 model for the following distresses conditions: faulting, cracking, and smoothness. The performance prediction and total cost analysis of RAP aggregates depict that the optimum proportions of coarse RAP aggregates in the PQC mix are 35% and 50% for high volume and low volume roads, respectively.Keywords: concrete pavement, RAP aggregate, performance prediction, pavement design
Procedia PDF Downloads 158456 Evaluating the Dosimetric Performance for 3D Treatment Planning System for Wedged and Off-Axis Fields
Authors: Nashaat A. Deiab, Aida Radwan, Mohamed S. Yahiya, Mohamed Elnagdy, Rasha Moustafa
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This study is to evaluate the dosimetric performance of our institution's 3D treatment planning system for wedged and off-axis 6MV photon beams, guided by the recommended QA tests documented in the AAPM TG53; NCS report 15 test packages, IAEA TRS 430 and ESTRO booklet no.7. The study was performed for Elekta Precise linear accelerator designed for clinical range of 4, 6 and 15 MV photon beams with asymmetric jaws and fully integrated multileaf collimator that enables high conformance to target with sharp field edges. Ten tests were applied on solid water equivalent phantom along with 2D array dose detection system. The calculated doses using 3D treatment planning system PrecisePLAN were compared with measured doses to make sure that the dose calculations are accurate for simple situations such as square and elongated fields, different SSD, beam modifiers e.g. wedges, blocks, MLC-shaped fields and asymmetric collimator settings. The QA results showed dosimetric accuracy of the TPS within the specified tolerance limits. Except for large elongated wedged field, the central axis and outside central axis have errors of 0.2% and 0.5%, respectively, and off- planned and off-axis elongated fields the region outside the central axis of the beam errors are 0.2% and 1.1%, respectively. The dosimetric investigated results yielded differences within the accepted tolerance level as recommended. Differences between dose values predicted by the TPS and measured values at the same point are the result from limitations of the dose calculation, uncertainties in the measurement procedure, or fluctuations in the output of the accelerator.Keywords: quality assurance, dose calculation, wedged fields, off-axis fields, 3D treatment planning system, photon beam
Procedia PDF Downloads 445455 Multivariate Analysis on Water Quality Attributes Using Master-Slave Neural Network Model
Authors: A. Clementking, C. Jothi Venkateswaran
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Mathematical and computational functionalities such as descriptive mining, optimization, and predictions are espoused to resolve natural resource planning. The water quality prediction and its attributes influence determinations are adopted optimization techniques. The water properties are tainted while merging water resource one with another. This work aimed to predict influencing water resource distribution connectivity in accordance to water quality and sediment using an innovative proposed master-slave neural network back-propagation model. The experiment results are arrived through collecting water quality attributes, computation of water quality index, design and development of neural network model to determine water quality and sediment, master–slave back propagation neural network back-propagation model to determine variations on water quality and sediment attributes between the water resources and the recommendation for connectivity. The homogeneous and parallel biochemical reactions are influences water quality and sediment while distributing water from one location to another. Therefore, an innovative master-slave neural network model [M (9:9:2)::S(9:9:2)] designed and developed to predict the attribute variations. The result of training dataset given as an input to master model and its maximum weights are assigned as an input to the slave model to predict the water quality. The developed master-slave model is predicted physicochemical attributes weight variations for 85 % to 90% of water quality as a target values.The sediment level variations also predicated from 0.01 to 0.05% of each water quality percentage. The model produced the significant variations on physiochemical attribute weights. According to the predicated experimental weight variation on training data set, effective recommendations are made to connect different resources.Keywords: master-slave back propagation neural network model(MSBPNNM), water quality analysis, multivariate analysis, environmental mining
Procedia PDF Downloads 477454 Systematic Review of Associations between Interoception, Vagal Tone, and Emotional Regulation
Authors: Darren Edwards, Thomas Pinna
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Background: Interoception and heart rate variability have been found to predict outcomes of mental health and well-being. However, these have usually been investigated independently of one another. Objectives: This review aimed to explore the associations between interoception and heart rate variability (HRV) with emotion regulation (ER) and ER strategies within the existing literature and utilizing systematic review methodology. Methods: The process of article retrieval and selection followed the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines. Databases PsychINFO, Web of Science, PubMed, CINAHL, and MEDLINE were scanned for papers published. Preliminary inclusion and exclusion criteria were specified following the patient, intervention, comparison, and outcome (PICO) framework, whilst the checklist for critical appraisal and data extraction for systematic reviews of prediction modeling studies (CHARMS) framework was used to help formulate the research question, and to critically assess for bias in the identified full-length articles. Results: 237 studies were identified after initial database searches. Of these, eight studies were included in the final selection. Six studies explored the associations between HRV and ER, whilst three investigated the associations between interoception and ER (one of which was included in the HRV selection too). Overall, the results seem to show that greater HRV and interoception are associated with better ER. Specifically, high parasympathetic activity largely predicted the use of adaptive ER strategies such as reappraisal, and better acceptance of emotions. High interoception, instead, was predictive of effective down-regulation of negative emotions and handling of social uncertainty, there was no association with any specific ER strategy. Conclusions: Awareness of one’s own bodily feelings and vagal activation seem to be of central importance for the effective regulation of emotional responses.Keywords: emotional regulation, vagal tone, interoception, chronic conditions, health and well-being, psychological flexibility
