Search results for: reliable facility location model

Authors: Walid Wahballah, Taher Bazan, Fawzy Eltohamy

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One of the important functions of the satellite attitude control system is to provide the required pointing accuracy and attitude stability for optical remote sensing satellites to achieve good image quality. Although offering noise reduction and increased sensitivity, time delay and integration (TDI) charge coupled devices (CCDs) utilized in high-resolution satellites (HRS) are prone to introduce large amounts of pixel smear due to the instability of the line of sight. During on-orbit imaging, as a result of the Earth’s rotation and the satellite platform instability, the moving direction of the TDI-CCD linear array and the imaging direction of the camera become different. The speed of the image moving on the image plane (focal plane) represents the image motion velocity whereas the angle between the two directions is known as the drift angle (β). The drift angle occurs due to the rotation of the earth around its axis during satellite imaging; affecting the geometric accuracy and, consequently, causing image quality degradation. Therefore, the image motion velocity vector and the drift angle are two important factors used in the assessment of the image quality of TDI-CCD based optical remote sensing satellites. A model for estimating the image motion velocity and the drift angle in HRS is derived. The six satellite attitude control parameters represented in the derived model are the (roll angle φ, pitch angle θ, yaw angle ψ, roll angular velocity φ֗, pitch angular velocity θ֗ and yaw angular velocity ψ֗ ). The influence of these attitude parameters on the image quality is analyzed by establishing a relationship between the image motion velocity vector, drift angle and the six satellite attitude parameters. The influence of the satellite attitude parameters on the image quality is assessed by the presented model in terms of modulation transfer function (MTF) in both cross- and along-track directions. Three different cases representing the effect of pointing accuracy (φ, θ, ψ) bias are considered using four different sets of pointing accuracy typical values, while the satellite attitude stability parameters are ideal. In the same manner, the influence of satellite attitude stability (φ֗, θ֗, ψ֗) on image quality is also analysed for ideal pointing accuracy parameters. The results reveal that cross-track image quality is influenced seriously by the yaw angle bias and the roll angular velocity bias, while along-track image quality is influenced only by the pitch angular velocity bias.

Keywords: high-resolution satellites, pointing accuracy, attitude stability, TDI-CCD, smear, MTF

Procedia PDF Downloads 399

Authors: Ebrahim Shayesteh, Nikolaos Styliaras, Alin George Raducu, Ozan Sahin, Daniel Pombo VáZquez, Jonas Funkquist, Sotirios Thanopoulos

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One of the important requirements in many code generation projects is defining some of the model parameters tunable. This helps to update the model parameters without performing the code generation again. This paper studies the concept of embedded code generation by MATLAB/Simulink coder targeting the TwinCAT Simulink system. The generated runtime modules are then tested and deployed to the TwinCAT 3 engineering environment. However, defining the parameters tunable in MATLAB/Simulink code generation targeting TwinCAT is not very straightforward. This paper focuses on this subject and reviews some of the techniques tested here to make the parameters tunable in generated runtime modules. Three techniques are proposed for this purpose, including normal tunable parameters, callback functions, and mask subsystems. Moreover, some test Simulink models are developed and used to evaluate the results of proposed approaches. A brief summary of the study results is presented in the following. First of all, the parameters defined tunable and used in defining the values of other Simulink elements (e.g., gain value of a gain block) could be changed after the code generation and this value updating will affect the values of all elements defined based on the values of the tunable parameter. For instance, if parameter K=1 is defined as a tunable parameter in the code generation process and this parameter is used to gain a gain block in Simulink, the gain value for the gain block is equal to 1 in the gain block TwinCAT environment after the code generation. But, the value of K can be changed to a new value (e.g., K=2) in TwinCAT (without doing any new code generation in MATLAB). Then, the gain value of the gain block will change to 2. Secondly, adding a callback function in the form of “pre-load function,” “post-load function,” “start function,” and will not help to make the parameters tunable without performing a new code generation. This means that any MATLAB files should be run before performing the code generation. The parameters defined/calculated in this file will be used as fixed values in the generated code. Thus, adding these files as callback functions to the Simulink model will not make these parameters flexible since the MATLAB files will not be attached to the generated code. Therefore, to change the parameters defined/calculated in these files, the code generation should be done again. However, adding these files as callback functions forces MATLAB to run them before the code generation, and there is no need to define the parameters mentioned in these files separately. Finally, using a tunable parameter in defining/calculating the values of other parameters through the mask is an efficient method to change the value of the latter parameters after the code generation. For instance, if tunable parameter K is used in calculating the value of two other parameters K1 and K2 and, after the code generation, the value of K is updated in TwinCAT environment, the value of parameters K1 and K2 will also be updated (without any new code generation).

Keywords: code generation, MATLAB, tunable parameters, TwinCAT

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Authors: Maatouk Khoukhi

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Nowadays the reduction of the energy consumed by buildings to achieve mainly the thermal comfort for the occupants represent the main concern for architects and building designers. The common and traditional solution to achieve this target is the design of a highly insulated envelope and reduce the opening and the transparent elements such windows. However, this will lead to the artificial lighting system to consume more energy to compensate the lack of natural lighting coming through the glazed parts of the building envelope. Therefore, a good balance between sufficient daylight and control thermal heat through the building envelope should be considered for energy saving purpose. To achieve a better indoor environment the windows size and spacing including the interior finishing and the location of the partition must be assessed accurately. Daylighting is the controlled admission of natural light into space through windows and transparent elements of the building envelope which helps create a visually stimulating and productive environment for building occupants. The main concern is not to provide enough daylight to an occupied space, but how to achieve this without any undesirable side effect. Indeed, the glare is a major problem in glazed façade buildings, and this could be reduced by using tinted windows. The main target of this research is to investigate the daylight adequacy of functional needs in old Omani Forts and how they have been designed and built to avoid glare and overheating with the appropriate window-to-floor ratio. Because more windows do not automatically result in more daylighting but that is natural light has been controlled and distributed properly throughout the space. Spaces from different Omani and Portuguese Forts under the same climate conditions are considered in order to compare the daylight illuminance levels and examine the similarities and differences in visual attributes between them. The result of this study indicates that lighting preference is not universal and people from different geographical locations are adapted to certain illuminance levels. Therefore, the standards could not be generalized for the entire world. This would be useful to practitioners who are designing to effectively address the diversity of user’s lighting levels preferences in our globally connected society.