Procedia PDF Downloads 112453 Conservation Planning of Paris Polyphylla Smith, an Important Medicinal Herb of the Indian Himalayan Region Using Predictive Distribution Modelling
Authors: Mohd Tariq, Shyamal K. Nandi, Indra D. Bhatt
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Paris polyphylla Smith (Family- Liliaceae; English name-Love apple: Local name- Satuwa) is an important folk medicinal herb of the Indian subcontinent, being a source of number of bioactive compounds for drug formulation. The rhizomes are widely used as antihelmintic, antispasmodic, digestive stomachic, expectorant and vermifuge, antimicrobial, anti-inflammatory, heart and vascular malady, anti-fertility and sedative. Keeping in view of this, the species is being constantly removed from nature for trade and various pharmaceuticals purpose, as a result, the availability of the species in its natural habitat is decreasing. In this context, it would be pertinent to conserve this species and reintroduce them in its natural habitat. Predictive distribution modelling of this species was performed in Western Himalayan Region. One such recent method is Ecological Niche Modelling, also popularly known as Species distribution modelling, which uses computer algorithms to generate predictive maps of species distributions in a geographic space by correlating the point distributional data with a set of environmental raster data. In case of P. polyphylla, and to understand its potential distribution zones and setting up of artificial introductions, or selecting conservation sites, and conservation and management of their native habitat. Among the different districts of Uttarakhand (28°05ˈ-31°25ˈ N and 77°45ˈ-81°45ˈ E) Uttarkashi, Rudraprayag, Chamoli, Pauri Garhwal and some parts of Bageshwar, 'Maximum Entropy' (Maxent) has predicted wider potential distribution of P. polyphylla Smith. Distribution of P. polyphylla is mainly governed by Precipitation of Driest Quarter and Mean Diurnal Range i.e., 27.08% and 18.99% respectively which indicates that humidity (27%) and average temperature (19°C) might be suitable for better growth of Paris polyphylla.Keywords: biodiversity conservation, Indian Himalayan region, Paris polyphylla, predictive distribution modelling
Procedia PDF Downloads 330452 Neural Networks Based Prediction of Long Term Rainfall: Nine Pilot Study Zones over the Mediterranean Basin
Authors: Racha El Kadiri, Mohamed Sultan, Henrique Momm, Zachary Blair, Rachel Schultz, Tamer Al-Bayoumi
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The Mediterranean Basin is a very diverse region of nationalities and climate zones, with a strong dependence on agricultural activities. Predicting long term (with a lead of 1 to 12 months) rainfall, and future droughts could contribute in a sustainable management of water resources and economical activities. In this study, an integrated approach was adopted to construct predictive tools with lead times of 0 to 12 months to forecast rainfall amounts over nine subzones of the Mediterranean Basin region. The following steps were conducted: (1) acquire, assess and intercorrelate temporal remote sensing-based rainfall products (e.g. The CPC Merged Analysis of Precipitation [CMAP]) throughout the investigation period (1979 to 2016), (2) acquire and assess monthly values for all of the climatic indices influencing the regional and global climatic patterns (e.g., Northern Atlantic Oscillation [NOI], Southern Oscillation Index [SOI], and Tropical North Atlantic Index [TNA]); (3) delineate homogenous climatic regions and select nine pilot study zones, (4) apply data mining methods (e.g. neural networks, principal component analyses) to extract relationships between the observed rainfall and the controlling factors (i.e. climatic indices with multiple lead-time periods) and (5) use the constructed predictive tools to forecast monthly rainfall and dry and wet periods. Preliminary results indicate that rainfall and dry/wet periods were successfully predicted with lead zones of 0 to 12 months using the adopted methodology, and that the approach is more accurately applicable in the southern Mediterranean region.Keywords: rainfall, neural networks, climatic indices, Mediterranean
Procedia PDF Downloads 312451 Developing a DNN Model for the Production of Biogas From a Hybrid BO-TPE System in an Anaerobic Wastewater Treatment Plant
Authors: Hadjer Sadoune, Liza Lamini, Scherazade Krim, Amel Djouadi, Rachida Rihani
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Deep neural networks are highly regarded for their accuracy in predicting intricate fermentation processes. Their ability to learn from a large amount of datasets through artificial intelligence makes them particularly effective models. The primary obstacle in improving the performance of these models is to carefully choose the suitable hyperparameters, including the neural network architecture (number of hidden layers and hidden units), activation function, optimizer, learning rate, and other relevant factors. This study predicts biogas production from real wastewater treatment plant data using a sophisticated approach: hybrid Bayesian optimization with a tree-structured Parzen estimator (BO-TPE) for an optimised deep neural network (DNN) model. The plant utilizes an Upflow Anaerobic Sludge Blanket (UASB) digester that treats industrial wastewater from soft drinks and breweries. The digester has a working volume of 1574 m3 and a total volume of 1914 m3. Its internal diameter and height were 19 and 7.14 m, respectively. The data preprocessing was conducted with meticulous attention to preserving data quality while avoiding data reduction. Three normalization techniques were applied to the pre-processed data (MinMaxScaler, RobustScaler and StandardScaler) and compared with the Non-Normalized data. The RobustScaler approach has strong predictive ability for estimating the volume of biogas produced. The highest predicted biogas volume was 2236.105 Nm³/d, with coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) values of 0.712, 164.610, and 223.429, respectively.Keywords: anaerobic digestion, biogas production, deep neural network, hybrid bo-tpe, hyperparameters tuning