Keywords: day lighting, energy, forts, thermal comfort

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia AbdulMajid, Maryam Zahedifard

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Colon cancer is one of the most prevalent cancers in the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. New schiff based compounds are reported to exhibit a wide spectrum of biological activities of therapeutic importance. To evaluate inhibitory properties of CdCl2(C14H21N3O2) complex on colonic aberrant crypt foci, five groups of 7-week-old male rats were used. Control group was fed with 10% Tween 20 once a day, cancer control group was intra-peritoneally injected with 15 mg/kg Azoxymethan, drug control group was injected with 15 mg/kg azoxymethan and 5-Flourouracil, experimental groups were fed with 2.5 and 5 mg/kg CdCl2(C14H21N3O2) compound each once a day. Administration of compound were found to be effectively chemoprotective. Andrographolide suppressed total colonic ACF formation up to 72% to 74%, respectively, when compared with control group. The results also showed a significant increase in glutathione peroxidase, superoxide dismutase, catalase activities and a decrease in malondialdehyde level. Immunohistochemical staining demonstrated down-regulation of PCNA protein. According to the Western blot comparison analysis, COX-2 and Bcl2 is up-regulated whilst the Bax is down-regulated. according to these data, this compound plays promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, Schiff based compound, aberrant crypt foci (ACF), immunohistochemical staining

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Authors: Trevor R. Higgins, Ben Lopez

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Australian football fans have a tendency to indulge in foreign football clubs, often assigning a greater value to foreign clubs, in preference to the Australian National football competition; the A-League. There currently exists a gap in the knowledge available in relation to football fans in Australia, their engagement with foreign football teams and the impact that this may have with their engagement with A-League. The purpose of this study was to compare the engagement of the members of the Manchester United Supporters Club - Australia (MUSC-Aus) with Manchester United and the A-League. An online survey was implemented to gather the relevant data from members of the MUSC-Aus. Results from completed surveys were collected, and analyzed in relation to engagement levels with Manchester United and the A-League. Members of MUSC-Aus who responded to the survey were predominantly male (94%) and born in Australia (46%), England (25%), Ireland (7%), were greatly influenced in their choice of Manchester United by family (43%) and team history (16%), whereas location was the overwhelming influence in supporting the A-League (88%). Importantly, there was a reduced level of engagement in the A-League on two accounts. Firstly, only 64% of MUSC-Aus engaged with the A-League, reporting perceptions of low standard as the major reason (50%). Secondly, MUSC-Aus members who engaged in the A-League reported reduced engagement in the A-League, identified through spending patterns. MUSC-Aus members’ expenditure on Manchester United engagement was 400% greater than expenditure on A-League engagement. Furthermore, additional survey responses indicated that the level of commitment towards the A-League overall was less than Manchester United. The greatest impact on fan engagement in the A-League by MUSC-Aus can be attributed to several primary factors; family support, team history and perceptions to on-field performance and quality of players. Currently, there is little that can be done in regards to enhancing family and history as the A-League is still in its infancy. Therefore, perceptions of on-field performances and player quality should be addressed. Introducing short-term international marquee contracts to A-League rosters, across the entire competition, may provide the platform to raise the perception of the A-League player quality with minimal impact on local player development. In addition, a national marketing campaign promoting the success of A-League clubs in the ACL, as well as promoting the skill on display in the A-League may address the negative association with the standard of the A-League competition.

Keywords: engagement, football, perceptions of performance, team

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Authors: Ankit Sinha, Soham Banerjee, Pratik Chattopadhyay

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Automated product recognition in retail stores is an important real-world application in the domain of Computer Vision and Pattern Recognition. In this paper, we consider the problem of automatically identifying the classes of the products placed on racks in retail stores from an image of the rack and information about the query/product images. We improve upon the existing approaches in terms of effectiveness and memory requirement by developing a two-stage object detection and recognition pipeline comprising of a Faster-RCNN-based object localizer that detects the object regions in the rack image and a ResNet-18-based image encoder that classifies the detected regions into the appropriate classes. Each of the models is fine-tuned using appropriate data sets for better prediction and data augmentation is performed on each query image to prepare an extensive gallery set for fine-tuning the ResNet-18-based product recognition model. This encoder is trained using a triplet loss function following the strategy of online-hard-negative-mining for improved prediction. The proposed models are lightweight and can be connected in an end-to-end manner during deployment to automatically identify each product object placed in a rack image. Extensive experiments using Grozi-32k and GP-180 data sets verify the effectiveness of the proposed model.

Keywords: retail stores, faster-RCNN, object localization, ResNet-18, triplet loss, data augmentation, product recognition

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Authors: Alastair Hales, Xi Jiang, Siming Zhang

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Numerical methods are used to generate vortices in a domain. Through considered design, two counter-rotating vortices may interact and effectively drive one another downstream. This phenomenon is comparable to the vortex interaction that occurs in a region immediately downstream from two counter-oscillating piezoelectric (PE) fan blades. PE fans are small blades clamped at one end and driven to oscillate at their first natural frequency by an extremely low powered actuator. In operation, the high oscillation amplitude and frequency generate sufficient blade tip speed through the surrounding air to create downstream air flow. PE fans are considered an ideal solution for low power hot spot cooling in a range of small electronic devices, but a single blade does not typically induce enough air flow to be considered a direct alternative to conventional air movers, such as axial fans. The development of face-to-face PE fan arrays containing multiple blades oscillating in counter-phase to one another is essential for expanding the range of potential PE fan applications regarding the cooling of power electronics. Even in an unoptimised state, these arrays are capable of moving air volumes comparable to axial fans with less than 50% of the power demand. Replicating the airflow generated by face-to-face PE fan arrays without including the actual blades in the model reduces the process’s computational demands and enhances the rate of innovation and development in the field. Vortices are generated at a defined inlet using a time-dependent velocity profile function, which pulsates the inlet air velocity magnitude. This induces vortex generation in the considered domain, and these vortices are shown to separate and propagate downstream in a regular manner. The generation and propagation of a single vortex are compared to an equivalent vortex generated from a PE fan blade in a previous experimental investigation. Vortex separation is found to be accurately replicated in the present numerical model. Additionally, the downstream trajectory of the vortices’ centres vary by just 10.5%, and size and strength of the vortices differ by a maximum of 10.6%. Through non-dimensionalisation, the numerical method is shown to be valid for PE fan blades with differing parameters to the specific case investigated. The thorough validation methods presented verify that the numerical model may be used to replicate vortex formation from an oscillating PE fans blade. An investigation is carried out to evaluate the effects of varying the distance between two PE fan blade, pitch. At small pitch, the vorticity in the domain is maximised, along with turbulence in the near vicinity of the inlet zones. It is proposed that face-to-face PE fan arrays, oscillating in counter-phase, should have a minimal pitch to optimally cool nearby heat sources. On the other hand, downstream airflow is maximised at a larger pitch, where the vortices can fully form and effectively drive one another downstream. As such, this should be implemented when bulk airflow generation is the desired result.