Procedia PDF Downloads 38450 Validation of the Linear Trend Estimation Technique for Prediction of Average Water and Sewerage Charge Rate Prices in the Czech Republic
Authors: Aneta Oblouková, Eva Vítková
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The article deals with the issue of water and sewerage charge rate prices in the Czech Republic. The research is specifically focused on the analysis of the development of the average prices of water and sewerage charge rate in the Czech Republic in the years 1994-2021 and on the validation of the chosen methodology relevant for the prediction of the development of the average prices of water and sewerage charge rate in the Czech Republic. The research is based on data collection. The data for this research was obtained from the Czech Statistical Office. The aim of the paper is to validate the relevance of the mathematical linear trend estimate technique for the calculation of the predicted average prices of water and sewerage charge rates. The real values of the average prices of water and sewerage charge rates in the Czech Republic in the years 1994-2018 were obtained from the Czech Statistical Office and were converted into a mathematical equation. The same type of real data was obtained from the Czech Statistical Office for the years 2019-2021. Prediction of the average prices of water and sewerage charge rates in the Czech Republic in the years 2019-2021 were also calculated using a chosen method -a linear trend estimation technique. The values obtained from the Czech Statistical Office and the values calculated using the chosen methodology were subsequently compared. The research result is a validation of the chosen mathematical technique to be a suitable technique for this research.Keywords: Czech Republic, linear trend estimation, price prediction, water and sewerage charge rate
Procedia PDF Downloads 120449 Effect of Concentration Level and Moisture Content on the Detection and Quantification of Nickel in Clay Agricultural Soil in Lebanon
Authors: Layan Moussa, Darine Salam, Samir Mustapha
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Heavy metal contamination in agricultural soils in Lebanon poses serious environmental and health problems. Intensive efforts are employed to improve existing quantification methods of heavy metals in contaminated environments since conventional detection techniques have shown to be time-consuming, tedious, and costly. The implication of hyperspectral remote sensing in this field is possible and promising. However, factors impacting the efficiency of hyperspectral imaging in detecting and quantifying heavy metals in agricultural soils were not thoroughly studied. This study proposes to assess the use of hyperspectral imaging for the detection of Ni in agricultural clay soil collected from the Bekaa Valley, a major agricultural area in Lebanon, under different contamination levels and soil moisture content. Soil samples were contaminated with Ni, with concentrations ranging from 150 mg/kg to 4000 mg/kg. On the other hand, soil with background contamination was subjected to increased moisture levels varying from 5 to 75%. Hyperspectral imaging was used to detect and quantify Ni contamination in the soil at different contamination levels and moisture content. IBM SPSS statistical software was used to develop models that predict the concentration of Ni and moisture content in agricultural soil. The models were constructed using linear regression algorithms. The spectral curves obtained reflected an inverse correlation between both Ni concentration and moisture content with respect to reflectance. On the other hand, the models developed resulted in high values of predicted R2 of 0.763 for Ni concentration and 0.854 for moisture content. Those predictions stated that Ni presence was well expressed near 2200 nm and that of moisture was at 1900 nm. The results from this study would allow us to define the potential of using the hyperspectral imaging (HSI) technique as a reliable and cost-effective alternative for heavy metal pollution detection in contaminated soils and soil moisture prediction.Keywords: heavy metals, hyperspectral imaging, moisture content, soil contamination
Procedia PDF Downloads 101448 Performance Evaluation of a Very High-Resolution Satellite Telescope
Authors: Walid A. Attia, Taher M. Bazan, Fawzy Eltohamy, Mahmoud Fathy
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System performance evaluation is an essential stage in the design of high-resolution satellite telescopes prior to the development process. In this paper, a system performance evaluation of a very high-resolution satellite telescope is investigated. The evaluated system has a Korsch optical scheme design. This design has been discussed in another paper with respect to three-mirror anastigmat (TMA) scheme design and the former configuration showed better results. The investigated system is based on the Korsch optical design integrated with a time-delay and integration charge coupled device (TDI-CCD) sensor to achieve a ground sampling distance (GSD) of 25 cm. The key performance metrics considered are the spatial resolution, the signal to noise ratio (SNR) and the total modulation transfer function (MTF) of the system. In addition, the national image interpretability rating scale (NIIRS) metric is assessed to predict the image quality according to the modified general image quality equation (GIQE). Based on the orbital, optical and detector parameters, the estimated GSD is found to be 25 cm. The SNR has been analyzed at different illumination conditions of target albedos, sun and sensor angles. The system MTF has been computed including diffraction, aberration, optical manufacturing, smear and detector sampling as the main contributors for evaluation the MTF. Finally, the system performance evaluation results show that the computed MTF value is found to be around 0.08 at the Nyquist frequency, the SNR value was found to be 130 at albedo 0.2 with a nadir viewing angles and the predicted NIIRS is in the order of 6.5 which implies a very good system image quality.Keywords: modulation transfer function, national image interpretability rating scale, signal to noise ratio, satellite telescope performance evaluation
Procedia PDF Downloads 384447 Crossover Memories and Code-Switching in the Narratives of Arabic-Hebrew and Hebrew-English Bilingual Adults in Israel