Keywords: piezoelectric fans, low energy cooling, vortex formation, computational fluid dynamics

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Authors: Anupriya, Bikramjit Sinfh, Radhay Shyam

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In order to improve mixing phenomena and combustion processes in supersonic flow, the current work has concentrated on identifying the ideal cavity parameters using CFD ANSYS Fluent. Offset ratios (OR) and aft ramp angles () have been manipulated in simulations of several models, but the length-to-depth ratio has remained the same. The length-to-depth ratio of all cavity flows is less than 10, making them all open. Hydrogen fuel was injected into a supersonic air flow with a Mach number of 3.75 using a chamber with a 1 mm diameter and a transverse slot nozzle. The free stream had conditions of a pressure of 1.2 MPa, a temperature of 299K, and a Reynolds number of 2.07x107. This method has the ability to retain a flame since the cavity facilitates rapid mixing of fuel and oxidizer and decreases total pressure losses. The impact of the cavity on combustion efficiency and total pressure loss is discussed, and the results are compared to those of a model without a cavity. Both the mixing qualities and the combustion processes were enhanced in the model with the cavity. The overall pressure loss as well as the effectiveness of the combustion process both increase with the increase in the ramp angle to the rear. When OR is increased, however, resistance to the supersonic flow field is reduced, which has a detrimental effect on both parameters. For a given ramp height, larger pressure losses were observed at steeper ramp angles due to increased eddy-viscous turbulent flow and increased wall drag.

Keywords: total pressure loss, flame holder, supersonic combustion, combustion efficiency, cavity, nozzle

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Authors: Lukman Abiodun Nafiu

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This study examines the impact evaluation of vaccination against eight-child-killer diseases on under-five children mortality at Mbale District. It was driven by three specific objectives which are to determine the proportion of under-five children mortality due to the eight-child-killer diseases to the total under-five children mortality; establish the cause-effect relationship between the eight-child-killer diseases and under-five children mortality; as well as establish the dependence of under-five children mortality in the location at Mbale District. A community based cross-sectional and longitudinal (panel) study design involving both quantitative and qualitative (focus group discussion and in-depth interview) approaches was employed over a period of 36 months. Multi-stage cluster design involving Health Sub-District (HSD), Forms of Ownership (FOO) and Health Facilities Centres (HFC) as the first, second and third stages respectively was used. Data was collected regarding the eight-child-killer diseases namely: measles, pneumonia, pertussis (whooping cough), diphtheria, poliomyelitis (polio), tetanus, haemophilus influenza, rotavirus gastroenteritis and mortality regarding immunized and non-immunized children aged 0-59 months. We monitored the children over a period of 24 months. The study used a sample of 384 children out of all the registered children for each year at Mbale Referral Hospital and other Primary Health Care Centres (HCIV, HCIII and HCII) at Mbale District between 2015 and 2019. These children were followed from birth to their current state (living or dead). The data collected in this study was analysed using cross tabulation and the chi-square test. The study concluded that majority of mothers at Mbale district took their children for immunization and thus reducing the occurrence of under-five children mortality. Overall, 2.3%, 4.6%, 3.1%, 5.4%, 1.5%, 3.8%, 0.0% and 0.0% of under-five children had polio, tetanus, diphtheria, measles, pertussis, pneumonia, haemophilus influenzae and rotavirus gastroenteritis respectively across all the sub counties at Mbale district during the period considered. Also, different locations (sub counties) do not have significant influence on the occurrence of these eight-child-killer diseases among the under-five children at Mbale district. Therefore, the study recommended that government and agencies should continue to work together to implement measures of vaccination programs and increasing access to basic health care with a continuous improvement on the social interventions to progress child survival.

Keywords: Diseases, Mortality, Children, Vaccination

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Authors: S. Mani, M. Kafil, E. Asadi

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Condition Monitoring (CM) of electrical equipment has gained remarkable importance during the recent years; due to huge production losses, substantial imposed costs and increases in vulnerability, risk and uncertainty levels. Power cables feed numerous electrical equipment such as transformers, motors, and electric furnaces; thus their condition assessment is of a very great importance. This paper investigates electrical, structural and environmental failure sources, all of which influence cables' performances and limit their uptimes; and provides a comprehensive framework entailing practical CM guidelines for maintenance of cables in industries. The multilevel CM framework presented in this study covers performance indicative features of power cables; with a focus on both online and offline diagnosis and test scenarios, and covers short-term and long-term threats to the operation and longevity of power cables. The study, after concisely overviewing the concept of CM, thoroughly investigates five major areas of power quality, Insulation Quality features of partial discharges, tan delta and voltage withstand capabilities, together with sheath faults, shield currents and environmental features of temperature and humidity; and elaborates interconnections and mutual impacts between those areas; using mathematical formulation and practical guidelines. Detection, location, and severity identification methods for every threat or fault source are also elaborated. Finally, the comprehensive, practical guidelines presented in the study are presented for the specific case of Electric Arc Furnace (EAF) feeder MV power cables in Mobarakeh Steel Company (MSC), the largest steel company in MENA region, in Iran. Specific technical and industrial characteristics and limitations of a harsh industrial environment like MSC EAF feeder cable tunnels are imposed on the presented framework; making the suggested package more practical and tangible.

Keywords: condition monitoring, diagnostics, insulation, maintenance, partial discharge, power cables, power quality

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Authors: Fally Titikpina, Abderafi Charki, Antoine Caucheteux, David Bigaud

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The building sector is one of the largest energy consumer with about 40% of the final energy consumption in the European Union. Ensuring building energy performance is of scientific, technological and sociological matter. To assess a building energy performance, the consumption being predicted or estimated during the design stage is compared with the measured consumption when the building is operational. When valuing this performance, many buildings show significant differences between the calculated and measured consumption. In order to assess the performance accurately and ensure the thermal efficiency of the building, it is necessary to evaluate the uncertainties involved not only in measurement but also those induced by the propagation of dynamic and static input data in the model being used. The evaluation of measurement uncertainty is based on both the knowledge about the measurement process and the input quantities which influence the result of measurement. Measurement uncertainty can be evaluated within the framework of conventional statistics presented in the \textit{Guide to the Expression of Measurement Uncertainty (GUM)} as well as by Bayesian Statistical Theory (BST). Another choice is the use of numerical methods like Monte Carlo Simulation (MCS). In this paper, we proposed to evaluate the uncertainty associated to the use of a simplified model for the estimation of the energy consumption of a given building. A detailed review and discussion of these three approaches (GUM, MCS and BST) is given. Therefore, an office building has been monitored and multiple sensors have been mounted on candidate locations to get required data. The monitored zone is composed of six offices and has an overall surface of 102 $m^2$. Temperature data, electrical and heating consumption, windows opening and occupancy rate are the features for our research work.