Authors: Amani Jaber-Awida
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This study examines two bilingual phenomena in the narratives of Arabic Hebrew and Hebrew-English bilingual adults in Israel: CO memories and code-switching (CS). The study examined these phenomena in the context of autobiographical memory, using a cue word technique. Student experimenters held two sessions in the homes of the participants. In separate language sessions, the participant was asked to look first at each of 16 cue words and then to state a concrete memory. After stating the memory, participants reported whether their memories were in the same language of the experiment session or different. Memories were classified as ‘Crossovers’ (CO) or ‘Same Language’ (SL) according to participants' self-reports. Participants were also required to elaborate about the setting, interlocutors and other languages involved in the specific memory. Beyond replicating the procedure of cuing technique, one memory from a specific lifespan period was chosen per participant, and the participant was required to provide further details about it. For the more detailed memories, CS count was conducted. Both bilingual groups confirmed the Reminiscence Bump phenomenon, retrieving more memories in the 10-30 age period. CO memories prevailed in second language sessions (L2). Same language memories were more abundant in first language sessions (L1). Higher CS frequency was found in L2 sessions. Finally, as predicted, 'individual' CS was prevalent in L2 sessions, but 'community-based' CS was not higher in L1 sessions. The two bilingual measures in this study, crossovers, and CS came from different research traditions, the former from an experimental paradigm in the psychology of autobiographical memory based on self-reported judgments, the latter a behavioral measure from linguistics. This merger of approaches offers new insight into the field of bilingual autobiographical memory. In addition, the study attempted to shed light on the investigation of motivations for CS, beginning with Walters’ SPPL Model and concluding with a distinction between ‘community-based’ and individual motivations.Keywords: bilinguals, code-switching, crossover memories, narratives
Procedia PDF Downloads 171446 Practical Modelling of RC Structural Walls under Monotonic and Cyclic Loading
Authors: Reza E. Sedgh, Rajesh P. Dhakal
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Shear walls have been used extensively as the main lateral force resisting systems in multi-storey buildings. The recent development in performance based design urges practicing engineers to conduct nonlinear static or dynamic analysis to evaluate seismic performance of multi-storey shear wall buildings by employing distinct analytical models suggested in the literature. For practical purpose, application of macroscopic models to simulate the global and local nonlinear behavior of structural walls outweighs the microscopic models. The skill level, computational time and limited access to RC specialized finite element packages prevents the general application of this method in performance based design or assessment of multi-storey shear wall buildings in design offices. Hence, this paper organized to verify capability of nonlinear shell element in commercially available package (Sap2000) in simulating results of some specimens under monotonic and cyclic loads with very oversimplified available cyclic material laws in the analytical tool. The selection of constitutive models, the determination of related parameters of the constituent material and appropriate nonlinear shear model are presented in detail. Adoption of proposed simple model demonstrated that the predicted results follow the overall trend of experimental force-displacement curve. Although, prediction of ultimate strength and the overall shape of hysteresis model agreed to some extent with experiment, the ultimate displacement(significant strength degradation point) prediction remains challenging in some cases.Keywords: analytical model, nonlinear shell element, structural wall, shear behavior
Procedia PDF Downloads 404445 Finite Element Analysis for Earing Prediction Incorporating the BBC2003 Material Model with Fully Implicit Integration Method: Derivation and Numerical Algorithm
Authors: Sajjad Izadpanah, Seyed Hadi Ghaderi, Morteza Sayah Irani, Mahdi Gerdooei
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In this research work, a sophisticated yield criterion known as BBC2003, capable of describing planar anisotropic behaviors of aluminum alloy sheets, was integrated into the commercial finite element code ABAQUS/Standard via a user subroutine. The complete formulation of the implementation process using a fully implicit integration scheme, i.e., the classic backward Euler method, is presented, and relevant aspects of the yield criterion are introduced. In order to solve nonlinear differential and algebraic equations, the line-search algorithm was adopted in the user-defined material subroutine (UMAT) to expand the convergence domain of the iterative Newton-Raphson method. The developed subroutine was used to simulate a challenging computational problem with complex stress states, i.e., deep drawing of an anisotropic aluminum alloy AA3105. The accuracy and stability of the developed subroutine were confirmed by comparing the numerically predicted earing and thickness variation profiles with the experimental results, which showed an excellent agreement between numerical and experimental earing and thickness profiles. The integration of the BBC2003 yield criterion into ABAQUS/Standard represents a significant contribution to the field of computational mechanics and provides a useful tool for analyzing the mechanical behavior of anisotropic materials subjected to complex loading conditions.Keywords: BBC2003 yield function, plastic anisotropy, fully implicit integration scheme, line search algorithm, explicit and implicit integration schemes
Procedia PDF Downloads 75444 Effect of Processing Parameters on the Physical Properties of Pineapple Pomace Based Aquafeed
Authors: Oluwafemi Babatunde Oduntan, Isaac A. Bamgboye