Keywords: building energy performance, uncertainty evaluation, GUM, bayesian approach, monte carlo method

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Authors: Zhaoan Wang

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Research in predictive maintenance modeling has improved in the recent years to predict failures and needed maintenance with high accuracy, saving cost and improving manufacturing efficiency. However, classic prediction models provide little valuable insight towards the most important features contributing to the failure. By analyzing and quantifying feature importance in predictive maintenance models, cost saving can be optimized based on business goals. First, multiple classifiers are evaluated with cross-validation to predict the multi-class of failures. Second, predictive performance with features provided by different feature selection algorithms are further analyzed. Third, features selected by different algorithms are ranked and combined based on their predictive power. Finally, linear explainer SHAP (SHapley Additive exPlanations) is applied to interpret classifier behavior and provide further insight towards the specific roles of features in both local predictions and global model behavior. The results of the experiments suggest that certain features play dominant roles in predictive models while others have significantly less impact on the overall performance. Moreover, for multi-class prediction of machine failures, the most important features vary with type of machine failures. The results may lead to improved productivity and cost saving by prioritizing sensor deployment, data collection, and data processing of more important features over less importance features.

Keywords: automated supply chain, intelligent manufacturing, predictive maintenance machine learning, feature engineering, model interpretation

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Authors: Kulin Dave, Kapil Mohan

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Earthquakes are considered to be the most destructive rapid-onset disasters human beings are exposed to. The amount of loss it brings in is sufficient to take careful considerations for designing of structures and facilities. Seismic Hazard Analysis is one such tool which can be used for earthquake resistant design. Ground Response Analysis is one of the most crucial and decisive steps for seismic hazard analysis. Rapar district of Kutch, Gujarat falls in Zone 5 of earthquake zone map of India and thus has high seismicity because of which it is selected for analysis. In total 8 bore-log data were studied at different locations in and around Rapar district. Different soil engineering properties were analyzed and relevant empirical correlations were used to calculate maximum shear modulus (Gmax) and shear wave velocity (Vs) for the soil layers. The soil was modeled using Pressure-Dependent Modified Kodner Zelasko (MKZ) model and the reference curve used for fitting was Seed and Idriss (1970) for sand and Darendeli (2001) for clay. Both Equivalent linear (EL), as well as Non-linear (NL) ground response analysis, has been carried out with Masing Hysteretic Re/Unloading formulation for comparison. Commercially available DEEPSOIL v. 7.0 software is used for this analysis. In this study an attempt is made to quantify ground response regarding generated acceleration time-history at top of the soil column, Response spectra calculation at 5 % damping and Fourier amplitude spectrum calculation. Moreover, the variation of Peak Ground Acceleration (PGA), Maximum Displacement, Maximum Strain (in %), Maximum Stress Ratio, Mobilized Shear Stress with depth is also calculated. From the study, PGA values estimated in rocky strata are nearly same as bedrock motion and marginal amplification is observed in sandy silt and silty clays by both analyses. The NL analysis gives conservative results of maximum displacement as compared to EL analysis. Maximum strain predicted by both studies is very close to each other. And overall NL analysis is more efficient and realistic because it follows the actual hyperbolic stress-strain relationship, considers stiffness degradation and mobilizes stresses generated due to pore water pressure.

Keywords: DEEPSOIL v 7.0, ground response analysis, pressure-dependent modified Kodner Zelasko model, MKZ model, response spectra, shear wave velocity

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Authors: Sajjad Hussain, Sabir Khan, Maria Del Pilar Taboada Sotomayor

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This work demonstrates the synthesis of magnetic molecularly imprinted polymers (MMIPs) for determination of a selected pesticide (ametryne) using high performance liquid chromatography (HPLC). Computational simulation can assist the choice of the most suitable monomer for the synthesis of polymers. The (MMIPs) were polymerized at the surface of Fe3O4@SiO2 magnetic nanoparticles (MNPs) using 2-vinylpyradine as functional monomer, ethylene-glycol-dimethacrylate (EGDMA) is a cross-linking agent and 2,2-Azobisisobutyronitrile (AIBN) used as radical initiator. Magnetic non-molecularly imprinted polymer (MNIPs) was also prepared under the same conditions without analyte. The MMIPs were characterized by scanning electron microscopy (SEM), Brunauer, Emmett and Teller (BET) and Fourier transform infrared spectroscopy (FTIR). Pseudo first order and pseudo second order model were applied to study kinetics of adsorption and it was found that adsorption process followed the pseudo first order kinetic model. Adsorption equilibrium data was fitted to Freundlich and Langmuir isotherms and the sorption equilibrium process was well described by Langmuir isotherm mode. The selectivity coefficients (α) of MMIPs for ametryne with respect to atrazine, ciprofloxacin and folic acid were 4.28, 12.32, and 14.53 respectively. The spiked recoveries ranged between 91.33 and 106.80% were obtained. The results showed high affinity and selectivity of MMIPs for pesticide ametryne in the food samples.

Keywords: molecularly imprinted polymer, pesticides, magnetic nanoparticles, adsorption

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Authors: Mohamed Ouzzane, Mahmoud Bady

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Due to energy and environment context, research is looking for the use of clean and energy efficient system in cooling industry. In this regard, the ejector represents one of the promising solutions. The thermal ejector is a passive component used for thermal compression in refrigeration and cooling systems, usually activated by heat either waste or solar. The present study introduces a theoretical analysis of the cooling system which uses a gas ejector thermal compression. A theoretical model is developed and applied for the design and simulation of the ejector, as well as the whole cooling system. Besides the conservation equations of mass, energy and momentum, the gas dynamic equations, state equations, isentropic relations as well as some appropriate assumptions are applied to simulate the flow and mixing in the ejector. This model coupled with the equations of the other components (condenser, evaporator, pump, and generator) is used to analyze profiles of pressure and velocity (Mach number), as well as evaluation of the cycle cooling capacity. A FORTRAN program is developed to carry out the investigation. Properties of refrigerant R134a are calculated using real gas equations. Among many parameters, it is thought that the generator pressure is the cornerstone in the cycle, and hence considered as the key parameter in this investigation. Results show that the generator pressure has a great effect on the ejector and on the whole cooling system. At high generator pressures, strong shock waves inside the ejector are created, which lead to significant condenser pressure at the ejector exit. Additionally, at higher generator pressures, the designed system can deliver cooling capacity for high condensing pressure (hot season).