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The solid waste disposal and its management from pineapple juice processing constitute environmental contamination affecting public health. The use of this by-product called pomace has potentials to reduce cost of aquafeed. Pineapple pomace collected after juice extraction was dried and milled. The interactive effects of feeding rate (1.28, 1.44 and 1.60kg/min), screw speed (305, 355 and 405rpm), moisture content (16, 19 and 22%), temperatures (60, 80, 100 and 120°C), cutting speed (1300, 1400 and 1500rpm), pomace inclusion ratio (5, 10, 15, 20%) and open surface die (50, 75 and 100%) on the extrudate physical properties (bulk density, unit density, expansion ratio, durability and floatability) were investigated using optimal custom design (OCD) matrix and response surface methodology. The predicted values were found to be in good agreement with the experimental values for, expansion ratio, durability and floatability (R2 = 0.7970; 0.9264; 0.9098 respectively) with the exceptions of unit density and bulk density (R2 = 0.1639; 0.2768 respectively). All the extrudates showed relatively high floatability, durability. The inclusion of pineapple pomace produced less expanded and more compact textured extrudates. Results indicated that increased in the value of pineapple pomace, screw speed, feeding rate decreased unit density, bulk density, expansion ratio, durability and floatability of the extrudate. However, increasing moisture content of feed mash resulted in increase unit density and bulk density. Addition of extrusion temperature and cutting speed increased the floatability and durability of extrudate. The proportion of pineapple pomace in aquafeed extruded product was observed to have significantly lower effect on the selected responses.Keywords: aquafeed, extrusion, physical properties, pineapple pomace, waste
Procedia PDF Downloads 271443 Energy Consumption and Economic Growth Nexus: a Sustainability Understanding from the BRICS Economies
Authors: Smart E. Amanfo
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Although the exact functional relationship between energy consumption and economic growth and development remains a complex social science, there is a sustained growing of agreement among energy economists and the likes on direct or indirect role of energy use in the development process, and as sustenance for many of societal achieved socio-economic and environmental developments in any economy. According to OECD, the world economy will double by 2050 in which the two members of BRICS (Brazil, Russia, India, China and South Africa) countries: China and India lead. There is a global apprehension that if countries constituting the epicenter of the present and future economic growth follow the same trajectory as during and after Industrial Revolution, involving higher energy throughputs, especially fossil fuels, the already known and models predicted threats of climate change and global warming could be exacerbated, especially in the developing economies. The international community’s challenge is how to address the trilemma of economic growth, social development, poverty eradication and stability of the ecological systems. This paper aims at providing the estimates of economic growth, energy consumption, and carbon dioxide emissions using BRICS members’ panel data from 1980 to 2017. The preliminary results based on fixed effect econometric model show positive significant relationship between energy consumption and economic growth. The paper further identified a strong relationship between economic growth and CO2 emissions which suggests that the global agenda of low-carbon-led growth and development is not a straight forward achievable The study therefore highlights the need for BRICS member states to intensify low-emissions-based production and consumption policies, increase renewables in order to avoid further deterioration of climate change impacts.Keywords: BRICS, sustainability, sustainable development, energy consumption, economic growth
Procedia PDF Downloads 94442 Uterine Cervical Cancer; Early Treatment Assessment with T2- And Diffusion-Weighted MRI
Authors: Susanne Fridsten, Kristina Hellman, Anders Sundin, Lennart Blomqvist
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Background: Patients diagnosed with locally advanced cervical carcinoma are treated with definitive concomitant chemo-radiotherapy. Treatment failure occurs in 30-50% of patients with very poor prognoses. The treatment is standardized with risk for both over-and undertreatment. Consequently, there is a great need for biomarkers able to predict therapy outcomes to allow for individualized treatment. Aim: To explore the role of T2- and diffusion-weighted magnetic resonance imaging (MRI) for early prediction of therapy outcome and the optimal time point for assessment. Methods: A pilot study including 15 patients with cervical carcinoma stage IIB-IIIB (FIGO 2009) undergoing definitive chemoradiotherapy. All patients underwent MRI four times, at baseline, 3 weeks, 5 weeks, and 12 weeks after treatment started. Tumour size, size change (∆size), visibility on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and change of ADC (∆ADC) at the different time points were recorded. Results: 7/15 patients relapsed during the study period, referred to as "poor prognosis", PP, and the remaining eight patients are referred to "good prognosis", GP. The tumor size was larger at all time points for PP than for GP. The ∆size between any of the four-time points was the same for PP and GP patients. The sensitivity and specificity to predict prognostic group depending on a remaining tumor on DWI were highest at 5 weeks and 83% (5/6) and 63% (5/8), respectively. The combination of tumor size at baseline and remaining tumor on DWI at 5 weeks in ROC analysis reached an area under the curve (AUC) of 0.83. After 12 weeks, no remaining tumor was seen on DWI among patients with GP, as opposed to 2/7 PP patients. Adding ADC to the tumor size measurements did not improve the predictive value at any time point. Conclusion: A large tumor at baseline MRI combined with a remaining tumor on DWI at 5 weeks predicted a poor prognosis.Keywords: chemoradiotherapy, diffusion-weighted imaging, magnetic resonance imaging, uterine cervical carcinoma
Procedia PDF Downloads 143441 Architectural Approaches to a Sustainable Community with Floating Housing Units Adapting to Climate Change and Sea Level Rise in Vietnam
Authors: Nguyen Thi Thu Trang
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Climate change and sea level rise is one of the greatest challenges facing human beings in the 21st century. Because of sea level rise, several low-lying coastal areas around the globe are at risk of being completely submerged, disappearing under water. Particularly in Viet Nam, the rise in sea level is predicted to result in more frequent and even permanently inundated coastal plains. As a result, land reserving fund of coastal cities is going to be narrowed in near future, while construction ground is becoming increasingly limited due to a rapid growth in population. Faced with this reality, the solutions are being discussed not only in tradition view such as accommodation is raised or moved to higher areas, or “living with the water”, but also forwards to “living on the water”. Therefore, the concept of a sustainable floating community with floating houses based on the precious value of long term historical tradition of water dwellings in Viet Nam would be a sustainable solution for adaptation of climate change and sea level rise in the coastal areas. The sustainable floating community is comprised of sustainability in four components: architecture, environment, socio-economic and living quality. This research paper is focused on sustainability in architectural component of floating community. Through detailed architectural analysis of current floating houses and floating communities in Viet Nam, this research not only accumulates precious values of traditional architecture that need to be preserved and developed in the proposed concept, but also illustrates its weaknesses that need to address for optimal design of the future sustainable floating communities. Based on these studies the research would provide guidelines with appropriate architectural solutions for the concept of sustainable floating community with floating housing units that are adapted to climate change and sea level rise in Viet Nam.Keywords: guidelines, sustainable floating community, floating houses, Vietnam
Procedia PDF Downloads 518440 In-silico Target Identification and Molecular Docking of Withaferin A and Withanolide D to Understand their Anticancer Therapeutic Potential
Authors: Devinder Kaur Sugga, Ekamdeep Kaur, Jaspreet Kaur, C. Rajesh, Preeti Rajesh, Harsimran Kaur
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Withanolides are steroidal lactones and are highly oxygenated phytoconstituents that can be developed as potential anti-carcinogenic agents. The two main withanolides, namely Withaferin A and Withanolides D, have been extensively studied for their pharmacological activities. Both these withanolides are present in the Withania somnifera (WS) leaves belonging to the family Solanaceae, also known as “Indian ginseng .”In this study effects of WS leaf extract on the MCF7 breast cancer cell line were investigated by performing a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects and in vitro wound-healing assay to study the effect on cancer cell migration. Our data suggest WS extracts have cytotoxic effects and are effective anti-migrating agents and thus can be a source of potential candidates for the development of potential agents against metastasis. Thus, it can be a source of potential candidates for the development of potential agents against metastasis. Insight into these results, the in-silico approach to identify the possible protein targets interacting with withanolides was taken. Protein kinase C alpha (PKCα) was among the selected 5 top-ranked target proteins identified by the Swiss Target Prediction tool. PKCα is known to promote the growth and invasion of cancer cells and is being evaluated as a prognostic biomarker and therapeutic target in clinically aggressive tumors. Molecular docking of Withaferin A and Withanolides D was performed using AutoDock Vina. Both the bioactive compounds interacted with PKCα. The targets predicted using this approach will serve as leads for the possible therapeutic potential of withanolides, the bioactive ingredients of WS extracts, as anti-cancer drugs.Keywords: withania somnifera, withaferin A, withanolides D, PKCα
Procedia PDF Downloads 146439 Sustainable Accommodation Design: Improving Residential Property Shortage for Low-Income People in Nigeria
Authors: Paulinus W. Ihuah, Iyenemi Ibimina Kakulu, Victor A. Akujuru
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The development of the residential property is very expensive in Nigeria, especially as it is observed in Port Harcourt, although it is also investment costly in the other cities of Nigeria. The costly development nature incidentally reasons to the high deficits in residential property availability and affordability for the low-income people. Therefore, the main purpose of this paper is to provide sustainable accommodation design, which should improve residential property expensiveness and shortages for the low-income people. This is achieved through investigation of the tangible requirements and needs of the end-user of the property (low-income people), which thereafter would enhance sustainable and affordable residential property accommodation design for the end-users. Both the quantitative and qualitative instruments of data collection were utilised. The quantitative instrument via questionnaires was designed to examine the real needs and r requirement of the low-income people. However, the qualitative instrument via structured interview was espoused for the gathering of professionals’ opinions on the three predicted sustainable accommodation design alternatives. The analysis employed content analysis parameters, which offered a sustainable accommodation design and designed alternatives minimises costs and environmental impacts whereas exploiting the social satisfaction in residential accommodation developments. The finding underscores that sustainable accommodation design and development is practicable in Nigeria, so that cost of residential accommodation provided through this system is cheap to the low-income people. Further, erection of multi-storey residential accommodation units such as bedsit structure by utilising the concrete frame structure and building the internal and external walls with hollow concrete blocks within areas 60-130 square meters is encouraged. This paper philosophy indicates that by using sustainable accommodation design practices in Nigeria, improvements in the costs and shortages of residential accommodation can be attained for low-income people. However, policies support the government cannot be overemphasised for proper implementation of the suggested scheme.Keywords: sustainable accommodation, housing design, residential property, low-income people