Keywords: air cooling system, refrigeration, thermal ejector, thermal compression

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Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Anamarija Mandic, Katarina Penov Gasi, Marija Sakac, Aleksandar Okljesa, Andrea Nikolic

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The present paper deals with chromatographic lipophilicity prediction of newly synthesized steroid derivatives. The prediction was achieved using in silico generated molecular descriptors and quantitative structure-retention relationship (QSRR) methodology with the artificial neural networks (ANN) approach. Chromatographic lipophilicity of the investigated compounds was expressed as retention factor value logk. For QSRR modeling, a feedforward back-propagation ANN with gradient descent learning algorithm was applied. Using the novel sum of ranking differences (SRD) method generated ANN models were ranked. The aim was to distinguish the most consistent QSRR model that can be found, and similarity or dissimilarity between the models that could be noticed. In this study, SRD was performed with average values of retention factor value logk as reference values. An excellent correlation between experimentally observed retention factor value logk and values predicted by the ANN was obtained with a correlation coefficient higher than 0.9890. Statistical results show that the established ANN models can be applied for required purpose. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation in Science and Technology).

Keywords: artificial neural networks, liquid chromatography, molecular descriptors, steroids, sum of ranking differences

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Authors: Kara J. Coffman-Rea, Karen E. Samonds

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Microplastic pollution is an urgent global threat to our planet and human health. Microplastic particles have been detected within our food, water, and atmosphere, and found within the human stool, placenta, and lung tissue. However, most spectrometric microplastic detection methods require chemical digestion which can alter or destroy microplastic particles and makes it impossible to acquire information about their in-situ distribution. MALDI TOF MS (Matrix-assisted laser desorption ionization-time of flight mass spectrometry) is an analytical method using a soft ionization technique that can be used for polymer analysis. This method provides a valuable opportunity to both acquire information regarding the in-situ distribution of microplastics and also minimizes the destructive element of chemical digestion. In addition, MALDI TOF MS allows for expanded analysis of the microplastics including detection of specific additives that may be present within them. MALDI TOF MS is particularly sensitive to sample preparation and has not yet been used to analyze environmental microplastics within their specific location (e.g., biological tissues, sediment, water). In this study, microplastics were created using polyethylene gloves, polystyrene micro-foam, and polyethylene terephthalate cable sleeving. Plastics were frozen using liquid nitrogen and ground to obtain small fragments. An artificial tissue was created using a cellulose sponge as scaffolding coated with a MaxGel Extracellular Matrix to simulate human lung tissue. Optimal preparation techniques (e.g., matrix, cationization reagent, solvent, mixing ratio, laser intensity) were first established for each specific polymer type. The artificial tissue sample was subsequently spiked with microplastics, and specific polymers were detected using MALDI-TOF-MS. This study presents a novel method for the detection of environmental polyethylene, polyethylene terephthalate, and polystyrene microplastics within a complex sample. Results of this study provide an effective method that can be used in future microplastics research and can aid in determining the potential threats to environmental and human health that they pose.

Keywords: environmental plastic pollution, MALDI-TOF MS, microplastics, polymer identification

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Authors: Jocelyn L. Alimondo, Juna O. Sabelo

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This study explored the MTB-MLE implementation practices of teachers in one monolingual elementary school and one multilingual elementary school in Benguet, Philippines. It used phenomenological approach employing participant-observation, focus group discussion and individual interview. Data were gathered using a video camera, an audio recorder, and an FGD guide and were treated through triangulation and coding. From the data collected, varied ways in implementing the MTB-MLE program were noted. These are: Teaching using a hybrid first language, teaching using a foreign LOI, using translation and multilingual instruction, and using L2/L3 to unlock L1. However, these practices come with challenges such as the a conflict between the mandated LOI and what pupils need, lack of proficiency of teachers in the mandated LOI, facing unreceptive parents, stagnation of knowledge resulting from over-familiarity of input, and zero learning resulting from an incomprehensible language input. From the practices and challenges experienced by the teachers, a model of MTB-MLE approach, the 3L-in-one approach, to teaching was created to illustrate the practice which teachers claimed to be the best way to address the challenges besetting them while at the same time satisfying the academic needs of their pupils. From the findings, this paper concludes that despite the challenges besetting the teachers, they still displayed creativity in coming up with relevant teaching practices, the unreceptiveness of some teachers and parents sprung from the fact that they do not understand the real concept of MTB-MLE, greater challenges are being faced by teachers in multilingual school due to the diverse linguistic background of their clients, and the most effective approach in implementing MTB-MLE is the multilingual approach, allowing the use of the pupils’ mother tongue, L2 (Filipino), L3 (English), and other languages familiar to the students.

Keywords: MTB-MLE Philippines, MTB-MLE model, first language, multilingual instruction

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Authors: Polina Prokopovich

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Disease-modifying osteoarthritis drugs (DMOADs) are a new therapeutic class for OA, preventing or inhibiting OA development. Unfortunately, none of the DMOADs have been clinically approved due to their poor therapeutic effects in clinical trials. The joint environment has played a role in the poor clinical performance of these drugs by limiting the amount of drug effectively delivered as well as the time that the drug spends within the joint space. The current study aims to enhance the cartilage uptake and retention time of the DMOADs-model (licofelone), which showed a significant therapeutic effect against OA progression and is currently in phase III. Licofelone will be covalently conjugated to the hydrolysable, cytocompatible, and cationic poly beta-amino ester polymers (PBAE). The cationic polymers (A16 and A87) can be electrostatically attached to the negatively charged cartilage component (glycosaminoglycan), which will increase the drug penetration through the cartilage and extend the drug time within the cartilage. In the cartilage uptake and retention time studies, an increase of 18 to 37 times of the total conjugated licofelone to A87 and A16 was observed when compared to the free licofelone. Furthermore, the conjugated licofelone to A87 was detectable within the cartilage at 120 minutes, while the free licofelone was not detectable after 60 minutes. Additionally, the A87-licofelone conjugate showed no effect on the chondrocyte viability. In conclusion, the cationic A87 and A16 polymers increased the percentage of licofelone within the cartilage, which could potentially enhance the therapeutic effect and pharmacokinetic performance of licofelone or other DMOADs clinically.

Keywords: PBAE, cartilage., osteoarthritis, injectable biomaterials, drug delivery

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Authors: H. Jalahi, A. Yazdanpanah Nozari

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Background and Purpose: Assessment of learners’ performance is an important factors in teaching-learning process. When a factor is sensitive and has high influence on life, their assessment should be done precisely. Thinking dispositions are very important factors in medical education because of its specific condition. In this study a model is designed for fostering thinking dispositions of learners in which authentic assessment is an important element. Materials and Methods: Objective based research is developmental, and such a model was not designed for curricula. Data collection and comparing approaches about assessment and analyzing current assessments offered applied proposals. Results: Based on research findings, the current assessments are response-based, that is students instead of product of response, only offers the specific response which the teachers expects; but authentic assessment is a form of assessment in which students are asked to perform real-word tasks that demonstrate meaningful application of essential knowledge and skills. Conclusion: Because of the difficulties and unexpected problems in life and individuals needs to lifelong learning and conditions in medical course that require decision making in specific times, we must pay attention to reach thinking dispositions and it should be included in curriculum. Authentic assessment as an important aspect of curriculum can help fostering thinking dispositions of learners. Using this kind of assessments which focus on application of information and skills to solve real-word tasks have more important role in medical courses.

Keywords: assessment, authentic, medical courses, developmental

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Authors: Song Hung Chi, Lee Chun Benn

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Follow by the “A Research on Types of Settlement Housing Alterations of Chinese New Village in Malaysia- A Study in Ampang New Village, Selangor” preliminary informed that the main factors for expansion and enlargement suitably due to the needs of user's life and restoration purpose. The alterations behavior generally derived at the rear position of main house with different types of derivatives, the averages expansion area are not exceeding of 100㎡, while building materials used were wooden, wooden structure, and zinc which are non-permanent building materials. Therefore, a subsequent studies taken in this paper, further to analyze the drawing with summarize method, to explore the derived forms and the constituted rules of housing alterations in Ampang Village, as a more complete presentation of housing alterations in New Village. Firstly, classified the existing housing alterations into three types by using summarize method, which are Type 1, Additional of Prototype House; Type 2, Expansion of Prototype House; and Type 3, Diffusion of Additional. The results shows that the derivative mode of alterations can be divided into the use of "continuous wall" or "non-continuous wall," this will affects the structural systems and roof styles of alterations, and formed the different layers of interior space with "stages" and "continuity". On the aspects of spatial distribution, sacrificial area as a prescriptive function of space, it was mostly remains in the original location which in the center of living area after alterations. It is an important characteristic in a New Village house, reflecting the traditional Ethics of Hakka Chinese communities in the settlement. In addition, wooden as the main building materials of constituted rules for the prototype house, although there were appeared other building materials, such as cement, brick, glass, metal and zinc after alterations, but still mostly as "wooden house" pattern. Result show because of the economy of village does not significantly improve, and also forming the similarity types in alterations and constructions of the additional building with the existing. It did not significantly improve on the quality of living, but only increased the area of usage space.

Keywords: Ampang new village, derived forms, constituted rules, alterations

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Authors: Bezhan Ghvaberidze

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A multiple criteria optimization approach for the solution of the Fuzzy Vehicle Routing Problem (FVRP) is proposed. For the possibility environment the levels of movements between customers are calculated by the constructed simulation interactive algorithm. The first criterion of the bi-criteria optimization problem - minimization of the expectation of total fuzzy travel time on closed routes is constructed for the FVRP. A new, second criterion – maximization of feasibility of movement on the closed routes is constructed by the Choquet finite averaging operator. The FVRP is reduced to the bi-criteria partitioning problem for the so called “promising” routes which were selected from the all admissible closed routes. The convenient selection of the “promising” routes allows us to solve the reduced problem in the real-time computing. For the numerical solution of the bi-criteria partitioning problem the -constraint approach is used. An exact algorithm is implemented based on D. Knuth’s Dancing Links technique and the algorithm DLX. The Main objective was to present the new approach for FVRP, when there are some difficulties while moving on the roads. This approach is called FVRP for extreme conditions (FVRP-EC) on the roads. Also, the aim of this paper was to construct the solving model of the constructed FVRP. Results are illustrated on the numerical example where all Pareto-optimal solutions are found. Also, an approach for more complex model FVRP with time windows was developed. A numerical example is presented in which optimal routes are constructed for extreme conditions on the roads.

Keywords: combinatorial optimization, Fuzzy Vehicle routing problem, multiple objective programming, possibility theory

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Authors: Faheem Ur Rehman, Muhammad Khalil Khan, Miao Qing

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This study investigated the asymmetric links and portfolio strategies between green bonds and the markets of three different cryptocurrencies, i.e., green, Islamic, and conventional, using data from January 1, 2018, to April 8, 2022, and employing asymmetric TVP-VAR model to quantify risk spillovers in the network analysis. In addition, we use the minimum variance, minimum correlation, and minimum connectedness methodologies to assess the portfolio implications. The results of the asymmetric dynamic connectedness index (TCI) model show that by adopting cryptocurrencies for digital finance, risk spillovers are found to be reduced. The findings of net directional connectedness demonstrate that during the study period, green bonds consistently get return spillovers from all other network variables. Positive return spillovers are bigger in magnitude than negative ones. These results imply that the influence of the green bond market on the cryptocurrency markets is decreasing. Positive return spillovers generate higher connectedness values for (HG, BNB, and TRX) coins and persistent net recipients in the specific network. On the other hand, Cardano and ADA coins are persistent net transmitters in the system. XLM and MIOTA's responsibilities shift over time, and there is evidence of asymmetry when both positive and negative returns are considered. According to the pairwise portfolio weights, BNB vs. BTC has the largest portfolio weights in the system, followed by BNB vs. Ethereum, suggesting the best investment strategies in the network.

Keywords: asymmetric TVP-VAR, global sustainable index, cryptocurrency, portfolios

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Authors: Meng-Cong Zheng, Yu-Sheng Chen

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The meeting behavior is a pervasive kind of interaction, which often occurs between the passenger and the shuttle. However, the meeting point set up at the Taoyuan International Airport is too far from the entry-exit, often causing passengers to stop searching near the entry-exit. When the number of people waiting for the rush hour increases, it often results in chaos in the waiting area. This study tried to find out what is the key factor to promote the rapid finding of each other between the passengers and the pick-ups. Then we implemented several design proposals to improve the meeting behavior of passengers and pick-ups based on behavior mapping and post-occupancy evaluation to enhance their meeting efficiency in unfamiliar environments. The research base is the reception hall of the second terminal of Taoyuan International Airport. Behavioral observation and mapping are implemented on the entry of inbound passengers into the welcome space, including the crowd distribution of the people who rely on the separation wall in the waiting area, the behavior of meeting and the interaction between the inbound passengers and the pick-ups. Then we redesign the space planning and signage design based on post-occupancy evaluation to verify the effectiveness of space plan and signage design. This study found that passengers ignore existing meeting-point designs which are placed on distant pillars at both ends. The position of the screen affects the area where the receiver is stranded, causing the pick-ups to block the passenger's moving line. The pick-ups prefer to wait where it is easy to watch incoming passengers and where it is closest to the mode of transport they take when leaving. Large visitors tend to gather next to landmarks, and smaller groups have a wide waiting area in the lobby. The location of the meeting point chosen by the pick-ups is related to the view of the incoming passenger. Finally, this study proposes an improved design of the meeting point, setting the traffic information in it, so that most passengers can see the traffic information when they enter the country. At the same time, we also redesigned the pick-ups desk to improve the efficiency of passenger meeting.