Procedia PDF Downloads 270438 Determination of the Phosphate Activated Glutaminase Localization in the Astrocyte Mitochondria Using Kinetic Approach
Authors: N. V. Kazmiruk, Y. R. Nartsissov
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Phosphate activated glutaminase (GA, E.C. 3.5.1.2) plays a key role in glutamine/glutamate homeostasis in mammalian brain, catalyzing the hydrolytic deamidation of glutamine to glutamate and ammonium ions. GA is mainly localized in mitochondria, where it has the catalytically active form on the inner mitochondrial membrane (IMM) and the other soluble form, which is supposed to be dormant. At present time, the exact localization of the membrane glutaminase active site remains a controversial and an unresolved issue. The first hypothesis called c-side localization suggests that the catalytic site of GA faces the inter-membrane space and products of the deamidation reaction have immediate access to cytosolic metabolism. According to the alternative m-side localization hypothesis, GA orients to the matrix, making glutamate and ammonium available for the tricarboxylic acid cycle metabolism in mitochondria directly. In our study, we used a multi-compartment kinetic approach to simulate metabolism of glutamate and glutamine in the astrocytic cytosol and mitochondria. We used physiologically important ratio between the concentrations of glutamine inside the matrix of mitochondria [Glnₘᵢₜ] and glutamine in the cytosol [Glncyt] as a marker for precise functioning of the system. Since this ratio directly depends on the mitochondrial glutamine carrier (MGC) flow parameters, key observation was to investigate the dependence of the [Glnmit]/[Glncyt] ratio on the maximal velocity of MGC at different initial concentrations of mitochondrial glutamate. Another important task was to observe the similar dependence at different inhibition constants of the soluble GA. The simulation results confirmed the experimental c-side localization hypothesis, in which the glutaminase active site faces the outer surface of the IMM. Moreover, in the case of such localization of the enzyme, a 3-fold decrease in ammonium production was predicted.Keywords: glutamate metabolism, glutaminase, kinetic approach, mitochondrial membrane, multi-compartment modeling
Procedia PDF Downloads 120437 Establishment and Validation of Correlation Equations to Estimate Volumetric Oxygen Mass Transfer Coefficient (KLa) from Process Parameters in Stirred-Tank Bioreactors Using Response Surface Methodology
Authors: Jantakan Jullawateelert, Korakod Haonoo, Sutipong Sananseang, Sarun Torpaiboon, Thanunthon Bowornsakulwong, Lalintip Hocharoen
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Process scale-up is essential for the biological process to increase production capacity from bench-scale bioreactors to either pilot or commercial production. Scale-up based on constant volumetric oxygen mass transfer coefficient (KLa) is mostly used as a scale-up factor since oxygen supply is one of the key limiting factors for cell growth. However, to estimate KLa of culture vessels operated with different conditions are time-consuming since it is considerably influenced by a lot of factors. To overcome the issue, this study aimed to establish correlation equations of KLa and operating parameters in 0.5 L and 5 L bioreactor employed with pitched-blade impeller and gas sparger. Temperature, gas flow rate, agitation speed, and impeller position were selected as process parameters and equations were created using response surface methodology (RSM) based on central composite design (CCD). In addition, the effects of these parameters on KLa were also investigated. Based on RSM, second-order polynomial models for 0.5 L and 5 L bioreactor were obtained with an acceptable determination coefficient (R²) as 0.9736 and 0.9190, respectively. These models were validated, and experimental values showed differences less than 10% from the predicted values. Moreover, RSM revealed that gas flow rate is the most significant parameter while temperature and agitation speed were also found to greatly affect the KLa in both bioreactors. Nevertheless, impeller position was shown to influence KLa in only 5L system. To sum up, these modeled correlations can be used to accurately predict KLa within the specified range of process parameters of two different sizes of bioreactors for further scale-up application.Keywords: response surface methodology, scale-up, stirred-tank bioreactor, volumetric oxygen mass transfer coefficient
Procedia PDF Downloads 206436 Potential Effects of Climate Change on Streamflow, Based on the Occurrence of Severe Floods in Kelantan, East Coasts of Peninsular Malaysia River Basin
Authors: Muhd. Barzani Gasim, Mohd. Ekhwan Toriman, Mohd. Khairul Amri Kamarudin, Azman Azid, Siti Humaira Haron, Muhammad Hafiz Md. Saad
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Malaysia is a country in Southeast Asia that constantly exposed to flooding and landslide. The disaster has caused some troubles such loss of property, loss of life and discomfort of people involved. This problem occurs as a result of climate change leading to increased stream flow rate as a result of disruption to regional hydrological cycles. The aim of the study is to determine hydrologic processes in the east coasts of Peninsular Malaysia, especially in Kelantan Basin. Parameterized to account for the spatial and temporal variability of basin characteristics and their responses to climate variability. For hydrological modeling of the basin, the Soil and Water Assessment Tool (SWAT) model such as relief, soil type, and its use, and historical daily time series of climate and river flow rates are studied. The interpretation of Landsat map/land uses will be applied in this study. The combined of SWAT and climate models, the system will be predicted an increase in future scenario climate precipitation, increase in surface runoff, increase in recharge and increase in the total water yield. As a result, this model has successfully developed the basin analysis by demonstrating analyzing hydrographs visually, good estimates of minimum and maximum flows and severe floods observed during calibration and validation periods.Keywords: east coasts of Peninsular Malaysia, Kelantan river basin, minimum and maximum flows, severe floods, SWAT model
Procedia PDF Downloads 262435 Advance Hybrid Manufacturing Supply Chain System to Get Benefits of Push and Pull Systems
Authors: Akhtar Nawaz, Sahar Noor, Iftikhar Hussain