Keywords: meeting point design, post-occupancy evaluation, behavioral mapping, international airport

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Authors: J. Leige Lopes, L. Aparecida Bastos, R. Monteiro da Silva

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The objective of this paper is to study the work of children and adolescents and the vicious circle of poverty from the perspective of Guinar Myrdal’s Theory of Circular Cumulative Causation. The objective is to show that if a person starts working in the juvenile phase of life they will be classified as poor or extremely poor when they are adult, which can to be observed in the case of Brazil, more specifically in the north and northeast. To do this, the methodology used was statistical and econometric analysis by applying a probit model. The main results show that: if people reside in the northeastern region of Brazil, and if they have a low educational level and if they start their professional life before the age 18, they will increase the likelihood that they will be poor or extremely poor. There is a consensus in the literature that one of the causes of the intergenerational transmission of poverty is related to child labor, this because when one starts their professional life while still in the toddler or adolescence stages of life, they end up sacrificing their studies. Because of their low level of education, children or adolescents are forced to perform low-paid functions and abandon school, becoming in the future, people who will be classified as poor or extremely poor. As a result of poverty, parents may be forced to send their children out to work when they are young, so that in the future they will also become poor adults, a process that is characterized as the "vicious circle of poverty."

Keywords: children, adolescents, Gunnar Myrdal, poverty, vicious circle

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Authors: Vinay C. Doranalu, Amba Shetty

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In recent days due to climate change, there is a large variation in spatial distribution of daily rainfall within a small region. Rainfall is one of the main end climatic variables which affect spatio-temporal patterns of water availability. The real task postured by the change in climate is identification, estimation and understanding the uncertainty of rainfall. This study intended to analyze the spatial variations and temporal trends of daily precipitation using high resolution (0.25º x 0.25º) gridded data of Indian Meteorological Department (IMD). For the study, 38 grid points were selected in the study area and analyzed for daily precipitation time series (113 years) over the period 1901-2013. Grid points were divided into two zones based on the elevation and situated location of grid points: Low Land (exposed to sea and low elevated area/ coastal region) and High Land (Interior from sea and high elevated area/western Ghats). Time series were applied to examine the spatial analysis and temporal trends in each grid points by non-parametric Mann-Kendall test and Theil-Sen estimator to perceive the nature of trend and magnitude of slope in trend of rainfall. Pettit-Mann-Whitney test is applied to detect the most probable change point in trends of the time period. Results have revealed remarkable monotonic trend in each grid for daily precipitation of the time series. In general, by the regional cluster analysis found that increasing precipitation trend in shoreline region and decreasing trend in Western Ghats from recent years. Spatial distribution of rainfall can be partly explained by heterogeneity in temporal trends of rainfall by change point analysis. The Mann-Kendall test shows significant variation as weaker rainfall towards the rainfall distribution over eastern parts of the Western Ghats region of Karnataka.

Keywords: change point analysis, coastal region India, gridded rainfall data, non-parametric

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Authors: Melanie Ostermann, Eivind Birkeland, Ying Xue, Alexander Sauter, Mihaela R. Cimpan

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Background: New reliable and robust techniques to assess biological effects of nanomaterials (NMs) in vitro are needed to speed up safety analysis and to identify key physicochemical parameters of NMs, which are responsible for their acute cytotoxicity. The central aim of this study was to validate and evaluate the applicability and reliability of an impedance-based flow cytometry (IFC) technique for the high-throughput screening of NMs. Methods: Eight inorganic NMs from the European Commission Joint Research Centre Repository were used: NM-302 and NM-300k (Ag: 200 nm rods and 16.7 nm spheres, respectively), NM-200 and NM- 203 (SiO₂: 18.3 nm and 24.7 nm amorphous, respectively), NM-100 and NM-101 (TiO₂: 100 nm and 6 nm anatase, respectively), and NM-110 and NM-111 (ZnO: 147 nm and 141 nm, respectively). The aim was to assess the biological effects of these materials on human monoblastoid (U937) cells. Dispersions of NMs were prepared as described in the NANOGENOTOX dispersion protocol and cells were exposed to NMs at relevant concentrations (2, 10, 20, 50, and 100 µg/mL) for 24 hrs. The change in electrical impedance was measured at 0.5, 2, 6, and 12 MHz using the IFC AmphaZ30 (Amphasys AG, Switzerland). A traditional toxicity assay, Trypan Blue Dye Exclusion assay, and dark-field microscopy were used to validate the IFC method. Results: Spherical Ag particles (NM-300K) showed the highest toxic effect on U937 cells followed by ZnO (NM-111 ≥ NM-110) particles. Silica particles were moderate to non-toxic at all used concentrations under these conditions. A higher toxic effect was seen with smaller sized TiO2 particles (NM-101) compared to their larger analogues (NM-100). No interferences between the IFC and the used NMs were seen. Uptake and internalization of NMs were observed after 24 hours exposure, confirming actual NM-cell interactions. Conclusion: Results collected with the IFC demonstrate the applicability of this method for rapid nanotoxicity assessment, which proved to be less prone to nano-related interference issues compared to some traditional toxicity assays. Furthermore, this label-free and novel technique shows good potential for up-scaling in directions of an automated high-throughput screening and for future NM toxicity assessment. This work was supported by the EC FP7 NANoREG (Grant Agreement NMP4-LA-2013-310584), the Research Council of Norway, project NorNANoREG (239199/O70), the EuroNanoMed II 'GEMN' project (246672), and the UH-Nett Vest project.

Keywords: cytotoxicity, high-throughput, impedance, nanomaterials

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Authors: Augustina Konadu Larbi-Ampofo, Ekemini Umoinwek

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Background: Hypercalcaemia is a common electrolyte imbalance that increases mortality if poorly controlled. Primary hyperparathyroidism often presents like this with a prevalence of 0.1-0.3%. Management due to an ectopic parathyroid adenoma in the mediastinum is challenging, especially in a patient with a pacemaker. Case Presentation: A 79-year-old woman with a history of a previous cardiac arrest, permanent pacemaker, ischaemic heart disease, bilateral renal calculi, rectal polyps, liver cirrhosis, and a family history of hyperthyroidism presented to the emergency department with acute back pain. Management and Outcome: The patient was diagnosed with primary hyperparathyroidism due to her elevated corrected calcium and parathyroid hormone levels. Parathyroid investigations consisting of an NM MIBI scan, SPECT-CT, 4D parathyroid scan, and an ultrasound scan of the neck and thorax confirmed an ectopic parathyroid adenoma in the mediastinum at the level of the aortic arch, along with benign thyroid nodules. The location of the adenoma warranted a thoracoscopic surgical approach; however, the presence of her pacemaker and other cardiovascular conditions predisposed her to a potentially poorer post-operative outcome. Discussion: Mediastinal ectopic parathyroid adenomas are rare and difficult to diagnose and treat, often needing a multimodal imaging approach for accurate localisation. Surgery is a definitive treatment; however, in this patient, long-term medical treatment with cinacalcet was the only next suitable treatment option. The difficulty with this is that cinacalcet tackles the biochemical markers of the disease entity and not the disease itself, leaving room for what happens next if there is refractory/uncontrolled hypercalcaemia in this patient with a pacemaker. Moreover, the coexistence of her multiple conditions raises the suspicion of an underlying multisystemic or multiple endocrine disorder, with multiple endocrine neoplasia coming to mind, necessitating further genetic or autoimmune investigations. Conclusion: Mediastinal ectopic parathyroid adenomas are rare, with diagnostic and management challenges.

Keywords: mediastinal ectopic parathyroid adenoma, hyperparathyroidism, SPECT/CT, nuclear medicine, multimodal imaging

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Authors: Abdallah M. Fayed

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The study area is located in south Darb El Arbaieen, western desert of Egypt. It occupies the area between latitudes 22° 00/ and 22° 30/ North and Longitudes 29° 30/ and 30° 00/ East, from southern border of Egypt to the area north Bir Kuraiym and from the area East of East Owienat to the area west Tushka district, its area about 2750 Km2. The famous features; southern part of Darb El Arbaieen road, G Baraqat El Scab El Qarra, Bir Dibis, Bir El Shab and Bir Kuraiym, Interpretation of soil stratification shows layers that are related to Quaternary and Upper-Lower Cretaceous eras. It is dissected by a series of NE-SW striking faults. The regional groundwater flow direction is in SW-NE direction with a hydraulic gradient is 1m / 2km. Mathematical model program has been applied for evaluation of groundwater potentials in the main Aquifer –Nubian Sandstone- in the area of study and Remote sensing technique is considered powerful, accurate and saving time in this respect. These techniques are widely used for illustrating and analysis different phenomenon such as the new development in the desert (land reclamation), residential development (new communities), urbanization, etc. The major issues concerning water development objective of this work is to determine the new development areas in western desert of Egypt during the period from 2003 to 2015 using remote sensing technique, the impacts of the present and future development have been evaluated by using the two-dimensional numerical groundwater flow Simulation Package (visual modflow 4.2). The package was used to construct and calibrate a numerical model that can be used to simulate the response of the aquifer in the study area under implementing different management alternatives in the form of changes in piezometric levels and salinity. Total period of simulation is 100 years. After steady state calibration, two different scenarios are simulated for groundwater development. 21 production wells are installed at the study area and used in the model, with the total discharge for the two scenarios were 105000 m3/d, 210000 m3/d. The drawdown was 11.8 m and 23.7 m for the two scenarios in the end of 100 year. Contour maps for water heads and drawdown and hydrographs for piezometric head are represented. The drawdown was less than the half of the saturated thickness (the safe yield case).

Keywords: remote sensing, management of aquifer systems, simulation modeling, western desert, South Darb El Arbaieen

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Authors: Jaco Oosthuizen, Nerina C. Van Der Merwe

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The National Health Laboratory Services in Bloemfontien has been the diagnostic testing facility for 1830 patients for familial breast cancer since 1997. From the cohort, 540 were comprehensively screened using High-Resolution Melting Analysis or Next Generation Sequencing for the presence of point mutations and/or indels. Approximately 90% of these patients stil remain undiagnosed as they are BRCA1/2 negative. Multiplex ligation-dependent probe amplification was initially added to screen for copy number variation detection, but with the introduction of next generation sequencing in 2017, was substituted and is currently used as a confirmation assay. The aim was to investigate the viability of utilizing internationally designed copy number variation detection assays based on mostly European/Caucasian genomic data for use within a South African context. The multiplex ligation-dependent probe amplification technique is based on the hybridization and subsequent ligation of multiple probes to a targeted exon. The ligated probes are amplified using conventional polymerase chain reaction, followed by fragment analysis by means of capillary electrophoresis. The experimental design of the assay was performed according to the guidelines of MRC-Holland. For BRCA1 (P002-D1) and BRCA2 (P045-B3), both multiplex assays were validated, and results were confirmed using a secondary probe set for each gene. The next generation sequencing technique is based on target amplification via multiplex polymerase chain reaction, where after the amplicons are sequenced parallel on a semiconductor chip. Amplified read counts are visualized as relative copy numbers to determine the median of the absolute values of all pairwise differences. Various experimental parameters such as DNA quality, quantity, and signal intensity or read depth were verified using positive and negative patients previously tested internationally. DNA quality and quantity proved to be the critical factors during the verification of both assays. The quantity influenced the relative copy number frequency directly whereas the quality of the DNA and its salt concentration influenced denaturation consistency in both assays. Multiplex ligation-dependent probe amplification produced false positives due to ligation failure when ligation was inhibited due to a variant present within the ligation site. Next generation sequencing produced false positives due to read dropout when primer sequences did not meet optimal multiplex binding kinetics due to population variants in the primer binding site. The analytical sensitivity and specificity for the South African population have been proven. Verification resulted in repeatable reactions with regards to the detection of relative copy number differences. Both multiplex ligation-dependent probe amplification and next generation sequencing multiplex panels need to be optimized to accommodate South African polymorphisms present within the genetically diverse ethnic groups to reduce the false copy number variation positive rate and increase performance efficiency.

Keywords: familial breast cancer, multiplex ligation-dependent probe amplification, next generation sequencing, South Africa

Procedia PDF Downloads 228