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This paper considers advanced hybrid manufacturing planning both push and pull system in which each customer order has a due date by demand forecast and customer orders. We present a tool for model for tool development that requires an absolute due dates and customer orders in a manufacturing supply chain. It is vital for the manufacturing companies to face the problem of variations in demands, increase in varieties by maintaining safety stock and to minimize components obsolescence and uselessness. High inventory cost and low delivery lead time is expected in push type of system and on contrary high delivery lead time and low inventory cost is predicted in the pull type. For this tool for model we need an MRP system for the push and pull environment and control of inventories in push parts and lead time in the pull part. To retain process data quickly, completely and to improve responsiveness and minimize inventory cost, a tool is required to deal with the high product variance and short cycle parts. In practice, planning and scheduling are interrelated and should be solved simultaneously with supply chain to ensure that the due dates of customer orders are met. The proposed tool for model considers alternative process plans for job types, with precedence constraints for job operations. Such a tool for model has not been treated in the literature. To solve the model, tool was developed, so a new technique was required to deal with the issue of high product variance and short life cycles in assemble to order.Keywords: hybrid manufacturing system, supply chain system, make to order, make to stock, assemble to order
Procedia PDF Downloads 564434 An Audit on the Quality of Pre-Operative Intra-Oral Digital Radiographs Taken for Dental Extractions in a General Practice Setting
Authors: Gabrielle O'Donoghue
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Background: Pre-operative radiographs facilitate assessment and treatment planning in minor oral surgery. Quality assurance for dental radiography advocates the As Low As Reasonably Achievable (ALARA) principle in collecting accurate diagnostic information. Aims: To audit the quality of digital intraoral periapicals (IOPAs) taken prior to dental extractions in a metropolitan general dental practice setting. Standards: The National Radiological Protection Board (NRPB) guidance outlines three grades of radiograph quality: excellent (Grade 1 > 70% of total exposures), diagnostically acceptable (Grade 2 <20%), and unacceptable (Grade 3 <10%). Methodology: A study of pre-operative radiographs taken prior to dental extractions across 12 private general dental practices in a large metropolitan area by 44 practitioners. A total of 725 extractions were assessed, allowing 258 IOPAs to be reviewed in one audit cycle. Results: First cycle: Of 258 IOPAs: 223(86.4%) scored Grade 1, 27(10.5%) Grade 2, and 8(3.1%) Grade 3. The standard was met. 35 dental extractions were performed without an available pre-operative radiograph. Action Plan & Recommendations: Results were distributed to all staff and a continuous professional development evening organized to outline recommendations to improve image quality. A second audit cycle is proposed at a six-month interval to review the recommendations and appraise results. Conclusion: The overall standard of radiographs met the published guidelines. A significant improvement in the number of procedures undertaken without pre-operative imaging is expected at a six-month interval period. An investigation into undiagnostic imaging and associated adverse patient outcomes is being considered. Maintenance of the standards achieved is predicted in the second audit cycle to ensure consistent high quality imaging.Keywords: audit, oral radiology, oral surgery, periapical radiographs, quality assurance
Procedia PDF Downloads 165433 Hydrogen Production at the Forecourt from Off-Peak Electricity and Its Role in Balancing the Grid
Authors: Abdulla Rahil, Rupert Gammon, Neil Brown
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The rapid growth of renewable energy sources and their integration into the grid have been motivated by the depletion of fossil fuels and environmental issues. Unfortunately, the grid is unable to cope with the predicted growth of renewable energy which would lead to its instability. To solve this problem, energy storage devices could be used. Electrolytic hydrogen production from an electrolyser is considered a promising option since it is a clean energy source (zero emissions). Choosing flexible operation of an electrolyser (producing hydrogen during the off-peak electricity period and stopping at other times) could bring about many benefits like reducing the cost of hydrogen and helping to balance the electric systems. This paper investigates the price of hydrogen during flexible operation compared with continuous operation, while serving the customer (hydrogen filling station) without interruption. The optimization algorithm is applied to investigate the hydrogen station in both cases (flexible and continuous operation). Three different scenarios are tested to see whether the off-peak electricity price could enhance the reduction of the hydrogen cost. These scenarios are: Standard tariff (1 tier system) during the day (assumed 12 p/kWh) while still satisfying the demand for hydrogen; using off-peak electricity at a lower price (assumed 5 p/kWh) and shutting down the electrolyser at other times; using lower price electricity at off-peak times and high price electricity at other times. This study looks at Derna city, which is located on the coast of the Mediterranean Sea (32° 46′ 0 N, 22° 38′ 0 E) with a high potential for wind resource. Hourly wind speed data which were collected over 24½ years from 1990 to 2014 were in addition to data on hourly radiation and hourly electricity demand collected over a one-year period, together with the petrol station data.Keywords: hydrogen filling station off-peak electricity, renewable energy, off-peak electricity, electrolytic hydrogen
Procedia PDF Downloads 231432 In Silico Exploration of Quinazoline Derivatives as EGFR Inhibitors for Lung Cancer: A Multi-Modal Approach Integrating QSAR-3D, ADMET, Molecular Docking, and Molecular Dynamics Analyses
Authors: Mohamed Moussaoui
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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeuticsKeywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer
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